Datasets:

Haxirus

/

Transformed_Enhanced_Interactions

like 0

Do Abatacept and Zileuton interact?

•Drug A: Abatacept •Drug B: Zileuton •Severity: MODERATE •Description: The metabolism of Zileuton can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP1A2 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Due to the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of 5-lipoxygenase activity may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): Rapidly and almost completely absorbed. The absolute bioavailability is unknown. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): 1.2 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 93% bound to plasma proteins, primarily to albumin. •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): Hepatic. Zileuton and its N-dehydroxylated metabolite are oxidatively metabolized by the cytochrome P450 isoenzymes 1A2, 2C9 and 3A4. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): Elimination of zileuton is predominantly via metabolism with a mean terminal half-life of 2.5 hours. The urinary excretion of the inactive N-dehydroxylated metabolite and unchanged zileuton each accounted for less than 0.5% of the dose. •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): 2.5 hours •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): Apparent oral cl=7 mL/min/kg •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): Minimum oral lethal dose of zileuton in various preparations was 500-4000 mg/kg in mice and 300-1000 mg/kg in rats (providing greater than 3 and 9 times the systemic exposure [AUC] achieved at the maximum recommended human daily oral dose, respectively). •Brand Names (Drug A): Orencia •Brand Names (Drug B): Zyflo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (±)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea Leutrol (common) N-(1-Benzo(b)thien-2-ylethyl)-N-hydroxyurea N-[1-(benzo[b]thiophen-2-yl)ethyl]-N-hydroxyurea Zileuton (common) Zileutón (common) Zileutonum (common)

Do Abatacept and Ziprasidone interact?

•Drug A: Abatacept •Drug B: Ziprasidone •Severity: MODERATE •Description: The metabolism of Ziprasidone can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP3A4 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): In its oral form, ziprasidone is approved for the treatment of schizophrenia, as monotherapy for acute treatment of manic or mixed episodes related to bipolar I disorder, and as adjunctive therapy to lithium or valproate for maintenance treatment of bipolar I disorder. The injectable formulation is approved only for treatment of acute agitation in schizophrenia. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): Ziprasidone is classified as a "second generation" or "atypical" antipsychotic and is a dopamine and 5HT2A receptor antagonist with a unique receptor binding profile. As previously mentioned, ziprasidone has a very high 5-HT2A/D2 affinity ratio, binds to multiple serotonin receptors in addition to 5-HT2A, and blocks monoamine transporters which prevents 5HT and NE reuptake. On the other hand, ziprasidone has a low affinity for muscarinic cholinergic M1, histamine H1, and alpha1-adrenergic receptors. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): The effects of ziprasidone are differentiated from other antispychotics based on its preference and affinity for certain receptors. Ziprasidone binds to serotonin-2A (5-HT2A) and dopamine D2 receptors in a similar fashion to other atypical antipsychotics; however, one key difference is that ziprasidone has a higher 5-HT2A/D2 receptor affinity ratio when compared to other antipsychotics such as olanzapine, quetiapine, risperidone, and aripiprazole. Ziprasidone offers enhanced modulation of mood, notable negative symptom relief, overall cognitive improvement and reduced motor dysfunction which is linked to it's potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in brain tissue. Ziprasidone can bind moderately to norepinephrine and serotonin reuptake sites which may contribute to its antidepressant and anxiolytic activity. Patient's taking ziprasidone will likely experience a lower incidence of orthostatic hypotension, cognitive disturbance, sedation, weight gain, and disruption in prolactin levels since ziprasidone has a lower affinity for histamine H1, muscarinic M1, and alpha1-adrenoceptors. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): In the absence of food, ziprasidone's oral bioavailability is 60%, and absorption may reach 100% if ziprasidone is taken with a meal containing at least 500 kcal. The difference in bioavailability has little to do with the fat content of the food and appears to be related to the bulk of the meal since more absorption occurs the longer ziprasidone remains in the stomach. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): The mean apparent volume of distribution of Ziprasidone is 1.5 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ziprasidone is extensively protein bound with over 99% of the drug bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein. •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): Ziprasidone is heavily metabolized in the liver with less than 5% of the drug excreted unchanged in the urine. The primary reductive pathway is catalyzed by aldehyde oxidase, while 2 other less prominent oxidative pathways are catalyzed by CYP3A4. Ziprasidone is unlikely to interact with other medications metabolized by CYP3A4 since only 1/3 of the antipsychotic is metabolized by the CYP3A4 system. There are 12 identified ziprasidone metabolites (abbreviations italicized): Ziprasidone sulfoxide, ziprasidone sulfone, (6-chloro-2-oxo-2,3-dihydro-1H-indol-5-yl)acetic acid ( OX-COOH ), OX-COOH glucuronide, 3-(piperazine-1-yl)-1,2-benzisothiazole ( BITP ), BITP sulfoxide, BITP sulfone, BITP sulfone lactam, S-Methyl-dihydro-ziprasidone, S-Methyl-dihydro-ziprasidone-sulfoxide, 6-chloro-5-(2-piperazin-1-yl-ethyl)-1,3-dihydro-indol-2-one ( OX-P ), and dihydro-ziprasidone-sulfone. As suggested by the quantity of metabolites, ziprasidone is metabolized through several different pathways. Ziprasidone is sequentially oxidized to ziprasidone sulfoxide and ziprasidone sulfone, and oxidative N-dealkylation of ziprasidone produces OX-COOH and BITP. OX-COOH undergoes phase II metabolism to yield a glucuronidated metabolite while BITP is sequentially oxidized into BITP sulfoxide, BITP sulfone, then BITP sulfone lactam. Ziprasidone can also undergo reductive cleavage and methylation to produce S-Methyl-dihydro-ziprasidone and then further oxidation to produce S-Methyl-dihydro-ziprasidone-sulfoxide. Finally dearylation of ziprasidone produces OX-P, and the process of hydration and oxidation transforms the parent drug into dihydro-ziprasidone-sulfone. Although CYP3A4 and aldehyde oxidase are the primary enzymes involved in ziprasidone metabolism, the pathways associated with each enzyme have not been specified. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): Ziprasidone is extensively metabolized after oral administration with only a small amount excreted in the urine (<1%) or feces (<4%) as unchanged drug. •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): The half life of ziprasidone is 6-7 hours. •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): The mean apparent systemic clearance is 7.5 mL/min/kg. •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): The most common adverse reactions reported with ziprasidone include somnolence, respiratory tract infections, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting, headache and nausea. •Brand Names (Drug A): Orencia •Brand Names (Drug B): Geodon, Zeldox •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abatacept and Zolmitriptan interact?

•Drug A: Abatacept •Drug B: Zolmitriptan •Severity: MODERATE •Description: The metabolism of Zolmitriptan can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP1A2 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): Zolmitriptan is indicated for the acute treatment of migraine with or without auras in patients aged 18 and over. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): Zolmitriptan, like other triptans, is a serotonin (5-hydroxytryptamine; 5-HT) receptor agonist, with enhanced specificity for the 5-HT 1B and 5-HT 1D receptor subtypes. It is through the downstream effects of 5-HT 1B/1D activation that triptans are proposed to provide acute relief of migraines. Zolmitriptan is also a vasoconstrictor, leading to possible adverse cardiovascular effects such as myocardial ischemia/infarction, arrhythmias, cerebral and subarachnoid hemorrhage, stroke, gastrointestinal ischemia, and peripheral vasospastic reactions. In addition, chest/throat/neck/jaw pain, tightness, and/or pressure has been reported, along with the possibility of medication overuse headaches and serotonin syndrome. Patients with phenylketonuria should be advised that ZOMIG-ZMT contains phenylalanine. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): Migraines are complex physiological events characterized by unilateral throbbing headaches combined with photophobia and other aversions to sensory input. Migraine attacks are generally divided into phases: the premonitory phase, which typically involves irritability, fatigue, yawning, and stiff neck; the headache phase, which lasts for between four and 72 hours; and the postdrome phase, which lasts for up to a day following resolution of pain and whose symptoms are similar to those of the premonitory phase. In addition, neurological deficits, collectively termed migraine aura, may precede the headache phase. The underlying pathophysiology of migraines is a matter of active research but involves both neurological and vascular components. The head pain associated with migraine is thought to be a consequence of activation of the nociceptive nerves comprising the trigeminocervical complex (TCC). Terminals of nociceptive nerves that innervate the dura matter release vasoactive peptides, such as calcitonin gene-related peptide (CGRP), resulting in cranial vasodilation. Finally, when present, migraine aura appears to correlate with a transient wave(s) of cortical depolarization, termed cortical spreading depression (CSD). Triptans, including zolmitriptan, are proposed to act in three ways. The main mechanism is through modulation of nociceptive nerve signalling in the central nervous system through 5-HT 1B/1D receptors throughout the TCC and associated areas of the brain. In addition, triptans can enhance vasoconstriction, both through direct 5-HT 1B -mediated dilation of cranial blood vessels, as well as through 5-HT 1D -mediated suppression of CGRP release. Although triptans are classically described solely in terms of their effects on 5-HT 1B/1D receptors, they also act as 5-HT 1F agonists as well. This 5-HT subtype is also found throughout the TCC, but is not present appreciably in cerebral vasculature; the significance of triptan-mediated 5-HT 1F activation is currently not well described. Additionally, CSD that initiates in the ipsilateral parietal region may exert its effects in a manner that relies on 5-HT 1B/1D receptor activation, suggesting that triptans may have some effect on CSD-mediated symptoms. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): Zolmitriptan tablets have a mean absolute oral bioavailability of approximately 40%, with food having no effect on the rate or extent of absorption. The dosing kinetics are linear over a range of 2.5 to 50 mg with 75% of the eventual C max being attained within 1 hour of dosing. The median T max for the tablet form is 1.5 hours, while for the orally disintegrating tablet form, it is 3 hours. The AUC across studies was in the range of 84.4-173.8 ng/mL*h while the C max was between 16 and 25.2 ng/mL. Zolmitriptan administered as a nasal spray is detected in the plasma within 2-5 minutes, compared to 10-15 minutes for the tablet form; the faster kinetics likely reflect fast absorption across the nasal mucosa. The bioavailability compared to the tablet is 102%, and plasma zolmitriptan concentration is maintained for 4-6 hours after intranasal delivery. The active N-desmethyl metabolite of zolmitriptan has a mean plasma concentration that is roughly two-thirds of zolmitriptan, regardless of dosage route or concentration. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): Zolmitriptan has a volume of distribution between 7 and 8.4 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Zolmitriptan and its active N-desmethyl metabolite remain approximately 25% bound to plasma proteins over a concentration range of 10-1000 ng/mL. •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): Zolmitriptan is metabolized in the liver, and studies using cytochrome P450 inhibitors like cimetidine suggest that it is likely metabolized by CYP1A2, as well as by monoamine oxidase (MAO). Zolmitriptan metabolism results in three major metabolites: an active N-desmethyl metabolite (183C91) as well as inactive N-oxide (1652W92) and indole acetic acid (2161W92) metabolites. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): Zolmitriptan is primarily excreted in urine (approximately 65%) and feces (approximately 30%). Within urine, the most common form is the indole acetic acid metabolite (31%), followed by the N-oxide (7%), and N-desmethyl (4%) metabolites; the majority of zolmitriptan recovered in feces remains unchanged. •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): Zolmitriptan has a mean elimination half-life of approximately three hours following oral or nasal administration. Its active N-desmethyl metabolite has a slightly longer (approximately 3.5 hours) half-life. •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): Zolmitriptan has a clearance of 31.5 mL/min/kg for oral tablets and 25.9 mL/min/kg for nasal administration; one-sixth of the clearance is renal. •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): Toxicity information regarding zolmitriptan is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as cardiovascular symptoms due to excessive vasoconstriction and activation of serotonergic receptors. Patients receiving a single 50 mg oral dose of zolmitriptan often experienced sedation. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): Orencia •Brand Names (Drug B): Zomig •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1,3-oxazolidin-2-one 4-[[3-(2-dimethylaminoethyl)-1H-indol-5-yl]methyl]oxazolidin-2-one Zolmitriptan (common) Zolmitriptán (common) Zolmitriptanum (common)

Do Abatacept and Zolpidem interact?

•Drug A: Abatacept •Drug B: Zolpidem •Severity: MODERATE •Description: The metabolism of Zolpidem can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP1A2 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): This drug is indicated for the short-term treatment of insomnia in adults characterized by difficulties with sleep initiation. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): Effects on the central nervous system (CNS) This drug has CNS depressant effects, which may include somnolence, decreased alertness, sedation, drowsiness, dizziness, and other changes in psychomotor function. Due to the above effects, the FDA has recommended an initial dose of zolpidem (immediate-acting) is a single dose of 5 mg for women and a single dose of 5 or 10 mg for men, immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening. Refer to product labeling for detailed information,. Effects on memory Controlled studies in adults using objective measures of memory demonstrated no significant evidence of next-day memory impairment after the administration of zolpidem. On the contrary, in a clinical study involving the administration of zolpidem doses of 10 and 20 mg, a marked reduction in a next-morning recall of information relayed to subjects during peak drug effect (90 minutes after dosing) was observed. These subjects experienced a condition known as anterograde amnesia. Subjective evidence from adverse event data has suggested that anterograde amnesia may occur after zolpidem administration, mainly at doses above 10 mg. Effects on psychomotor function This drug may cause decreased psychomotor performance. Additive psychomotor effects may occur with other drugs that cause depression of psychomotor function, including alcohol. Patients taking zolpidem should be cautioned against participating in hazardous activities or occupations requiring complete mental alertness or motor coordination, including operating machinery or driving a motor vehicle after ingesting the drug. Potential impairment of the performance of the above types of activities may also occur the day after zolpidem ingestion, especially at higher doses and ingestion of the extended-release form,. Effects on insomnia and sleep stages Evidence suggests that this drug is associated with minimal rebound insomnia. During clinical trials with patients using zolpidem on an ‘as-needed’ basis, zolpidem use resulted in global improvements in sleep. Zolpidem has been demonstrated to decrease sleep latency (the time it takes to fall asleep) for up to 35 days in controlled clinical studies. In studies measuring the percentage of sleep time spent in each sleep stage, zolpidem has primarily been shown to preserve sleep stages. Sleep time spent in stages 3 and 4 (deep sleep) was measured as similar to placebo with only minor and inconsistent changes in REM (paradoxical) sleep at the recommended dose. Next-day residual effects In 2013, the FDA issued a statement warning that patients who take zolpidem extended-release (Ambien CR)―either 6.25 mg or 12.5 mg―should not drive or participate in other activities requiring full mental alertness the day after taking the drug, due to the fact that zolpidem concentrations can remain increased the next day, and impair the ability to perform these activities,. Patients may decrease their risk of next-morning impairment by taking the lowest dose of their insomnia medicine that treats their symptoms, according to the FDA. Specific dosing recommendations for both men and women are included in this statement. This information is also available on product labeling,. Rebound effects There was no polysomnographic (objective) evidence of rebound insomnia at normal doses, in studies evaluating sleep on the nights following discontinuation of zolpidem tartrate. Subjective evidence of impaired sleep in the elderly on the first post-treatment night was observed at doses higher than the recommended 5mg dose for elderly patients. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with a GABA-BZ receptor complex and shares various pharmacological properties with the benzodiazepine class of drugs. Subunit binding of the GABAA receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of zolpidem. The main regulatory site of the GABAA receptor complex can be found on its alpha (α) subunit and is called the benzodiazepine (BZ) or omega (ω) receptor. At least three different subtypes of the (ω) receptor have been identified to this date. In contrast to benzodiazepine drugs, which are found to modulate all benzodiazepine receptor subtypes in a non-selective fashion, zolpidem binds the (BZ1) receptor specifically with a potent affinity for the alpha 1/alpha 5 subunits (in vitro). More recent studies suggest that zolpidem binds primarily to the alpha 1, 2, and 3 subunits of the GABA receptor,,, and not the alpha 5 subunit. The ( BZ1 ) receptor is found primarily on the Lamina IV of the brain sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. Specific and selective binding of zolpidem on the (BZ1) receptor is not considered absolute, however, this binding could potentially explain the relative lack of myorelaxant and anticonvulsant activity in animal studies in addition to the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): Zolpidem is rapidly absorbed from the gastrointestinal tract. In a single-dose crossover study in 45 healthy subjects given 5 and 10 mg zolpidem tartrate tablets, the average peak zolpidem concentrations (Cmax) were 59 and 121 ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for both doses. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): 0.54 to 0.68 L/kg (in humans). In patients with long term renal insufficiency who were not yet on hemodialysis, the volume of distribution was found to increase significantly, AUC increased by 60%, and half-life nearly doubled. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 92.5 ± 0.1% •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): Zolpidem is metabolized to three pharmacologically by various hepatic cytochrome P450 (CYP) isoenzymes, mainly CYP3A4, but also CYP1A2 and CYP2C9,. Although zolpidem is heavily metabolized, all three metabolites are inactive. The major metabolic routes in humans are oxidation of the methyl group on the phenyl ring or the methyl group on the imidazopyridine moiety, to produce carboxylic acids (metabolites I and II), and hydroxylation of one of the imidazopyridine groups (to produce metabolite X). Another less common pathway is by the oxidation of the methyl groups on the substituted amide. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated mainly by renal excretion. •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): The average zolpidem elimination half-life was 2.6 and 2.5 hours, for the 5 and 10 mg tablets, respectively. •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): In a clinical trial, after a 20mg dose, total clearance of zolpidem 0.24 to 0.27 ml/min/kg. •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): Oral (male rat) LD 50 = 695 mg/kg. Overdose Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma, in addition to cardiorespiratory collapse resulting in fatal outcomes have been reported. Withdrawal effects Following rapid decreases in dose or abrupt discontinuation of zolpidem and other sedative/hypnotics, reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs have been made. Carcinogenesis Zolpidem was administered to rats and mice over a span of 2 years at dietary dosages of 4, 18, and 80 mg/kg/day. In mice, these doses are considered 26 to 520 times or 2 to 35 times the maximum 10 mg human dose, respectively. In rats, these doses are 43 to 876 times or 6 to 115 times the maximum 10 mg human dose. No evidence of carcinogenicity was seen in mice. Renal liposarcomas were observed in 4/100 rats (3 males, 1 female) receiving 80 mg/kg/day, and a renal lipoma was observed in one male rat at the 18 mg/kg/day dose. Incidence rates of lipoma and liposarcoma for zolpidem were similar to those seen in historical control cases, and the tumor findings are presumed to be a spontaneous occurrence, not causally related to zolpidem. Mutagenesis Zolpidem did not show mutagenic activity in several tests including the Ames test, genotoxicity in mouse lymphoma cells in vitro, chromosomal aberrations in cultured human lymphocytes, abnormal DNA synthesis in rat hepatocytes in vitro, and the micronucleus test performed in mice. Impairment of fertility In a rat reproduction study, the high dose (100 mg base/kg) of zolpidem lead to irregular estrus cycles and prolonged precoital intervals, however, there was no effect on male or female fertility after daily oral doses comparable to 5 to 130 times the recommended human dose. No effects on any other fertility parameters were observed. Use in pregnancy This drug is considered a pregnancy category C drug. There are currently no sufficient conclusive studies completed in pregnant women to determine the safety of zolpidem use during pregnancy. Zolpidem should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Use in nursing From 0.004% to 0.019% of the total administered zolpidem dose is excreted into milk. The effect of zolpidem on the nursing infant is unknown at this time. Caution should be observed when zolpidem is administered to a nursing mother. •Brand Names (Drug A): Orencia •Brand Names (Drug B): Ambien, Edluar, Intermezzo, Tovalt •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): N,N,6-Trimethyl-2-(4-methylphenyl)imidazo(1,2-a)pyridine-3-acetamide Zolpidem (common) Zolpidemum (common)

Do Abatacept and Zonisamide interact?

•Drug A: Abatacept •Drug B: Zonisamide •Severity: MODERATE •Description: The metabolism of Zonisamide can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP2C19 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): Zonisamide capsules are indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy. Zonisamide oral suspension is indicated as adjunctive therapy for the treatment of partial-onset seizures in adults and pediatric patients 16 years of age and older. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): By stopping the spread of seizure discharges, zonisamide prevents the extensor component of tonic convulsion, restricts the spread of focal seizures and prevents the propagation of seizures from the cortex to subcortical structures. In animal models, zonisamide was effective against tonic extension seizures but ineffective against clonic seizures. It also increased the threshold for generalized seizures and reduced the duration of cortical focal seizures. Aside from its antiepileptic effects, zonisamide is capable of activating neuroprotective mechanisms. It inhibits nitric oxide synthase and ​​reduces ischemia-induced memory impairment and lipid peroxidation. The use of zonisamide may lead to potentially fatal reactions. Severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, and aplastic anemia have been reported in patients treated with sulfonamides such as zonisamide. Zonisamide may also lead to the development of serious hematological events, drug reaction with eosinophilia and systemic symptoms (DRESS) and multi-organ hypersensitivity, acute myopia and secondary angle closure glaucoma, as well as suicidal behaviour and ideation. Zonisamide is a carbonic anhydrase inhibitor, which may lead to metabolic acidosis in patients treated with this drug. Its therapeutic effects due to this pharmacological action are unknown. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): The mechanism of action by which zonisamide controls seizures has not been fully established. However, its antiepileptic properties may be due to its effects on sodium and calcium channels. Zonisamide blocks sodium channels and reduces voltage-dependent, transient inward currents, stabilizing neuronal membranes and suppressing neuronal hypersynchronization. It affects T-type calcium currents, but has no effect on L-type calcium currents. Zonisamide suppresses synaptically-driven electrical activity by altering the synthesis, release, and degradation of neurotransmitters, such as glutamate, gamma-aminobutyric acid (GABA), dopamine, serotonin (5-hydroxytryptamine 5-HT ), and acetylcholine. Furthermore, it binds to the GABA/benzodiazepine receptor ionophore complex without producing changes in chloride flux. In vitro studies have suggested that zonisamide does not affect postsynaptic GABA or glutamate responses, nor the neuronal or glial uptake of [ H]-GABA. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): Between 200 and 400 mg, zonisamide follows a dose-proportional pharmacokinetic profile. At concentrations higher than 800 mg, the C max and AUC increase in a disproportional manner, possibly due to zonisamide binding red blood cells. In healthy volunteers given 200 to 400 mg of zonisamide orally, peak plasma concentrations (C max ) range between 2 and 5 µg/mL and are reached within 2–6 hours (T max ). In healthy volunteers given 100 mg of zonisamide oral suspension, the T max ranged from 0.5 to 5 hours. Zonisamide has a high oral bioavailability (95%). The T max of zonisamide was delayed by food intake (4-6 hours); however, food has no effect on its bioavailability. Steady state is achieved 14 days after a stable dose is reached. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): Following a 400 mg oral dose, zonisamide has an apparent volume of distribution (V/F) of 1.45 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): At concentrations between 1.0 and 7.0 μg/mL, zonisamide is approximately 40% bound to human plasma proteins. The concentration of zonisamide is 8-fold higher in red blood cells than in plasma due to its ability to bind extensively to erythrocytes. The presence of therapeutic concentrations of phenytoin, phenobarbital, or carbamazepine does not affect zonisamide protein binding. •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): Zonisamide metabolites are generated mainly by principally reductive and conjugative mechanisms. Oxidation reactions play a minor role in the metabolism of zonisamide. Zonisamide is metabolized by N-acetyl-transferases to form N-acetyl zonisamide and reduced to form the open ring metabolite, 2–sulfamoylacetylphenol (SMAP). The reduction of zonisamide to SMAP is mediated by CYP3A4. Zonisamide does not induce liver enzymes or its own metabolism. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): Zonisamide is mainly excreted as the parent drug and the glucuronide of a metabolite. Urine is the main route of zonisamide excretion, and only a small portion of this drug is excreted in feces. Following multiple doses of radiolabeled zonisamide, 62% of the dose was recovered in the urine, and 3% in feces by day 10. Of the excreted dose of zonisamide, 35% was recovered unchanged, 15% as N-acetyl zonisamide, and 50% as the glucuronide of 2–sulfamoylacetylphenol (SMAP). •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): In plasma, the elimination half-life of zonisamide is approximately 63 hours. In red blood cells, it is approximately 105 hours. •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): In patients not taking enzyme-inducing antiepilepsy drugs (AEDs), the plasma clearance of oral zonisamide is approximately 0.30-0.35 mL/min/kg. In patients treated with AEDs, this value increases to 0.5 mL/min/kg. Renal clearance is approximately 3.5 mL/min after a single-dose of zonisamide. In red blood cells, the clearance of an oral dose of zonisamide is 2 mL/min. •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): Information on daily doses over 800 mg/day of zonisamide is limited. During clinical development, three patients ingested unknown amounts of zonisamide as suicide attempts, and all of them were hospitalized with central nervous system symptoms. One patient became comatose and developed bradycardia, hypotension, and respiratory depression; 31 hours after zonisamide ingestion, plasma level was 100.1 µg/mL. Zonisamide plasma levels fell with a half-life of 57 hours, and the patient became alert five days later. There are no specific antidotes for zonisamide overdosage. In case of a suspected recent overdose, emesis should be induced or gastric lavage performed with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation. Due to its long half-life and low protein binding, renal dialysis may be effective in treating zonisamide overdose; however, the effectiveness of this procedure has not been formally studied. In vivo studies found no evidence of carcinogenicity at zonisamide doses equivalent to or higher than the maximum recommended human dose (MRHD). In an in vitro chromosomal aberration assay in CHL cells, zonisamide displayed mutagenicity. Signs of reproductive toxicity were also detected in rats treated with a dose 0.5 times the MRHD. •Brand Names (Drug A): Orencia •Brand Names (Drug B): Zonegran, Zonisade •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,2-Benzisoxazole-3-methanesulfonamide 3-(Sulfamoylmethyl)-1,2-benzisoxazole Benzo[d]isoxazol-3-yl-methanesulfonamide Zonisamida (common) Zonisamide (common) Zonisamidum (common)

Do Abatacept and Zopiclone interact?

•Drug A: Abatacept •Drug B: Zopiclone •Severity: MODERATE •Description: The metabolism of Zopiclone can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP2C9 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): For the short-term treatment of insomnia. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABA B Z) receptor complex. Subunit modulation of the GABA B Z receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABA B Z receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α1, α2, α3 and α5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): Rapidly absorbed following oral administration. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 45% •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): Elimination half life is approximately 5 hours (range 3.8 to 6.5 hours) and is prolonged to 11.9 hours in patients with hepatic insufficiency. •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): No clearance available •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agent. Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing. •Brand Names (Drug A): Orencia •Brand Names (Drug B): Imovane •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (+-)-zopiclone (±)-zopiclone 6-(5-Chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methyl-1-piperazinecarboxylate Zopiclona (common) Zopiclone (common) Zopiclonum (common)

Do Abatacept and Zuclopenthixol interact?

•Drug A: Abatacept •Drug B: Zuclopenthixol •Severity: MODERATE •Description: The metabolism of Zuclopenthixol can be increased when combined with Abatacept. •Extended Description: The formation of CYP450 enzymes is inhibited by the presence of increased levels of cytokines during chronic inflammation. Agents that reduce cytokine levels can normalize CYP450 formation and increase the metabolism of drugs. This interaction may significantly alter the therapeutic efficacy of CYP2D6 substrates. •References: 1. Liptrott NJ, Penny M, Bray PG, Sathish J, Khoo SH, Back DJ, Owen A: The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol. 2009 Feb;156(3):497-508. doi: 10.1111/j.1476-5381.2008.00050.x. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A40066] 2. Morgan ET: Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. [https://go.drugbank.com/articles/A40067] 3. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E: The Role of Cytochromes P450 in Infection. Front Immunol. 2018 Jan 31;9:89. doi: 10.3389/fimmu.2018.00089. eCollection 2018. [https://go.drugbank.com/articles/A40068] •Indication (Drug A): Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis. In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. •Indication (Drug B): Used in the management of acute psychoses such as mania or schizophrenia. However, the use of zuclopenthixol acetate in psychiatric emergencies as an alternative to standard treatments (haloperidol, clotiapine, etc.) should be cautioned, since well executed and documented trials of zuclopenthixol acetate for this use have yet to be conducted. Zuclopenthixol acetate is not intended for long-term use. •Pharmacodynamics (Drug A): Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G 1 (IgG 1. The Fc portion of the drug consists of the hinge region, the C H 2 domain, and the C H 3 domain of IgG 1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy. •Pharmacodynamics (Drug B): Zuclopenthixol is a thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. •Mechanism of action (Drug A): Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. •Mechanism of action (Drug B): Zuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene class. It mainly acts by antagonism of D1 and D2 dopamine receptors. Zuclopenthixol also has high affinity for alpha1-adrenergic and 5-HT2 receptors. It has weaker histamine H1 receptor blocking activity, and even lower affinity for muscarinic cholinergic and alpha2-adrenergic receptors. •Absorption (Drug A): When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. •Absorption (Drug B): Upon reaching the body water phase, the decanoate ester is slowly released from the oil depot, which is resultantly hydrolyzed to the active substance, zuclopenthixol. The decanoate ester provides a means of slow release since zuclopenthixol itself is a short-acting drug. •Volume of distribution (Drug A): 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] •Volume of distribution (Drug B): 20 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 98-99% •Metabolism (Drug A): No metabolism available •Metabolism (Drug B): The metabolism of zuclopenthixol is mainly by sulphoxidation, side chain N-dealkylation and glucuronic acid conjugation. The metabolites are devoid of pharmacological activity. •Route of elimination (Drug A): Kidney and liver •Route of elimination (Drug B): Primarily in the feces with approximately 10% in the urine. •Half-life (Drug A): 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. •Half-life (Drug B): 20 hours (range 12-28 hours) for the tablet form, 19 days for the depot form. •Clearance (Drug A): 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. •Clearance (Drug B): approximately 0.9 L/min. •Toxicity (Drug A): Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. •Toxicity (Drug B): Although there have not been any cases of overdosage reported, the symptoms are likely to be somnolence, coma, extrapyramidal symptoms, convulsions, hypotension, shock, or hyper- or hypothermia. Neuroleptic malignant syndrome may occur. Zuclopenthixol may potentiate anticholinergic effects of concurrent medications. Zuclopenthixol has a demonstrated antiemetic effect in animals, and may mask signs of toxicity due to other drug overdoses, or may mask symptoms of disease. •Brand Names (Drug A): Orencia •Brand Names (Drug B): Clopixol, Clopixol Acuphase, Clopixol Depot •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (Z)-4-(3-(2-Chlorothioxanthen-9-ylidene)propyl)-1-piperazineethanol Zuclopenthixol (common) Zuclopenthixolum (common) Zuclopentixol (common)

Do Abciximab and Abrocitinib interact?

•Drug A: Abciximab •Drug B: Abrocitinib •Severity: MAJOR •Description: The risk or severity of bleeding and thrombocytopenia can be increased when Abciximab is combined with Abrocitinib. •Extended Description: In clinical trials, abrocitinib was shown to decrease platelet counts in a dose-dependent fashion. Reduced platelet count is associated with a bleeding risk. In addition, in five clinical trials of abrocitinib , including the long-term extension trial, six subjects (0.9 per 100 patient-years) treated with 200 mg abrocitinib experienced thrombocytopenia. No patients treated with 100 mg abrocitinib experienced thrombocytopenia. Since antiplatelet agents aim to reduce blood clots, coadministration of abrocitinib with antiplatelet drugs may increase the risk of bleeding with thrombocytopenia. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Abrocitinib is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. In the US, it is indicated to treat refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when the use of those therapies is inadvisable. Abrocitinib is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Abrocitinib mediates anti-inflammatory effects by blocking the signalling of pro-inflammatory cytokines implicated in atopic dermatitis. It dose-dependently reduces the serum markers of inflammation in atopic dermatitis, including high sensitivity C-reactive protein (hsCRP), interleukin-31 (IL-31), and thymus and activation regulated chemokine (TARC). These changes returned to near baseline within four weeks following drug discontinuation. At two weeks of treatment, the mean absolute lymphocyte count increased, which returned to baseline by nine months of treatment. Treatment with abrocitinib was associated with a dose-related increase in B cell counts and a dose-related decrease in NK cell counts: the clinical significance of these changes is unknown. Treatment with 200 mg abrocitinib once-daily was associated with a transient, dose-dependent decrease in platelet count with the nadir occurring at a median of 24 days. Recovery of platelet count (~40% recovery by 12 weeks) occurred without discontinuation of the treatment. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Janus kinases (JAKs) are a family consisting of four receptor-associated kinases - JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Upon ligand binding and subsequent dimerization of cytokine and hormone receptors, receptor-associated JAKs are activated and phosphorylated. This allows the binding of Signal Transducers and Activators of Transcription (STATs), which are transcription factors. STAT binds to the receptor, and JAK phosphorylates and activates STAT to create a STAT dimer. The STAT dimer translocates to the nucleus to upregulate the gene transcription of pro-inflammatory cytokines and growth factors implicated in atopic dermatitis. Blocking the JAK-STAT pathway is advantageous, as it is an intracellular signalling pathway where many pro-inflammatory pathways converge. Each JAK plays a role in the signalling and regulation of different cytokines and immune cells. In atopic dermatitis, JAK1 is the therapeutic target of focus as it is involved in the signalling of the γc family of cytokines involved in immune responses and disease pathophysiology, including IL-2, IL-4, IL-7, IL-9, and IL-15. Abrocitinib reversibly inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site. Biochemical assays demonstrate that abrocitinib is selective for JAK1 over JAK2 (28-fold), JAK3 (>340-fold), and tyrosine kinase (TYK) 2 (43-fold), as well as the broader kinome. Similarly, in cellular settings, abrocitinib preferentially inhibited cytokine-induced STAT phosphorylation by signalling pairs involving JAK1, while sparing signalling by JAK2/JAK2, or JAK2/TYK2 pairs. The relevance of inhibition of specific JAK enzymes to the drug's therapeutic effectiveness is currently unknown. •Absorption (Drug A): No absorption available •Absorption (Drug B): Abrocitinib is absorbed with over 91% extent of oral absorption and absolute oral bioavailability of approximately 60%. The peak plasma concentrations of abrocitinib are reached within one hour. Steady-state plasma concentrations of abrocitinib are achieved within 48 hours after once-daily administration. Both C max and AUC of abrocitinib increased dose proportionally up to 200 mg. A high-fat meal, high-calorie meal increased AUC by 26% and C max by 29%, and prolongs T max by two hours; however, there are ultimately no clinically relevant effect on abrocitinib exposures. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After intravenous administration, the volume of distribution of abrocitinib was approximately 100 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 64%, 37% and 29% of circulating abrocitinib and its active metabolites M1 and M2, respectively, are bound to plasma proteins. Abrocitinib and its active metabolites M1 and M2 bind predominantly to albumin and distribute equally between red blood cells and plasma. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Abrocitinib undergoes CYP-mediated oxidative metabolism. CYP2C19 is the predominant enzyme, accounting for about 53% of drug metabolism. CYP2C9 is responsible for 30% of drug metabolism. About 11% and 6% of the drug is metabolized by CYP3A4 and CYP2B6, respectively. In a human radiolabeled study, the parent drug was the most prevalent circulating species. Polar mono-hydroxylated metabolites of abrocitinib - M1 (3-hydroxypropyl; PF-06471658), M2 (2-hydroxypropyl; PF-07055087), and M4 (pyrrolidinone pyrimidine; PF-07054874) - were also identified in the systemic circulation. M2 has a chiral center, thus has an enantiomer M3 (PF-07055090). At steady state, M2 and M4 are major metabolites and M1 is a minor metabolite. M2 has a pharmacological activity comparable to abrocitinib while M1 is less pharmacologically active than abrocitinib. M3 and M4 are inactive metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of the parent molecule (~60%) as well as M1 (~10%) and M2 (~30%) in the systemic circulation. The sum of unbound exposures of abrocitinib, M1 and M2, each expressed in molar units and adjusted for relative potencies, is referred to as the abrocitinib active moiety. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Abrocitinib is eliminated primarily by metabolic clearance mechanisms, with less than 1% of the dose being excreted in urine as an unchanged parent drug. The metabolites of abrocitinib are excreted predominantly in urine. Pharmacokinetics data up to and including a single oral dose of 800 mg in healthy adult volunteers indicate that more than 90% of the administered dose is expected to be eliminated within 48 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean elimination half-lives of abrocitinib and its two active metabolites, M1 and M2, range from three to five hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is no information available. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no experience regarding human overdosage with abrocitinib. In clinical trials, there were no specific toxicities observed when abrocitinib was administered in single oral doses of 800 mg and 400 mg daily for 28 days. An overdose should be responded with symptomatic and supportive treatment, as there is no specific antidote for overdose with abrocitinib. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Aceclofenac interact?

•Drug A: Abciximab •Drug B: Aceclofenac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •References: 1. Teklay G, Shiferaw N, Legesse B, Bekele ML: Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: a prospective observational study. Thromb J. 2014 Sep 17;12:20. doi: 10.1186/1477-9560-12-20. eCollection 2014. [https://go.drugbank.com/articles/A33535] 2. Choi KH, Kim AJ, Son IJ, Kim KH, Kim KB, Ahn H, Lee EB: Risk factors of drug interaction between warfarin and nonsteroidal anti-inflammatory drugs in practical setting. J Korean Med Sci. 2010 Mar;25(3):337-41. doi: 10.3346/jkms.2010.25.3.337. Epub 2010 Feb 17. [https://go.drugbank.com/articles/A33536] 3. Chan TY: Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother. 1995 Dec;29(12):1274-83. doi: 10.1177/106002809502901214. [https://go.drugbank.com/articles/A33538] 4. Moore N, Pollack C, Butkerait P: Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015 Jul 15;11:1061-75. doi: 10.2147/TCRM.S79135. eCollection 2015. [https://go.drugbank.com/articles/A33539] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Aceclofenac is indicated for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM. Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF). It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL-6 is thought to be mediated by diclofenac converted from aceclofenac. Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes. In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CD62L), which is a cell adhesion molecule expressed on lymphocytes. Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL-1 production and activity. The chrondroprotective effects are generated by 4'-hydroxyaceclofenac which suppresses IL-1 mediated production of promatrix metalloproteinase-1 and metalloproteinase-3 and interferes with the release of proteoglycan from chrondrocytes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Aceclofenac is rapidly and completely absorbed from the gastrointestinal tract and circulates mainly as unchanged drug following oral administration. Peak plasma concentrations are reached around 1.25 to 3 hours post-ingestion, and the drug penetrates into the synovial fluid where the concentration may reach up to 60% of that in the plasma. There is no accumulation in regular dosing, with similar maximum plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) after single and multiple doses. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution is approximately 25 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): It is reported to be highly protein-bound (>99%). •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): 4'-hydroxyaceclofenac is the main metabolite detected in plasma however other minor metabolites include diclofenac, 5-hydroxyaceclofenac, 5-hydroxydiclofenac, and 4'-hydroxydiclofenac. It is probable that the metabolism of aceclofenac is mediated by CYP2C9. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main route of elimination is via the urine where the elimination accounts for 70-80% of clearance of the drug. Approximately two thirds of the administered dose is excreted via the urine, mainly as glucuronidated and hydroxylated forms of aceclofenac. About 20% of the dose is excreted into feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean plasma elimination half-life is approximately 4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance rate is approximately 5 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Some common adverse effects include gastro-intestinal disorders (dyspepsia, abdominal pain, nausea), rash, ruber, urticaria, symptoms of enuresis, headache, dizziness, and drowsiness. Oral LD50 value in rats is 130 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid carboxymethyl ester 2-[(2,6-dichlorophenyl)amino]phenylacetoxyacetic acid 2-[(2',6'-dichlorophenyl)amino]phenylacetoxyacetic acid Aceclofenac (common) Acéclofénac (common) Aceclofenac betadex (common) Aceclofenaco (common) Aceclofenacum (common) glycolic acid [o-(2,6-dichloroanilino)phenyl]acetate ester

Do Abciximab and Acemetacin interact?

•Drug A: Abciximab •Drug B: Acemetacin •Severity: MINOR •Description: The risk or severity of bleeding and hemorrhage can be increased when Abciximab is combined with Acemetacin. •Extended Description: Acemetacin exerts a similar pharmacological action as NSAIDs and is associated with gastrointestinal bleeding or ulceration. Co-administration of acemetacin with medications known to cause bleeding, such as anticoagulants, may further increase the gastric bleeding events. •References: 1. Pelletier JP, Martel-Pelletier J, Rannou F, Cooper C: Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S22-7. doi: 10.1016/j.semarthrit.2015.11.009. Epub 2015 Dec 2. [https://go.drugbank.com/articles/A33597] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Acemetacin is not FDA, Canada or EMA approved, but in the countries where it is marketed it is indicated for the symptomatic treatment of pain and swelling in acute inflammation of the joints in rheumathoid arthritis, osteoarthritis, low back pain and post-surgical pain. It is also indicated for the treatment of chronic inflammation of the joints in presence of rheumatoid arthritis, treatment of ankylosing spondylitis, treatment of irritation in the joints and spinal column caused by degenerative disorders, treatment of inflammatory soft-tissue rheumatism syndrome and painful swelling and inflammation caused by injury. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): The effect of acemetacin causes a weak reduction of prostaglandin synthesis which generates an anti-inflammatory and analgesic effect. The weak inhibition of prostaglandin reduces significantly the damage caused in the mucous membrane of the gastrointestinal tract. Studies have shown that acemetacin strongly inhibits the release of histamine from mast cells and the generation of hyperthermia. Acemetacin effect also causes changes in systolic and diastolic blood pressure as well as inhibition of platelet aggregation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Acemetacin is a non-selective inhibitor of the production of pro-inflammatory mediators derived from the action of the enzyme COX. COX is essential for the synthesis of prostaglandin E2 and F2 which are molecules derived from fatty acids and stored in the cell membrane. Acetometacine is metabolized and forms its major metabolite indometacin which is also a non-selective inhibitor of COX and exhibits the capacity to inhibit the motility of polymorphonuclear leukocytes and decreased cerebral flow by modulating the nitric oxide pathway and vasoconstriction. •Absorption (Drug A): No absorption available •Absorption (Drug B): After 8 days of oral administration twice daily of acemetacin there was an age-dependant Cmax of 276.8 ng/ml in elderly compared to 187 ng/ml for younger individuals. There was also a Tmax of 2.5 h and AUC in a range of 483-712 ng h/ml. The bioavailability of acemetacin after repeated doses is aproximately 66% in plasma and 64% in urine. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of acemetacin is in a range of 0.5-0.7 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Acemetacin is found highly bound to plasma proteins, reaching a percentage higher than 90% of the administered dose. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Acemetacin is highly metabolized and degraded by esterolytic cleavage to form its major and active metabolite indometacin. It presents other inactive metabolites made by reaction of O-demethylation, N-desacylation and part of them are also transformed by conjugation with glucuronic acid. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of acemetacin is divided in renal elimination that covers 40% of the complete administered dose and the restant 60% is excreted in feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half-life of acemetacin after steady-state is 4.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Intravenous administration of acemetacin in healthy subjects reported a clearance rate of 4.59 ml min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The pharmacological activity of acemetacin causes blockage of prostaglandin synthesis. Prostaglandin is one of the mediators of renal blood flow and glomerular filtration thus, acemetacin causes a decreased renal function, transient renal insufficiency, interstitial nephritis and papillary necrosis especially in elderly patients, patients with congestive heart failure, hepatic cirrhosis and impaired renal function. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Acenocoumarol interact?

•Drug A: Abciximab •Drug B: Acenocoumarol •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Acenocoumarol. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 98.7% protein bound, mainly to albumin •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mostly via the kidney as metabolites •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 8 to 11 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin 3-(alpha-(p-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin 3-(alpha-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin 3-(alpha-p-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one 4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one Acenocoumarin (common) Acénocoumarol (common) Acenocoumarol (common) Acenocoumarolum (common) Acenocumarol (common) Acenocumarolo (common) Acenokumarin (common) Nicoumalone (common) Nicumalon (common) Nitrophenylacetylethyl-4-hydroxycoumarine Nitrovarfarian (common) Nitrowarfarin (common)

Do Abciximab and Acetylsalicylic acid interact?

•Drug A: Abciximab •Drug B: Acetylsalicylic acid •Severity: MODERATE •Description: Acetylsalicylic acid may increase the antiplatelet activities of Abciximab. •Extended Description: The coadministration of these agents can lead to potentiated antiplatelet effects due to additive pharmacological actions. This may result in bleeding, sometimes serious and fatal in nature. Additionally, in some cases, certain antiplatelet drugs may compete for protein binding sites of acetylsalicylic acid on the platelet, reducing the efficacy of either drug. •References: 1. Russo NW, Petrucci G, Rocca B: Aspirin, stroke and drug-drug interactions. Vascul Pharmacol. 2016 Dec;87:14-22. doi: 10.1016/j.vph.2016.10.006. Epub 2016 Oct 17. [https://go.drugbank.com/articles/A177451] 2. Mackenzie IS, Coughtrie MW, MacDonald TM, Wei L: Antiplatelet drug interactions. J Intern Med. 2010 Dec;268(6):516-29. doi: 10.1111/j.1365-2796.2010.02299.x. Epub 2010 Nov 14. [https://go.drugbank.com/articles/A33736] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Absorption (Drug A): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Protein binding (Drug A): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Route of elimination (Drug A): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Clearance (Drug A): No clearance available •Toxicity (Drug A): No toxicity available •Brand Names (Drug A): No brand names available •Synonyms (Drug A): No synonyms listed

Do Abciximab and Adalimumab interact?

•Drug A: Abciximab •Drug B: Adalimumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Adalimumab is combined with Abciximab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Adalimumab is indicated for the following conditions: Moderately to severely active Rheumatoid Arthritis (RA) in adults, as monotherapy or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). Moderately to severely active polyarticular Juvenile Idiopathic Arthritis (JIA) in patients two years of age and older, as monotherapy or in combination with methotrexate. Psoriatic Arthritis (PsA) in adults. Ankylosing Spondylitis (AS) in adults. Moderately to severely active Crohn’s Disease (CD) in adults and pediatric patients six years of age and older. Moderately to severely active Ulcerative Colitis (UC) in adults. Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers. Moderate to severe chronic plaque psoriasis in adult candidates for systemic therapy or phototherapy and when other systemic therapies are medically less appropriate. Moderate to severe Hidradenitis Suppurativa (HS) in adults. Non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients two years of age and older. Adalimumab has also been used off-label to treat Pyoderma gangrenosum. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): After treatment with adalimumab, a decrease in levels of acute phase reactant proteins of inflammation (C­ reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was measured compared to baseline in patients diagnosed with rheumatoid arthritis. A decrease in CRP levels was also observed in patients diagnosed with Crohn’s disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that lead to the tissue remodeling responsible for cartilage destruction were also found to be decreased after administration of adalimumab. A reduction in signs and symptoms of disease, the induction of clinical response, inhibition of structural damage, and improvements in physical function in adult and pediatric patients with various inflammatory conditions have been demonstrated. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Adalimumab binds with specificity to tumor necrosis factor-alpha (TNF-alpha) and inhibits its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface tumor necrosis factor expressing cells in vitro when in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (Tumor necrosis factor-beta). TNF is a naturally occurring cytokine that plays a role in normal inflammatory and immune responses. Increased levels of TNF are found in the joint synovial fluid of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients, and play an imperative role in pathologic inflammation and joint destruction that are major complications of these diseases. Increased levels of TNF are also measured in psoriasis plaques. In plaque psoriasis, treatment with adalimumab may decrease the epidermal thickness and inflammatory cell infiltration. The relationship between these pharmacodynamics and the mechanism(s) by which adalimumab achieves its clinical effects is not known. Additionally, adalimumab alters biological responses that are induced/regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration during inflammation (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10M). •Absorption (Drug A): No absorption available •Absorption (Drug B): The maximum serum concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 4.7 ± 1.6 μg/mL and 131 ± 56 hours respectively, following a single 40 mg subcutaneous administration of adalimumab to healthy adult subjects. The average absolute bioavailability of adalimumab estimated from three clinical studies after a single 40 mg subcutaneous dose of adalimumab was 64%. The pharmacokinetics of adalimumab showed a linear pattern over the dose range of 0.5 to 10.0 mg/kg following a single intravenous dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution volume (Vss) ranged from 4.7 to 6.0 L following intravenous administration of doses ranging from 0.25 to 10 mg/kg in RA patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Adalimumab is most likely removed by opsonization via the reticuloendothelial system. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. •Clearance (Drug A): No clearance available •Clearance (Drug B): The single-dose pharmacokinetics of adalimumab in RA patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The systemic clearance of adalimumab is approximately 12 mL/hr. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time in RA patients. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Amjevita, Cyltezo, Humira, Hyrimoz, Yusimry •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Aducanumab interact?

•Drug A: Abciximab •Drug B: Aducanumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Aducanumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Aducanumab is indicated for the treatment of Alzheimer’s disease. Treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β, reducing amyloid plaques in the brain. It has a long duration of action as it is given once every 4 weeks. Patients should be counselled regarding the risk of amyloid related imaging abnormalities, including microhemorrhages, and hypersensitivity reactions. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alzheimer's disease is a neurodegenerative disease. Part of the pathology of Alzheimer's disease is the presence of plaques forming extracellularly in the brain. These plaques are mostly composed of amyloid-β, a peptide of varying length formed by the cleavage of the amyloid precursor protein. The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-β oligopeptides in the brain drives the pathogenesis of Alzheimer's disease. Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β at amino acids 3-7. The amyloid-β residues Phe4, His6, Glu3, and Arg5 are responsible for the majority of the contact between amyloid-β and aducanumab's Fab region. Data from studies in mice and humans shows aducanumab treatment reduces amyloid-β, however human trials show non-significant changes in amyloid-β40 and amyloid-β42 across a dose range of 0.3-30 mg/kg and an increase in amyloid-β40 and amyloid-β42 at 60 mg/kg. Aducanumab treatment is associated with slowing the rate of progression of Alzheimer's disease, based on Mini-Mental State Examination, Clinical Dementia Rating, and levels of p-tau in the cerebrospinal fluid. •Absorption (Drug A): No absorption available •Absorption (Drug B): A 10 mg/kg intravenous dose of aducanumab reached a C max of 182.7 µg/mL, with a T max of 3.0 hours, and an AUC inf of 31,400 h*µg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of aducanumab is 9.63 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Aducanumab is expected to be broken down into smaller oligopeptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal IgG is predominantly eliminated by catabolism to individual amino acids that are either recycled in the body or metabolized for energy. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half life of aducanumab is 24.8 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): A 10 mg/kg intravenous dose of aducanumab has a clearance of 0.39 mL/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Patients experiencing dose-limiting toxicity may present with amyloid-related imaging abnormalities including edema or microhemorrhages of the brain. Symptoms of dose limiting toxicity were generally transient, however patients may need to be treated with symptomatic and supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aduhelm •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Albutrepenonacog alfa interact?

•Drug A: Abciximab •Drug B: Albutrepenonacog alfa •Severity: MAJOR •Description: The therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Under the EMA and FDA, rIX-RFP is indicated in the treatment of hemophilia B. For Health Canada, rIX-FRP is also indicated to prevent or reduce bleeding episodes. Hemophilia B is the second most common type of hemophilia. It is a rare inherited bleeding disorder caused by reduced or absent levels of factor IX (FIX). The FIX is a vitamin K-dependent plasma protease that when activated is involved in the blood coagulation cascade. The hemophilia B is caused by mutations in the FIX gene which can cause different phenotypes. The severe form is characterized by the presence of spontaneous and recurring bleeds into the joints and muscles and excessive bleeding after trauma or surgery. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Clinical trials with rIX-RFP in patients with moderately to severe hemophilia B demonstrated a lower annualized spontaneous, total and joint bleeding rates. It was also efficient against bleeding episodes and maintenance of hemostasis in the perioperative setting when compared with on-demand treatment. The administration of rIX-RFP presented no reports of inhibitor development. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The current therapies against hemophilia B are hampered by the short half-life of the replacement FIX therapy. Thus, to solve this problem, in rIX-RFP there is the fusion of rFIX with rAlbumin which presents a much longer half-life and it does not present interactions with the immune system. The administration of rIX-RFP increases the plasma concentration of FIX, thus addressing the coagulation deficiency of the patient. rIX-RFP is able to circulate in the plasma as an intact zymogen thanks to the pH-dependent binding to FcRn which is a normal protection pathway from lysosomal degradation of albumin. When the FIX is needed, rAlbumin is cleaved by the same proteases that activate the FIX. •Absorption (Drug A): No absorption available •Absorption (Drug B): rIX-RFP absorption is very rapid as it is directly administered intravenously. In clinical trials, the maximum plasma concentration, area under the curve and mean residence time are reported to be approximately 55 IU/dL, 5500 IU.h/dL and 125 hours respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The reported volume of distribution for rIX-RFP according to phase I/II and III clinical trials is 95 ml/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): This pharmacokinetic value is not relevant as this drug is part of the plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolism of rIX-RFP is not relevant as it is a recombinant protein and it is thought to be metabolized to peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): rIX-RFP is mainly eliminated in the urine. In preclinical studies, the distribution of urine and feces 240 hours post administration corresponded to 72.9% and 4.3% of the administered dose respectively. The elimination on the first 24 hours in urine and feces only corresponded to the 39.9% and 0.92% of the dose. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The fusion of the rFIX with rAlbumin prolongs the elimination half-life of rIX-RFP in the circulation. The reported half-life in clinical trials is 92 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): In clinical trials, the weight-adjusted clearance in children and adults is reported to be 1.1 and 0.9 ml/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): rIX-RFP is very well tolerated. Mutaginicity trials were performed and they confirmed an absent mutagenic potential. Fertility studies have not been performed. Developmental studies are not of major importance as there is a very low rate of incidence of hemophilia B in females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Idelvion •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Aldesleukin interact?

•Drug A: Abciximab •Drug B: Aldesleukin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Aldesleukin. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of adults with metastatic renal cell carcinoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Used to treat renal cell carcinoma, Aldesleukin induces the enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines, the enhancement of lymphocyte cytotoxicity, the induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and the induction of interferon-gamma production. IL-2 is normally produced by the body, secreted by T cells, and stimulates growth and differentiation of T cell response. It can be used in immunotherapy to treat cancer. It enhances the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Aldesleukin binds to the IL-2 receptor which leads to heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These events led to the creation of an activated receptor complex, to which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. These events stimulate growth and differentiation of T cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.18 l/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The pharmacokinetic profile of Proleukin is characterized by high plasma concentrations following a short IV infusion, rapid distribution into the extravascular space and elimination from the body by metabolism in the kidneys with little or no bioactive protein excreted in the urine. Following the initial rapid organ distribution, the primary route of clearance of circulating proleukin is the kidney. Greater than 80% of the amount of Proleukin distributed to plasma, cleared from the circulation and presented to the kidney is metabolized to amino acids in the cells lining the proximal convoluted tubules. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 13 min-85 min •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Proleukin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Alemtuzumab interact?

•Drug A: Abciximab •Drug B: Alemtuzumab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Alemtuzumab. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): LEMTRADA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. LEMTRADA contains the same active ingredient (alemtuzumab) found in CAMPATH, and CAMPATH is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), although generally administered at higher and more frequent doses (e.g., 30 mg) than recommended in the treatment of MS. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Alemtuzumab depletes circulating T and B lymphocytes after each treatment course. In clinical trials, the lowest cell counts occurred 1 month after a course of treatment at the time of the first post-treatment blood count. Lymphocyte counts then increased over time: B cell counts usually recovered within 6 months; T cell counts increased more slowly and usually remained below baseline 12 months after treatment. Approximately 60% of patients had total lymphocyte counts below the lower limit of normal 6 months after each treatment course and 20% had counts below the lower limit of normal after 12 months. Reconstitution of the lymphocyte population varies for the different lymphocyte subtypes. At Month 1 in clinical trials, the mean CD4+ lymphocyte count was 40 cells per microliter, and, at Month 12, 270 cells per microliter. At 30 months, approximately half of patients had CD4+ lymphocyte counts that remained below the lower limit of normal. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism by which alemtuzumab exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD52, a cell surface antigen present on T and B lymphocytes, and on natural killer cells, monocytes, and macrophages. Following cell surface binding to T and B lymphocytes, alemtuzumab results in antibody-dependent cellular cytolysis and complement-mediated lysis. Research suggests that alemtuzumab can also exert immunomodulatory effects through the depletion and repopulation of lymphocytes, including alterations in the number, proportions, and properties of some lymphocyte subsets posttreatment, increasing representation of regulatory T cell subsets, and increasing representation of memory T- and B-lymphocytes. The reduction in the level of circulating B and T cells by alemtuzumab and subsequent repopulation may reduce the potential for relapse, which ultimately delays disease progression. •Absorption (Drug A): No absorption available •Absorption (Drug B): Serum concentrations increased with each consecutive dose within a treatment course, with the highest observed concentrations occurring following the last infusion of a treatment course. The mean maximum concentration was 3014 ng/mL on Day 5 of the first treatment course, and 2276 ng/mL on Day 3 of the second treatment course. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Alemtuzumab is largely confined to the blood and interstitial space with a central volume of distribution of 14.1 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Alemtuzumab is a large-molecule monoclonal antibody and as such, it is cleared primarily through target-mediated clearance and through simple non-target specific IgG clearance mechanisms. Alemtuzumab is not excreted renally or eliminated via cytochrome P450 (CYP450) isoenzymes. Alemtuzumab is most likely removed by opsonization via the reticuloendothelial system when bound to B or T lymphocytes. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half-life was approximately 2 weeks and was comparable between courses. The serum concentrations were generally undetectable (<60 ng/mL) within approximately 30 days following each treatment course. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of alemtuzumab ranged from 0.012 – 0.096 l/h depending on the study, dose group, and anti-alemtuzumab antibody status. The inter-subject variability for clearance was large (58 %). Higher clearance values were observed in cycle 1 compared to cycle 2, with the decrease in clearance from cycle 1 to cycle 2 being less than 20%. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LEMTRADA induces persistent thyroid disorders [see Warnings and Precautions (5.8)]. Untreated hypothyroidism in pregnant women increases the risk of miscarriage and may have effects on the fetus including mental retardation and dwarfism. In mothers with Graves’ disease, maternal thyroid stimulating hormone receptor antibodies can be transferred to a developing fetus and can cause neonatal Graves’ disease. In a patient who developed Graves’ disease after treatment with alemtuzumab, placental transfer of anti-thyrotropin receptor antibodies resulted in neonatal Graves’ disease with thyroid storm in her infant who was born 1 year after alemtuzumab dosing. When LEMTRADA was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6-10 or GD 11-15) at doses of 3 or 10 mg/kg IV, no teratogenic effects were observed. However, there was an increase in embryo lethality (increased postimplantation loss and the number of dams with all fetuses dead or resorbed) in pregnant animals dosed during GD 11-15. In a separate study in pregnant huCD52 transgenic mice, administration of LEMTRADA during organogenesis (GD 6-10 or GD 11-15) at doses of 3 or 10 mg/kg IV, decreases in B- and T-lymphocyte populations were observed in the offspring at both doses tested. In pregnant huCD52 transgenic mice administered LEMTRADA at doses of 3 or 10 mg/kg/day IV throughout gestation and lactation, there was an increase in pup deaths during the lactation period at 10 mg/kg. Decreases in T- and B-lymphocyte populations and in antibody response were observed in offspring at both doses tested. Before initiation of LEMTRADA treatment, women of childbearing potential should be counseled on the potential for serious risk to the fetus. To avoid in-utero exposure to LEMTRADA, women of childbearing potential should use effective contraceptive measures when receiving a course of treatment with LEMTRADA and for 4 months following that course of treatment. In huCD52 transgenic mice, administration of LEMTRADA prior to and during the mating period resulted in adverse effects on sperm parameters in males and a reduced number of corpora lutea and implantations in females. Two MS patients experienced serious reactions (headache, rash, and either hypotension or sinus tachycardia) after a single accidental infusion of up to 60 mg of LEMTRADA. Doses of LEMTRADA greater than those recommended may increase the intensity and/or duration of infusion reactions or their immune effects. There is no known antidote for alemtuzumab overdosage. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Campath, Lemtrada, MabCampath •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Alirocumab interact?

•Drug A: Abciximab •Drug B: Alirocumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Alirocumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Alirocumab is an antibody eliciting proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor activity that is indicated for: (i) use in reducing the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease, and/or (ii) use as an adjunct to diet or use alone or in combination with other lipid-lowering therapies (statins, ezetimibe, for example) for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C) levels in the body. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Alirocumab reduces levels of PCSK9 in a concentration-dependent manner. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have "gain of function" mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. As statin therapy increases the production of PCSK9, statin co-administration is thought to shorten alirocumab half-life; therefore the median apparent half-life of alirocumab was reduced to 12 days at equivalent alirocumab doses. However, this difference is not considered clinically significant and does not change dosing recommendations. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Praluent •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Alteplase interact?

•Drug A: Abciximab •Drug B: Alteplase •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Alteplase. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Alteplase is indicated for the treatment of acute ischemic stroke (AIS) and for use in acute myocardial infarction (AMI) for the reduction of mortality and incidence of heart failure. Alteplase is also indicated for the lysis of acute massive pulmonary embolism, defined as acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments, and acute pulmonary emboli accompanied by unstable hemodynamics. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Alteplase binds to fibrin and plasminogen. Alteplase specificity for fibrin is achieved thanks to its high affinity for lysine residues. Also, it can bind plasminogen via loop structures called kringles, stabilized by three disulphide linkages similar to the ones in plasminogen. The specificity of alteplase for plasminogen bound to fibrin allows this drug to act in a clot- or fibrin-specific manner, leading to low concentrations of circulating plasmin and a lower risk of hemorrhagic transformation. In patients with acute myocardial infarction, alteplase reduces fibrinogen levels 3 to 6 hours after treatment. In patients with acute ischemic stroke, patients treated with alteplase have a significantly higher resolution of hyperdense artery sign, a marker of clot formation in the proximal middle cerebral artery, compared to those treated with placebo. The use of alteplase increases the risk of bleeding and thromboembolic events. Rare cases of cholesterol embolism have also been reported. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alteplase is a recombinant tissue plasminogen activator (rt-PA) that converts plasminogen to plasmin in a fibrin-dependent process. In the absence of fibrin, alteplase converts a limited amount of plasminogen. However, in the presence of fibrin clots, alteplase binds to fibrin and cleaves the arginine-valine bond at positions 560 and 561 of plasminogen, converting it into its active form, plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus and promotes clot dissolution. Alteplase initiates local fibrinolysis with limited systemic proteolysis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Healthy volunteers with a baseline endogenous tissue plasminogen activator (t-PA) of 3.3 ng/ml had a 290-fold increase in baseline concentrations after receiving alteplase at an infusion rate of 0.25 mg/kg for 30 min; with an infusion rate of 0.5 mg/kg, a 550-fold increase was observed. Acute myocardial infarction patients (n=12) given 10 mg of alteplase in a 2-minute infusion reached a peak plasma concentration of 3310 ng/ml. This was followed by 50 mg of alteplase in 1 h and 30 mg in 1.5 h, resulting in steady-state plasma levels of 2210 ng/ml and 930 ng/ml, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The initial volume of distribution approximates plasma volume. The average volume of distribution of the central compartment goes from 3.9 to 4.3 L, and the volume of distribution at steady state goes from 7.2 to 12 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Not available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Alteplase is mainly metabolized by the liver. The carbohydrate and polypeptide domains of alteplase interact with hepatic glycoprotein receptors, leading to receptor-mediated endocytosis. In vivo studies suggest that alteplase follows zero-order kinetics, meaning that its metabolism is saturable at higher plasma concentrations. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In healthy volunteers, more than 80% of alteplase is eliminated through urine 18 hours after administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Alteplase has an initial half-life of less than 5 minutes in patients with acute myocardial infarction (AMI). The dominant initial plasma half-life of the 3-hour and the accelerated regimens for AMI are similar. •Clearance (Drug A): No clearance available •Clearance (Drug B): Alteplase has a plasma clearance between 380 and 570 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding alteplase is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as risk of bleeding and thromboembolic events. Symptomatic and supportive measures are recommended. The carcinogenic potential of alteplase or its effect on fertility have not been evaluated. In vivo studies evaluating tumorigenicity and in vitro studies evaluating mutagenicity were negative. It has been estimated that the acute oral and dermal toxicity of alteplase is above 5,000 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Activase, Cathflo, Cathflo Activase •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Aminosalicylic acid interact?

•Drug A: Abciximab •Drug B: Aminosalicylic acid •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Aminosalicylic acid is combined with Abciximab. •Extended Description: .Concurrent use of salicylates and anticoagulants may lead to increased anticoagulant activity and therefore an increased risk of bleeding, due to additive anticoagulant effects. •References: 1. Yip AS, Chow WH, Tai YT, Cheung KL: Adverse effect of topical methylsalicylate ointment on warfarin anticoagulation: an unrecognized potential hazard. Postgrad Med J. 1990 May;66(775):367-9. [https://go.drugbank.com/articles/A33575] 2. Roncaglioni MC, Reyers I, Cerletti C, Donati MB, de Gaetano G: Moderate anticoagulation by salicylate prevents thrombosis without bleeding complications. An experimental study in rats. Biochem Pharmacol. 1988 Dec 15;37(24):4743-5. [https://go.drugbank.com/articles/A33576] 3. Undas A, Brummel-Ziedins KE, Mann KG: Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions. Blood. 2007 Mar 15;109(6):2285-92. doi: 10.1182/blood-2006-01-010645. Epub 2006 Dec 5. [https://go.drugbank.com/articles/A35088] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of tuberculosis •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 50-60% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hepatic. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =4 gm/kg (orally in mice); LD 50 =3650 mg/kg (orally in rabbits) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Granupas, Paser D/r •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4-amino-2-hydroxybenzoic acid 4-aminosalicylate (common) 4-aminosalicylic acid (common) Aminosalicylic acid (common) p-aminosalicylic acid (common) para-amino salicylic acid (common) para-aminosalicylic acid (common) PAS

Do Abciximab and Amivantamab interact?

•Drug A: Abciximab •Drug B: Amivantamab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Amivantamab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Amivantamab is indicated in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Amivantamab is an EGF and MET receptor targeted antibody indicated in the treatment of non-small cell lung cancer with an EGFR 20 exon insertion mutation. It has a long duration of action, as activity can be detected up to 8 weeks after treatment. Patients should be counselled regarding the risk of infusion-related reactions, interstitial lung disease and pneumonitis, skin reactions, ocular toxicity, and paronychia. Patients should not take amivantamab if they are pregnant or breastfeeding. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Mesenchymal-epithelial transition factor (MET) is a receptor with tyrosine kinase activity expressed on epithelial cells that, upon signalling, dimerizes and activates downstream pathways that signal cell division. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase activity that can further activate downstream pathways that signal cell division, survival, and angiogenesis. Patients with NSCLC with exon 20 insertion mutations in EGFR do not respond to tyrosine kinase inhibitors, and are generally treated with platinum-based therapy. Exon 20 insertion mutations in EGFR also lead to conformational changes that activate EGFR. Amivantamab targets both EGFR and MET, preventing ligands from binding to the receptors, blocking signalling, marking the cancerous cells for antibody-dependant cellular cytotoxicity by natural killer cells, and allowing macrophages to perform trogocytosis. Amivantamab's binding to the EGFR H epitope shares some of the same amino acids that cetuximab binds to. Amivantamab's binding to the alpha chain of MET stabilizes the Sema domain loop 1 to 2 in a position 6 Angstroms away from the position it would be in under normal binding, preventing its interaction with the hepatocyte growth factor's (HGF) beta chain. Another smaller conformational change in the MET Sema domain loop 1 to 3 also contributes to preventing the interaction of the MET Sema domain with HGF's beta chain. HGF is no longer able to bind to MET, preventing downstream signalling. Amivantamab's Fc portion contains 90% less fucose than normal antibodies, allowing for increased binding to the FcγRIIIa region. Binding of the Fc portion of Amivantamab signals the complement system and innate immune system to target the bound cells for complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. Binding of amivantamab to the Fc receptor also leads to and increase in levels of IFNγ. Amivantamab also significantly downregulates the expression of EGFR and MET on NSCLC cell surfaces, further reducing downstream signalling. EGFR and MET on the cell surface are internalized, and possibly degrading by fusing endosomes with lysosomes. Alternatively, EGFR and MET are the subjects of monocyte-dependent trogocytosis. Trogocytosis allows monocytes to internalize and break down EGFR and MET from the NSCLC cells without cytotoxicity, downmodulating EGFR and MET receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Antibodies are expected to be metabolized to oligopeptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance of amivantamab-vmjw is 360 ± 144 mL/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses of amivantamab are not readily available. Patients experiencing an overdose should be treated with symptomatic and supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rybrevant •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Amsacrine interact?

•Drug A: Abciximab •Drug B: Amsacrine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Amsacrine. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of acute myeloid leukaemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Amsacrine is an aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Amsacrine binds to DNA through intercalation and external binding. It has a base specificity for A-T pairs. Rapidly dividing cells are two to four times more sensitive to amsacrine than are resting cells. Amsacrine appears to cleave DNA by inducing double stranded breaks. Amsacrine also targets and inhibits topoisomerase II. Cytotoxicity is greatest during the S phase of the cell cycle when topoisomerase levels are at a maximum. •Absorption (Drug A): No absorption available •Absorption (Drug B): Poorly absorbed •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 96-98% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Extensive, primarily hepatic, converted to glutathione conjugate. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 8-9 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include nausea and vomiting, diarrhea, some cardiotoxicity (rarely). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4'-(9-Acridinylamino)-3'-methoxymethanesulfonanilide 4'-(9-Acridinylamino)methanesulfon-m-anisidide 4'-(9-Acridinylamino)methanesulfon-meta-anisidide 4'-(9-Acridinylamino)methanesulphon-m-anisidide Acridinyl anisidide (common) Amsacrina (common) Amsacrine (common) Amsacrinum (common) m-AMSA (common) mAMSA (common)

Do Abciximab and Anagrelide interact?

•Drug A: Abciximab •Drug B: Anagrelide •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Anagrelide is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Anagrelide is indicated for the treatment of thrombocythemia, secondary to malignant neoplasms, to reduce platelet count and the associated risk of thrombosis. It is also beneficial in the amelioration of thrombocythemia symptoms including thrombo-hemorrhagic events. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Anagrelide decreases platelet counts by suppressing transcription factors necessary for the synthesis and maturation of platelet-producing cells. The drug itself appears to have a relatively short residence time in the body necessitating twice or four times daily dosing. However, given that the pharmacological effect of anagrelide therapy is reliant on a gradual suppression of platelet-producing cells, it may take 7 to 14 days for its administration to be reflected in reduced platelet counts - for this reason any changes to anagrelide doses should not exceed 0.5 mg/day in any one week. Evidence from animal studies suggests anagrelide may impair female fertility. Female patients of reproductive age should be advised of the potential for adverse effects on fertility prior to initiating therapy. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The exact mechanism by which anagrelide lowers platelet count is unclear. Evidence from human trials suggests a dose-related suppression of megakaryocyte maturation, the cells responsible for platelet production - blood drawn from patients receiving anagrelide showed a disruption to the post-mitotic phase of megakaryocyte development and a subsequent reduction in their size and ploidy. This may be achieved via indirect suppression of certain transcription factors required for megakaryocytopoeisis, including GATA-1 and FOG-1. Anagrelide is a known inhibitor of phosphodiesterase 3A (PDE3A), although its platelet-lowering effects appear unrelated to this inhibition. While PDE3 inhibitors, as a class, can inhibit platelet aggregation, this effect is only seen at higher anagrelide doses (i.e. greater than those required to reduce platelet count). Modulation of PDE3A has been implicated in causing cell cycle arrest and apoptosis in cancer cells expressing both PDE3A and SLFN12, and may be of value in the treatment of gastrointestinal stromal tumours. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, the bioavailability of anagrelide is approximately 70%. Given on an empty stomach, the C max is reached within 1 hour (T max ) of administration. Co-administration with food slightly lowers the C max and increases the AUC, but not to a clinically significant extent. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Anagrelide is extensively metabolized, primarily in the liver by cytochrome P450 1A2 (CYP1A2), into two major metabolites: 6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (3-hydroxy anagrelide) and 2-amino-5,6-dichloro-3,4,-dihydroquinazoline (RL603). The 3-hydroxy metabolite is considered pharmacologically active and carries a similar potency and efficacy in regards to its platelet-lowering effects, but inhibits PDE3 with a potency 40x greater than that of the parent drug. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following metabolism, urinary excretion of metabolites appears to be the primary means of anagrelide elimination. Less than 1% of an administered dose is recovered in the urine as unchanged parent drug, while approximately 3% and 16-20% of the administered dose is recovered as 3-hydroxy anagrelide and RL603, respectively. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The t 1/2 of anagrelide and its active metabolite, 3-hydroxy anagrelide, are approximately 1.5 hours and 2.5 hours, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 of anagrelide as reported in rats and mice is >1500mg/kg and >2500mg/kg, respectively. Symptoms of overdose may include hypotension, sinus tachycardia, and vomiting. As the therapeutic effect of anagrelide (i.e. platelet reduction) is dose-related, significant thrombocytopenia is expected in instances of overdose. Treatment of overdose should involve careful monitoring of platelet counts and complications such as bleeding. Employ symptomatic and supportive measures if clinically indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Agrylin, Xagrid •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Andexanet alfa interact?

•Drug A: Abciximab •Drug B: Andexanet alfa •Severity: MAJOR •Description: The therapeutic efficacy of Andexanet alfa can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Andexanet alfa is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. Andexxa has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any Factor Xa inhibitors other than apixaban and rivaroxaban. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In vitro, andexanet alfa was shown to dose-dependently reverse the activity of apixaban, betrixaban, edoxaban, rivaroxaban, enoxaparin and fondaparinux on Factor Xa in human and rat plasma. In a randomized placebo-controlled study of healthy elderly volunteers, co-administration of andexanet alfa bolus with 5 mg of apixaban twice daily resulted in a reduction of anti-factor Xa activity by 94% compared to 21% among those who received placebo, and thrombin generation was fully restored in 100%. The anti-factor Xa activity was reduced by 92% and thrombin generation was fully restored in 96% of the subjects upon andexanet alfa bolus administration in subjects receiving 20 mg of rivaroxaban daily. A multicenter, prospective, open-label, single-group study involving elderly patients with acute major bleeding within 18 hours after the administration of a factor Xa inhibitor was performed. In this study, the median anti-factor Xa activity in patients receiving rivaroxaban and apixaban was reduced by 89% and 93%, respectively, upon administration of andexanet alfa infusion. In dose-ranging studies of healthy volunteers, the anti-FXa activity activity was observed within two minutes after the completion of the bolus administration. Elevation of Tissue Factor (TF)-initiated thrombin generation above the baseline range (prior to anticoagulation) occurred within two minutes following a bolus administration of andexanet alfa and was maintained throughout the duration of the continuous infusion. The anti-FXa activity returned to the placebo levels approximately 2 hours after completion of a bolus or continuous infusion. In contrast, TFPI activity in plasma was sustained for at least 22 hours following andexanet alfa administration. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Factor Xa inhibitors promote anticoagulation by binding to both free Factor Xa in plasma and Factor Xa attached to the prothrombinase complex. This ultimately leads to the blockade of thrombin generation or clot formation. Andexanet alfa is a factor Xa decoy that binds to factor Xa inhibitors such as apixaban and rivaroxaban with high affinity and prevents them from binding to endogenous factor Xa. It was also shown to sequester factor Xa inhibitors, leading to reversing their anticoagulant effects and restoring the activity of endogenous factor Xa. Andexanet alfa may also achieve procoagulation via binding and inhibiting the activity of Tissue Factor Pathway Inhibitor (TFPI), which is an endogenous inhibitor of Factor Xa. Inhibition of TFPI by andexanet alfa resulted in a transient increase in the level of prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer. Subsequently, this may result in increased tissue factor-initiated thrombin generation. Since it is a genetically modified variant of human factor Xa, andexanet alfa is not able to cleave and activate prothrombin nor assemble into the prothrombinase complex. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration of bolus doses > 30 mg in healthy subjects, the exposure of andexanet alfa increased in a dose-dependent manner. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution (Vd) for andexanet alfa is approximately equivalent to the blood volume of 5 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No information available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): There is limited information regarding the metabolism of andexanet alfa. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is limited information regarding the elimination of andexanet alfa. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half-life ranges from 5 to 7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance for andexanet alfa is approximately 4.3 L/hr. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Andexxa •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Anifrolumab interact?

•Drug A: Abciximab •Drug B: Anifrolumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Anifrolumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus who are receiving standard therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1κ monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus. It has a long duration of action as it is given every 4 weeks. Patients should be counseled regarding the risks of serious infections, hypersensitivity reactions, and malignancies. In patients with SLE, following the administration of anifrolumab- at 300 mg dose, via intravenous infusion every 4 weeks for 52 weeks, neutralization (≥80%) of a type I IFN gene signature was observed from Week 4 to Week 52 in blood samples of patients with elevated levels of type I IFN inducible genes and returned to baseline levels within 8 to 12 weeks following withdrawal of anifrolumab at the end of the 52-week treatment period. However, the clinical relevance of the type I IFN gene signature neutralization is unclear. In SLE patients with positive anti-dsDNA antibodies at baseline (Trials 2 and 3), treatment with anifrolumab 300 mg led to numerical reductions in anti-dsDNA antibodies over time through Week 52. In patients with low complement levels (C3 and C4), increases in complement levels were observed in patients receiving anifrolumab through Week 52. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body. SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system. Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE. Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription. Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE). Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons. Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens. CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells. This self-reactive immune response damages otherwise healthy tissue throughout the body. Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1κ) monoclonal antibody that selectively binds to subunit 1 of INFAR1. This binding inhibits type I IFN signaling, thereby blocking the biological activity of type I IFNs. Anifrolumab also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Blockade of receptor-mediated type I IFN signaling inhibits IFN-responsive gene expression as well as downstream inflammatory and immunological processes. Inhibition of type I IFN blocks plasma cell differentiation and normalizes peripheral T-cell subsets. The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors. In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group. Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment. •Absorption (Drug A): No absorption available •Absorption (Drug B): The PK of anifrolumab was studied in adult patients with SLE following intravenous doses ranging from 100 to 1000 mg once every 4 weeks, and healthy volunteers following a single intravenous dose at 300 mg. Anifrolumab exhibits non-linear PK in the dose range of 100 mg to 1000 mg with more than dose-proportional increases in the exposure as measured by AUC. Following the 300 mg every 4 weeks intravenous administrations of anifrolumab, a steady state was reached by Day 85. The accumulation ratio was approximately 1.36 for C max and 2.49 for C trough. A 300 mg intravenous dose reaches a mean C max of 82.4 µg/mL, with a T max of 0.03 days, and an AUC of 907 day*µg/mL. A 300 mg subcutaneous dose reaches a mean C max of 36.2 µg/mL, with a T max of 4.1 days, and an AUC of 785 day*µg/mL. A 600 mg subcutaneous dose reaches a mean C max of 63.9 µg/mL, with a T max of 7.0 days, and an AUC of 1828 day*µg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on population PK analysis, the estimated volume of distribution at steady state for a typical patient with SLE (69.1 kg) is 6.23 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal IgG is predominantly eliminated by catabolism to individual amino acids that are either recycled in the body or metabolized for energy. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following the administration of anifrolumab at a dose of 300 mg via intravenous infusion every 4 weeks, the estimated systemic clearance (CL) for anifrolumab was 0.193 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdose is not readily available. In a phase 1 clinical trial, patients given a single dose of 20.0 mg/kg experienced upper respiratory tract infections, headache, diarrhea, and nausea. 2 patients in the 3.0 mg/kg single dose group experienced osteomyelitis and skin ulcer. A single patient in the 1.0 mg/kg/week group developed chronic myelogenous leukemia. The frequency and severity of adverse effects does not appear to be closely related to dose. In the event of an overdose, treat patients with symptomatic and supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Saphnelo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Ansuvimab interact?

•Drug A: Abciximab •Drug B: Ansuvimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ansuvimab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Absorption (Drug A): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Protein binding (Drug A): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Route of elimination (Drug A): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Clearance (Drug A): No clearance available •Toxicity (Drug A): No toxicity available •Brand Names (Drug A): No brand names available •Synonyms (Drug A): No synonyms listed

Do Abciximab and Anthrax immune globulin human interact?

•Drug A: Abciximab •Drug B: Anthrax immune globulin human •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Anthrax immune globulin human. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Anthrax immune globulin is indicated for the treatment of inhalational anthrax in adult and pediatric patients in combination with appropriate antibacterial drugs. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Polyclonal anthrax immune globulin is a passive immunizing agent that neutralizes anthrax toxin by binding to Protective Antigen (PA) to prevent PA-mediated cellular entry of anthrax edema factor and lethal factor. It is administered in combination with appropriate antibiotic therapy as the immunoglobulin itself is not known to have direct antibacterial activity against anthrax bacteria, which otherwise may continue to grow and produce anthrax toxins. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peak levels were reached immediately after infusion and then declined over the duration of study (84 days). Mean activity remained above the lower limit of quantitation (5 milliunits per mL) over the entire 84-day post-dose period for the three doses studied. Cmax was found to be 83.0 mU/mL while Tmax was found to be 0.116 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 5714.8 mL •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 24.3 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 174.2 mL/day •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common adverse reactions to Anthrasil observed in >5% of healthy volunteers in clinical trials were headache, infusion site pain and swelling, nausea, and back pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Anthrasil •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Anti-inhibitor coagulant complex interact?

•Drug A: Abciximab •Drug B: Anti-inhibitor coagulant complex •Severity: MAJOR •Description: The therapeutic efficacy of Anti-inhibitor coagulant complex can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For use in the control of bleeding episodes, perioperative management, and routine prophylaxis against bleeding episodes in hemophilia A and B patients with inhibitors. It is not indicated in the absence of factor VIII or IX inhibitors. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): FEIBA contains several clotting factors which act at various points in the caogulation cascade to promote thrombosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Factor VIIa present in FEIBA forms a complex with tissue factor and calcium which converts endogenous and FEIBA contained factor X to Xa. Endogenous and FEIBA contained factor Xa act as parrt of the prothrombinase complex to convert endogenous and FEIBA contained prothrombin to thrombin. Endogenous and FEIBA contained thrombin then cleave fibrinogen to insulouble fibrin and activate factor XIII which covalently cross-links fibrin to form a polymer mesh. FEIBA also contains factor IX and IXa which act as part of the tenase complex to convert factor X to Xa. Thrombin activates factor V, VII, and VIII as part of the amplification phase of the clotting cascade. These events promote the formation of blood clots to prevent or stop bleeding. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Plasma half lives of included clotting factors are as follows: Prothrombin - 65h Factor VII - 5h Factor IX - 25h Factor X - 40h •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): FEIBA is associated with increased risk of thromboembolic events such as stroke, myocardial infarction, and deep vein thrombosis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Feiba •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antihemophilic factor (recombinant), PEGylated interact?

•Drug A: Abciximab •Drug B: Antihemophilic factor (recombinant), PEGylated •Severity: MAJOR •Description: The therapeutic efficacy of Antihemophilic factor (recombinant), PEGylated can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the management of hemophilia A (congenital factor VIII deficiency),. This medication is a human antihemophilic factor indicated in adolescent and adult patients (12 years and older) with hemophilia A (congenital factor VIII deficiency). It is also used for on-demand treatment and control of bleeding and routine prophylaxis of bleeding episodes. It is not indicated for the treatment of von Willebrand disease. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): This drug temporarily replaces the missing coagulation factor VIII, required for effective hemostasis in patients with congenital hemophilia A. Hemophilia A patients have a deficiency of factor VIII, resulting in a prolonged, patient plasma clotting time as demonstrated by the activated partial thromboplastin time (aPTT). Treatment with recombinant factor VIII normalizes the aPTT. Hemophilia A is a sex-linked hereditary disorder of blood coagulation caused by decreased levels of Factor VIII activity, resulting in severe bleeding into the joints, muscles or internal organs, spontaneously/as a result of trauma,. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): PEG with Factor VIII effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce the susceptibility of this molecule to proteolytic degradation. It is also believed that PEGylation alters the surface charge of the protein that inhibits receptor-mediated clearance. This drug reduces binding to the LRP1 receptor, which normally clears factor VIII from the circulation,. The plasma levels of Factor VIII are increased with replacement therapy, which allows for a temporary correction of the factor deficiency, thus a correction of the bleeding tendency. •Absorption (Drug A): No absorption available •Absorption (Drug B): AUC0-Inf [IU·h/dL]: 1642 ± 752 in children aged 12 to <18 years 2264 ± 729 in adults ≥18 years •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): At steady state: 0.56 ± 0.18 dL/Kg in children aged 12 to <18 years 0.43 ± 0.11 dL/kg in adults aged ≥18 years •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 14.69 ± 3.79h for adults aged ≥18 years 13.43 ± 4.05 for children 12 to <18 years •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.27 ± 0.84 for adults ≥18 years 3.87 ± 3.31 for children 12 to <18 years •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Common adverse reactions reported in ≥1% of subjects in the clinical studies were headache and nausea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Adynovate •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antihemophilic factor human interact?

•Drug A: Abciximab •Drug B: Antihemophilic factor human •Severity: MAJOR •Description: The therapeutic efficacy of Antihemophilic factor human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): The human antihemophilic factor is indicated for the cases of hemophilia A, also known as classical hemophilia for the prevention and control of hemorrhagic episodes. If surgery is needed in patients with hemophilia A there is a need of correction of the clotting abnormality. In this cases, the human antihemophilic factor may be administered followed by intermittent maintenance doses. The hemophilia A is characterized by the deficiency of the coagulation factor VIII that results in prolonged blood flow after injury or surgery as well as recurrent bleeding. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): The human antihemophilic factor assists in the convertion of prothrombin to thrombin. Its administration generates the formation of a complex constituted by the Factor IXa, Factor X and the antihemophilic factor which triggers the normal coagulation cascade for the formation of blood clots. The human antihemophilic factor is increased in the plasma thus enabling temporary correction of the hemophilia A bleeding. Its effect is reported as the normalization of the partial thromboplastin time. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The human antihemophilic factor replaces the coagulation factor VIII. It acts as a co-factor for factor IX to activate factor X in the intrinsic pathway of blood coagulation. •Absorption (Drug A): No absorption available •Absorption (Drug B): After intravenous administration of the human antihemophilic factor the values of Cmax, AUC and Tmax were 100 IU/ml, 1450 IU h/ml and 0.43 h respectively. In a second clinical trial, the treatment was administered for six months and the values of Cmax, AUC and Tmax were 99 units/ 100 ml, 1471 units h/ 100ml and 16 h, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The pharmacokinetic profile of the human antihemophilic factor needed to be studied by the two-compartment theory as not all of it stays just in blood plasma. The central and peripheral volume of distribution in adults weight an average of 68 kg were 2.81 L and 1.90 L respectively. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The human antihemophilic factor is retained mainly in the blood as its major function is to start the coagulation cascade. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolism of the human antihemophilic factor is identical to the normal inactivation and elimination pathway of the natural coagulation factor VIII. After activation, the human antihemophilic factor gets metabolized by activated protein C in R336 and R562 and this action inactivates this cofactor. The proteolysis generates two major fragments which are recognized by an anti-factor VIII A2 domain antibody. This process is followed by a further degradation into smaller fragments. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Intravenous administration of human antihemophilic factor is rapidly eliminated primarly through the reticuloendothelial system. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean half-life of human antihemophilic factor administered in hemophilic A patients is 14.8 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The reported clearance for the administration of antihemophilic factor is 0.15 L/h in adults with an average weight of 68 kg. In the same study, there was a separation of the intercompartment clearance which is 0.16 L/h. The clearance rate was reported to be significantly decreased with increasing age and significantly increased in patients that presented a blood type of gourp O. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The highest toxicity is the risk of viral hepatitis transmition as well as intravascular hemolyisis can occur if large or frequent doses are used in blood groups A, B or AB. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hemofil, Koate, Wilate •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antihemophilic factor, human recombinant interact?

•Drug A: Abciximab •Drug B: Antihemophilic factor, human recombinant •Severity: MAJOR •Description: The therapeutic efficacy of Antihemophilic factor, human recombinant can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): The human recombinant antihemophilic factor is indicated for use in adults and children with hemophilia A for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Antihemophilic Factor binds factor IXa along with calcium and phospholipid, This complex converts factor X to factor Xa to facilitate clotting cascade. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Antihemophilic factor (AHF) is a protein found in normal plasma which is necessary for clot formation. The administration of AHF provides an increase in plasma levels of AHF and can temporarily correct the coagulation defect of patients with hemophilia A (classical hemophilia). •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 8.4-19.3 hrs •Clearance (Drug A): No clearance available •Clearance (Drug B): 4.1 mL/h•kg [Previously treated pediatric patients] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Advate, Adynovate, Helixate, Kogenate, Kovaltry, Novoeight, Recombinate •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antilymphocyte immunoglobulin (horse) interact?

•Drug A: Abciximab •Drug B: Antilymphocyte immunoglobulin (horse) •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Antilymphocyte immunoglobulin (horse). •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For prevention of renal transplant rejection and for the treatment of aplastic anemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): During infusion of 10 to 15 mg/kg/day, the mean peak value (n = 27 renal transplant patients) was found to be 727 ± 310 μg/mL. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of equine immunoglobulin after ATGAM infusion was found to be 5.7 ± 3.0 days in one group of recipients. The range for half-life was 1.5 to 13 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most commonly reported adverse reactions (occurring in greater than 10% of patients) are pyrexia, chills, rash, thrombocytopenia, leukopenia and arthralgia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Atgam •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antipyrine interact?

•Drug A: Abciximab •Drug B: Antipyrine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Antipyrine is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •References: 1. Teklay G, Shiferaw N, Legesse B, Bekele ML: Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: a prospective observational study. Thromb J. 2014 Sep 17;12:20. doi: 10.1186/1477-9560-12-20. eCollection 2014. [https://go.drugbank.com/articles/A33535] 2. Choi KH, Kim AJ, Son IJ, Kim KH, Kim KB, Ahn H, Lee EB: Risk factors of drug interaction between warfarin and nonsteroidal anti-inflammatory drugs in practical setting. J Korean Med Sci. 2010 Mar;25(3):337-41. doi: 10.3346/jkms.2010.25.3.337. Epub 2010 Feb 17. [https://go.drugbank.com/articles/A33536] 3. Chan TY: Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother. 1995 Dec;29(12):1274-83. doi: 10.1177/106002809502901214. [https://go.drugbank.com/articles/A33538] 4. Moore N, Pollack C, Butkerait P: Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015 Jul 15;11:1061-75. doi: 10.2147/TCRM.S79135. eCollection 2015. [https://go.drugbank.com/articles/A33539] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Antipyrine is an analgesic often used to test effects of other drugs on liver enzymes. In combination with benzocaine in otic solutions, antipyrine is indicated for the symptomatic relief of acute otitis media arising from various etiologies. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Antipyrine is an analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29) •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Antipyrine is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,2-Dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one 2,3-Dimethyl-1-phenyl-5-pyrazolone Analgesine (common) Antipyrine (common) Fenazon (common) Fenazona (common) Phenazon (common) Phenazone (common)

Do Abciximab and Antithrombin Alfa interact?

•Drug A: Abciximab •Drug B: Antithrombin Alfa •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Antithrombin Alfa. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Antithrombin alfa is a recombinant antithrombin it is indicated for the prevention of peri-operative and peri-partum thromboembolic events in patients with hereditary deficiency of antithrombin. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Hereditary antithrombin deficiency causes an increased risk of venous thromboembolism (VTE). In high risk situations, such as surgery or trauma or for pregnant women during the peri-partum period, the risk of development of VTEs is 10-50 times greater than the general population. In hereditary antithrombin deficient patients antithrombin alfa normalizes plasma antthrombin activity levels during peri-operative and peri-partum periods. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Antithrombin is the main inhibitor of thrombin and Factor Xa, the serine proteases involved in blood coagulation. Antithrombin neutralizes the activity of thrombin and Factor Xa by forming a complex which is rapidly removed from the circulation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Given IV so not absorbed. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Dose of: 50IU/kg: 126.2 ml/kg 100IU/kg: 156.1 ml/kg Vd in hereditary deficient pregnant women in high risk situations had increased Vd of 14.3L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binds and inhibits thrombin and factor Xa. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Not metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Irreversible complexes formed between antithrombin III and its target protease are rapidly removed by the liver. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Dose of: 50IU/kg: 11.6 h 100IU/kg: 17.7 h •Clearance (Drug A): No clearance available •Clearance (Drug B): Dose of: 50IU/kg: 9.6 ml/hr/kg 100IU/kg: 7.2 ml/hr/kg Cl in hereditary deficient pregnant women in high risk situations had increased Cl of 1.38L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Highest dose tested was 360mg/kg/day in rats resulted in transient limb swelling. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Atryn •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antithrombin III human interact?

•Drug A: Abciximab •Drug B: Antithrombin III human •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Antithrombin III human. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Antithrombin III human is a human antithrombin (AT) indicated in patients with hereditary antithrombin deficiency for the treatment and prevention of thromboembolism and prevention of peri-operative and peri-partum thromboembolism •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Hereditary AT deficiency causes an increased risk of venous thromboembolism (VTE). During high-risk situations such as surgery or trauma or for pregnant women, during the peri-partum period, the risk of development of VTEs as compared to the normal population in these situations is increased by a factor 10 to 50. In hereditary antithrombin deficient patients ATryn restores (normalize) plasma AT activity levels during peri-operative and peri-partum periods. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Antithrombin, an alpha2-glycoprotein of molecular weight 58,000, is normally present in human plasma at a concentration of approximately 12.5 mg/dL and is the major plasma inhibitor of thrombin. Inactivation of thrombin by AT occurs by formation of a covalent bond resulting in an inactive 1:1 stoichiometric complex between the two, involving an interaction of the active serine of thrombin and an arginine reactive site on AT. AT is also capable of inactivating other components of the coagulation cascade including factors IXa, Xa, XIa, and XIIa, as well as plasmin. The neutralization rate of serine proteases by AT proceeds slowly in the absence of heparin, but is greatly accelerated in the presence of heparin. As the therapeutic antithrombotic effect of heparin is mediated by AT, heparin in vivo is ineffective in the absence or near absence of AT. After administration, Antithrombin III human temporarily replaces the missing AT in patients with hereditary antithrombin deficiency. •Absorption (Drug A): No absorption available •Absorption (Drug B): Therapeutic target plasma concentrations in patients with congenital antithrombin III deficiency range from 80–120% of values in healthy adults. At plasma concentrations ≤70% of normal, increased thrombin generation. Supraphysiologic plasma concentrations (e.g., 150–200% of normal) have increased bleeding risk in patients with sepsis and disseminated intravascular coagulation, not known whether supraphysiologic concentrations increase bleeding risk in patients with congenital antithrombin III deficiency. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Distributed into plasma (39%), extravascular space (49%), and vascular endothelial cells (11%). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): <5% metabolized to low molecular weight breakdown products. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Complexes of antithrombin III with thrombin or other proteinases cleared principally by liver and excreted in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2.5 - 3.8 hs •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Thrombate III •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Antithymocyte immunoglobulin (rabbit) interact?

•Drug A: Abciximab •Drug B: Antithymocyte immunoglobulin (rabbit) •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Antithymocyte immunoglobulin (rabbit). •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For prevention of renal transplant rejection •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Antithymocyte Globulin (ATG) is a concentrated anti-human T-lymphocyte immunoglobulin preparation derived from rabbits after immunization with a T-lympoblast cell line. ATG is an immunosuppressive product for the prevention and treatment of acute rejection following organ transplantation. ATG reduces the host immune response against tissue transplants or organ allografts. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Binds to multiple, T-cell specific antigens leading to T-lymphocyte cell death via complement mediated cytotoxicity or apoptosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): T-cell depletion usually observed within 1 day after initiating therapy. Average 21.5 and 87 mcg/mL 4–8 hours post-infusion after first and last IV doses, respectively, when given for 7–11 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2-3 days, may increase after multiple doses administration •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Not known whether ATG (rabbit) distributes into human milk; however, other immunoglobulins are distributed into human milk. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Apixaban interact?

•Drug A: Abciximab •Drug B: Apixaban •Severity: MAJOR •Description: Apixaban may increase the anticoagulant activities of Abciximab. •Extended Description: Due to a synergistic effect, concomitant use of apixaban and other anticoagulants may lead to more profound anticoagulant activities of those drugs. As with most anticoagulant drugs, apixaban increases the risk for bleeding and may cause serious, potentially fatal bleeding events. Co-administration of apixaban with other anticoagulants may significantly increase the bleeding potential of anticoagulant agents. •References: 1. Mueck W, Schwers S, Stampfuss J: Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. Thromb J. 2013 Jun 28;11(1):10. doi: 10.1186/1477-9560-11-10. [https://go.drugbank.com/articles/A35862] 2. Di Minno A, Frigerio B, Spadarella G, Ravani A, Sansaro D, Amato M, Kitzmiller JP, Pepi M, Tremoli E, Baldassarre D: Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Blood Rev. 2017 Jul;31(4):193-203. doi: 10.1016/j.blre.2017.02.001. Epub 2017 Feb 5. [https://go.drugbank.com/articles/A35863] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Apixaban is indicated for reducing the risk of stroke and systemic embolism in patients who have nonvalvular atrial fibrillation, prophylaxis of deep vein thrombosis(DVT) leading to pulmonary embolism(PE) in patients after a hip or knee replacement surgery, and treatment of DVT and PE to reduce the risk of recurrence. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin III. Apixaban also inhibits prothrominase. These effects prevent the formation of a thrombus. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin III. Apixaban also inhibits prothrominase. These effects prevent the formation of a thrombus. •Absorption (Drug A): No absorption available •Absorption (Drug B): Apixaban is approximately 50% bioavailable though other studies report 43-46% oral bioavailability. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Approximately 21L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 92-94%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): 50% of the orally administered dose is excreted as the unchanged parent compound, however 25% of the dose is excreted as O-demethyl apixaban sulfate. All apixaban metabolites account for approximately 32% of the excreted dose though the structure of all metabolites are not well defined. Apixaban is mainly metabolized by cytochrome p450(CYP)3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2J2. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 56% of an orally administered dose is recovered in the feces and 24.5-28.8% of the dose is recovered in the urine. 83-88% of the dose recovered in the urine was the unchanged parent compound. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 12.7±8.55h. •Clearance (Drug A): No clearance available •Clearance (Drug B): 3.3L/h though other studies report 4876mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Animal studies have shown an increased risk of maternal bleeding during pregnancy but no increase in fetal malformations or fetal or maternal deaths. It is unknown if this animal data also translates to humans so apixaban should only be used in pregnancy if the benefits outweigh the risks. It is not know whether apixaban is safe and effective in labor and during birth, though animal studies have shown an increased rate of maternal bleeding. Animal studies in rats show apixaban excreted in milk, though it is not know if this also applies to humans. Nursing mothers should either stop breastfeeding or stop taking apixaban depending on the risk and benefit of each option. Studies to determine safety and effectiveness in pediatric patients have yet to be performed. Studies that involved geriatric patients (at least 75 years old) saw no difference in safety or effectiveness compared to younger patients, though geriatric patients at an especially advanced age may be more susceptible to adverse effects. Dosage adjustments for patients with end stage renal disease(ESRD) are based on estimates of pharmacokinetic principles and not clinical study. Patients with ESRD may experience pharmacodynamics similar to those seen in well controlled studies but it may not lead to the same clinical effects. Dosage adjustments are not necessary in mild hepatic impairment. In moderate hepatic impairment patients may already experience abnormalities in coagulation and so no dose recommendations are possible. Apixaban is not recommended for patients with severe hepatic impairment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Eliquis •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Argatroban interact?

•Drug A: Abciximab •Drug B: Argatroban •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Argatroban. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Argatroban is indicated for prevention and treatment of thrombosis caused by heparin-induced thrombocytopenia (HIT). It is also indicated for use in patients with, or at risk for, HIT who are undergoing percutaneous coronary intervention. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (K i ) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). Argatroban is capable of inhibiting the action of both free and clot-associated thrombin. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability is 100% (intravenous). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 174 mL/kg 12.18 L [70-kg adult] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 54% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Liver via hydroxylation and aromatization of the 3-methyltetrahydroquinoline ring. Age and gender do not substantially affect the pharmacodynamic or pharmacokinetic profile of argatroban. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Argatroban is excreted primarily in the feces (65%), presumably through biliary secretion; 22% is eliminated via urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 39 and 51 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): 5.1 L/kg/hr [infusion doses up to 40 mcg/kg/min] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Excessive bleeding •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Argatroban (common) Argatroban anhydrous

Do Abciximab and Arsenic trioxide interact?

•Drug A: Abciximab •Drug B: Arsenic trioxide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Arsenic trioxide. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Arsenic Trioxide is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The mechanism of action of Arsenic Trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR-alpha. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 75% bound •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Inorganic, lyophilized arsenic trioxide, when placed in solution, is immediately hydrolyzed to arsenous acid - this appears to be the pharmacologically active species of arsenic trioxide. Further metabolism involves the oxidation of arsenous acid to arsenic acid, and an oxidative methylation of arsenous acid to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) by methyltransferases in the liver. Both MMA and DMA have relatively long half-lives and can accumulate following multiple doses, the extent of which depends upon the dosing regimen in question. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Trivalent arsenic is mostly methylated in humans and excreted in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include convulsions, muscle weakness and confusion. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trisenox •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Asfotase alfa interact?

•Drug A: Abciximab •Drug B: Asfotase alfa •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Asfotase alfa. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of patients with perinatal/infantile and juvenile onset hypophosphatasia (HPP). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Perinatal/infantile- and juvenile-onset HPP patients treated with Asfotase alfa had reductions in plasma TNSALP (tissue non-specific alkaline phosphatase) substrates, PPi and pyridoxal 5'-phosphate (PLP) within 6 to 12 weeks of treatment. Reductions in plasma PPi and PLP levels did not correlate with clinical outcomes. Bone biopsy data from perinatal/infantile-onset and juvenile-onset HPP patients treated with Asfotase alfa demonstrated decreases in osteoid volume and thickness indicating improved bone mineralization. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): HPP is caused by a deficiency in TNSALP (tissue non-specific alkaline phosphatase) enzyme activity, which leads to elevations in several TNSALP substrates, including inorganic pyrophosphate (PPi). Elevated extracellular levels of PPi block hydroxyapatite crystal growth which inhibits bone mineralization and causes an accumulation of unmineralized bone matrix which manifests as rickets and bone deformation in infants and children and as osteomalacia (softening of bones) once growth plates close, along with muscle weakness. Replacement of the TNSALP enzyme upon Asfotase alfa treatment reduces the enzyme substrate levels. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Approximately 5 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no available human data on Asfotase Alfa use in pregnant women to inform a drug associated risk. In animal reproduction studies, Asfotase Alfa administered intravenously to pregnant rats and rabbits during the period of organogenesis showed no evidence of fetotoxicity, embryolethality or teratogenicity at doses causing plasma exposures up to 21 and 24 times, respectively, the exposure at the recommended human dose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Strensiq •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Atezolizumab interact?

•Drug A: Abciximab •Drug B: Atezolizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Atezolizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Atezolizumab has approved indications for the following conditions: Non-Small Cell Lung Cancer (NSCLC) as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage II to IIIA NSCLC whose tumours have PD-L1 expression on ≥ 1% of tumour cells, as determined by an FDA-approved test. for the first-line treatment of adult patients with metastatic NSCLC whose tumours have high PD-L1 expression (PD-L1 stained ≥ 50% of tumour cells [TC ≥ 50%] or PD-L1 stained tumour-infiltrating immune cells [IC] covering ≥ 10% of the tumour area [IC ≥ 10%]), as determined by an FDAapproved test, with no EGFR or ALK genomic tumour aberrations. in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations. in combination with paclitaxel protein-bound and carboplatin for the firstline treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. for the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA-approved therapy for NSCLC harbouring these aberrations prior to receiving atezolizumab. Small Cell Lung Cancer (SCLC) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). Hepatocellular Carcinoma (HCC) in combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy. Melanoma in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. Alveolar Soft Part Sarcoma (ASPS) for the treatment of adult and pediatric patients 2 years of age and older with unresectable or metastatic ASPS. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers. This drug has a long duration of action as it is usually given every 3-4 weeks. Atezolizumab should not be used in patients with immune mediated penumonitis, hepatitis, colitis, and some endocrinopathies. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Atezolizumab is a humanized IgG antibody that binds PD-L1, preventing its interaction with PD-1 and B7-1. Preventing the interaction of PD-L1 and PD-1 removes inhibition of immune responses such as the anti-tumor immune response but not antibody dependent cellular cytotoxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pharmacokinetic analysis was performed in patients with metastatic urothelial carcinoma. In these patients, the AUC was 2.19-2.73day*µg/mL/mg, the C max was 0.27-0.35µg/mL/mg, and the C min was 0.004-0.008µg/mL/mg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of atezolizumab is 6.91L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are not expected to bind to proteins in plasma they are not designed to target. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Monoclonal antibodies are broken down into smaller polypeptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Atezolizumab is not renally excreted. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half life of atezolizumab is 27 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of atezolizumab is 0.200L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Most common adverse reactions (≥ 20% of patients) included: fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Overdose data for atezolizumab is scarce but the most common adverse reactions are fatigue, nausea, cough, dyspnea, decreased appetite, alopecia, constipation, diarrhea, peripheral neuropathies, anemia, headache, neutropenia, and vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tecentriq •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Avelumab interact?

•Drug A: Abciximab •Drug B: Avelumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Avelumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Avelumab is indicated for the treatment of adults with metastatic Merkel cell carcinoma (MCC). In the US, it is also used in patients 12 years and older. It is also indicated as the maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (UC), which has not progressed with first-line platinum-containing chemotherapy. In the US, avelumab is also indicated to treat locally advanced or metastatic UC with disease progression during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Avelumab is indicated, in combination with axitinib, for the first-line treatment of advanced renal cell carcinoma (RCC). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Avelumab is an immunotherapeutic and antineoplastic agent belonging to the immune checkpoint blockade cancer therapies group. It induces antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro; however it is unclear whether ADCC contributes to the therapeutic actions of avelumab. Avelumab decreased tumour growth in syngeneic mouse tumour models. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Programmed death ligand 1 (PD-L1) is a transmembrane protein and a co-inhibitory co-inhibitory immune checkpoint to suppress cytotoxic T-cell activity, proliferation, and cytokine production. It binds to PD receptor-1 (PD-1) and B7.1 receptors expressed on cytotoxic T cells and antigen-presenting cells to mediate its actions. PD-L1 is often expressed in tumours and surrounding tumour-infiltrating immune cells as an adaptive immune mechanism, decreasing the anti-tumour immune response in the tumour microenvironment. Avelumab binds PD-L1 and blocks its interaction with its receptors PD-1 and B7.1, disinhibiting PD-L1 effects on tumour-infiltrating lymphocytes and restoring anti-tumor immune responses. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients who received doses ranging from 1 to 20 mg/kg every two weeks, avelumab exposure increased dose proportionally in the dose range of 10 to 20 mg/kg. Steady-state concentrations of avelumab were reached after approximately four to six weeks (two to three cycles) of repeated dosing, and the systemic accumulation was approximately 1.25-fold. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The geometric mean volume of distribution at steady state for a subject receiving 10 mg/kg is 4.72 L. Avelumab is expected to be distributed in the systemic circulation and, to a lesser extent, in the extracellular space. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Avelumab undergoes nonspecific proteolytic degradation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life is approximately 6.1 days in patients with solid tumours receiving 10 mg/kg. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total systemic clearance is approximately 0.59 L/day in patients with solid tumours receiving 10 mg/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information regarding the LD 50 of avelumab. Three patients who received a dose of avelumab that was 5% to 10% above the recommended dose experienced an overdose: the patients reported no symptoms and continued on avelumab therapy without requiring any treatment for the overdose. In the case of an overdose, patients should be closely monitored for signs or symptoms of adverse reactions. The treatment is directed to the management of symptoms. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bavencio •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Azacitidine interact?

•Drug A: Abciximab •Drug B: Azacitidine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Azacitidine. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Azacitidine (for subcutaneous or intravenous use) is indicated for the treatment of adult patients with the following French-American-British (FAB) myelodysplastic syndrome (MDS) subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). Azacitidine is also indicated for the treatment of pediatric patients aged 1 month and older with newly diagnosed Juvenile Myelomonocytic Leukemia (JMML). Azacitidine (for oral use) is indicated for continued treatment of adult patients with acute myeloid leukemia (AML) who achieved first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis, and hypomethylation may restore normal function to genes critical for differentiation and proliferation. Genome-wide DNA methylation levels in bone marrow granulocytes were reduced in patients with juvenile myelomonocytic leukemia after the first treatment cycle of azacitidine (75 mg/m or 2.5 mg/kg), confirming the DNA-hypomethylating activity of azacitidine. The use of azacitidine causes anemia, neutropenia and thrombocytopenia in adult patients with myelodysplastic syndrome and pediatric patients with juvenile myelomonocytic leukemia. Azacitidine may cause renal toxicity, tumor lysis syndrome and embryo-fetal toxicity. It may also lead to the development of hepatotoxicity in patients with severe pre-existing hepatic impairment. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside present in DNA and RNA. It induces antineoplastic activity by inhibiting DNA methyltransferase at low doses and inducing cytotoxicity by incorporating itself into RNA and DNA at high doses. Covalent binding to DNA methyltransferase results in DNA hypomethylation and prevents DNA synthesis. On the other hand, the incorporation of azacitidine into RNA and DNA leads to cytotoxicity as follows: Following cellular uptake, azacitidine is phosphorylated by uridine-cytidine kinase to form 5-azacytidine monophosphate. Afterwards, pyrimidine monophosphate and diphosphate kinases phosphorylate 5-azacytidine monophosphate to form 5-azacytidine diphosphate and triphosphate, respectively. Azacitidine triphosphate is able to incorporate into RNA, disrupting RNA metabolism and protein synthesis. The reduction of azacytidine diphosphate leads to the formation of 5-aza-deoxycytidine diphosphate, which is then phosphorylated to form 5-azadeoxycitidine triphosphate, a compound able to incorporate into DNA and inhibit DNA synthesis. As a ribonucleoside, azacitidine incorporates into RNA to a larger extent than into DNA. Incorporating into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and the inhibition of protein production, resulting in cell death. During the S-phase of the cell cycle, azacitidine exhibits the highest toxicity; however, the predominant mechanism of cytotoxicity has not been elucidated. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine. It is believed that azacitidine exerts its antineoplastic effects through direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. •Absorption (Drug A): No absorption available •Absorption (Drug B): Azacitidine is rapidly absorbed after subcutaneous administration. In adult patients with myelodysplastic syndrome given a single subcutaneous dose of 75 mg/m of azacitidine, the C max and T max were 750 ng/ml and 0.5 hours, respectively. Based on the area under the curve, the bioavailability of subcutaneous azacitidine relative to intravenous azacitidine is approximately 89%. In 21 patients with cancer given subcutaneous azacitidine, the AUC and C max were approximately dose-proportional between 25 and 100 mg/m. Multiple subcutaneous or intravenous doses of azacitidine are not expected to result in drug accumulation. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients given an intravenous dose of azacitidine, the volume of distribution is 76 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Not available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): An in vitro study of azacitidine incubation in human liver fractions indicated that cytochrome P450 (CYP) enzymes do not participate in the metabolism of azacitidine. Azacitidine is metabolized through spontaneous hydrolysis and deamination mediated by cytidine deaminase. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Azacitidine and its metabolites are mainly excreted through urine. In five cancer patients given radioactive azacitidine intravenously, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for less than 1% of administered radioactivity over three days. Following the subcutaneous administration of 14C-azacitidine, the mean excretion of radioactivity in urine was 50%. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean half-life of azacitidine after subcutaneous administration is 41 minutes. The mean elimination half-life of azacitidine and its metabolites was about 4 hours for intravenous and subcutaneous administrations. •Clearance (Drug A): No clearance available •Clearance (Drug B): Azacitidine has an apparent subcutaneous clearance of 167 L/hour in adults. In pediatric patients, the geometric mean clearance was 21.8 L/hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): One case of overdose with azacitidine was reported during clinical trials. After receiving a single dose of 290 mg/m of azacitidine intravenously (almost 4 times the recommended starting dose), a patient experienced diarrhea, nausea, and vomiting. These adverse events resolved without sequelae, and the correct dose was resumed the following day. In case of overdose, patients should be monitored with appropriate blood counts and receive supportive treatment as necessary. There is no known specific antidote for azacitidine overdosage. In mice, the oral LD 50 of azacitidine is 572 mg/kg, while the intravenous LD 50 is approximately 117 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Onureg, Vidaza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4-amino-1-beta-D-ribofuranosyl-s-triazin-2(1H)-one 5-azacytidine Azacitidina (common) Azacitidine (common) Azacitidinum (common) Azacytidine (common)

Do Abciximab and Azithromycin interact?

•Drug A: Abciximab •Drug B: Azithromycin •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Azithromycin is combined with Abciximab. •Extended Description: In a study of 22 healthy volunteers, a 5-day azithromycin course did not affect the prothrombin time from subsequently administered warfarin. Despite this, post-marketing reports indicate that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants . The mechanism of this interaction is unknown, and unlikely to be due to any involvement of hepatic cytochrome enzyme metabolism . •References: 1. Shrader SP, Fermo JD, Dzikowski AL: Azithromycin and warfarin interaction. Pharmacotherapy. 2004 Jul;24(7):945-9. doi: 10.1592/phco.24.9.945.36100. [https://go.drugbank.com/articles/A174205] 2. Foster DR, Milan NL: Potential interaction between azithromycin and warfarin. Pharmacotherapy. 1999 Jul;19(7):902-8. [https://go.drugbank.com/articles/A34617] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Azithromycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria in order to prevent the development antimicrobial resistance and maintain the efficacy of azithromycin. Azithromycin is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the microorganisms listed in the specific conditions below. Recommended dosages, duration of therapy and considerations for various patient populations may vary among these infections. Refer to the FDA label and "Indications" section of this drug entry for detailed information. Adults: Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae. Abscesses usually require surgical drainage. Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae. Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the efficacy of azithromycin in the treatment of chancroid in women has not been established. Pediatric Patients Acute otitis media caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy. Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Macrolides stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections. Azithromycin has additional immunomodulatory effects and has been used in chronic respiratory inflammatory diseases for this purpose. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Azithromycin binds to the 23S rRNA of the bacterial 50S ribosomal subunit. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit,. This results in the control of various bacterial infections,. The strong affinity of macrolides, including azithromycin, for bacterial ribosomes, is consistent with their broad‐spectrum antibacterial activities. Azithromycin is highly stable at a low pH, giving it a longer serum half-life and increasing its concentrations in tissues compared to erythromycin. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability of azithromycin is 37% following oral administration. Absorption is not affected by food. Macrolide absorption in the intestines is believed to be mediated by P-glycoprotein (ABCB1) efflux transporters, which are known to be encoded by the ABCB1 gene. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After oral administration, azithromycin is widely distributed in tissues with an apparent steady-state volume of distribution of 31.1 L/kg. Significantly greater azithromycin concentrations have been measured in the tissues rather than in plasma or serum,. The lung, tonsils and prostate are organs have shown a particularly high rate of azithromycin uptake. This drug is concentrated within macrophages and polymorphonucleocytes, allowing for effective activity against Chlamydia trachomatis. In addition, azithromycin is found to be concentrated in phagocytes and fibroblasts, shown by in vitro incubation techniques. In vivo studies demonstrate that concentration in phagocytes may contribute to azithromycin distribution to inflamed tissues. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The serum protein binding of azithromycin varies in humans, decreasing from 51% at 0.02 µg/mL to 7% at 2 µg/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed, however, this drug is eliminated by the liver,. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Biliary excretion of azithromycin, primarily as unchanged drug, is a major route of elimination. Over a 1 week period, approximately 6% of the administered dose is found as unchanged drug in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Terminal elimination half-life: 68 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean apparent plasma cl=630 mL/min (following single 500 mg oral and i.v. dose) •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Rat Oral LD50: >2000 mk/kg Possible major adverse effects include cardiovascular arrhythmias and hearing loss. Macrolide resistance is also an ongoing issue. Hepatotoxicity has been observed in rare cases. A note on the risk of liver toxicity: Due to the act that azithromycin is mainly eliminated by the liver, caution should be observed when azithromycin is given to patients with decreased hepatic function. A note on potential renal toxicity: Because limited data in patients with renal GFR <10 mL/min, caution should be exercised when prescribing azithromycin to these patients. Use in Pregnancy: This drug is categorized as a pregnancy category B drug. Reproduction studies have been done in rats and mice at doses up to moderately maternally toxic doses (for example, 200 mg/kg/day). These doses, based on a mg/m2 basis, are approximately 4 and 2 times, respectively, the human daily dose of 500 mg. In the animal studies, no harmful effects to the fetus due to azithromycin were observed. There are, at this time, no conclusive and well-controlled studies that have been done in pregnant women. Because animal reproduction studies do not always predict human response, azithromycin should be used during pregnancy only if clearly needed. Nursing Mothers: It is unknown at this time whether azithromycin is excreted in human milk. Because many other drugs are excreted in human milk, caution should be observed when azithromycin is given to a nursing woman. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to study carcinogenic potential. Azithromycin has demonstrated no potential to be mutagenic in standard laboratory tests. No evidence of negative effects on fertility due to azithromycin was found. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Azasite, Zithromax, Zmax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Balsalazide interact?

•Drug A: Abciximab •Drug B: Balsalazide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Balsalazide is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •References: 1. Teklay G, Shiferaw N, Legesse B, Bekele ML: Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: a prospective observational study. Thromb J. 2014 Sep 17;12:20. doi: 10.1186/1477-9560-12-20. eCollection 2014. [https://go.drugbank.com/articles/A33535] 2. Choi KH, Kim AJ, Son IJ, Kim KH, Kim KB, Ahn H, Lee EB: Risk factors of drug interaction between warfarin and nonsteroidal anti-inflammatory drugs in practical setting. J Korean Med Sci. 2010 Mar;25(3):337-41. doi: 10.3346/jkms.2010.25.3.337. Epub 2010 Feb 17. [https://go.drugbank.com/articles/A33536] 3. Chan TY: Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother. 1995 Dec;29(12):1274-83. doi: 10.1177/106002809502901214. [https://go.drugbank.com/articles/A33538] 4. Moore N, Pollack C, Butkerait P: Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015 Jul 15;11:1061-75. doi: 10.2147/TCRM.S79135. eCollection 2015. [https://go.drugbank.com/articles/A33539] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of mildly to moderately active ulcerative colitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Balsalazide is a prodrug that has little or no pharmacologic activity until it is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid), an anti inflammatory drug indicated for the treatment of mildly to moderately active ulcerative colitis. Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the intert 4-aminobenzoyl-(beta)-alanine. As a result, the spectrum of pharmacologic activity of balsalazide is similar to that of mesalamine. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The mechanism of action of 5-aminosalicylic acid is unknown, but appears exert its anti-inflammatory effects locally (in the GI tract) rather than systemically. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways (catalyzes the formation of prostaglandin precursors from arachidonic acid), and through the lipoxygenase pathways (catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid and its metabolites), is increased in patients with chronic inflammatory bowel disease. Therefore, it is possible that 5-aminosalicylic acid diminishes inflammation by blocking production of arachidonic acid metabolites in the colon through both the inhibition of cyclooxygenase and lipoxygenase. •Absorption (Drug A): No absorption available •Absorption (Drug B): Low and variable, intact balsalazide is poorly absorbed systemically. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): ≥99% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Cleaved in the colon via bacterial azoreduction to 5–aminosalicylic acid (5–ASA) and 4–aminobenzoyl-beta-alanine, the inactive carrier moiety. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The products of the azoreduction of this compound, 5-ASA and 4-aminobenzoyl-ß-alanine, and their N-acetylated metabolites have been identified in plasma, urine and feces. Following single-dose administration of 2.25 g COLAZAL (three 750 mg capsules) under fasting conditions in healthy subjects, mean urinary recovery of balsalazide, 5-ASA, and N-Ac-5-ASA was 0.20%, 0.22% and 10.2%, respectively. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Half-life could not be determined. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): A single oral dose of balsalazide disodium at 5 grams/kg or 4-aminobenzoyl-(beta)-alanine, a metabolite of balsalazide disodium, at 1 gram/kg was non-lethal in mice and rats. No symptoms of acute toxicity were seen at these doses. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Colazal •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (E)-5-((4-(((2-carboxyethyl)amino)carbonyl)phenyl)azo)-2-hydroxybenzoic acid (E)-5-({p-[(2-carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid 3-(2-{4-[(2-carboxyethyl)carbamoyl]phenyl}hydrazinylidene)-6-oxocyclohexa-1,4-diene-1-carboxylic acid 5-[4-(2-carboxy-ethylcarbamoyl)-phenylazo]-2-hydroxy-benzoic acid Balsalazida (common) Balsalazide (common) Balsalazidum (common)

Do Abciximab and Bamlanivimab interact?

•Drug A: Abciximab •Drug B: Bamlanivimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Bamlanivimab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bamlanivimab is not currently approved for any indication by the FDA. Bamlanivimab is authorized under an Emergency Use Authorization (EUA) for the treatment of mild to moderate COVID-19 in patients aged 12 years and older weighing at least 40 kg who are at high risk for progressing to severe COVID-19 and/or hospitalization due to COVID-19. Patients should have confirmed COVID-19, with identification of SARS-CoV-2 viral load by an approved test. Under this EUA, bamlanivimab is not authorized in patients who are hospitalized due to COVID-19, who require oxygen due to COVID-19, or in patients on oxygen therapy for non-COVID-19-related comorbidity who require an increased oxygen flow rate due to COVID-19. Bamlanivimab in combination with etesevimab is used to treat mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients, including neonates, with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. This combination regimen is also used for post-exposure prophylaxis of COVID-19 in unvaccinated or immunocompromised adults and pediatric individuals, including neonates, who are at high risk of progression to severe COVID-19, including hospitalization or death. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bamlanivimab is a recombinant human IgG1κ monoclonal antibody directed against the spike (S) surface protein of SARS-CoV-2. Patients in a phase 2 trial were administered up to 7000 mg (ten times the authorized dose) with no increase in treatment-related adverse effects and a flat exposure-response relationship over ranges of 700-7000 mg. Despite generally mild adverse effects noted in the phase 2 trial, there is a risk of serious infusion-related hypersensitivity reactions with bamlanivimab, including anaphylaxis, which may necessitate slowing the infusion rate or discontinuing treatment entirely. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Bamlanivimab is a neutralizing recombinant human IgG1κ monoclonal antibody directed against the spike (S) surface protein of SARS-CoV-2 derived from screening antigen-specific B-cells from a convalescent COVID-19 patient. X-ray crystallography and cryo-EM structural determination suggest that bamlanivimab binds the receptor-binding domain (RBD) of the S protein at a position overlapping the ACE2 binding site and which is accessible in both the up and down conformations of the RBD. Specifically, bamlanivimab binds to the S protein with a K D of 0.071 nM and blocks S protein-ACE2 interactions with an IC 50 value of 0.025 μg/mL. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As a monoclonal antibody, it is expected that bamlanivimab will be degraded by proteases in various locations throughout the body. Bamlanivimab is not metabolized by cytochrome P450 enzymes, making drug interactions unlikely. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Bamlanivimab has been administered at doses of 7000 mg (ten times the authorized dose) during phase 2 clinical trials without any observed dose-limiting toxicity. In the event of an overdose, the recommended treatment is symptomatic and supportive measures; there is no antidote for bamlanivimab overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Basiliximab interact?

•Drug A: Abciximab •Drug B: Basiliximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Basiliximab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For prophylactic treatment of kidney transplant rejection •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Basiliximab functions as an IL-2 receptor antagonist. Specifically it inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Basiliximab binds with high-affinity to the alpha-subunit (CD25) of the high-affinity IL-2 receptor. This inhibits IL-2 binding, which inhibits T-cell activation and prevents the body from mounting an immune response against the foreign kidney. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 7.8 ± 5.1 L [Pediatric] 4.8 ± 2.1 L [Adult] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes, or by human antimurine antibody production •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 7.2 +/- 3.2 days (adults) •Clearance (Drug A): No clearance available •Clearance (Drug B): 41 +/- 19 mL/h [Adult patients undergoing first kidney transplantation] 17 +/- 6 mL/h [pediatric patients undergoing renal transplantation] 31 +/- 19 mL/h [adolescent patients undergoing renal transplantation] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Simulect •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Belantamab mafodotin interact?

•Drug A: Abciximab •Drug B: Belantamab mafodotin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Belantamab mafodotin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Belantamab mafodotin is indicated in the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Belantamab mafodotin treats multiple myeloma through antibody dependant cell mediated cytotoxicity as well as G2/M cell cycle arrest. It has a narrow therapeutic index due to the incidence of adverse effects, and a long duration of action as it is given every 3 weeks. Patients should be counselled regarding the risk of keratopathy. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Belantamab mafodotin, or GSK2857916, is an afucosylated monoclonal antibody that targets B cell maturation antigen (BCMA) conjugated to the microtubule distrupter monomethyl auristatin-F (MMAF). Afucosylation of the Fc region of monoclonal antibodies enhances binding to the Fc region, which enhances antibody dependant cell mediated cytoxicity. BCMA is uniquely expressed on CD138-positive myeloma cells. Targeting BCMA allows belantamab mafodotin to be highly selective in its delivery of MMAF to multiple myeloma cells. Belantamab mafodotin binds to BCMA, is internalised into cells, and releases MMAF. The MMAF payload binds to tubulin, stopping the cell cycle at the DNA damage checkpoint between the G2 and M phases, resulting in apoptosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Belantamab mafodotin at a dose of 2.5mg/kg reaches a C max of 42 µg/mL, with a T max of 0.78 hours, and an AUC of 4666 µg*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean steady state volume of distribution of belantamab mafodotin was 11 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are generally not protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Monoclonal antibodies are expected to be metabolized to smaller peptides and amino acids. MMAF is expected to be metabolized by oxidation and demethylation, however further data is not readily available. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acids which are eliminated in a similar fashion to other proteins. Monoclonal antibodies are generally not eliminated in the urine, and only a small amount is excreted in bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half life of belantamab mafodotin was 12 days after the first dose and 14 days at steady state. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of belantamab mafodotin was 0.9 L/day after the first dose and 0.7 L/day at steady state. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdose is not readily available. However, keratopathy was seen in 71% of patients. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): BLENREP •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Belimumab interact?

•Drug A: Abciximab •Drug B: Belimumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Belimumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): In the US, belimumab is indicated to treat active systemic lupus erythematosus (SLE) and active lupus nephritis in patients aged five years and older who are receiving standard therapy. In Europe, belimumab is also used to treat SLE and lupus nephritis but only in adults. The efficacy of belimumab has not been evaluated in patients with severe active central nervous system lupus. Use of belimumab is not recommended in this situation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Belimumab works to inhibit the actions of autoreactive, pro-inflammatory B cells that cause chronic inflammation and tissue damage. In patients with SLE, belimumab significantly reduced levels of circulating B (CD20+) cells. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Systemic lupus erythematosus (SLE) and lupus nephritis, a common and serious manifestation of SLE, are autoimmune disorders characterized by the presence of autoreactive B lymphocytes (B cells), which promotes the production of autoantibodies that cause inflammation and progressive and irreversible tissue damage. One of the key cytokines involved in B cell homeostasis and survival is B lymphocyte stimulator protein (BLyS), which is a member of tumour necrosis factor (TNF) superfamily of cytokines. While the contribution of BLyS to the pathophysiology of autoimmune diseases is not fully understood, BLyS has been identified as a key therapeutic target for the treatment of SLE as BLyS levels are elevated in patients with SLE along with other autoimmune diseases. Belimumab is an antibody directed against BLyS: it selectively binds BLyS with high affinity, neutralizes it, and blocks its interaction with B cell receptors - transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and BLyS receptor 3 (BR3). Belimumab ultimately inhibits the survival of B cells, promotes apoptosis, and reduces the differentiation and maturation of B cells into immunoglobulin-producing plasma cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability was 74-82% following single belimumab SC doses in healthy adults. Following administration of 10 mg/kg belimumab via intravenous infusion in adults with SLE, the C max was 313 mcg/mL and the AUC 0-∞ was 3,083 day x mcg/mL. Following subcutaneous administration of 200 mg belimumab once-weekly in adults with SLE, the C max was 108 mcg/mL and the AUC 0-∞ was 726 day x mcg/mL. In healthy Japanese volunteers, the T max was 6.5 days after administration of a single subcutaneous dose of 200 mg/mL belimumab. Steady-state exposure was reached after approximately 11 weeks of subcutaneous administration in healthy subjects of patients with SLE. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following administration of 10 mg/kg belimumab via intravenous infusion or 200 mg belimumab once-weekly in adults with SLE, the volume of distribution (V ss ) was 5 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No formal metabolism studies have been conducted. As belimumab is an antibody, it is expected to undergo degradation mediated by proteolytic enzymes to form small peptides and individual amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is no information available. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Following administration of 10 mg/kg belimumab via intravenous infusion in adults with SLE, the distribution and terminal half-lives were 1.8 days and 19.4 days, respectively. Following subcutaneous administration of 200 mg belimumab once-weekly in adults with SLE, the distribution and terminal half-lives were 1.1 days and 18.3 days, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following administration of 10 mg/kg belimumab via intravenous infusion in adults with SLE, systemic clearance was 215 mL/day. Following subcutaneous administration of 200 mg belimumab once-weekly in adults with SLE, systemic clearance was 204 mL/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no LD 50 data available for belimumab. There is limited experience with overdosage of belimumab. Two doses of up to 20 mg/kg have been given intravenously to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg. In the case of inadvertent overdose, patients should be carefully observed and supportive care administered, as appropriate •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Benlysta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Belinostat interact?

•Drug A: Abciximab •Drug B: Belinostat •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Belinostat. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Belinostat is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) with manageable safety profile. It is a potential alternative therapy for patients who did not experience adequate response to first-line drugs for PTCL. It can be used in patients with baseline thrombocytopenia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Beleodaq is a histone deacetylase (HDAC) inhibitor that exhibits pan-HDAC inhibition and potent growth inhibitory and pro-apoptotic activities in a variety of tumor cells, including PTCL cells, at nanomolar concentrations. None of the trials show any clinically relevant changes caused by Beleodaq on heart rate, PR duration or QRS duration as measures of autonomic state, atrio-ventricular conduction or depolarization; there were no cases of Torsades de Pointes. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Belinostat inhibits the activity of histone deacetylase (HDAC) thus prevents the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, increased the expression of tumor-suppressor genes. It ultimately induces cell cycle arrest, inhibition of angiogenesis and/or apoptosis of some transformed cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution is 409 ± 76.7 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 92.9% and 95.8% of belinostat is bound to protein. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Primarily metabolized by hepatic UGT1A1. Strong UGT1A1 inhibitors are expected to increase exposure to belinostat. Belinostat also undergoes hepatic metabolism by CYP2A6, CYP2C9, and CYP3A4 enzymes to form belinostat amide and belinostat acid. The enzymes responsible for the formation of methyl belinostat and 3-(anilinosulfonyl)-benzenecarboxylic acid, (3-ASBA) are not known •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 40% of the belinostat dose is excreted renally, primarily as metabolites and less than 2% of total dose recovered as unchanged parent drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Displays a three-compartment pharmacokinetic property with elimination half life of 1.1 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 1240 mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Belinostat is genotoxic according to Ames test and may impair male fertility. Weekly complete blood count should be monitored during treatment to adjust the dosage as intravenous infusion of belinostat is frequently associated with hematologic toxicity such as leukopenia and thrombocytopenia. Incidences of infections such as sepsis, hepatotoxicity, tumor lysis syndrome, gastrointestinal toxicity, and embryo-fetal toxicity may occur. No specific information is available on the treatment of overdosage of Beleodaq. There is no antidote for Beleodaq and it is not known if Beleodaq is dialyzable. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Beleodaq •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Bemiparin interact?

•Drug A: Abciximab •Drug B: Bemiparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Bemiparin. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bemiparin is indicated in the following cases: To prevent blood clots in the veins after general abdominal surgery in patients with a moderate risk of venous thromboembolism; in the prevention of the thromboembolic disease in non-surgical patients; prevention of clotting in the extracorporeal circuit during hemodialysis; to prevent blood clots in the veins after a major orthopedic surgery in patients with high risk of venous thromboembolism; secondary prevention of venous thromboembolism; recurrence in patients with deep vein thrombosis; transient prevention and treatment of deep vein thrombosis (DVT). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bemiparin is an anticoagulant classified under the broad category of low molecular weight heparins. In humans, bemiparin has been proven to possess antithrombotic activity and, at therapeutic doses, does not significantly prolong global clotting laboratory tests. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): This drug is a second-generation low molecular weight heparin (LMWH). It has a very low mean molecular weight (3600 Dalton), a long half-life (5.3 hrs) and a large anti-Xa: anti-IIa ratio (8:1). The mechanism of action of bemiparin is inhibition of factor Xa, which is a necessary step in the clotting cascade. Factor-Xa is necessary for the propagation of a thrombus. Combined with various co-factors that bind to activated platelets, Factor-Xa increases coagulation by converting prothrombin to thrombin. Activated Factor-X, bound as part of the prothrombinase complex on the external surface of activated platelets, converts significant amounts of prothrombin to thrombin, promoting the so-called ‘thrombin burst’, referring to a burst of thrombin release. A secondary but less potent mechanism of action of this drug is binding to antithrombin III and activated factor II (Factor IIa), which further prevents the propagation of thrombi. Due to its excellent pharmacological profile-the second-generation LMWH with the lowest molecular weight, the longest half-life and the highest anti-Factor Xa/anti-Factor IIa activity ratio-it can be safely used in special categories of patients (children, elderly, patients with renal impairment and congestive heart failure). Several studies demonstrated its safety and efficacy, while cost analyses show the economic benefits of bemiparin treatment as compared to other heparins. •Absorption (Drug A): No absorption available •Absorption (Drug B): Hemiparin sodium is rapidly absorbed following its subcutaneous dose of injection, and the bioavailability is estimated to be 96%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 5.1 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There are currently no data available with regards to plasma protein binding, metabolism and excretion of bemiparin in humans. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): In a study of healthy volunteers, bemiparin 3500 IU achieved more anti-Xa activity than enoxaparin 4000 IU, measured by the area under the curve. The peak of anti-Xa activity was reached at 3h post-administration, and there were anti-Xa measurable levels up to 16 h after subcutaneous injection. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): This drug is eliminated by the renal and hepatic routes. Elimination is prolonged in those with renal or hepatic impairment. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Bemiparin, when administered in the dose range of 2,500 IU to 12,500 (therapeutic dosing), it has an approximate half-life of 5-6 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Elimination occurs in a linear fashion, with a mean clearance time of over 7 h and total clearance of 0.9 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Bemiparin, like other drugs in its class, may suppress adrenal secretion of aldosterone, leading to elevated potassium (hyperkalemia). This may occur more frequently in patients with conditions such as diabetes mellitus, chronic renal failure, metabolic acidosis, an increased plasma potassium, and those ingesting potassium sparing drugs. There is a linear relationship between duration of therapy and adverse effects, but this is usually reversible with cessation of treatment. Serum electrolytes should be measured in at-risk patients before starting bemiparin, and these patients should be monitored regularly thereafter particularly if treatment is prolonged beyond 1 week. In rare cases, mild transient thrombocytopenia (HIT type I) at the beginning of therapy with heparin with platelet counts between 100,000/mm3 and 150,000/mm3 due to temporary platelet activation has been noted in clinical studies. On rare occasions, antibody-mediated severe thrombocytopenia (HIT type II) with platelet counts clearly below 100,000/mm3 has been observed (see section 4.8). This effect usually occurs within 5-21 days after the initiation of treatment, although in patients with a history of heparin-induced thrombocytopenia this may occur more rapidly. Platelet count studies are recommended before the administration of bemiparin, on the first day of therapy and then every 3-4 days, in addition to repeating platelet studies at the end of therapy. Treatment must be discontinued immediately and an alternate therapy initiated if significant reductions in platelet counts are observed ( 30% decrease and above). As with other heparin products, cases of cutaneous necrosis, often preceded by purpura or painful erythematous, ecchymose-like lesions have been reported with bemiparin. In these cases, treatment should cease immediately. Overdosage after subcutaneous or other routes of administration of bemiparin may lead to hemorrhagic complications. Neutralization can be obtained by slow intravenous of a suitable dose of the antidote protamine sulphate. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Bendamustine interact?

•Drug A: Abciximab •Drug B: Bendamustine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Bendamustine. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bendamustine is indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No mean changes in QTc interval greater than 20 milliseconds were detected up to one hour post-infusion. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single IV dose of bendamustine hydrochloride Cmax typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean steady-state volume of distribution (Vss) of bendamustine was approximately 20-25 L. Steady-state volume of distribution for total radioactivity was approximately 50 L, indicating that neither bendamustine nor total radioactivity are extensively distributed into the tissues. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, the binding of bendamustine to human serum plasma proteins ranged from 94-96% and data suggest that bendamustine is not likely to displace or to be displaced by highly protein-bound drugs. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): In vitro data indicate that bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxy-bendamustine (HP2) metabolites with low cytotoxic activity. Two active minor metabolites, M3 and M4, are primarily formed via CYP1A2. However, concentrations of these metabolites in plasma are 1/10th and 1/100th that of the parent compound, respectively, suggesting that the cytotoxic activity is primarily due to bendamustine. Results of a human mass balance study confirm that bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mean recovery of total radioactivity in cancer patients following IV infusion of [14C] bendamustine hydrochloride was approximately 76% of the dose. Approximately 50% of the dose was recovered in the urine and approximately 25% of the dose was recovered in the feces. Urinary excretion was confirmed as a relatively minor pathway of elimination of bendamustine, with approximately 3.3% of the dose recovered in the urine as parent. Less than 1% of the dose was recovered in the urine as M3 and M4, and less than 5% of the dose was recovered in the urine as HP2. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 40 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): 700 mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Risk for tumor-lysis syndrome. Discontinue use in the event of severe/progressive skin reactions. Hematologic malignancies of different forms reported. Discontinue use in the case of severe infusion reactions. May cause extravasation. Mild to moderate renal impairment. Mild hepatic impairment. Sepsis (infections) may occur. Avoid use if pregnant. Possibility of anaphylaxis or infusion reactions- severe in rare cases. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Belrapzo, Bendeka, Treanda, Vivimusta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Benralizumab interact?

•Drug A: Abciximab •Drug B: Benralizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Benralizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Benralizumab is indicated as a maintenance treatment of patients 12 years or older with severe asthma and an eosinophilic phenotype. The pathology of severe asthma with eosinophilic phenotype is also denotated as TH2-high phenotype. The patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE and eosinophilia in blood and airway. In the TH2-high phenotype, IL-5 presents a central role as it is responsible for eosinophil differentiation, survival, activation and migration to the lungs. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eosinophils are the key target of inflammatory respiratory diseases and they undergo apoptosis in absence of IL-5. Therefore, benralizumab action on the IL-5 receptor in basophils and eosinophils produces the apoptosis and its significant reduction in the blood. On the other hand, Benralizumab binding to natural killer cells FcγRIIIα receptor produces a direct antibody-dependent cell-mediated cytotoxicity. All these effects produce a reduction in eosinophil count in airway mucosa, submucosa, sputum, blood and bone marrow. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Subcutaneous administration of Benralizumab presented a dose-proportional pharmacokinetic profile. The administration of 20-200 mg presented an absorption half-life of 3.6 days with a bioavailability of 58%. It is also reported for Benralizumab a Cmax of 82 mcg/ml and AUC of 775 mcg day/ml. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pharmacokinetic reports of Benralizumab showed a volume of distribution in a range of 52-93ml/kg. For a 70kg individual, the central volume of distribution of Benralizumab is 3.2 L while the peripheral volume of distribution is reported to be 2.5 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no reports indicating that Benralizumab binds to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As any monoclonal IgG antibody, Beralizumab is degraded by proteases widely spread in the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Benraluzimab presents a linear pharmacokinetic without target-receptor mediated clearance. The presence of a dose-proportional pharmacokinetics suggests a rapid depletion of the target and an elimination mainly mediated through the reticuloendothelial system. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of Benralizumab is estimated to be 15-18 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): For a subject weighting 70kg, the typical systemic clearance is 0.29L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are not reports of long-term studies regarding tumorgenesis or carcinogenesis. Fertility studies performed in aminal trials showed no adverse histopathological findings. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fasenra •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Benzydamine interact?

•Drug A: Abciximab •Drug B: Benzydamine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Benzydamine is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •References: 1. Teklay G, Shiferaw N, Legesse B, Bekele ML: Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: a prospective observational study. Thromb J. 2014 Sep 17;12:20. doi: 10.1186/1477-9560-12-20. eCollection 2014. [https://go.drugbank.com/articles/A33535] 2. Choi KH, Kim AJ, Son IJ, Kim KH, Kim KB, Ahn H, Lee EB: Risk factors of drug interaction between warfarin and nonsteroidal anti-inflammatory drugs in practical setting. J Korean Med Sci. 2010 Mar;25(3):337-41. doi: 10.3346/jkms.2010.25.3.337. Epub 2010 Feb 17. [https://go.drugbank.com/articles/A33536] 3. Chan TY: Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother. 1995 Dec;29(12):1274-83. doi: 10.1177/106002809502901214. [https://go.drugbank.com/articles/A33538] 4. Moore N, Pollack C, Butkerait P: Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015 Jul 15;11:1061-75. doi: 10.2147/TCRM.S79135. eCollection 2015. [https://go.drugbank.com/articles/A33539] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Available predominantly as a liquid mouthwash, oromucosal spray, or topical cream, benzydamine is most frequently employed as a locally acting analgesic and anti-inflammatory treatment for the relief of painful inflammatory conditions. When formulated as a mouthwash or spray, benzydamine may be used to treat traumatic conditions like pharyngitis following tonsillectomy or the use of a naso-gastric tube, inflammatory conditions like pharyngitis, aphthous ulcers and oral ulceration due to radiation therapy, dentistry operations and procedures, or more general conditions like sore throat, sore tongue, sore gums, mouth ulcers, or discomfort caused by dentures. When used as a topical cream, benzydamine may be employed to relieve symptoms associated with painful inflammatory conditions of the muscolo-skeletal system including acute inflammatory disorders such as myalgia and bursitis or traumatic conditions like sprains, strains, bruises, sore muscles, stiff joints, or even the after-effects of fractures. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into the oral mucosa and intact skin. Once absorbed in the local area of pain or inflammation, benzydamine binds selectively to local inflamed tissues, usually allowing it to act with few adverse systemic effects. On average a period of 2 to 4 hours is necessary for the substance to reach peak plasma concentration. Benzydamine can be synthesized with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give N-nitoso derivative. This is next reduced by sodium thiosulfate to give transient hydrazine. This hydrazine can then undergo spontaneous internal hydrazide formation. Treating this resultant enolate with 3-chloro-1-dimethylamkino propane ultimately yields benzydamine. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Despite being categorized as a non-steroidal anti-inflammatory drug (NSAID), benzydamine demonstrates various mechanisms of action that differ from those of traditional aspirin-like NSAIDs. In particular, benzydamine predominantly acts by inhibiting the synthesis of pro inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) without largely affecting other pro inflammatory cytokines (ie. such as IL-6 and IL-8) or anti-inflammatory cytokines (ie. like IL-10 or IL-1 receptor antagonist). Moreover, benzydamine is largely a weak inhibitor of prostaglandin synthesis as it has been shown to effectively inhibit cyclooxygenase (COX) and lipoxygenase enzyme activity only at concentrations of 1mM or greater. Considering most contemporary usages of benzydamine are topical applications that are generally not well absorbed through the skin and/or non-specialized mucosae, benzydamine does not often achieve the kind of absorption or blood concentrations necessary to cause any extraneous distant systemic effects or COX inhibition, allowing it to localize its action. Additionally, it is also hypothesized that benzydamine is capable of inhibiting the oxidative burst of neutrophils and membrane stabilization. These actions are exhibited by the substance’s ability to inhibit the release of granules from neutrophils and to stabilize lysosomes. Furthermore, benzydamine is capable of a local anaesthetic effect that may be related to its capability for inhibiting the release of inflammatory mediators like substance P and calcitonin gene related peptide from sensory nerve endings. Since substance P is capable of causing the release of histamine from mast cells, benzydamine’s prevention of substance P release further contributes to an anti-inflammatory effect. Benzydamine also demonstrates a non-specific antibacterial activity against various bacterial strains that are resistant to broad-spectrum antibiotics such as ampicillin, chloramphenicol, and tetracycline at concentrations of about 3 mmol/L. Combinatorial use of benzydamine and other antibiotics like tetracycline and chloramphenicol are also synergistic against antibiotic resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral doses of benzydamine are well absorbed and plasma drug concentrations reach a peak fairly rapidly and then decline with a half-life of approximately 13 hours. When applied topically, although the local drug concentrations are relatively large, the systemic absorption of topically applied benzydamine is relatively low compared to oral doses. This low topical absorption contributes to a decreased potential for any systemic drug side-effects when benzydamine is administered in this way. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of benzydamine is 10 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Benzydamine exhibits < 20% plasma protein binding after oral administration. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Benzydamine is primarily metabolized by oxidation, dealkylation, and conjugation into hydroxy, dealkylated, and N-oxide metabolites. In general, however, when used at the recommended doses the levels at which benzydamine is absorbed or exposed into the body are usually not sufficient to produce systemic pharmacological effects [L •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The relatively high lipid solubility of the weak base benzydamine is thought to be associated with considerable passive resorption within the renal tubule, which suggests that only approximately 5% of benzydamine is excreted unchanged in the urine. At the same time however, other studies have suggested that considerably larger amounts (50-65%) of the drug is excreted unchanged in urine. While several inactive oxidized metabolites of benzydamine are excreted in urine, the benzydamine N-oxide metabolite can remain in plasma and demonstrate a half-life that is longer than the parent benzydamine compound. Nevertheless, it is generally believed that excretion occurs mainly through urine and is mostly in the form of inactive metabolites or conjugation products. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Approximately 13 h after oral administration, with a terminal half life of about 7.7 h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Benzydamine demonstrateas a systemic clearance of 170 ml/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): A possible adverse reaction associated with the use of the mouthwash or oromucosal spray formulations of benzymadine is potential numbness and/or stinging in the mouth and/or throat. Some possible adverse reactions that tend to be associated more with topical cream formulations of benzymadine include increased sensitivity to sunlight, and localized itching, skin rash, redness, or swelling. The prescribing information for all formulations of benzymadine however, warn against the possibility of severe allergic reaction (anaphylaxis) associated with swelling of the throat and mouth, difficulty in swallowing, speaking, and breathing, or wheezing. As benzydamine is a non-steroidal anti-inflammatory drug (NSAID), it is necessary to determine if a patient is allergic to NSAIDs before considering its use. Intoxication is expected as a consequence of accidental ingestion of large quantities of benzydamine (over 300 mg ingestion). Other symptoms associated with overdose of ingested benzydamine include gastrointestinal and central nervous system symptoms like nausea, vomiting, abdominal pain, oesophageal irritation, dizziness, hallucinations, agitation, anxiety, and irritability. The official prescribing information for benzydamine generally suggest that benzydamine mouthwashes and sprays should not be used in pregnancy. Similarly, the official prescribing information for benzydamine also generally suggest that benzydamine mouthwashes and sprays should not be used during lactation unless considered essential by a physician. The prescribing information for topical cream formulations of benzydamine note that benzydamine cream should not be used in pregnancy or lactation unless considered necessary by the physician. Overall, non-clinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated toxicity, genotoxicity, cardiogenic potential, and toxicity to reproduction. Additionally, there is no evidence of teratogenic effects in animal studies. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pharixia, Tantum •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Beroctocog alfa interact?

•Drug A: Abciximab •Drug B: Beroctocog alfa •Severity: MAJOR •Description: The therapeutic efficacy of Beroctocog alfa can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Beroctocog alfa is indicated for the prevention and control of bleeding in patients with hemophilia A or acquired Factor VIII (FVIII) deficiency. It is also indicated for surgical/invasive procedures in adult and pediatric patients with von Willebrand Disease in who desmopression is either ineffective or contraindicated. It is not indicated for patients with severe (i.e. type 3) von Willebrand Disease whom are undergoing major surgery. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alphanate •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Besilesomab interact?

•Drug A: Abciximab •Drug B: Besilesomab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Besilesomab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis. When utilized as such, this medicinal product is for diagnostic use only. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells. In general however, besilesomab does not bind significantly to blood vessels and connective tissue. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA). CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal. •Absorption (Drug A): No absorption available •Absorption (Drug B): As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100%. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Studies demonstrate that prepared kit besilesomab binds up to 97.45% and 96.58% of peripheral blood granulocytes in males and females respectively and less than 5% of other peripheral blood cells. Moreover, no significant binding of the antibody to other human peripheral blood cells like erythrocytes, platelets, lymphocytes, and monocytes was observed. As well, besilesomab demonstrates no cross-reactivity with human platelets. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Measurement of radioactivity levels in urine shows that up to 14% of the administered activity is excreted via the bladder during the 24 h post-injection period. Low renal clearance activity (of 0.2 L/h for a glomerular filtration rate of approximately 7 L/h) also suggests that the kidney is not the primary route of besilesomab elimination. Additionally, over 30 hours rat pharmacokinetic studies also similarly demonstrated that 31-34% of the radioactivity was excreted in the urine and only 7-13% in the faeces. The faecal elimination was observed primarily from the 17h time period onward. Furthermore, while radioactivity associated with intact antibody tends to stay in the vascular compartment for a long time, metabolized radioactive fragments, small radio-metabolites, and free pertechnetate (Tc99m) clears quickly from blood and will accumulate in the kidneys and further in the urine. In all besilesomab studies to date, approximately 14% of the injected radioactivity was recovered in the urine, which was only collected for 24 hours after administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h). After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h. The terminal half-life in man is estimated to be approximately 23 h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m). The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection. Patients who are HAMA positive are consequently contraindicated from using besilesomab. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication. Some patients have also reported hypotension as a common adverse reaction. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours). At that time, the remaining activity represents about 1/1000 of the initial activity in the body. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Betrixaban interact?

•Drug A: Abciximab •Drug B: Betrixaban •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Betrixaban. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Betrixaban is indicated for prophylaxis of venous thromboembolism (VTE) in conditions of moderate to severe restricted mobility or in patients that qualify as in risk of VTE. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Betrixaban is an oral anticoagulant that excerts its action by preventing thrombin generation without having a direct effect on platelet aggregation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Betrixaban is a cofactor-independent direct inhibitor of the Factor Xa and inhibits free and prothrombinase-bound Factor Xa. •Absorption (Drug A): No absorption available •Absorption (Drug B): Betrixaban presents a rapid absorption at a dose of 80 mg. Its peak plasma concentration is registered within 3-4 hours after oral administration in healthy humans. The oral bioavailability is 34%, and it can be reduced with the consumption of food. Specifically, the C max and AUC is reduced by an average of 70% and 61% with a low-fat meal, and 50% and 48% with a high-fat meal compared to the fasted state, an effect which is apparent up to six hours following food intake. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution os 32 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Betrixaban is reported to be present a proteing binding of about 60%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): One of the major characteristics of Betrixaban is its minimal hepatic metabolism (< 1%), preventing potential accumulation with liver impariment. Unchanged Betrixaban is the main form found in human plasma, followed by two hydolitic CYP-independent inactive metabolites (15-18%). The minimal hepatic metabolism produces an unlikely drug-to-drug interaction with inhibitors or agonists of CYP450. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Betrixaban is reported to present mainly a gastrointestinal elimination route, it has been shown that even 85% of it gets disposed in the feces and only 11% of it can be found in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Betrixaban presents a long half-life of between 19-27 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Betrixaban presents a minimal renal clearance (being 5-7% of the administered dose). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Betrixaban presents a minimal hepatotoxicity, which is the main adverse effect found in this class of drugs. Some of the major adverse effects of Betrixaban are bleeding or hypersensitivity. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): BEVYXXA •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Betrixaban (common) N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide N-(5-chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide

Do Abciximab and Bevacizumab interact?

•Drug A: Abciximab •Drug B: Bevacizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Bevacizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): As a vascular endothelial growth factor (VEGF) inhibitor, bevacizumab is used in several chemotherapy regimens to treat metastatic colorectal cancer; metastatic, unresectable, locally advanced or recurrent non-squamous non-small cell lung cancer; metastatic renal cell carcinoma; metastatic, persistent, or recurrent cervical cancer; primary peritoneal cancer; epithelial ovarian cancer; fallopian tube cancer; breast cancer; and recurrent glioblastoma. Interestingly, bevacizumab is currently under investigation for the treatment of COVID-19 complications including acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bevacizumab binds circulating vascular endothelial-derived growth factor (VEGF) and blocks it from binding to its associated receptors, effectively blunting downstream signaling. The effects of bevacizumab have been shown to re-establish normal vasculature at the tumor site resulting in increased nutrient and oxygen supply, while also improving the delivery of chemotherapeutic drugs to the target area. On the other hand, VEGF signaling is a vital component of several processes including angiogenesis, lymphangiogenesis, blood pressure regulation, wound healing, coagulation, and renal filtration. Although blocking VEGF may inhibit metastatic disease progression, it may also result in unintended effects due to the role of VEGF in several other physiologic processes. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Transcription of the VEGF protein is induced by 'hypoxia inducible factor' (HIF) in a hypoxic environment. When circulating VEGF binds to VEGF receptors (VEGFR-1 and VEGFR-2) located on endothelial cells, various downstream effects are initiated. It should be noted that VEGF also binds to the neuropilin co-receptors (NRP-1 and NRP-1), leading to enhanced signaling. Cancer cells promote tumor angiogenesis by releasing VEGF, resulting in the creation of an immature and disorganized vascular network. The hypoxic microenvironment promoted by cancer cells favors the survival of more aggressive tumor cells, and gives rise to a challenging environment for immune cells to respond appropriately. As a result, VEGF has become a well-known target for anti-cancer drugs like bevacizumab. Bevacizumab is a mAb that exerts its effects by binding and inactivating serum VEGF. When bound to the mAb, VEGF is unable to interact with its cell surface receptors, and proangiogenic signalling is inhibited. This prevents formation of new blood vessels, decreases tumor vasculature, and reduces tumor blood supply. There is also evidence to suggest that VEGF is upregulated in COVID-19 patients, hence, bevacizumab is being investigated for the treatment of associated complications. Higher levels of VEGF may contribute to pulmonary edema, leading to acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Researchers are hopeful that by inhibiting VEGF, bevacizumab may effectively treat ARDS and ALI - both common features of severe COVID-19 cases. •Absorption (Drug A): No absorption available •Absorption (Drug B): Monoclonal antibodies (mAbs) are large in size, do not readily cross cell membranes, and are unable to withstand proteolysis in the gastrointestinal tract. Given these characteristics, mAbs are poorly absorbed via the oral route and are instead administered intravenously, intramuscularly or subcutaneously. In a single dose (1mg/kg) pharmacokinetic study assessing the bioequivalence of bevacizumab and TAB008 (a biosimilar product), the pharmacokinetic parameters of Avastin (bevacizumab) were as follows: Geometric mean Cmax = 17.38 ug/mL Geometric mean AUCinf = 5,358 ugxh/mL Geometric mean Tmax = 2.50 hrs •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of bevacizumab is approximately 3.29 L and 2.39 L for the average male and female, respectively. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): >97% of serum VEGF is bound to bevacizumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): There are several pathways through which monoclonal antibodies (mAbs) may be cleared. Non-specific clearance of mAbs refers to target independent pinocytosis, and proteolysis of the protein into small amino acids and peptides in the reticuloendothelial system (RES) and the liver. Target-mediated clearance is a result of specific interactions between the mAb and its target antigen. Once bound, the antibody-antigen complex may be cleared via lysosomal degradation. Additionally, the production of anti-drug antibodies (ADA), which are a result of an immunogenic response to mAb-based treatment, can form complexes with mAb’s and may impact the rate of mAb clearance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Due to their size, monoclonal antibodies are not renally eliminated under normal physiological conditions. Catabolism or excretion are the primary processes of elimination. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of bevacizumab is estimated to be 20 days (range of 11-50 days). •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance (CL) of bevacizumab is approximately 0.207 L/day. The CL of bevacizumab can increase or decrease by 30% in patients who weigh >114 kg or <49 kg respectively. Males tend to clear bevacizumab at a faster rate than females (26% faster on average). Other factors including alkaline phosphatase (ALP), serum aspartate aminotransferase (AST), serum albumin, and tumor burden may cause the CL to fluctuate. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Bevacizumab toxicities are distinct from the effects of cytotoxic agents used in chemotherapy, and are normally linked to impaired VEGF function. Common toxicities associated with bevacizumab include hypertension, gastrointestinal perforation, arterial thromboembolism, reversible posterior leukoencephalopathy syndrome (RPLS), venous thromboembolism, proteinuria, bleeding/hemorrhage, and wound-healing complications. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Avastin, Mvasi •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Bexarotene interact?

•Drug A: Abciximab •Drug B: Bexarotene •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Bexarotene. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used orally for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Also used topically for the treatment of skin lesions in early (stage IA and IB) CTCL in patients who experience refractory or persistent disease with the use of other therapies or are intolerant of other therapies. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXR α, RXR β, RXR γ ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Bexarotene selectively binds with and activates retinoid X receptor subtypes. There are three subtypes in total: RXR α, RXR β, RXR γ. The exact mechanism of action of bexarotene in the treatment of CTCL is unknown but the drug has activity in all clinical stages of CTCL. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): >99% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary elimination of bexarotene and its known metabolites is a minor excretory pathway (<1% of administered dose). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Targretin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoic acid 4-[1-(5,6,7,8,-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl)ethenyl]benzoic acid Bexaroten (common) Bexarotène (common) Bexarotene (common) Bexaroteno (common) Bexarotenum (common) p-(1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)vinyl)benzoic acid

Do Abciximab and Bezlotoxumab interact?

•Drug A: Abciximab •Drug B: Bezlotoxumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Bezlotoxumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bezlotoxumab is indicated to reduce the recurrence of Clostridioides difficile infection (CDI) in patients who are receiving antibacterial drug treatment for CDI and are at high risk for CDI recurrence. In the US, the drug is approved for use in patients one year of age and older. In Europe, it is approved in adults only. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bezlotoxumab directly neutralizes the toxic effects of C. difficile by binding to the toxin with high affinity. In vitro, bezlotoxumab inhibited C. difficile toxin B-mediated expression of tumour necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) in human peripheral blood monocyte cells and human colonic and explants. In clinical trials, the rate of recurrent C. difficile infection was lower in patients at risk for recurrent C. difficile infection receiving bezlotoxumab compared to placebo. The administration of bezlotoxumab plus actoxumab, another antibody directed against the C. difficile toxin resulted in dose-dependent protection against C. difficile toxin-induced damage and inflammation, as well as a reduced recurrence of C. difficile infection in mice. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): C. difficile infections are caused by two exotoxins, toxin A and toxin B. Exotoxins are believed to bind to cell surface receptors expressed on colonocytes and are internalized via endocytosis. This process is followed by the acidification of the endosome, leading to a conformation change of the toxin, allowing for the transport of the endosome, autocleavage of the toxin via a cysteine protease domain, and the release of glucosyltransferase domain (GTD) from the endosome to the host cell cytoplasm. GTD glucosylates and inactivates small GTPases, such as Rac and Rho, critical for maintaining the actin cytoskeleton, cell adhesion, epithelial permeability, and other cellular function and homeostasis processes. Exotoxins eventually induce apoptosis and cell loss. Endotoxins also promote the release of proinflammatory mediators that recruit neutrophils and macrophages to the injury site, further aggravating the gut injury and damage. C. difficile infections are associated with a high risk of recurrence. Bezlotoxumab binds to C. difficile toxin B and neutralizes it. According to the findings of surface plasmon resonance analysis, bezlotoxumab binds to the toxin via two epitopes in the C-terminal CROP domain of the toxin, partially blocking the putative receptor binding pockets and preventing it from binding to host cell receptors. Bezlotoxumab does not bind to C. difficile toxin A. •Absorption (Drug A): No absorption available •Absorption (Drug B): After a single intravenous dose of 10 mg/kg bezlotoxumab, geometric mean AUC 0-∞ and C max were 53000 mcg x h/mL and 185 mcg/mL, respectively, in patients with CDI. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a population pharmacokinetic analysis, the geometric mean (%CV) volume of distribution was 7.33 L (16%). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No information is available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Bezlotoxumab undergoes protein catabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Bezlotoxumab is mainly eliminated by catabolism. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Based on a population pharmacokinetic analysis, the geometric mean (%CV) elimination half-life is approximately 19 days (28%). •Clearance (Drug A): No clearance available •Clearance (Drug B): Based on a population pharmacokinetic analysis, the geometric mean (%CV) clearance of bezlotoxumab was 0.317 L/day (41%). The clearance of bezlotoxumab increased with increasing body weight: the resulting exposure differences are adequately addressed by the administration of a weight-based dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The intravenous LD 50 was >125 mg/kg in mice. There is no clinical experience with the overdosage of bezlotoxumab. In clinical trials, healthy subjects received up to 20 mg/kg, which was generally well tolerated. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Zinplava •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Bimekizumab interact?

•Drug A: Abciximab •Drug B: Bimekizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Bimekizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bimekizumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bimekizumab exerts its pharmacologic effects by binding to and inhibiting one of the pro-inflammatory cytokines involved in psoriasis pathogenesis. It is administered once-monthly as a subcutaneous injection. Bimekizumab may increased the risk of infection, including upper respiratory tract infections and oral candidiasis. Any clinically important active infections should be resolved prior to therapy. In addition, the use of live vaccines during bimekizumab therapy is not recommended - ensure patients beginning therapy have completed all age appropriate immunizations prior to initiation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The pathophysiology of psoriasis involves a dysregulation of the immune system and is facilitated by a variety of cytokines released by dendritic cells and T-helper cells. Plaque psoriasis, the most common subtype of psoriasis, is driven primarily by tumor necrosis factor-alpha (TNF-α) and interleukins 17 and 23 (IL-17 and IL-23), with the axis between these three cytokines integral to the maintenance phase of psoriasis. IL-17 acts through two separate mechanisms: the first, dependent on the cytoplasmic adaptor protein ACT1, involves the activation of NF-κB and the transcription of inflammatory genes. The second, independent of ACT1, involves the activation of the JAK/STAT signaling cascade, which leads to further transcription of pro-inflammatory proteins and continued psoriasis pathogenicity. Bimekizumab is a monoclonal antibody targeted against IL-17A, IL-17F, and a heterodimer of the two called IL-17AF. It blocks the interaction of these interleukins with their respective receptors, thus reducing psoriatic inflammation. •Absorption (Drug A): No absorption available •Absorption (Drug B): In healthy volunteers, the absolute bioavailability of bimekizumab following subcutaneous injection was 70.1%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with plaque psoriasis, the median volume of distribution at steady-state was 11.2 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As a monoclonal antibody, bimekizumab is likely degraded into smaller peptides and amino acids via catabolic processes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean terminal elimination half-life of bimekizumab in patients with plaque psoriasis was 23 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The median apparent clearance of bimekuzmab in patients with plaque psoriasis was 0.337 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Single doses of up to 640mg given both intravenously and subcutaneously have been administered in clinical studies without evidence of dose-limiting toxicities. If overdosage of bimekizumab is suspected, monitor the patient for adverse reactions and institute symptomatic treatment as clinically indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Bismuth subsalicylate interact?

•Drug A: Abciximab •Drug B: Bismuth subsalicylate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Abciximab. •Extended Description: .Concurrent use of salicylates and anticoagulants may lead to increased anticoagulant activity and therefore an increased risk of bleeding, due to additive anticoagulant effects. •References: 1. Yip AS, Chow WH, Tai YT, Cheung KL: Adverse effect of topical methylsalicylate ointment on warfarin anticoagulation: an unrecognized potential hazard. Postgrad Med J. 1990 May;66(775):367-9. [https://go.drugbank.com/articles/A33575] 2. Roncaglioni MC, Reyers I, Cerletti C, Donati MB, de Gaetano G: Moderate anticoagulation by salicylate prevents thrombosis without bleeding complications. An experimental study in rats. Biochem Pharmacol. 1988 Dec 15;37(24):4743-5. [https://go.drugbank.com/articles/A33576] 3. Undas A, Brummel-Ziedins KE, Mann KG: Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions. Blood. 2007 Mar 15;109(6):2285-92. doi: 10.1182/blood-2006-01-010645. Epub 2006 Dec 5. [https://go.drugbank.com/articles/A35088] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bismuth subsalicylate is indicated to temporarily relieve diarrhea, travelers' diarrhea, and upset stomach due to overindulgence in food and drink, including heartburn, indigestion, nausea, gas, belching, and fullness. Bismuth subsalicylate is a component of HELIDAC Therapy (bismuth subsalicylate, metronidazole, and tetracycline ), which is a treatment regimen indicated for the eradication of H. pylori for treatment of patients with H. pylori infection and duodenal ulcer disease. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bismuth subsalicylate is an antacid and antimicrobial, gastroprotective, anti-secretory, and anti-inflammatory actions. It works to reduce the severity and incidence of flatulence and diarrhea, and consequently relieving gastrointestinal discomfort. In one study, bismuth subsalicylate was prevented traveler's diarrhea with a protection rate >60%. Organobismuth compounds, formed by the breakdown of bismuth subsalicylate in the gastrointestinal tract, inhibit the growth of Helicobacter pylori and other bacteria implicated in gastrointestinal disorders, and some fungi. In one study, bismuth subsalicylate was shown to eradicate up to 90% of H. pylori infection when used as part of a quadruple therapy regimen containing a proton pump inhibitor, tetracycline, and metronidazole. Bismuth subsalicylate exhibited antimicrobial activity against Clostridium difficile, enterotoxigenic Escherichia coli O157:H7, norovirus, and other common enteric pathogens such as Salmonella and Shigella. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The exact mechanism of bismuth subsalicylate is not fully understood. Bismuth subsalicylate is an insoluble complex that constitutes salicylic acid and trivalent bismuth. Once orally administered, bismuth subsalicylate hydrolyzes in the stomach into bismuth oxychloride, which is minimally absorbed into the bloodstream, and salicylic acid, which is almost completely absorbed. Bismuth interacts with other anions and compounds, such as hydrochloric acid, bicarbonate, phosphate, and hydrogen sulfide, in the gastrointestinal tract to form bismuth salts such as bismuth oxychloride, bismuth subcarbonate, bismuth phosphate, and bismuth sulfide. Bismuth salts possess bactericidal and antimicrobial activity, mainly by preventing bacteria from binding and growing on the mucosal cells of the stomach. It has no effects on normal gut flora. By preventing bacteria from binding to mucosal cells, bismuth subsalicylate prevents intestinal secretion and fluid loss, promotes fluid and electrolyte reabsorption, reduces gastrointestinal inflammation, and promotes the healing of pre-existing ulcer in the stomach. Salicylic acid from dissociated bismuth subsalicylate adds to the anti-inflammatory actions of bismuth salts by inhibiting the cyclooxygenase enzyme and limiting the formation of prostaglandin, a pro-inflammatory mediator. Bismuth subsalicylate exhibits cytoprotective and demulcent activity, which makes it an effective drug in peptic ulcer disease. It blocks the adhesion of H. pylori to the gastric epithelial cells and blocks the bacteria's enzyme activities, including phospholipase, protease, and urease. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, bismuth subsalicylate hydrolyzes into bismuth and salicylic acid in the stomach. Salicylic acid is almost completely absorbed in the small intestine and reaches plasma peak levels one to two hours after dosing. In one study involving healthy male subjects, oral administration of 60 mL Pepto-Bismol, a common over-the-counter product of bismuth subsalicylate, equivalent to 1050 mg of bismuth subsalicylate, resulted in the peak plasma concentration of salicylate of 40.1 μg/mL, with a time to peak concentration (T max ) of 1.8 hours. Less than 1% of bismuth from bismuth subsalicylate is absorbed from the gastrointestinal tract into the systemic circulation. In one study, oral administration of 787 mg bismuth subsalicylate in the chewable tablet form for two weeks resulted in the mean trough blood bismuth concentration was 5.1 ± 3.1 ng/mL. In another study, the mean trough blood bismuth concentration ranged from five to 32 ng/mL following oral administration of 525 mg bismuth subsalicylate in the liquid suspension form. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): There is no information available. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Salicylic acid is about 90% plasma protein bound. Bismuth is about >90% bound to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Bismuth subsalicylate undergo hydrolysis at pH levels lesser than three. It is largely hydrolyzed in the stomach to bismuth oxychloride and salicylic acid. In the small intestine, unchanged bismuth subsalicylate reacts with other anions such as bicarbonate and phosphate to form insoluble bismuth salts. In the colon, unchanged bismuth subsalicylate and other bismuth salts react with hydrogen sulfide produced by anaerobic bacteria to form bismuth sulfide, a highly insoluble black salt responsible for the darkening of the stools. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following oral administration, salicylate dissociated from bismuth subsalicylate is excreted in the urine. Bismuth is primarily eliminated via urinary and biliary routes. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life of salicylic acid following a single oral dose of 525 mg bismuth subsalicylate is ranges from two to five hours. Bismuth has an intermediate half-life of 5 to 11 days and a terminal half-life of 21 to 72 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The renal clearance of bismuth is 50 ± 18 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Lowest Lethal Dose (LDLo) in humans is 700 mg/kg. LD 50 in rats is 1200 mg/kg via oral route, 542 mg/kg via intraperitoneal route, and 980 mg/kg via subcutaneous route. Overdose of bismuth subsalicylate over an extended period of time and consequently, bismuth toxicity, can lead to blackening of the tongue and teeth, fatigue, mood changes, deterioration of mental status, and neurotoxicity. Other signs and symptoms include impaired cognition, tremors, lethargy, somnolence, insomnia, delirium, myoclonus, seizures, depressed mood, anxiety, and a depressed mood. Salicylate toxicity can occur from chronic bismuth subsalicylate use: it mostly occurs from ingestion of more than 150 mg/kg of salicylates (or >6.5 g of aspirin equivalent). As there are no specific antidotes for bismuth salicylate toxicity, overdose should be managed with supportive care, with or without decontamination with activated charcoal. Hemodialysis may be considered in more severe cases and with the presence of altered mental status and metabolic acidosis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Diphen, Kaopectate Reformulated Aug 2006, Kola-pectin, Pepto-bismol, Percy Medicine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 2-Hydroxy-benzo[1,3,2]dioxabismin-4-one Basic bismuth salicylate Bismuth oxide salicylate (common) Bismuth oxysalicylate (common) Bismuth subsalicylate (common) Pink bismuth (common) Wismutsubsalicylat (common)

Do Abciximab and Bivalirudin interact?

•Drug A: Abciximab •Drug B: Bivalirudin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Bivalirudin. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of heparin-induced thrombocytopenia and for the prevention of thrombosis. Bivalirudin is indicated for use in patients undergoing percutaneous coronary intervention (PCI), in patients at moderate to high risk acute coronary syndromes due to unstable angina or non-ST segment elevation in whom a PCI is planned. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bivalirudin mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration, bivalirudin exhibits linear pharmacokinetics. The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.2L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Other than thrombin and red blood cells, bivalirudin does not bind to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): 80% proteolytic cleavage •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Bivalirudin is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Normal renal function: 25 min (in normal conditions) Creatinine clearance 10-29mL/min: 57min Dialysis-dependant patients: 3.5h •Clearance (Drug A): No clearance available •Clearance (Drug B): 3.4 mL/min/kg [Normal renal function] 3.4 mL/min/kg [mild renal function] 2.7 mL/min/kg [moderate renal function] 2.8 mL/min/kg [severe renal function] 1 mL/min/kg [Dialysis-dependent patients] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Based on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Angiomax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Blinatumomab interact?

•Drug A: Abciximab •Drug B: Blinatumomab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Blinatumomab. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Blinatumomab is indicated for the treatment of adults and children with relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL). It is also indicated in adults and children for the treatment of CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Blinatumomab promoted peripheral T-cell redistribution at the start of infusion or dose escalation. In most patients, T-cell counts were lower in the first 1-2 days of treatment and returned to baseline levels within 7-14 days. An increase in T-cell levels, also known as T-cell expansion, was observed in a few patients. In the first treatment cycle, blinatumomab doses higher than ≥ 5 mcg/m2/day or ≥ 9 mcg/day decreased peripheral B-cell counts to 10 cells/microliter or less. During the blinatumomab-free period between treatment cycles (2 weeks), peripheral B-cell counts did not recover. The use of blinatumomab may lead to an elevation of IL-6, IL-10, and IFN-γ; however, cytokine levels return to baseline within 24 to 48 hours. Blinatumomab may lead to the development of cytokine release syndrome, neurological toxicities, infections, tumor lysis syndrome, neutropenia and febrile neutropenia, pancreatitis, leukoencephalopathy and transient elevations in liver enzymes. The use of blinatumomab can also affect a patient’s ability to drive and use machines. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Blinatumomab is a bispecific T-cell engager (BiTE) that targets CD19, an antigen expressed on the surface of B-cells, and CD3, an antigen expressed on the surface of T-cells. B-cell malignancies, such as acute lymphoblastic leukemia (ALL), express high levels of CD19, making it a therapeutic target for the treatment of these conditions. Blinatumomab recruits and activates endogenous T-cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on both benign and malignant B cells. By bringing T-cells and tumor cells together, blinatumomab induces an immune response that leads to T-cell activation and proliferation. It promotes the release of cytokines such as TNF-α, IFN-γ, IL-6, and IL-10 by T-cells, the induction of activation markers, such as CD69 and CD25, and the expression of adhesion molecules on the T-cell surface. Altogether, blinatumomab promotes the lysis of CD19+ tumor cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): In adult patients, the pharmacokinetic profile of blinatumomab appears to be linear between 5 to 90 mcg/m /day (equivalent to 9 to 162 mcg/day). The steady-state serum concentration (C ss ) of blinatumomab was achieved within a day of continuous intravenous infusion, and in the range tested, the mean C ss was approximately dose-proportional. At the clinical doses for the treatment of relapsed or refractory acute lymphoblastic leukemia (9 mcg/day and 28 mcg/day), the C ss was 228 (356) pg/mL and 616 (537) pg/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Blinatumomab has a volume of distribution based on terminal phase of 4.35 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolic pathway of blinatumomab has not been characterized. As a monoclonal antibody, blinatumomab is expected to be metabolized into small peptides and amino acids via catabolic pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): At clinical doses, negligible amounts of blinatumomab were excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Blinatumomab has a half-life of 2.10 hours. In pediatric patients, the half-life was 2.19 hours in the first cycle of blinatumomab at the recommended dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): Blinatumomab has an estimated systemic clearance of 3.11 L/hour in patients receiving blinatumomab with continuous intravenous infusion. There is a 2-fold difference in clearance values between patients with normal renal function and those with moderate renal impairment. Pediatric patients had an estimated clearance of 1.88 L/hour/m in the first cycle of blinatumomab at the recommended dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Blinatumomab overdose cases have been reported, including a patient that received 133-fold the recommended therapeutic dose over a short period of time. In a study that included pediatric and adolescent patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), a patient receiving 30 mcg/m2/day of blinatumomab (higher than the maximum tolerated dose) experienced a fatal cardiac failure event in the setting of life-threatening cytokine release syndrome (CRS). The adverse reactions observed during blinatumomab overdoses included fever, tremors, and headache, consistent with those observed at the recommended dose. If a patient is experiencing an overdose, the blinatumomab product label recommends to interrupt the infusion, monitor the patient for signs of adverse reactions, and provide supportive care. Re-initiating blinatumomab at the recommended dose should be considered after all adverse reactions have been resolved and no earlier than 12 hours after the infusion is interrupted. The carcinogenic, genotoxic, and fertility effects of blinatumomab have not been evaluated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Blincyto •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Bortezomib interact?

•Drug A: Abciximab •Drug B: Bortezomib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Bortezomib. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bortezomib is indicated for the treatment of adults with multiple myeloma or mantle cell lymphoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Bortezomib works to target the ubiquitin-proteasome pathway, an essential molecular pathway that regulates intracellular concentrations of proteins and promotes protein degradation. The ubiquitin-proteasome pathway is often dysregulated in pathological conditions, leading to aberrant pathway signalling and the formation of malignant cells. In one study, patient-derived chronic lymphocytic leukemia (CLL) cells contained 3-fold higher levels of chymotrypsin-like proteasome activity than normal lymphocytes. By reversibly inhibiting proteasome, bortezomib prevents proteasome-mediated proteolysis. Bortezomib exerts a cytotoxic effect on various cancer cell types in vitro and delays tumour growth in vivo in nonclinical tumour models. Bortezomib inhibits the proteasome activity in a dose-dependent manner. In one pharmacodynamic study, more than 75% of proteasome inhibition was observed in whole blood samples within one hour after dosing of bortezomib. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The ubiquitin-proteasome pathway is a homeostatic proteolytic pathway for intracellular protein degradation: proteins marked with a poly-ubiquitin chain are degraded to small peptides and free ubiquitin by the proteasome, which is a large multimeric protease. Aberrant proteasome-dependent proteolysis, as seen in some malignancies, can lead to uncontrolled cell division, leading to tumorigenesis, cancer growth, and spread. Bortezomib is a reversible inhibitor of the 26S proteasome, which is made up of a 20S core complexed with a 19S regulatory complex. Individual β-subunits allow specific catalytic action of the 20S core. In mammalian cells, bortezomib is a potent inhibitor of the proteasome’s chymotryptic-like activity, which is attributed to the β5-subunit of the 20S core particle. Bortezomib binds to the active site of the threonine hydroxyl group in the β5-subunit. A probing study showed bortezomib also binding to and inhibiting the β1-subunit, which mediates the caspase-like activity of the proteasome, and β1i-subunit, which is an altered subunit that is expressed to form immunoproteasomes in response to cell stress or inflammation. By inhibiting the proteasome-mediated degradation of key proteins that promote cell apoptosis, bortezomib induces a cell cycle arrest during the G2-M phase. It is believed that multiple mechanisms, other than proteasome inhibition, may be involved in the anticancer activity of bortezomib. The anticancer activity of bortezomib was largely associated with suppression of the NF-κB signalling pathway, resulting in the downregulation of anti-apoptotic target genes and expression of anti-apoptic proteins. This may be explained by bortezomib preventing uncontrolled degradation of IκB, which is an inhibitory protein of NF-κB. NOXA, which is a pro-apoptotic factor, induced by bortezomib selectively in cancer cells; thus, it is suggested to be another key mechanism of bortezomib. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration of 1 mg/m and 1.3 mg/m doses, the mean C max of bortezomib were 57 and 112 ng/mL, respectively. In a twice-weekly dosing regimen, the C max ranged from 67 to 106 ng/mL at the dose of 1 mg/m and 89 to 120 ng/mL for the 1.3 mg/m dose. In patients with multiple myeloma, the C max of bortezomib followig subcutaneous administration was lower than that of intravenously-administered dose; however, the total systemic exposure of the drug was equivalent for both routes of administration. There is a wide interpatient variability in drug plasma concentrations. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean distribution volume of bortezomib ranged from approximately 498 to 1884 L/m in patients with multiple myeloma receiving a single- or repeat-dose of 1 mg/m or 1.3 mg/m. Bortezomib distributes into nearly all tissues, except for the adipose and brain tissue. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Over the concentration range of 100 to 1000 ng/mL, bortezomib is about 83% bound to human plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Bortezomib is primarily metabolized by CYP3A4, CYP2C19, and CYP1A2. CYP2D6 and CYP2C9 are also involved in drug metabolism, but to a smaller extent. Oxidative deboronation, which involves the removal of boronic acid from the parent compound, is the main metabolic pathway. Metabolites of bortezomib are pharmacologically inactive and more than 30 metabolites have been identified in human and animal studies. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Bortezomib is eliminated by both renal and hepatic routes. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean elimination half-life of bortezomib ranged from 40 to 193 hours following a multiple dosing regimen at a 1 mg/m dose. The half-life ranged from 76 to 108 hours after multiple dosing of 1.3 mg/m bortezomib. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following the administration of a first dose of 1 mg/m and 1.3 mg/m, the mean mean total body clearances were 102 and 112 L/h, respectively. The clearances were 15 and 32 L/h after the subsequent dose of 1 and 1.3 mg/m, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The Lowest published toxic dose (TD Lo ) in mouse was 5 mg/kg/14D following intraperitoneal administration of an intermittent dose and 1.6 mg/kg/12D following subcutaneous administration of a continuous dose. The therapeutic dose of bortezomib is individualized in each patient to prevent overdose. Fatal outcomes occurred in humans following the administration of more than twice the recommended therapeutic dose of bortezomib. The symptoms from overdose included the acute onset of symptomatic hypotension and thrombocytopenia. As there is no known antidote for bortezomib overdosage, monitoring of vital signs and appropriate supportive care should be initiated when drug overdosage is suspected. In monkeys and dogs, increased heart rate, decreased contractility, hypotension, and death were observed with the intravenous dose as low as two times the recommended clinical dose on a mg/m2 basis. A case of a slight increase in the corrected QT interval leading to death occurred in dog studies. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Velcade •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): [(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid Bortezomib (common) N-[(1R)-1-(DIHYDROXYBORYL)-3-methylbutyl]-N-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide

Do Abciximab and Bosutinib interact?

•Drug A: Abciximab •Drug B: Bosutinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Bosutinib. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Bosutinib is indicated for the treatment of adult and pediatric patients 1 year of age and older with chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy. It is also indicated for the treatment of adult patients with accelerated or blast phase Philadelphia chromosome-positive chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): A greater likelihood of response and a greater likelihood of safety events were observed with higher bosutinib exposure in clinical studies. The time course of bosutinib pharmacodynamic response has not been fully characterized. At a single oral dose of 500 mg bosutinib with ketoconazole (a strong CYP3A inhibitor), bosutinib does not prolong the QT interval to any clinically relevant extent. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Bosutinib is a tyrosine kinase inhibitor. Bosutinib inhibits the BCR-ABL kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bosutinib exhibits dose-proportional increases in C max and AUC over the oral dose range of 200 to 800 mg (0.33 to 1.3 times the maximum approved recommended dosage of 600 mg). Bosutinib steady-state C max was 127 ng/mL (31%), C trough was 68 ng/mL (39%) and AUC was 2370 ng•h/mL (34%) following multiple oral doses of bosutinib 400 mg. Bosutinib steady-state C max was 171 ng/mL (38%), C trough was 91 ng/mL (42%) and AUC was 3150 ng•h/mL (38%) following multiple oral doses of bosutinib 500 mg. No clinically significant differences in the pharmacokinetics of bosutinib were observed following administration of either the tablet or capsule dosage forms of bosutinib at the same dose, under fed conditions. The median bosutinib (minimum, maximum) t max was 6.0 (6.0, 6.0) hours following oral administration of a single oral dose of bosutinib 500 mg with food. The absolute bioavailability was 34% in healthy subjects. Bosutinib C max increased 1.8-fold and AUC increased 1.7-fold when bosutinib tablets were given with a high-fat meal to healthy subjects compared to administration under fasted conditions. Bosutinib C max increased 1.6-fold and AUC increased 1.5-fold when bosutinib capsules were given with a high-fat meal to healthy subjects compared to administration under fasted conditions. The high-fat meal (800-1000 total calories) consisted of approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (SD) apparent bosutinib volume of distribution is 6080 ± 1230 L after an oral dose of 500 mg of bosutinib. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Bosutinib protein binding is 94% in vitro and 96% ex vivo and is independent of concentration. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Bosutinib is primarily metabolized by CYP3A4. The major circulating metabolites identified in plasma are oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite. All the metabolites were deemed inactive. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following a single oral dose of [ C] radiolabeled bosutinib without food, 91.3% of the dose was recovered in feces and 3.3% of the dose was recovered in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean (SD) bosutinib terminal phase elimination half-life (t ) was 22.5 ± 1.7 hours following a single oral dose of bosutinib. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (SD) apparent clearance was 189 ± 48 L/h following a single oral dose of bosutinib. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In a rat fertility and early embryonic development study, bosutinib was administered orally to female rats for approximately 3 to 6 weeks, depending on the day of mating (2 weeks prior to cohabitation with untreated breeder males until gestation day [GD] 7). Increased embryonic resorptions occurred at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). In an embryo-fetal development study conducted in rabbits, bosutinib was administered orally to pregnant animals during organogenesis at doses of 3, 10, and 30 mg/kg/day. At the maternally-toxic dose of 30 mg/kg/day of bosutinib, there were fetal anomalies (fused sternebrae and 2 fetuses had various visceral observations), and an approximate 6% decrease in fetal body weight. The dose of 30 mg/kg/day resulted in exposures (AUC) approximately 5.1 and 3.8 times the human exposures at the recommended doses of 400 and 500 mg/day, respectively. Fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats. In a rat pre-and postnatal development study, bosutinib was administered orally to pregnant animals during the period of organogenesis through lactation day 20 at doses of 10, 30, and 70 mg/kg/day. Reduced number of pups born occurred at greater than or equal to 30 mg/kg/day bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and increased incidence of total litter loss and decreased growth of offspring after birth occurred at 70 mg/kg/day bosutinib (6.9 and 5.1 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). Experience with bosutinib overdose in clinical studies was limited to isolated cases. There were no reports of any serious adverse events associated with the overdoses. Patients who take an overdose of BOSULIF should be observed and given appropriate supportive treatment. Bosutinib was not carcinogenic in rats or transgenic mice. The rat 2-year carcinogenicity study was conducted at bosutinib oral doses up to 25 mg/kg in males and 15 mg/kg in females. Exposures at these doses were approximately 1.5 times (males) and 3.1 times (females) the human exposure at the 400 mg dose and 1.2 times (males) and 2.4 times (females) exposure in humans at the 500 mg dose. The 6-month RasH2 transgenic mouse carcinogenicity study was conducted at bosutinib oral doses up to 60 mg/kg. Bosutinib was not mutagenic or clastogenic in a battery of tests, including the bacteria reverse mutation assay (Ames Test), the in vitro assay using human peripheral blood lymphocytes and the micronucleus test in orally treated male mice. In a rat fertility study, drug-treated males were mated with untreated females or untreated males were mated with drug-treated females. Females were administered the drug from pre-mating through early embryonic development. The dose of 70 mg/kg/day of bosutinib resulted in reduced fertility in males as demonstrated by 16% reduction in the number of pregnancies. There were no lesions in the male reproductive organs at this dose. This dose of 70 mg/kg/day resulted in exposure (AUC) in male rats approximately 1.5 times and equal to human exposure at the recommended doses of 400 and 500 mg/day, respectively. Fertility (number of pregnancies) was not affected when female rats were treated with bosutinib. However, there were increased embryonic resorptions at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 and 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bosulif •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile Bosutinib (common)

Do Abciximab and Brentuximab vedotin interact?

•Drug A: Abciximab •Drug B: Brentuximab vedotin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Brentuximab vedotin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Brentuximab vedotin is indicated in adult patients for the treatment of previously untreated stage III or IV classical Hodgkin's lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine. It is also indicated for the treatment of cHL post-autologous hematopoietic stem cell transplantation (auto-HSCT) in patients at high risk of relapse or progression. Finally, it may be used in the treatment of adult patients with cHL who have previously failed either auto-HSCT or at least two prior multi-agent chemotherapy regimens if they are not candidates for auto-HSCT. Brentuximab vedotin is additionally indicated in the treatment of previously untreated systemic anaplastic large cell lymphoma (sALCL), or other CD30-expressing peripheral T-cell lymphomas (PTCL), in combination with cyclophosphamide, doxorubicin, and prednisone. It may also be used as monotherapy in sALCL after therapeutic failure of a least one prior multi-agent chemotherapy regimen. Brentuximab vedotin is also indicated in the treatment of primary cutaneous large anaplastic large cell lymphoma, or CD30-expressing mycosis fungoides, who have received prior systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Brentuximab vedotin causes apoptosis of tumor cells by preventing cell cycle progression of the G2 to M phase through disruption of the cytosolic microtuble network, thus preventing tumor growth and proliferation. Hodgkin lymphoma (HL) is characterized by malignant Reed-Sternberg cells which express CD30, a marker of large cell lymphoma. Until March 2018, USA National Comprehensive Cancer Network guidelines for patients with advanced HL (stage III/IV disease) recommend treatment with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), or escalated bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as first-line regimens. ABVD appears to be as effective, with fewer side effects, as escalated BEACOPP. Escalated BEACOPP leads to a greater progression-free survival but no difference in overall survival. Recent progress in technology has enabled a new shift to cancer therapy targeting specific molecules. Brentuximab vedotin, a CD30-directed antibody conjugate, selectively targets malignant HL cells. The effect of Brentuximab vedotin (1.8 mg/kg) on the QTc interval was studied in an open-label, single-group study in 46 patients diagnosed with CD30-expressing hematologic malignancies. Ingestion of brentuximab vedotin did not prolong the mean cardiac QTc interval >10 ms from baseline levels. Smaller increases in the mean QTc interval (<10 ms) cannot be ruled out because this study did not include a placebo arm and a positive control arm. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Brentuximab vedotin is composed of 3 parts: a chimeric human-murine IgG1 that selectively targets CD30, monomethyl auristatin E (MMAE), which is a microtubule-disrupting agent, and a protease-susceptible linker that links the antibody and MMAE. The IgG1 antibody enables Brentuximab vedotin to target tumor cells expressing CD30 on their surface. Following this Brentuximab vedotin enters the cell. Once inside, the linker is cleaved releasing MMAE which binds disrupts the microtubule network. The antibody component of this drug is a chimeric IgG1 directed against CD30. The small molecule, MMAE, is a microtubule-disrupting particle. MMAE is covalently attached to the antibody by a linker. Data suggest that the anticancer activity of Adcertris is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC-CD30 complex, and the subsequent release of MMAE by proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, inducing cell cycle arrest and apoptotis of the malignant cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): Steady-state of the ADC is achieved within 21 days with every 3-week dosing of Adcetris. Minimal to no accumulation of ADC is observed with multiple doses at the every 3-week schedule. The time to maximum concentration for MMAE ranges from approximately 1 to 3 days. Similar to the ADC, steady-state of MMAE is achieved within 21 days with every 3-week dosing of Adcetris. MMAE exposures decrease with continued administration of Adcetris with about 50% to 80% of the exposure of the first dose being observed at future doses. The AUC of MMAE was measured to be approximately 2.2-fold higher in patients with hepatic impairment in comparison with patients with normal hepatic function. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): MMAE is unlikely to displace or to be displaced by highly protein-bound drugs. In vitro studies show that MMAE is a substrate of P-gp and was not a potent inhibitor of P-gp. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, the binding of MMAE to human plasma proteins is in the range of 68–82%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Data in both animals and humans suggest that only a small fraction of MMAE released from brentuximab vedotin is metabolized. In vitro data indicate that the MMAE metabolism that occurs is primarily via oxidation by CYP3A4/5. In vitro studies using human liver microsomes indicate that MMAE inhibits CYP3A4/5 but not other CYP isoforms. MMAE did not induce any major CYP450 enzymes in primary cultures of human hepatocytes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): This drug appears follow metabolite kinetics, with the elimination of appearing to be limited by its rate of release from the antibody-drug conjugate (ADC). An excretion study was done in patients receiving a dose of 1.8 mg/kg of Adcetris. About 24% of the total MMAE ingested as part of the ADC during an ADCETRIS infusion was recovered in both urine and feces over a 7-day time frame. Of the recovered MMAE, approximately 72% was found in the feces and the majority of the excreted MMAE was excreted as unchanged drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life is approximately 4-6 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The liver is the primary route of clearance for MMAE. The pharmacokinetics and safety of Brentuximab vedotin and MMAE were examined after the administration of 1.2 mg/kg of Adcetris to patients with mild, moderate, and severe hepatic impairment. In patients with moderate and severe hepatic impairment, the rate of ≥Grade 3 adverse reactions was 6/6 (100%) compared to 3/8 (38%) in patients with normal hepatic function. It is recommended to avoid use in patients with severe renal impairment (CrCl <30mL/min). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most severe toxic reaction seen in patients is progressive multifocal leukoencephalopathy. Progressive multifocal leukoencephalopathy (PML) follows infection by the JC virus (which is not related to Creutzfeldt-Jakob disease). Symptoms of this condition begin insidiously and usually worsen progressively. The symptoms vary depending on which region of the brain is infected. In about two out of three patients, mental function deteriorates rapidly, leading to dementia. Speaking and walking may become increasingly difficult. Vision may be impaired, and total blindness may occur. Rarely, headaches and seizures can occur, mainly in immunocompromised patients. The most serious sequela of this condition is death. Common adverse effects of Adcetris may include: neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and fever. In one trial, neutropenia occurred in 91 percent of patients treated with Adcetris plus chemotherapy, which was associated with a 19 percent rate of febrile neutropenia (neutropenia and fever). Preventive treatment with G-CSF, a growth factor for the bone marrow to produce white blood cells, is recommended with Adcetris plus chemotherapy for the first-line treatment of Stage III or IV cHL. Adcetris has a boxed warning that emphasizes the risk of John Cunningham virus infection leading to progressive multifocal leukoencephalopathy, or PML, a rare but serious brain infection that may be lethal. Serious risks of Adcetris include peripheral neuropathy; severe allergic (anaphylaxis) or infusion-site reactions; damage to the blood, lungs and liver (hematologic, pulmonary and hepato-toxicities); severe/opportunistic infections; metabolic abnormalities (tumor lysis syndrome); dermatologic reactions and gastrointestinal complications. Adcetris may cause harm to the fetus and newborn baby; women should be warned of the potential risk to the fetus and to use effective contraception, and to avoid breastfeeding while taking Adcetris. MMAE was found to be genotoxic in the rat bone marrow micronucleus study through an aneugenic mechanism. This effect is consistent with the pharmacological effect of MMAE as a microtubule-disrupting drug. Fertility studies with Brentuximab vedotin or MMAE have not been conducted. Despite this, results of repeat-dose toxicity studies in rats suggest the potential for Brentuximab vedotin to have a negative effect on male reproductive function and fertility. In a 4-week repeated-dose toxicity study in rats with weekly dosing at 0.5, 5 or 10 mg/kg brentuximab vedotin, seminiferous tubule degeneration, Sertoli cell vacuolation, reduced spermatogenesis, and aspermia were observed. Effects in animals were seen mostly at 5 and 10 mg/kg doses of brentuximab vedotin. These dosages are approximately 3 and 6-fold the human recommended dose of 1.8 mg/kg, respectively, based on individual body weight. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Adcetris •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Brodalumab interact?

•Drug A: Abciximab •Drug B: Brodalumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Brodalumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Brodalumab has been approved for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Increase in the level of IL-17 due to blocking of its receptors. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Brodalumab binds with high affinity to interleukin (IL)-17 receptor A, thereby inhibiting several pro-inflammatory cytokines from the IL-17 family. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 4.62 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.223 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Siliq •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Brolucizumab interact?

•Drug A: Abciximab •Drug B: Brolucizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Brolucizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Brolucizumab is a monoclonal antibody indicated to treat neovascular age related macular degeneration. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Brolucizumab is a vascular endothelial growth factor (VEGF) inhibitor which reduces proliferation of endothelial cells, vascularization of the tissue, and permeability of the vasculature. It has a long duration of action as it is given monthly. Patients should be counselled regarding the risk of endophthalmitis, retinal detachment, and arterial thromboembolic events following administration of this medication. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Brolucizumab is a vascular endothelial growth factor (VEGF) inhibitor which targets the major VEGF-A isoforms: VEGF 110, VEGF 121, and VEGF 165. Inhibition of these VEGF-A isoforms reduce proliferation of endothelial cells, vascularization of the tissue, and permeability of the vasculature. •Absorption (Drug A): No absorption available •Absorption (Drug B): A 3mg dose of brolucizumab reaches a C max of 20.7ng/mL with a T max of 20.3h and an AUC of 2480ng*h/mL. A 6mg dose of brolucizumab reaches a C max of 77.6ng/mL with a T max of 17.4h and an AUC of 9169ng*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Data regarding the volume of distribution is not readily available. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are generally not protein bound in serum. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Monoclonal antibodies are expected to undergo proteolysis to smaller peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Data regarding the route of elimination is not readily available. Monoclonal antibodies are generally not eliminated in the urine, and only a small amount is excreted in bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The systemic half life of bolucizumab is 4.4±2.0 days. The elimination half life is 108h for a 3mg dose and 103h for a 6mg dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): Data regarding the clearance of brolucizumab is not readily available. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding the toxicity of brolucizumab is not readily available. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Beovu •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Burosumab interact?

•Drug A: Abciximab •Drug B: Burosumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Burosumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): This drug is indicated for the treatment of X-linked hypophosphatemia with radiological evidence of bone disease in children of 1 year of age and older and adolescents with growing skeletons. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): This drug has the ability to reduce the loss of phosphate, to improve pathologically low serum phosphate concentrations and other metabolic changes, as well as to reduce the severity of rickets as seen radiographically. In summary, this drug works to support of bone mineralization. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Burosumab is a recombinant human monoclonal antibody (IgG1) that both binds to and inhibits the actions of fibroblast growth factor 23 (FGF23). By inhibiting this growth factor, burosumab increases the tubular reabsorption of phosphate from the kidney and thus increases serum concentration of 1, 25 dihydroxy-Vitamin D. This form of vitamin D enhances intestinal absorption of phosphate and calcium, supporting bone mineralization. •Absorption (Drug A): No absorption available •Absorption (Drug B): Burosumab absorption after subcutaneous injection sites into to the blood circulation is nearly complete. Following the subcutaneous route of administration, the time to reach maximum serum concentrations (Tmax) of burosumab is estimated at 5-10 days. The peak serum concentration (Cmax) and area under the concentration-time curve (AUC) of serum burosumab is proportional to the dose, over the dose range of 0.1-2.0 mg/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Burosumab is comprised solely of amino acids and carbohydrates as a native immunoglobulin and is not likeluy to be eliminated by hepatic metabolic mechanisms. The metabolism of burosumab and elimination are expected to follow the immunoglobulin clearance pathways, which results in its degradation to smaller peptides and amino acids. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Burosumab is composed solely of amino acids and carbohydrates as a native immunoglobulin and is unlikely to be eliminated via hepatic metabolic mechanisms. Its metabolism and elimination are expected to follow the immunoglobulin clearance pathways, resulting in degradation to small peptides and individual amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Because of its molecular size, burosumab is not likely to be directly excreted. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): About 19 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of burosumab depends on weight and is estimated to be 0.290 L/day and 0.136 L/day in a typical adult (70 kg) and pediatric (30 kg) XLH patient, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The toxicity of Crysvita can be classified into several categories: Ectopic mineralisation: Clinically manifested by nephrocalcinosis, has been seen in patients with XLH treated with oral phosphorous and vitamin D analogues. These drugs should be stopped at least 1 week before starting burosumab treatment. Monitoring for signs and symptoms of nephrocalcinosis, e.g. by renal ultrasonography, is recommended at the beginning of treatment and at intervals of every 6 months for the first 12 months of treatment, and yearly thereafter. Regular monitoring of plasma alkaline phosphatases, Calcium, PTH, and creatinine is advised at 6 months intervals(every 3 months for children 1- 2 years) or as indicated. Monitoring of urine calcium and phosphate is suggested every 3 months. Hyperphosphatemia Fasting serum phosphate level must be followed due to the risk of hyperphosphatemia while taking this drug. To decrease the risk for ectopic mineralization, it is advised that fasting serum phosphate is aimed to be in the lower end of the normal reference range for any given age. Dose interruption and/or dose reduction may be required. Regular measurement of postprandial serum phosphate is advised. Serum parathyroid hormone increases Increases in serum parathyroid hormone have been measured in some XLH patients while undergoing treatment with burosumab. Regular measurement of serum parathyroid hormone is recommended. Injection site reactions Administration of burosumab, like other injections, can lead to local injection site reactions. Administration of this drug should cease in any patient experiencing severe injection site reactions and appropriate medical therapy administered. Hypersensitivity Burosumab should be discontinued if serious hypersensitivity reactions occur and appropriate medical treatment should be provided. Reproductive toxicity/pregnancy There are no or limited amount of data available from the use of burosumab in pregnant women. Studies in animals have demonstrated reproductive toxicity. Burosumab use is not advised during pregnancy and in women of childbearing potential/age currently not using contraception. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Crysvita •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Busulfan interact?

•Drug A: Abciximab •Drug B: Busulfan •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Busulfan. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous (myeloid, myelocytic, granulocytic) leukemia (FDA has designated busulfan as an orphan drug for this use). It is also used as a component of pretransplant conditioning regimens in patients undergoing bone marrow transplantation for acute myeloid leukemia and nonmalignant diseases. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn leads to a miscoding of DNA. Alkylating agents are cell cycle-nonspecific and work by three different mechanisms, all of which achieve the same end result - disruption of DNA function and cell death. Overexpression of MGST2, a glutathione s-transferase, is thought to confer resistance to busulfan. The role of MGST2 in the metabolism of busulfan is unknown however. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Busulfan is an alkylating agent that contains 2 labile methanesulfonate groups attached to opposite ends of a 4-carbon alkyl chain. Once busulfan is hydrolyzed, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, which results in the interference of DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function. Specifically, its mechanism of action through alkylation produces guanine-adenine intrastrand crosslinks. These crosslinks occur through a SN2 reaction guanine N7 nucleophilically attacks the carbon adjacent to the mesylate leaving group. This kind of damage cannot be repaired by cellular machinery and thus the cell undergoes apoptosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Completely absorbed from the gastrointestinal tract. Busulfan is a small, highly lipophilic molecule that crosses the blood-brain-barrier. The absolute bioavailability, if a single 2 mg IV bolus injection is given to adult patients, is 80% ± 20%. In children (1.5 - 6 years old), the absolute bioavailability was 68% ± 31%. When a single oral dose is given to patients, the area under the curve (AUC) was 130 ng•hr/mL. The peak plasma concentration when given orally is 30 ng/mL (after dose normalization to 2 mg). It takes 0.9 hours to reach peak plasma concentration after dose normalization to 4 mg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 32% bound to plasma proteins and 47% bound to red blood cells. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Busulfan is extensively metabolizes in the hepatic. Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis. GSTA1 is the primary GST isoform that facilitates the the metabolism of busulfan. Other GST isoforms that are also involved are GSTM1 and GSTP1. At least 12 metabolites have been identified among which tetrahydrothiophene, tetrahydrothiophene 12-oxide, sulfolane, and 3-hydroxysulfolane were identified. These metabolites do not have cytotoxic activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following administration of 14C- labeled busulfan to humans, approximately 30% of the radioactivity was excreted into the urine over 48 hours; negligible amounts were recovered in feces. Less than 2% of the administered dose is excreted in the urine unchanged within 24 hours. Elimination of busulfan is independent of renal function. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2.6 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.52 ml/min/kg [Following an infusion of dose of 0.8 mg/kg every six hours, for a total of 16 doses over four days] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Signs of overdose include allergic reaction, unusual bleeding or bruising, sudden weakness or unusual fatigue, persistent cough, congestion, or shortness of breath; flank, stomach or joint pain; pronounced nausea, vomiting, diarrhea, dizziness, confusion, or darkening of the skin, chills, fever, collapse, and loss of consciousness. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Busulfex, Myleran •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,4-Bis(methanesulfonoxy)butane 1,4-Butanediol dimethanesulfonate 1,4-Dimesyloxybutane (common) 1,4-Dimethanesulfonoxybutane Busulfan (common) Busulfano (common) Busulfanum (common) Busulphan (common) Tetramethylene bis(methanesulfonate)

Do Abciximab and Cabazitaxel interact?

•Drug A: Abciximab •Drug B: Cabazitaxel •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cabazitaxel. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cabazitaxel is indicated, in combination with prednisone, for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel -containing treatment regimen. In Europe and Canada, it can also be used in combination with prednisolone. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cabazitaxel demonstrates a broad spectrum of antitumour activity against advanced human tumours xenografted in mice, including intracranial human glioblastomas. Cabazitaxel has a low affinity to P-glycoprotein, allowing it to penetrate the blood-brain barrier without being subject to extensive P-gp-mediated active efflux. Cabazitaxel works against docetaxel-sensitive tumours and tumour models resistant to docetaxel and other chemotherapy drugs. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Microtubules are cytoskeletal polymers that regulate cell shape, vesicle transport, cell signalling, and cell division. They are made up of alpha-tubulin and beta-tubulin heterodimers. Microtubules extend toward the mitotic spindle during mitosis to allow the separation and distribution of chromosomes during cell division. Cabazitaxel binds to the N-terminal amino acids of the beta-tubulin subunit and promotes microtubule polymerization while simultaneously inhibiting disassembly: this results in the stabilization of microtubules, preventing microtubule cell division. Cabazitaxel ultimately blocks mitotic and interphase cellular functions and tumour proliferation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Based on the population pharmacokinetic analysis, after an intravenous dose of cabazitaxel 25 mg/m every three weeks, the mean C max in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (T max ). The mean AUC in patients with metastatic prostate cancer was 991 ng x h/mL (CV 34%). No major deviation from the dose proportionality was observed from 10 to 30 mg/m in patients with advanced solid tumours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Steady-state volume of distribution (V ss ) was 4,864 L (2,643 L/m for a patient with a median BSA of 1.84 m ). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, the binding of cabazitaxel to human serum proteins was 89% to 92% and was not saturable up to 50,000 ng/mL. Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL). The in vitro blood-to-plasma concentration ratio in human blood ranged from 0.90 to 0.99, indicating that cabazitaxel was equally distributed between blood and plasma. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): More than 95% of cabazitaxel is extensively metabolized in the liver. CYP3A4 and CYP3A5 are responsible for 80% to 90% of drug metabolism, while CYP2C8 is involved to a lesser extent. While cabazitaxel is the main circulating moiety in human plasma, seven metabolites have been detected in plasma, including three active metabolites arising from O-demethylation - docetaxel, RPR112698, and RPR123142. The main metabolite accounts for 5% of total cabazitaxel exposure. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After a one-hour intravenous infusion [ C]-cabazitaxel 25 mg/m, approximately 80% of the administered dose was eliminated within two weeks. Cabazitaxel is mainly excreted in the feces as numerous metabolites (76% of the dose), while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine). Around 20 metabolites of cabazitaxel are excreted into human urine and feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ- half-lives of four minutes, two hours, and 95 hours, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Based on the population pharmacokinetic analysis, cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m for a patient with a median BSA of 1.84 m ) in patients with metastatic prostate cancer. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is 500 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jevtana •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Canakinumab interact?

•Drug A: Abciximab •Drug B: Canakinumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Canakinumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Canakinumab is indicated for the treatment of periodic fever syndromes in specific patient populations. In patients ≥4 years of age, canakinumab is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS). In adult and pediatric patients, canakinumab is also indicated for the treatment of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD), and Familial Mediterranean Fever (FMF). Canakinumab is additionally indicated in patients ≥2 years of age for the treatment of active Still's disease, including Adult-Onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA). Canakinumab is also indicated for the treatment of gout flares in adult patients in whom standard therapies (e.g. NSAIDs, colchicine) are contraindicated, not tolerated, or ineffective, and in whom repeated courses of corticosteroids are not appropriate. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Canakinumab neutralizes the activity of human IL-1β, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): In inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra). •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of subcutaneously administered canakinumab is estimated to be 66%. Peak serum concentration is 16 ± 3.5 mcg/mL and occurs approximately 7 days following a single subcutaneous dose of 150mg. Exposure to canakinumab increases proportionately to the administered dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution of canakinumab is variable based on weight - it was estimated to be 6.01 liters in a typical CAPS patient weighing 70 kg, 3.2 liters in a SJIA patient weighing 33 kg, 6.34 liters for a Periodic Fever Syndrome (TRAPS, HIDS/MKD, FMF) patient weighing 70 kg and 7.9 liters in a typical patient with gout flares weighing 93 kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Canakinumab binds to plasma IL-1β, but plasma protein binding has not been quantified. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Canakinumab, like other therapeutic proteins, is likely degraded via non-specific catabolic processes to smaller peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The route of elimination for canakinumab has not yet been determined. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 26 days •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of canakinumab is variable based on weight - it was estimated to be 0.174 L/day in a typical CAPS patient weighing 70 kg, 0.11 L/day in an SJIA patient weighing 33 kg, 0.17 L/day in a Periodic Fever Syndrome (TRAPS, HIDS/MKD, FMF) patient weighing 70 kg and 0.23 L/day in a typical patient with gout flares of body weight 93 kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no confirmed cases of overdosage with canakinumab. In the event of an overdose, the patient should be monitored closely and appropriate symptomatic treatment should be administered immediately as clinically indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ilaris •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Cangrelor interact?

•Drug A: Abciximab •Drug B: Cangrelor •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cangrelor. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For use as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients in who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cangrelor is a selective, reversible, P2Y12 platelet receptor antagonist which inhibits ADP platelet aggregation. ADP is typically released by damaged blood vessels, red blood cells, and/or platelets due to agonists stimulating platelet activity. ADP binds to P2Y12 to stimulate and complete platelet aggregation by inhibiting adenylyl cyclase by a Gi protein, thus potentiating dense granule secretion and increasing coagulation activity. Cangrelor acts on the same target as oral irreversible inhibitors clopidogrel and ticlopidine and has a similar mechanism of action, but is reversible and provides a fast onset and offset of action. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In a study in healthy volunteers administration at a dose of 30 mcg/kg bolus plus 4 mcg/kg/min showed a volume of distribution of 3.9 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): about 97-98%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Cangrelor is deactivated rapidly in the circulation by dephosphorylation to its primary metabolite, a nucleoside, which has negligible anti-platelet activity. Cangrelor's metabolism is independent of hepatic function and it does not interfere with other drugs metabolized by hepatic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following IV administration of [3H] cangrelor, 58% of radioactivity was recovered in urine. The remaining 35% of radioactivity was in feces, presumably following biliary excretion. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The average elimination half-life of cangrelor is about 3-6 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance is about 43.2 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kengreal, Kengrexal •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): [dichloro-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2-methylsulfanylethylamino)-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methyl]phosphonic acid Cangrelor (common)

Do Abciximab and Capecitabine interact?

•Drug A: Abciximab •Drug B: Capecitabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Capecitabine. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Capecitabine is indicated as treatment for a variety of cancer types. For colorectal cancer, capecitabine is indicated as a single agent or a component of a combination chemotherapy regiment for the adjuvant treatment of stage III colon cancer and treatment unresectable or metastatic colorectal cancer. It can also be used as a part of a combination chemotherapy perioperative treatment of adult locally advanced rectal cancer. For breast cancer, capecitabine is indicated for advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated or as a regimen with docetaxel after disease progression on prior anthracycline-containing chemotherapy. For gastric, esophageal, or gastroesophageal junction (GEJ) cancer, capecitabine is indicated as a component of a combination chemotherapy treatment for the treatment of adult unresectable or metastatic gastric, esophageal, or GEJ cancer or adult HER2-overexpressing metastatic gastric or GEJ adenocarcinoma who have not received prior treatment for metastatic disease. Finally, for pancreatic cancer, capecitabine is indicated as adjuvant treatment for adult pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Capecitabine is a fluoropyrimidine carbamate belonging to a group of antineoplastic agents called antimetabolites, which kill cancerous cells by interfering with DNA synthesis. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to 5-fluorouracil (5-FU) by enzymes that are expressed in higher concentrations in many tumors. Capecitabine was designed specifically to overcome the disadvantages of 5-FU and to mimic the infusional pharmacokinetics of 5-FU without the associated complexity and complications of central venous access and infusion pumps. Particularly, since the enzymes converting 5-FU into active metabolites exist in the gastrointestinal tract, infusion of 5-FU can have gastrointestinal toxicity while also losing efficacy. Since capecitabine can be transported intact across the intestinal mucosa, it can be selectively delivered 5-FU to tumor tissues through enzymatic conversion preferentially inside tumor cells. 5-FU exerts its pharmacological action through the inhibition and interference of 3 main targets: thymidylate synthase, DNA, and RNA, leading through protein synthesis disruption and apoptosis. Population-based exposure-effect analyses demonstrated a positive association between AUC of 5-FU and grade 3-4 hyperbilirubinemia. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Capecitabine is metabolized to 5-fluorouracil in vivo by carboxylesterases, cytidine deaminase, and thymidine phosphorylase/uridine phosphorylase sequentially. 5-fluorouracil is further metabolized through a series of enzymatic reactions into 3 main active metabolites: 5-fluorouridine triphosphate (5-FUTP), 5-fluoro-2’-deoxyuridine monophosphate (5-FdUMP), and 5-fluorodeoxyuridine triphosphate (5-FdUTP).. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate (CH 2 THF), bind to thymidylate synthase (TS) to form a covalently bound ternary complex. TS is an enzyme that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Under normal physiological conditions, dUMP binds to TS first before CH 2 THF, followed by a 1,4 or Michael addition from the pyrimidine C (6)atom to the Cys146 nucleophile. If correctly positioned, dUMP, CH 2 THF, and TS would form a ternary complex to facilitate the donation of the methyl group from CH 2 THF to dUMP. However, the substitution of dUMP with FdUMP results in a new time-dependent TS–FdUMP–CH2THF complex. Since the fluorine group prevents dissociation of FdUMP from the pyrimidine ring, the whole complex is rendered irreversibly deactivated, terming this reaction "suicide inhibition". TS inhibition prevents the conversion of dUMP to dTMP, depleting the pool of dTMP that could be phosphorylated into dTTP to be incorporated as DNA nucleotides. This disrupts the nucleotides balance, particularly the the ATP/dTTP ratio, thus impairing DNA synthesis and repair and causing apoptosis. 5-FdUMP can also be phosphorylated into 5-FdUTP, further increasing the pool of dUTP base to potentially overwhelm the activity of dUTPase. Coupled with the decrease in dTTP, 5-FdUMP, and 5-FdUTP increase the probability of mistakenly incorporating a uracil base into DNA strands in place of thymine. Although this mistake can often be resolved by the nucleotide excision repair enzyme uracil-DNA-glycosylase (UDG), the high (F)dUTP/dTTP ratio would result in re-incorporation of uracil into DNA, leading to a futile cycle of misincorporation, excision, and repair. Repeated base excision repair can result in abasic sites, which can lead to DNA mutagenesis and thus protein miscoding, replication forks collapse, and DNA fragmentation through single or double strand breaks However, several reports have found that the incorporation of uracil in genomic DNA does not significantly affect the cytotoxicity of 5-FU, suggesting that the cytotoxic effect of 5-FU is dominated by the perturbation of RNA through 5-FUTP. Similar to 5-dFUTP, 5-FUTP can be mistakenly incorporated into RNA in place of regular UTP and disrupt regular RNA biology through various mechanisms. 5-FUTP can be incorporated into the spliceosomal U2 snRNA at pseudouridylated sites to prevent further pseudouridylation and thus pre-mrNA splicing. 5-FUTP can also change the structure of U4 and U6 snRNA and reduce the turnover rate of U1 snrNA once incorporated. For tRNA, 5-FUTP can affect tRNA's post-transcriptional RNA modifications activity, particularly by inhbiting pseudouridine synthase through formation of covalent complex. Recently, the effect of 5-FUTP on miRNAs and lncRNA was also observed through profound changes in expression, although the precise mechanism is still unknown. Although the main mechanism of 5-FU cytotoxicity was thought to be attributed to DNA damages, recent reports have shown that the majority of 5-FU pharmacological action is mediated through RNA, since 5-FU is accumulated ~3000- to 15 000-fold more in RNA compared to that of DNA. •Absorption (Drug A): No absorption available •Absorption (Drug B): The AUC of capecitabine and its metabolite 5’-DFCR increases proportionally over a dosage range of 500 mg/m2/day to 3,500 mg/m2/day (0.2 to 1.4 times the approved recommended dosage). The AUC of capecitabine’s metabolites 5’-DFUR and fluorouracil increased greater than proportional to the dose. The interpatient variability in the Cmax and AUC of fluorouracil was greater than 85%. Following oral administration of capecitabine 1,255 mg/m orally twice daily (the recommended dosage when used as a single agent), the median Tmax of capecitabine and its metabolite fluorouracil was approximately 1.5 hours and 2 hours, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In colorectal cancer patients with a mean age of 58 ± 9.5 years and ECOG Performance Status of 0–1, the volume of distribution is calculated to be 186 ± 28 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding of capecitabine and its metabolites is less than 60% and is not concentration dependent. Capecitabine was primarily bound to human albumin (approximately 35%). •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Capecitabine undergoes metabolism by carboxylesterase and is hydrolyzed to 5’-DFCR. 5’-DFCR is subsequently converted to 5’-DFUR by cytidine deaminase. 5’-DFUR is then hydrolyzed by thymidine phosphorylase (dThdPase) enzymes to the active metabolite fluorouracil. Fluorouracil is subsequently metabolized by dihydropyrimidine dehydrogenase to 5-fluoro-5, 6-dihydro-fluorouracil (FUH2). The pyrimidine ring of FUH2 is cleaved by dihydropyrimidinase to yield 5-fluoro-ureido-propionic acid (FUPA). Finally, FUPA is cleaved by β-ureido-propionase to α-fluoro-β-alanine (FBAL). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following administration of radiolabeled capecitabine, 96% of the administered capecitabine dose was recovered in urine (3% unchanged and 57% as metabolite FBAL) and 2.6% in feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half-lives of capecitabine and fluorouracil were approximately 0.75 hour. •Clearance (Drug A): No clearance available •Clearance (Drug B): In colorectal cancer patients with a mean age of 58 ± 9.5 years and ECOG Performance Status of 0–1, the clearance of capecitabine is calculated to be 775 ± 213 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adequate studies investigating the carcinogenic potential of capecitabine have not been conducted. Capecitabine was not mutagenic in vitro to bacteria (Ames test) or mammalian cells (Chinese hamster V79/HPRT gene mutation assay). Capecitabine was clastogenic in vitro to human peripheral blood lymphocytes but not clastogenic in vivo to mouse bone marrow (micronucleus test). Fluorouracil causes mutations in bacteria and yeast. Fluorouracil also causes chromosomal abnormalities in the mouse micronucleus test in vivo. In studies of fertility and general reproductive performance in female mice, oral capecitabine doses of 760 mg/kg/day (about 2,300 mg/m2/day) disturbed estrus and consequently caused a decrease in fertility. In mice that became pregnant, no fetuses survived this dose. The disturbance in estrus was reversible. In males, this dose caused degenerative changes in the testes, including decreases in the number of spermatocytes and spermatids. In separate pharmacokinetic studies, this dose in mice produced 5’-DFUR AUC values about 0.7 times the corresponding values in patients administered the recommended daily dose. Based on findings in animal reproduction studies and its mechanism of action [see Clinical Pharmacology (12.1)], XELODA can cause fetal harm when administered to a pregnant woman. Available human data on XELODA use in pregnant women is not sufficient to inform the drug-associated risk. In animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryo lethality and teratogenicity in mice and embryo lethality in monkeys at 0.2 and 0.6 times the exposure (AUC) in patients receiving the recommended dose of 1,250 mg/m2 twice daily, respectively. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Administer uridine triacetate within 96 hours for management of XELODA overdose. Although no clinical experience using dialysis as a treatment for XELODA overdose has been reported, dialysis may be of benefit in reducing circulating concentrations of 5’-DFUR, a low–molecular-weight metabolite of the parent compound. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ecansya, Xeloda •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (1-(5-Deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-carbamic acid pentyl ester Capecitabin (common) Capecitabina (common) Capécitabine (common) Capecitabine (common) Capecitabinum (common) Pentyl [1-(5-deoxy-β-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate pentyl 1-(5-deoxy-β-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamate

Do Abciximab and Caplacizumab interact?

•Drug A: Abciximab •Drug B: Caplacizumab •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Caplacizumab is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •References: 1. Vazquez SR: Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018 Nov 22;132(21):2230-2239. doi: 10.1182/blood-2018-06-848747. [https://go.drugbank.com/articles/A173602] 2. Becker DE: Antithrombotic drugs: pharmacology and implications for dental practice. Anesth Prog. 2013 Summer;60(2):72-9; quiz p.80. doi: 10.2344/0003-3006-60.2.72. [https://go.drugbank.com/articles/A173605] 3. Delaney JA, Opatrny L, Brophy JM, Suissa S: Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. doi: 10.1503/cmaj.070186. [https://go.drugbank.com/articles/A33532] 4. Vranckx P, Valgimigli M, Heidbuchel H: The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):55-61. doi: 10.15420/aer.2017.50.1. [https://go.drugbank.com/articles/A36072] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older. aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications. Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In vitro studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex. In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP as well as a significant reduction in the median time to response of about 39%. However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation. The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours and it presents a very high bioavailability reaching approximately 90%. The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The reported volume of distribution of caplacizumab is 6.33 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): This antibody acts directly on plasma proteins and thus, this parameter is not significant for drug description. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of caplacizumab is divided between target-driven disposition which is driven by the binding to the von Willebrand factor and non-target disposition driven by the combination of catabolism and renal elimination. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The reported half-life is reported to be in the range of 16-27 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done. To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cablivi •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Carbamazepine interact?

•Drug A: Abciximab •Drug B: Carbamazepine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Carbamazepine. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Carbamazepine is indicated for the treatment of epilepsy and pain associated with true trigeminal neuralgia. In particular, carbamazepine has shown efficacy in treating mixed seizures, partial seizures with complex symptoms, and generalized tonic-clonic seizures. Carbamazepine is also indicated for the treatment of manic episodes and mixed manic-depressive episodes caused by bipolar I disorder. Some off-label, unapproved uses of carbamazepine include the treatment of alcohol withdrawal syndrome and restless leg syndrome. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): General effects Carbamazepine treats seizures and the symptoms of trigeminal neuralgia by inhibiting sodium channels. In bipolar 1 disorder, carbamazepine has been found to decrease mania symptoms in a clinically significant manner according to the Young Mania Rating Scale (YMRS). Carbamazepine has a narrow therapeutic index. A note on genetic variation and carbamazepine use In studies of Han Chinese ancestry patients, a pronounced association between the HLA-B*1502 genotype and Steven Johnson syndrome and/or toxic epidermal necrolysis (SJS/TEN) resulting from carbamazepine use was observed. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Carbamazepine's mechanism of action is not fully elucidated and is widely debated. One major hypothesis is that carbamazepine inhibits sodium channel firing, treating seizure activity. Animal research studies have demonstrated that carbamazepine exerts its effects by lowering polysynaptic nerve response and inhibiting post-tetanic potentiation. In both cats and rats, carbamazepine was shown to decrease pain caused by infraorbital nerve stimulation. A decrease in the action potential in the nucleus ventralis of the thalamus in the brain and inhibition of the lingual mandibular reflex were observed in other studies after carbamazepine use. Carbamazepine causes the above effects by binding to voltage-dependent sodium channels and preventing action potentials, which normally lead to stimulatory effects on nerves. In bipolar disorder, carbamazepine is thought to increase dopamine turnover and increase GABA transmission, treating manic and depressive symptoms. A common issue that has arisen is resistance to this drug in up to 30% of epileptic patients, which may occur to altered metabolism in patients with variant genotypes. A potential therapeutic target to combat carbamazepine resistance has recently been identified as the EPHX1 gene promoter, potentially conferring resistance to carbamazepine through methylation. •Absorption (Drug A): No absorption available •Absorption (Drug B): The bioavailability of carbamazepine is in the range of 75-85% of an ingested dose. After one 200 mg oral extended-release dose of carbamazepine in a pharmacokinetic study, the Cmax carbamazepine was measured to be 1.9 ± 0.3 mcg/mL. The Tmax was 19 ± 7 hours. After several doses of 800 mg every 12 hours, the peak concentrations of carbamazepine were measured to be 11.0 ± 2.5 mcg/mL. The Tmax was reduced to 5.9 ± 1.8 hours. Extended-release carbamazepine demonstrated linear pharmacokinetics over a range of 200–800 mg. Effect of food on absorption A meal containing high-fat content increased the rate of absorption of one 400 mg dose but not the AUC of carbamazepine. The elimination half-life remained unchanged between fed and fasting state. The pharmacokinetics of an extended-release carbamazepine dose was demonstrated to be similar when administered in the fasted state or with food. Based on these findings, food intake is unlikely to exert significant effects on carbamazepine absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of carbamazepine was found to be 1.0 L/kg in one pharmacokinetic study. Another study indicates that the volume of distribution of carbamazepine ranges between 0.7 to 1.4 L/kg.. Carbamazepine crosses the placenta, and higher concentrations of this drug are found in the liver and kidney as opposed to lung and brain tissue. Carbamazepine crosses variably through the blood-brain barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Carbamazepine is 75%-80% bound to plasma proteins. One pharmacokinetic study indicates that it is 72% bound to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Carbamazepine is largely metabolized in the liver. CYP3A4 hepatic enzyme is the major enzyme that metabolizes carbamazepine to its active metabolite, carbamazepine-10,11-epoxide, which is further metabolized to its trans-diol form by the enzyme epoxide hydrolase. Other hepatic cytochrome enzymes that contribute to the metabolism of carbamazepine are CYP2C8, CYP3A5, and CYP2B6. Carbamazepine also undergoes hepatic glucuronidation by UGT2B7 enzyme and several other metabolic reactions occur, resulting in the formation of minor hydroxy metabolites and quinone metabolites. Interestingly, carbamazepine induces its own metabolism. This leads to enhanced clearance, reduced half-life, and a reduction in serum levels of carbamazepine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After an oral dose of radiolabeled carbamazepine, 72% of the administered radioactive dose was detected in the urine and the remainder of the ingested dose was found in the feces. Carbamazepine is mainly excreted as hydroxylated and conjugated metabolites, and minimal amounts of unchanged drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean elimination half-life of carbamazepine was 35 to 40 hours after one dose of carbamazepine extended-release formulations. The half-life ranged from 12-17 hours after several doses of carbamazepine. One pharmacokinetic study determined the elimination half-life of carbamazepine to range between 27 to 36.8 hours in healthy volunteers. •Clearance (Drug A): No clearance available •Clearance (Drug B): In a pharmacokinetic study, the apparent oral clearance of carbamazepine was 25 ± 5 mL/min after one dose of carbamazepine and 80 ± 30 mL/min after several doses. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information Oral LDLO (female): 1920 mg/kg/17W (intermittent); Oral LDLO (male): 54 mg/kg/9D (intermittent) Oral LD50 (rat): 1957 mg/kg Overdose information The initial signs of carbamazepine overdose occur 1-3 hours post ingestion. These signs and symptoms may vary in case of an overdose between carbamazepine and other drugs. Carbamazepine may cause various cardiovascular, neurological, respiratory, urinary symptoms as well as laboratory abnormalities including leukocytosis, reduced leucocytes, acetonuria, and glycosuria. Neuromuscular symptoms may occur initially, followed by mild cardiac symptoms such as tachycardia, hypertension, or hypotension. Higher doses of carbamazepine may cause more severed cardiovascular effects. Restlessness, muscular twitching, tremor, dilated pupils, nystagmus, psychomotor disturbances, and other neurological symptoms may occur. Hyperreflexia in the initial stages of overdose may be followed by hyporeflexia. Nausea, vomiting, urinary retention, dizziness or drowsiness may also occur. In cases of overdose, contact the local poison control center. Ensure to provide supportive and symptomatic treatment, which may include monitoring and careful supervision by a medical professional. The possibility of overdose with multiple drugs must be considered in the case of carbamazepine overdose. Maintain an adequate airway, oxygen, in addition to ventilation. Vital signs should be monitored. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Carbatrol, Carnexiv, Epitol, Equetro, Tegretol •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-Carbamoyl-5H-dibenz(b,f)azepine 5-carbamoyl-5H-dibenz[b,f]azepine 5-Carbamoyl-5H-dibenzo(b,f)azepine 5-Carbamyl-5H-dibenzo(b,f)azepine 5H-Dibenz(b,f)azepine-5-carboxamide Carbamazepen (common) Carbamazepin (common) Carbamazepina (common) Carbamazépine (common) Carbamazepine (common) Carbamazepinum (common) CBZ Molecusol-Carbamazepine (common)

Do Abciximab and Carbimazole interact?

•Drug A: Abciximab •Drug B: Carbimazole •Severity: MODERATE •Description: Carbimazole may increase the anticoagulant activities of Abciximab. •Extended Description: Due to potential inhibition of vitamin K activity by methimazole and other antithyroid agents, the activity of anticoagulants (for example, warfarin) may be increased. The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole and other antithyroid medications. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of hyperthyroidism and thyrotoxicosis. It is also used to prepare patients for thyroidectomy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Carbimazole is a carbethoxy derivative of methimazole. Its antithyroid action is due to its conversion to methimazole after absorption. It is used to treat hyperthyroidism and thyrotoxicosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Carbimazole is an aitithyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 85% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Athyromazole (common) Carbethoxymethimazole (common) Carbimazol (common) Carbimazole (common) Carbimazolo (common) Carbimazolum (common) Carbinazole (common) Ethyl 3-methyl-2-thioimidazoline-1-carboxylate

Do Abciximab and Carboplatin interact?

•Drug A: Abciximab •Drug B: Carboplatin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Carboplatin. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Carboplatin is indicated in combination with an established combination of chemotherapeutic agents for the initial treatment of advanced ovarian carcinoma. Carboplatin is also indicated for the palliative treatment of ovarian carcinoma, recurrent after prior chemotherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma. Carboplatin has a long duration of action as it is given every 4 weeks, and a narrow therapeutic index. Patients should be counselled regarding bone marrow suppression and anemia. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Carboplatin predominantly acts by attaching alkyl groups to the nucleotides, leading to the formation of monoadducts, and DNA fragmenting when repair enzymes attempt to correct the error. 2% of carboplatin's activity comes from DNA cross-linking from a base on one strand to a base on another, preventing DNA strands from separating for synthesis or transcription. Finally, carboplatin can induce a number of different mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): The C max and AUC of carboplatin increase proportionally with increasing doses. A 75 mg/m dose reaches a C max of 9.06 ± 0.74 µg/mL, with an AUC of 27.18 ± 11.28 h*µg/mL. A 450 mg/m dose reaches a C max of 55.39 ± 18.30 µg/mL, with an AUC of 224.41 ± 69.07 h*µg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution after a 30 minute intravenous infusion of 300-500 mg/m was 16 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Carboplatin is not bound to plasma protein. However, the free platinum is 40% irreversibly bound to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Carboplatin is predominantly eliminated as the unchanged parent compound. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Carboplatin is 65% eliminated in the urine within 12 hours, and 71% eliminated within 24 hours. An additional 3-5% is eliminated in urine from 24 hours to 96 hours. Biliary elimination has not been determined. Carboplatin is predominantly eliminated as the unchanged parent compound. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The distribution half life of carboplatin is 1.1-2 hours, and the elimination half life was2.6-5.9 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total body clearance after a 30 minute intravenous infusion of 300-500 mg/m was 4.4 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Patients experiencing an overdose of carboplatin may present with pronounced neutropenia and hepatotoxicity. Treat patients with symptomatic and supportive measures, which may include delaying their next treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Paraplatin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Carboplatin (common) Carboplatine (common) Carboplatino (common) CBDCA (common) cis-(1,1-cyclobutanedicarboxylato)diammineplatinum(II) cis-diammine(1,1-cyclobutanedicarboxylato)platinum cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)

Do Abciximab and Carfilzomib interact?

•Drug A: Abciximab •Drug B: Carfilzomib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Carfilzomib. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Carfilzomib is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with lenalidomide and dexamethasone; or dexamethasone; or daratumumab and dexamethasone; or daratumumab and hyaluronidase-fihj and dexamethasone; or isatuximab and dexamethasone. It is also indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Intravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Carfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. This 20S core has 3 catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (β5 and β5i subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax, single IV dose of 27 mg/m^2 = 4232 ng/mL; AUC, single IV dose of 27 mg/m^2 = 379 ng•hr/mL; Carfilzomib does not accumulation in the systemic. At doses between 20 and 36 mg/m2, there was a dose-dependent increase in exposure. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Vd, steady state, 20 mg/m^2 = 28 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Over the concentration range of 0.4 - 4 micromolar, carfilzomib was 97% protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Carfilzomib was rapidly and extensively metabolized by the liver. The predominant metabolites were the peptide fragments and the diol of carfilzomib which suggests that the main metabolic pathways are peptidase cleavage and epoxide hydrolysis. The cytochrome P450 enzyme system is minimally involved in the metabolism of carfilzomib. All metabolites are inactive. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Following intravenous administration of doses ≥ 15 mg/m^2, carfilzomib was rapidly cleared from the systemic circulation with a half-life of ≤ 1 hour on Day 1 of Cycle 1. •Clearance (Drug A): No clearance available •Clearance (Drug B): Systemic clearance = 151 - 263 L/hour. As this value exceeds hepatic blood flow, it suggests that carfilozmib is cleared extrahepatically. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Most commonly reported adverse reactions (incidence ≥ 30%) are fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. The two dose limiting toxicities are thrombocytopenia and febrile neutropenia. Maximum tolerate dose = 15 mg/m^2 •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kyprolis •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Carmustine interact?

•Drug A: Abciximab •Drug B: Carmustine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Carmustine. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •References: 1. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D: Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019 Feb 14;19(1):151. doi: 10.1186/s12885-019-5354-5. [https://go.drugbank.com/articles/A259327] 2. Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 2019 Nov 26;57(12):1808-1817. doi: 10.1515/cclm-2019-0380. [https://go.drugbank.com/articles/A259332] 3. Carey PJ: Drug-induced myelosuppression : diagnosis and management. Drug Saf. 2003;26(10):691-706. [https://go.drugbank.com/articles/A37561] 4. Smith RE: Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors. J Natl Compr Canc Netw. 2006 Aug;4(7):649-58. [https://go.drugbank.com/articles/A39445] 5. Kenney B, Stack G: Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009 Feb;133(2):309-14. doi: 10.1043/1543-2165-133.2.309. [https://go.drugbank.com/articles/A39446] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of brain tumors, multiple myeloma, Hodgkin's disease and Non-Hodgkin's lymphomas. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Carmustine is one of the nitrosoureas indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Carmustine causes cross-links in DNA and RNA, leading to the inhibition of DNA synthesis, RNA production and RNA translation (protein synthesis). Carmustine also binds to and modifies (carbamoylates) glutathione reductase. This leads to cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): 5 to 28% bioavailability •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 80% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hepatic and rapid with active metabolites. Metabolites may persist in the plasma for several days. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO2. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 15-30 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 s in rat and mouse are 20 mg/kg and 45 mg/kg, respectively. Side effects include leukopenia, thrombocytopenia, nausea. Toxic effects include pulmonary fibrosis (20-0%) and bone marrow toxicity. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bicnu, Gliadel •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): BCNU (common) bis-chloroethylnitrosourea (common) Bischloroethyl nitrosourea (common) Carmustina (common) Carmustine (common) Carmustinum (common) N,N'-Bis(2-chloroethyl)-N-nitrosourea

Do Abciximab and Casirivimab interact?

•Drug A: Abciximab •Drug B: Casirivimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Casirivimab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •References: 1. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, Engert A, Coiffier B, Hoelzer DF, Wegener WA, Teoh NK, Goldenberg DM, Lister TA: Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3880-6. Epub 2006 Jul 24. [https://go.drugbank.com/articles/A3069] 2. Genovese MC, Breedveld FC, Emery P, Cohen S, Keystone E, Matteson EL, Baptiste Y, Chai A, Burke L, Reiss W, Sweetser M, Shaw TM: Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009 Dec;68(12):1894-7. doi: 10.1136/ard.2008.101675. Epub 2009 Jan 20. [https://go.drugbank.com/articles/A33445] 3. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, Katz S, Goldblum R, Harrigan R, Hilton D, Hanauer SB: Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007 Jan;13(1):2-11. doi: 10.1002/ibd.20014. [https://go.drugbank.com/articles/A33446] 4. Corominas M, Gastaminza G, Lobera T: Hypersensitivity reactions to biological drugs. J Investig Allergol Clin Immunol. 2014;24(4):212-25; quiz 1p following 225. [https://go.drugbank.com/articles/A36676] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19. This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required. Limitations of use Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2. In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell. Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Catridecacog interact?

•Drug A: Abciximab •Drug B: Catridecacog •Severity: MAJOR •Description: The therapeutic efficacy of Catridecacog can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •References: 1. Butenas S, Mann KG: Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. [https://go.drugbank.com/articles/A38166] 2. Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. [https://go.drugbank.com/articles/A38167] 3. Harter K, Levine M, Henderson SO: Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933. Epub 2015 Jan 12. [https://go.drugbank.com/articles/A38174] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For routine prophylaxis of bleeding in patients with congenital factor XIII A-Subunit deficiency. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration, the maximum concentration (Cmax) was found to be 0.48 IU/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 7.1 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.41 mL/h/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common adverse reactions reported in clinical trials (≥1%), were headache, pain in the extremities, injection site pain, and increase in fibrin D dimer levels. Due to the anti-clotting activity of this medication, thromboembolic complications may occur with its usage. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Novothirteen, Tretten •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Blood Coagulation Factor XIII (Synthetic Human A-Chain Precursor) Catridecacog (common) Coagulation Factor XIII A-Subunit (recombinant) (common) Factor XIII A-Subunit (Recombinant) (common) Human Factor XIII (A2) homodimer (allele F13A*1B), recombinant DNA origin Recombinant Coagulation Factor XIII (common)

Do Abciximab and Cefaclor interact?

•Drug A: Abciximab •Drug B: Cefaclor •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefaclor. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of certain infections caused by bacteria such as pneumonia and ear, lung, skin, throat, and urinary tract infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefaclor is a second generation cephalosporin antibiotic with a spectrum resembling first-generation cephalosporins. In vitro tests demonstrate that the bactericidal action of the cephalosporins results from inhibition of cell-wall synthesis. As indicated by in vitro and in vivo clinical studies, cefaclor was shown to be effective against most strains of Gram positive aerobes - Staphylococci (including coagulase-positive, coagulase-negative, and penicillinase-producing strains), Streptococcus pneumoniae, Streptococcus pyogenes (group A ß-hemolytic streptococci), as well as Gram-negative aerobes - Escherichia coli, Haemophilus influenzae (including ß-lactamase-producing ampicillin-resistant strains), Klebsiella sp, and Proteus mirabilis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefaclor, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that cefaclor interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed after oral administration, independent of food intake. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 23.5% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No appreciable biotransformation in liver (approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours, the greater portion being excreted within the first 2 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 0.6-0.9 hour •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include diarrhea, nausea, stomach upset, and vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 3-Chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid CCL Cefaclor (common) Céfaclor (common) Cefaclor anhydrous Cefaclorum (common) Céfeaclor (common) Cephaclor (common)

Do Abciximab and Cefadroxil interact?

•Drug A: Abciximab •Drug B: Cefadroxil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefadroxil. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of the following infections (skin, UTI, ENT) caused by; S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staphylococci and Streptococcus pyogenes •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefadroxil, a first-generation cephalosporin antibiotic, is used to treat urinary tract infections, skin and skin structure infections, pharyngitis, and tonsillitis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Like all beta-lactam antibiotics, cefadroxil binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefadroxil interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cefadroxil is well absorbed on oral administration; food does not interfere with its absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binding rates of cefadroxil were 28.1% by U.F. method •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Over 90% of the drug is excreted unchanged in the urine within 24 hours. Cefadroxil was detected in the placenta and breast milk. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Nausea, vomiting, diarrhoea, allergic rashes may occur •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): CDX Cefadroxil (common) Cefadroxil anhydrous Cefadroxilo (common) Cefadroxilum (common) Cephadroxil (common) D-Cefadroxil (common)

Do Abciximab and Cefalotin interact?

•Drug A: Abciximab •Drug B: Cefalotin •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefalotin. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used to prevent infection during surgery and to treat many kinds of infections of the blood, bone or joints, respiratory tract, skin, and urinary tract. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefalotin (INN) or cephalothin (USAN) is a semisynthetic first generation cephalosporin having a broad spectrum of antibiotic activity that is administered parenterally. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal activity of cefalotin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). The PBPs are transpeptidases which are vital in peptidoglycan biosynthesis. Therefore, their inhibition prevents this vital cell wall compenent from being properly synthesized. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 65-80% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Metabolized to a less active desacetyl metabolite, although 50-75% of the drug is eliminated unchanged in the urine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 30 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Rat intravenous LD 50 is 4000 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 3-Acetoxymethyl-7-(2-thienylacetamido)-3-cephem-4-carboxylic acid 7-(2-Thienylacetamido)cephalosporanic acid 7-(2'-thienylacetamido)cephalosporanic acid 7-(Thiophene-2-acetamido)cephalosporin Cefalothin (common) Cefalotin (common) Cefalotina (common) Céfalotine (common) Cefalotinum (common) Cephalothin (common) Cephalotin (common) CET

Do Abciximab and Cefamandole nafate interact?

•Drug A: Abciximab •Drug B: Cefamandole nafate •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefamandole nafate. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): No indication available •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Cefapirin interact?

•Drug A: Abciximab •Drug B: Cefapirin •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefapirin. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of infections caused by susceptible bacteria. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cephapirin is a first-generation cephalosporin that has a wide spectrum of activity against gram-positive and gram-negative organisms. Cephapirin is more resistant to beta-lactamases than are the penicillins and so is effective against staphylococci, with the exception of methicillin-resistant staphylococci. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal activity of cephapirin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Major metabolite detected is desacetylcephapirin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Rats exposed via the oral route to cephapirin displayed low acute toxicity (LD 50 = 14000 mg/kg). The most common adverse reactions are hypersensitivity reactions and alterations to liver function. Evidence of white blood cell disorders and anaemia were noted in some subjects. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R)-3-(acetoxymethyl)-8-oxo-7-{[(pyridin-4-ylsulfanyl)acetyl]amino}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefapirin (common) Cefapirina (common) Cefapirine (common) Cefapirinum (common) Cefaprin (common) Cephapirin (common) Cephapirine (common) CEPR

Do Abciximab and Cefazolin interact?

•Drug A: Abciximab •Drug B: Cefazolin •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefazolin. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Mainly used to treat bacterial infections of the skin. It can also be used to treat moderately severe bacterial infections involving the lung, bone, joint, stomach, blood, heart valve, and urinary tract. It is clinically effective against infections caused by staphylococci and streptococci species of Gram positive bacteria. May be used for surgical prophylaxis; if required metronidazole may be added to cover B. fragilis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefazolin (also known as cefazoline or cephazolin) is a semi-synthetic first generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. •Absorption (Drug A): No absorption available •Absorption (Drug B): Not absorbed from GI tract. Must be administered parenterally. Peak serum concentrations attained 1-2 hours post intramuscular injection. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 74-86% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Not metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cefazolin is present in very low concentrations in the milk of nursing mothers. Cefazolin is excreted unchanged in the urine. In the first six hours approximately 60% of the drug is excreted in the urine and this increases to 70%-80% within 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The serum half-life is approximately 1.8 hours following IV administration and approximately 2.0 hours following IM administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefamezin (common) Cefazolin (common) Cefazolina (common) Cefazoline (common) Cefazolinum (common) Cephamezine (common) Cephazolidin (common) Cephazolin (common) Cephazoline (common) CEZ

Do Abciximab and Cefdinir interact?

•Drug A: Abciximab •Drug B: Cefdinir •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefdinir. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cefdinir is indicated to treat acute bacterial otitis media, acute maxillary sinusitis, community-acquired (CA) pneumonia, acute bacterial exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections in children and adults. The organisms susceptible to cefdinir have been listed below in addition to their associated clinical condition that may be treated with cefdinir. Various beta-lactamase producing organisms may be treated, as indicated in certain sections below. Respiratory Acute bacterial exacerbations of chronic bronchitis caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis Community-acquired pneumonia caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis Ear, nose, and throat Acute bacterial otitis media caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (penicillin-susceptible only) Tonsillitis caused by Streptococcus pyogenes Pharyngitis caused by Streptococcus pyogenes Acute maxillary sinusitis caused by Haemophilus pneumoniae and Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis Skin and skin structure infections Uncomplicated skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefdinir is a bactericidal agent that treats bacterial infections by interfering with cell wall synthesis. Cefdinir exerts broad-spectrum activity against a variety of gram-positive and gram-negative bacterial infections. It is effective against several beta-lactamase enzyme producing bacteria. As a result, many organisms that are resistant to other cephalosporins may be susceptible to cefdinir. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Five-member thiazolidine rings that make up penicillins are replaced in cephalosporins by a six-member dihydrothiazine ring, conferring greater bactericidal activity. This This 6-member ring enables cefdinir and other cephalosporins to resist inactivation by certain bacterial enzymes. With a mechanism similar to other beta-lactam antibiotics, the bactericidal activity of cefdinir is caused by the inhibition of cell wall synthesis via binding to penicillin-binding proteins (PBPs). Cefdinir, like other cephalosporins, penetrates the bacterial cell wall, combats inactivation by beta-lactamase enzymes, and inactivates penicillin-binding proteins. This interferes with the final step of transpeptidation in cell walls, eventually leading to cell lysis, which eventually leads to the death of bacteria that are susceptible to this drug. Cefdinir has shown affinity to penicillin protein binding proteins 2 and 3. It has also been shown to inhibit transpeptidase enzymes of various bacteria, which may play a role in its bactericidal action. One in vitro study suggests that cefdinir inhibits myeloperoxidase release extracellularly. The impact of this potential drug target in relation to its mechanism of action is unknown. •Absorption (Drug A): No absorption available •Absorption (Drug B): Maximal plasma cefdinir concentration can be attained between 2-4 hours after an ingested dose. The bioavailability of cefdinir depends on the formulation used. The estimated bioavailability of cefdinir in the capsule form is approximately 16%-21%, depending on the dose. Absolute bioavailability after the administration of a suspension of cefdinir is 25%.. The Cmax of cefdinir is 1.60 μg/mL after a 300 mg dose with an AUC of 7.05. Cmax is 2.87 μg/mL after a 600 mg dose with an AUC of 11. A meal high in fat can reduce the absorption of cefdinir by up to 15%, however, this is not a cause for clinically significant changes, therefore cefdinir may be taken with or without food. When given with aluminum or magnesium-containing antacids or iron, cefdinir absorption may decrease. It is recommended to allow 2 hours between cefdinir administration and the administration of these agents. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The average volume of distribution of cefdinir in adults is about 0.35 L/kg and 0.67 L/kg in children. Another resource estimates the volume of distribution in adults at 1.56–2.09 L/kg. Cefdinir is found to be distributed in various tissues at clinically effective concentrations. It may be found in the epithelial lining fluid, bronchial mucosa, tonsils, sinuses, skin blister fluid, as well as the middle ear fluid. Third-generation cephalosporins such as cefdinir cross the blood-brain barrier and are found in high concentrations in the cerebrospinal fluid, unlike their first and second generation counterparts. The wide tissue distribution of cefdinir allows it to treat a variety of infections throughout the body. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The plasma protein binding of cefdinir ranges from 60% to approximately 70%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): This drug is not significantly metabolized and its pharmacological actions are mainly attributed to the parent drug. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): This drug is mainly excreted by the kidneys. Dose adjustments may be required for patients with renal impairment or patients on dialysis. Approximately 18.4% of a 300 mg dose of cefdinir was found unchanged in the urine after a 300 mg dose was administered during a pharmacokinetic study of 21 individuals. A large proportion of the administered dose is excreted in the feces, although the majority is found in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The average plasma elimination half-life is about 1.7 hours in adults. In children and healthy infants, plasma elimination half-life ranges from 1.2–1.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The renal clearance in healthy adults in a pharmacokinetic study was 2.0 (± 1.0) mL/min/kg and the clearance in patients with renal failure was lower, decreasing in proportion to the degree of renal impairment. Dose adjustment is required in patients with renal impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information Oral LD50 of cefdinir in the rat is >2000 mg/kg. There are limited data regarding cefdinir overdose in the literature. In studies of rodents, one 5600-mg/kg dose administered orally did not lead to adverse effects. Signs of toxicity and overdose caused by other beta-lactam antibiotics included nausea, vomiting, diarrhea, abdominal pain, and seizures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R,Z)-7-(2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetamido)-8-oxo-3-vinyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (6R,7R)-7-{2-(2-Amino-thiazol-4-yl)-2-[(Z)-hydroxyimino]-acetylamino}-8-oxo-3-vinyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefdinir (common) Cefdinirum (common) CFDN (common)

Do Abciximab and Cefditoren interact?

•Drug A: Abciximab •Drug B: Cefditoren •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefditoren. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of microorganisms in acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin and skin-structure infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefditoren pivoxil is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren. Cefditoren is a cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens. Cefditoren is effective against Staphylococcus aureus (methicillin-susceptible strains, including b-lactamase-producing strains), penicillin-susceptible strains of Staphylococcus aureus and Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae (including b-lactamase-producing strains), Haemophilus parainfluenzae (including b-lactamase-producing strains), Moraxella catarrhalis (including b-lactamase-producing strains), Streptococcus agalactiae, Streptococcus Groups C and G, and Streptococcus, viridans group (penicillin-susceptible and -intermediate strains). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal activity of cefditoren results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefditoren is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, cefditoren pivoxil is absorbed from the gastrointestinal tract and hydrolyzed to cefditoren by esterases. Under fasting conditions, the estimated absolute bioavailability of cefditoren pivoxil is approximately 14%. The absolute bioavailability of cefditoren pivoxil administered with a low fat meal (693 cal, 14 g fat, 122 g carb, 23 g protein) is 16.1 ± 3.0%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 9.3 ± 1.6 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binding of cefditoren to plasma proteins averages 88% from in vitro determinations, and is concentration-independent at cefditoren concentrations ranging from 0.05 to 10 mg/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hydrolysis of cefditoren pivoxil to its active component, cefditoren, results in the formation of pivalate. Cefditoren is not appreciably metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pivalate is mainly eliminated (>99%) through renal excretion, nearly exclusively as pivaloylcarnitine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Mean terminal elimination half-life is 1.6 ± 0.4 hours in young healthy adults. •Clearance (Drug A): No clearance available •Clearance (Drug B): renal cl=4-5 L/h [oral administration] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Information on cefditoren pivoxil overdosage in humans is not available. However, with other b-lactam antibiotics, adverse effects following overdosage have included nausea, vomiting, epigastric distress, diarrhea, and convulsions. In acute animal toxicity studies, cefditoren pivoxil when tested at the limit oral doses of 5100 mg/kg in rats and up to 2000 mg/kg in dogs did not exhibit any health effects of concern. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Spectracef •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed

Do Abciximab and Cefepime interact?

•Drug A: Abciximab •Drug B: Cefepime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefepime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cefepime is indicated for the treatment of pneumonia caused by susceptible bacteria, and for empiric therapy for febrile neutropenic patients. Cefepime is also indicated for the treatment of uncomplicated and complicated urinary tract infections (cUTI) including pyelonephritis, uncomplicated skin and skin structure infections, and complicated intra-abdominal infections (used in combination with metronidazole ) in adults caused by susceptible bacteria. Cefepime is also used in combination with enmetazobactam to treat cUTI. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefepime is a fourth-generation cephalosporin antibiotic. It is active against Gram-negative bacteria such as Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa, and Gram-positive bacteria such as Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pneumoniae, Streptococcus pyogenes and Viridans group streptococci. Compared to third-generation cephalosporins, cefepime has an extended Gram-negative coverage. Whereas other cephalosporins are degraded by plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and not significantly hydrolyzed by these enzymes. Cefepime is also a poor inducer of type 1 beta-lactamases and, therefore, a good alternative against bacteria resistant to third-generation cephalosporins. In animal models of infection, the time that the unbound plasma concentration of cefepime exceeds the minimum inhibitory concentration (MIC) of infecting organisms has been shown to correlate with treatment efficacy. It has been suggested that cefepime can cross the inflamed blood-brain barrier. This, along with its ability to inhibit γ-aminobutyric acid (GABA), could lead to the neurotoxic effects observed in some of the patients treated with cefepime. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefepime is a bactericidal cephalosporin with a mode of action similar to other beta-lactam antibiotics. Cefepime disrupts bacterial cell walls by binding and inhibiting transpeptidases known as penicillin-binding proteins (PBPs), which are enzymes involved in the final stages of peptidoglycan layer synthesis. This results in the lysis and death of susceptible microorganisms. Cefepime has a broad spectrum of in vitro activity that includes both Gram-positive and Gram-negative bacteria. Cefepime has affinity for PBP-3 and PBP-1 in Escherichia coli and Pseudomonas aeruginosa, as well as PBP-2 in E. coli and Enterobacter cloacae. •Absorption (Drug A): No absorption available •Absorption (Drug B): Healthy adult male volunteers (n=9) given a single intravenous infusion of 500 mg, 1 g, and 2 g of cefepime had a corresponding C max of 39.1, 81.7 and 163.9 μg/mL, and a corresponding AUC of 70.8, 148.5 and 284.8 h⋅μg/mL. On the other hand, healthy adult male volunteers given a single intramuscular infusion of 500 mg, 1 g, and 2 g of cefepime had a corresponding C max of 13.9, 29.6 and 57.5 μg/mL, a corresponding AUC of 60, 137 and 262 h⋅μg/mL, and a corresponding T max of 1.4, 1.6 and 1.5 h. A study in healthy adult male volunteers (n=7) that received clinically relevant doses for 9 days suggests that cefepime is not accumulated in the body. Between 250 mg and 2 g, cefepime follows a linear pharmacokinetic model, and the absolute bioavailability of cefepime in pediatric patients (n=8) given an intramuscular dose of 50 mg/kg was 82.3%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The average steady-state volume of distribution of cefepime is 18.0 L. In pediatric patients, the average steady-state volume of distribution is 0.3 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The serum protein binding of cefepime is approximately 20%, independent of its concentration in serum. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Less than 1% of cefepime is metabolized in the liver. Cefepime is metabolized to N-methylpyrrolidine (NMP), which then undergoes rapid oxidation to form NMP-N-oxide, a more stable compound. NMP-N-oxide is the predominant metabolite of cefepime, while NMP and the 7-epimer of cefepime are minor byproducts. It has been suggested that flavin-containing mixed-function oxygenase mediates the oxidation of NMP to NMP-N-oxide. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cefepime is mainly eliminated by the kidneys, and most of it is excreted unchanged. Approximately 85% of cefepime administered to normal subjects is excreted unchanged in urine. Less than 1% of the administered dose is recovered from urine as N-methylpyrrolidine (NMP), 6.8% as NMP-N-oxide, and 2.5% as an epimer. Dosage adjustments are required in patients with renal dysfunction or those undergoing hemodialysis, due to the importance of renal excretion in eliminating cefepime. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Healthy adult male volunteers (n=9) given cefepime had an average half-life of 2 hours. In patients requiring hemodialysis, the average half-life was 13.5 hours, and in patients requiring continuous peritoneal dialysis, the average half-life was 19 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Cefepime has a total body clearance of 120 mL/min in healthy volunteers, and in pediatric patients, the average total body clearance is 3.3 mL/min/kg. In geriatric patients (65 years of age and older) and patients with abnormal renal function, cefepime total body clearance decreases proportionally with creatinine clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Patients who receive a cefepime overdose should be carefully observed and given supportive treatment. In case of renal insufficiency, peritoneal dialysis should not be performed. Instead, hemodialysis is recommended to aid in the removal of cefepime from the body. Some of the symptoms of a cefepime overdose are encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus. In vivo carcinogenicity studies for cefepime have not been performed. In chromosomal aberration studies, this antibiotic was positive for clastogenicity in primary human lymphocytes, but negative in Chinese hamster ovary cells. Cefepime does not exhibit genotoxic effects in in vitro assays, and in vivo assessments of clastogenicity are negative. In rats given up to 1000 mg/kg/day (1.6 times the recommended maximum human dose), cefepime did not have negative effects on fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Exblifep •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-[(1-methylpyrrolidinium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Cefepima (common) Cefepime (common) Cefepimum (common)

Do Abciximab and Cefixime interact?

•Drug A: Abciximab •Drug B: Cefixime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefixime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cefixime is indicated for the treatment of uncomplicated urinary tract infections caused by Escherichia coli and Proteus mirabilis, otitis media caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes, pharyngitis and tonsillitis caused by Streptococcus pyogenes, acute exacerbations of chronic bronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae, and uncomplicated gonorrhea (cervical/urethral) caused by Neisseria gonorrhoeae (penicillinase-and non-penicillinase-producing isolates). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefixime, a broad-spectrum antibiotic, is an orally-active third-generation semisynthetic cephalosporin. Like other cephalosporins, the antibacterial action of cefixime results from inhibition of cell wall synthesis. Also like other cephalosporins, cefixime is stable when in the presence of certain beta-lactamase enzymes, which means certain organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases could be susceptible to cefixime. Use of cefixime can result in hypersensitivity reactions including anaphylactic/anaphylactoid reactions and Clostridium difficile -associated diarrhea (CDAD); it may also be associated with a fall in prothrombin activity. Cefixime doses should be adjusted for patients that have renal impairment and patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD), while patients on dialysis should be monitored while taking cefixime. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal. Cefixime is a cephalosporin and cephalosporins work by using their beta-lactam rings to inhibit bacterial cell wall synthesis by binding to the penicillin-binding proteins transpeptidases on bacteria. The inhibition of synthesis of the bacteria cell wall will cause lysis, particularly in fast growing organisms such as bacteria. Specifically, cephalosporins inhibit penicillin-sensitive enzymes responsible for the final 3D structure of the bacterial cell wall which in turn inhibit bacterial cell wall peptidoglycan synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): With oral administration of cefixime, about 40%-50% is absorbed whether administered with or without food. However, time to maximal absorption is increased approximately 0.8 hours when administered with food. Cefixime administered as an single oral 200 mg tablet in healthy male volunteers had a corresponding C max of 3.25 mg/L and a corresponding T max of 4 hours. Administration of cefixime as a 200 mg oral solution in healthy volunteers results in a C max of 3.22 micrograms/mL, while administration of 200 mg and 400 mg cefixime capsules results in a C max of 2.92 micrograms/mL and 4.84 micrograms/mL, respectively. Administration of cefixime as a 200 mg intravenous solution, a 200 mg oral solution, a 200 mg capsule, and 400 mg capsule results in mean areas under the curve (AUC) of 47.0 μg.h/mL, 26.0 μg.h/mL, 23.6 μg.h/mL, and 39.4 μg.h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Cefixime has a volume of distribution averaging 0.1 L/kg of body weight when administered orally. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 65% of cefixime is bound to serum protein, the serum protein binding is also concentration-independent. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): There is no evidence of metabolism of cefixime in vivo. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 50% of absorbed cefixime is excreted unchanged in the urine in 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Cefixime has a serum half-life averaging 3 to 4 hours in healthy subjects and is independent of dosage form. It has ranged up to 9 hours in some normal volunteers. In individuals with severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life of cefixime increased to an average of 11.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Cefixime administered as an oral suspension with a dose of 8 mg/kg in children with urinary tract infections aged from 6 to 13 years resulted in a mean apparent total clearance rate of 4.74 ml/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information specific to cefixime is not conclusive. Symptoms of overdose can include severe vomiting and seizures. As cefixime is a cephalosporin, it may trigger seizures, particularly in patients with renal impairment when the dosage was not reduced. Additionally, patients experiencing an overdose are at an increased risk of severe adverse effects such as diarrhea, nausea, loose stools, abdominal pain, dyspepsia, and vomiting. In case of overdose, no specific antidote exists and this drug is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis; however, gastric lavage may be indicated. Symptomatic and supportive measures are recommended. Animal studies revealed an oral LD 50 greater than 10g/kg in rats. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Suprax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (−)-cefixim Cefixim (common) Cefixima (common) Céfixime (common) Cefixime (common) Cefixime anhydrous Cefiximum (common)

Do Abciximab and Cefmetazole interact?

•Drug A: Abciximab •Drug B: Cefmetazole •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefmetazole. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of infections caused by susceptible organisms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefmetazole is a second-generation cephalosporin. The cephalosporins are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillins. Cefmetazole is more active than 1st-generation cephalosporins against indole-positive Proteus, Serratia, anaerobic gram-negative bacilli (including B. fragilis ), and some E. coli, Klebsiella, and P. mirabilis, but is less active than cefoxitin or cefotetan against most gram-negative bacilli. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal activity of cefmetazole results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability is approximately 100% following intramuscular injection. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No appreciable metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.50 ±0.14 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD 50 in rats is 3,204 mg/kg. With other b-lactam antibiotics, adverse effects following overdosage have included nausea, vomiting, epigastric distress, diarrhea, and convulsions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7S)-7-({[(cyanomethyl)sulfanyl]acetyl}amino)-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefmetazole (common) Cefmetazolo (common) Cefmetazolum (common)

Do Abciximab and Cefoperazone interact?

•Drug A: Abciximab •Drug B: Cefoperazone •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefoperazone. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of following infections caused by susceptible bacteria: 1) Respiratory tract infections caused by S. pneumoniae, H. influenzae, S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes (Group A beta-hemolytic streptococci), P. aeruginosa, Klebsiella pneumoniae, E. coli, Proteus mirabilis, and Enterobacter species. 2) Peritonitis and other intra-abdominal infections caused by E. coli, P. aeruginosa, and anaerobic gram-negative bacilli (including Bacteroides fragilis ). 3) Bacterial septicemia caused by S. pneumoniae, S. agalactiae, S. aureus, Pseudomonas aeruginosa, E. coli, Klebsiella spp., Klebsiella pneumoniae, Proteus species (indole-positive and indole-negative), Clostridium spp. and anaerobic gram-positive cocci. 4) Infections of the skin and skin structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes, and P. aeruginosa. 5) Pelvic Inflammatory Disease, Endometritis, and Other Infections of the Female Genital Tract caused by N. gonorrhoeae, S. epidermidis, S. agalactiae, E. coli, Clostridium spp., Bacteroides species (including Bacteroides fragilis), and anaerobic gram-positive cocci. 6) Urinary tract infections caused by Escherichia coli and Pseudomonas aeruginosa. 7) Enterococcal Infections. Although cefoperazone has been shown to be clinically effective in the treatment of infections caused by enterococci in cases of peritonitis and other intra-abdominal infections, infections of the skin and skin structures, pelvic inflammatory disease, endometritis and other infections of the female genital tract, and urinary tract infections, the majority of clinical isolates of enterococci tested are not susceptible to cefoperazone but fall just at or in the intermediate zone of susceptibility, and are moderately resistant to cefoperazone. However, in vitro susceptibility testing may not correlate directly with in vivo results. Despite this, cefoperazone therapy has resulted in clinical cures of enterococcal infections, chiefly in polymicrobial infections. Cefoperazone should be used in enterococcal infections with care and at doses that achieve satisfactory serum levels of cefoperazone. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Like all beta-lactam antibiotics, cefoperazone binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The degree of reversible protein binding varies with the serum concentration from 93% at 25 mcg/mL to 90% at 250 mcg/mL and 82% at 500 mcg/mL. Cefotetan is 88% plasma protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No significant quanitity of metabolites have been identified in urine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cefoperazone is excreted mainly in the bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean serum half-life is approximately 2.0 hours, independent of the route of administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R)-7-((R)-2-(4-Ethyl-2,3-dioxo-1-piperazinylcarboxamido)-2-(4-hydroxyphenyl)acetamido)-3-((1-methyl-1H-tetrazol-5-yl)thiomethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-2-carbonsaeure (6R,7R)-7-[[2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefoperazone (common) Cefoperazono (common) Cefoperazonum (common)

Do Abciximab and Cefotaxime interact?

•Drug A: Abciximab •Drug B: Cefotaxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefotaxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used to treat gonorrhoea, meningitis, and severe infections including infections of the kidney (pyelonephritis) and urinary system. Also used before an operation to prevent infection after surgery. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefotaxime is a third generation intravenous cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity against Pseudomonas aeruginosa. Cefotaxime works by inhibiting bacterial cell wall biosynthesis. A positive feature of cefotaxime is that it display a resistance to penicillinases and is useful to treat infections that are resistant to penicillin derivatives. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal activity of cefotaxime results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefotaxime shows high affinity for penicillin-binding proteins in the cell wall including PBP Ib and PBP III. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed following intramuscular injection. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M2 and M3) account for about 20-25%. They lack bactericidal activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Approximately 1 hour. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adverse effects following overdosage include nausea, vomiting, epigastric distress, diarrhea, and convulsions. Oral rat LD 50 is over 20,000 mg/kg while intravenous rat LD 50 is over 7,000 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Claforan •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R,Z)-3-(acetoxymethyl)-7-(2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (6R,7R)-3-(acetoxymethyl)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (6R,7R)-3-Acetoxymethyl-7-{2-(2-amino-thiazol-4-yl)-2-[(Z)-methoxyimino]-acetylamino}-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefotaxim (common) Cefotaxima (common) Céfotaxime (common) Cefotaxime (common) Cefotaximum (common) Cephotaxime (common)

Do Abciximab and Cefotetan interact?

•Drug A: Abciximab •Drug B: Cefotetan •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefotetan. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For prophylaxis and treatment of bacterial infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefotetan is a semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal action of cefotetan results from inhibition of cell wall synthesis by binding and inhibiting the bacterial penicillin binding proteins which help in the cell wall biosynthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 10.4 L [elderly patients (greater than 65 years) with normal renal function] 10.3 L [healthy volunteers (aged 25 to 28 years)] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Cefotetan is 88% plasma protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No active metabolites of cefotetan have been detected; however, small amounts (less than 7%) of cefotetan in plasma and urine may be converted to its tautomer, which has antimicrobial activity similar to the parent drug. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No active metabolites of cefotetan have been detected; however, small amounts (less than 7%) of cefotetan in plasma and urine may be converted to its tautomer, which has antimicrobial activity similar to the parent drug. In normal patients, from 51% to 81% of an administered dose of Cefotetan is excreted unchanged by the kidneys over a 24 hour period, which results in high and prolonged urinary concentrations. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In volunteers with reduced renal function, the plasma half-life of cefotetan is prolonged •Clearance (Drug A): No clearance available •Clearance (Drug B): 1.8 +/- 0.1 L/h [elderly patients with normal renal function (.65 years)] 1.8 +/- 0.3 L/h [healthy volunteers (aged 25 to 28 years)] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cefotan •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7S)-7-(4-(carbamoylcarboxymethylene)-1,3-dithiethane-2-carboxamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5- yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2- carboxylic acid Cefotetan (common) Cefotetanum (common)

Do Abciximab and Cefotiam interact?

•Drug A: Abciximab •Drug B: Cefotiam •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefotiam. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of severe infections caused by susceptible bacteria. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefotiam is a third generation beta-lactam cephalosporin antibiotic that works by inhibiting bacterial cell wall biosynthesis. It is a broad spectrum antibiotic that is effective against Gram positive and Gram negative bacteria. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal activity of cefotiam results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed following intramuscular injection. Bioavailability is 60% following intramuscular injection. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 40% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Approximately 1 hour. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adverse effects following overdosage include nausea, vomiting, epigastric distress, diarrhea, and convulsions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7R)-7-[2-(2-Amino-thiazol-4-yl)-acetylamino]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefotiam (common) Cefotiamum (common) CTM

Do Abciximab and Cefoxitin interact?

•Drug A: Abciximab •Drug B: Cefoxitin •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefoxitin. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of serious infections caused by susceptible strains microorganisms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefoxitin is a cephamycin antibiotic often grouped with the second-generation cephalosporins. It is active against a broad range of gram-negative bacteria including anaerobes. The methoxy group in the 7a position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bactericidal action of cefoxitin results from inhibition of cell wall synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Minimal (approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period, resulting in high urinary concentrations. Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life after an intravenous dose is 41 to 59 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The acute intravenous LD50 in the adult female mouse and rabbit was about 8.0 g/kg and greater than 1.0 g/kg, respectively. The acute intraperitoneal LD50 in the adult rat was greater than 10.0 g/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (6R,7S)-4-[(carbamoyloxy)methyl]-7-methoxy-8-oxo-7-[(thiophen-2-enyl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Cefoxitin (common) Cefoxitina (common) Cefoxitine (common) Cefoxitinum (common) Ceftoxitin (common) Cephoxitin (common) CFX Rephoxitin (common)

Do Abciximab and Cefpirome interact?

•Drug A: Abciximab •Drug B: Cefpirome •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefpirome. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •References: 1. Aria N, Kauffman CL: Important drug interactions and reactions in dermatology. Dermatol Clin. 2003 Jan;21(1):207-15, ix. [https://go.drugbank.com/articles/A39953] •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): No indication available •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed