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Does Abciximab and Methyl salicylate interact?

•Drug A: Abciximab •Drug B: Methyl salicylate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Methyl salicylate 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. •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): Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine. •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): Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth. •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): Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves. This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2. •Absorption (Drug A): No absorption available •Absorption (Drug B): Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Degree of albumin binding depends on the plasma concentration of the compound •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): Minor metabolism may occur in various tissues but hepatic metabolism constitutes the majority of metabolic processes of absorbed methyl salicylate. It is mainly hydrolyzed to salicylic acid via hepatic esterase enzymes. Conjugation with glycine forms salicyluric acid and conjugation with glucuronic forms ester or acyl and ether or phenolic glucuronide, which are the three main metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%). •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 plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dendracin Neurodendraxcin, Flexall Ultra Plus, Lidopro, Listerine Antiseptic, Medi-derm, Medi-derm With Lidocaine, Medrox, Mentholatum, Rematex, Salonpas Pain Relieving Patch, Tiger Balm, Xoten-C •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 2-(Methoxycarbonyl)phenol 2-Carbomethoxyphenol Betula oil Gaultheria oil Methyl 2-hydroxybenzoate Methyl o-hydroxybenzoate Methyl salicylate Natural wintergreen oil Oil of wintergreen Spicewood Oil Sweet birch oil Teaberry oil •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methyl salicylate is a topical counter-irritant used for the symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons.

.Concurrent use of salicylates and anticoagulants may lead to increased anticoagulant activity and therefore an increased risk of bleeding, due to additive anticoagulant effects. The severity of the interaction is moderate.

Question: Does Abciximab and Methyl salicylate interact? Information: •Drug A: Abciximab •Drug B: Methyl salicylate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Methyl salicylate 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. •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): Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine. •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): Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth. •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): Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves. This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2. •Absorption (Drug A): No absorption available •Absorption (Drug B): Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Degree of albumin binding depends on the plasma concentration of the compound •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): Minor metabolism may occur in various tissues but hepatic metabolism constitutes the majority of metabolic processes of absorbed methyl salicylate. It is mainly hydrolyzed to salicylic acid via hepatic esterase enzymes. Conjugation with glycine forms salicyluric acid and conjugation with glucuronic forms ester or acyl and ether or phenolic glucuronide, which are the three main metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%). •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 plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dendracin Neurodendraxcin, Flexall Ultra Plus, Lidopro, Listerine Antiseptic, Medi-derm, Medi-derm With Lidocaine, Medrox, Mentholatum, Rematex, Salonpas Pain Relieving Patch, Tiger Balm, Xoten-C •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 2-(Methoxycarbonyl)phenol 2-Carbomethoxyphenol Betula oil Gaultheria oil Methyl 2-hydroxybenzoate Methyl o-hydroxybenzoate Methyl salicylate Natural wintergreen oil Oil of wintergreen Spicewood Oil Sweet birch oil Teaberry oil •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methyl salicylate is a topical counter-irritant used for the symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons. Output: .Concurrent use of salicylates and anticoagulants may lead to increased anticoagulant activity and therefore an increased risk of bleeding, due to additive anticoagulant effects. The severity of the interaction is moderate.

Does Abciximab and Methylene blue interact?

•Drug A: Abciximab •Drug B: Methylene blue •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Methylene blue is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 pediatric and adult patients with acquired methemoglobinemia. Other clinical applications of methylene blue include improvement of hypotension associated with various clinical states, an antiseptic in urinary tract infections, treatment of hypoxia and hyperdynamic circulation in cirrhosis of liver and severe hepatopulmonary syndrome, and treatment of ifofosamide induced neurotoxicity. •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): Main mechanism of action involves inhibition of nitric oxide synthase and guanylate cyclase. In Alzheimers Disease: a mechanistic study found that methylene blue oxidizes cysteine sulfhydryl groups on tau to keep tau monomeric. One preclinical treatment study in tauopathy mice reported anti-inflammatory or neuroprotective effects mediated by the Nrf2/antioxidant response element (ARE); another reported insoluble tau reduction and a learning and memory benefit when given early. In Methemoglobinemia: Methylene Blue acts by reacting within RBC to form leukomethylene blue, which is a reducing agent of oxidized hemoglobin converting the ferric ion (fe+++) back to its oxygen-carrying ferrous state(fe++). As antimalarial agent: Methylene Blue, a specific inhibitor of P.falciparum glutathione reductase has the potential to reverse CQ resistance and it prevents the polymerization of haem into haemozoin similar to 4-amino-quinoline antimalarials. For ifosfamide induced neurotoxicity: Methylene blue functions as an alternate electron acceptor. It acts to reverse the NADH inhibition caused by gluconeogenesis in the liver while blocking the transformation of chloroethylamine into chloroacetaldehyde. In addition, it inhibits various amine oxidase activities, which also prevents the formation of chloroacetaldehyde. •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 mg/kg (in rats). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Methylene blue was reported to bind strongly to rabbit plasma (71–77% of bound drug). •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): Following distribution into tissues, rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excreted in urine and bile. About 75% of an oral dose excreted in urine, primarily as stabilized colorless leukomethylene blue. •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): 5–6.5 hours (after IV dose). •Clearance (Drug A): No clearance available •Clearance (Drug B): 3.0 ± 0.7 L/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 = 1180 mg/kg ( Rat ). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hyophen, Phosphasal, Provayblue, Proveblue, Urelle, Uribel, Urimar Reformulated Oct 2013, Urin DS, Urogesic Blue Reformulated Apr 2012, Ustell •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Azul de metileno Basic Blue 9 C.I. basic blue 9 Chlorure de méthylthioninium Cloruro de metiltioninio Methylene blue Methylenium ceruleum Methylthioninii chloridum Methylthioninium chloride •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methylene blue is an oxidation-reduction agent used for the treatment of pediatric and adult patients with acquired methemoglobinemia.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Methylene blue interact? Information: •Drug A: Abciximab •Drug B: Methylene blue •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Methylene blue is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 pediatric and adult patients with acquired methemoglobinemia. Other clinical applications of methylene blue include improvement of hypotension associated with various clinical states, an antiseptic in urinary tract infections, treatment of hypoxia and hyperdynamic circulation in cirrhosis of liver and severe hepatopulmonary syndrome, and treatment of ifofosamide induced neurotoxicity. •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): Main mechanism of action involves inhibition of nitric oxide synthase and guanylate cyclase. In Alzheimers Disease: a mechanistic study found that methylene blue oxidizes cysteine sulfhydryl groups on tau to keep tau monomeric. One preclinical treatment study in tauopathy mice reported anti-inflammatory or neuroprotective effects mediated by the Nrf2/antioxidant response element (ARE); another reported insoluble tau reduction and a learning and memory benefit when given early. In Methemoglobinemia: Methylene Blue acts by reacting within RBC to form leukomethylene blue, which is a reducing agent of oxidized hemoglobin converting the ferric ion (fe+++) back to its oxygen-carrying ferrous state(fe++). As antimalarial agent: Methylene Blue, a specific inhibitor of P.falciparum glutathione reductase has the potential to reverse CQ resistance and it prevents the polymerization of haem into haemozoin similar to 4-amino-quinoline antimalarials. For ifosfamide induced neurotoxicity: Methylene blue functions as an alternate electron acceptor. It acts to reverse the NADH inhibition caused by gluconeogenesis in the liver while blocking the transformation of chloroethylamine into chloroacetaldehyde. In addition, it inhibits various amine oxidase activities, which also prevents the formation of chloroacetaldehyde. •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 mg/kg (in rats). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Methylene blue was reported to bind strongly to rabbit plasma (71–77% of bound drug). •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): Following distribution into tissues, rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excreted in urine and bile. About 75% of an oral dose excreted in urine, primarily as stabilized colorless leukomethylene blue. •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): 5–6.5 hours (after IV dose). •Clearance (Drug A): No clearance available •Clearance (Drug B): 3.0 ± 0.7 L/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 = 1180 mg/kg ( Rat ). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hyophen, Phosphasal, Provayblue, Proveblue, Urelle, Uribel, Urimar Reformulated Oct 2013, Urin DS, Urogesic Blue Reformulated Apr 2012, Ustell •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Azul de metileno Basic Blue 9 C.I. basic blue 9 Chlorure de méthylthioninium Cloruro de metiltioninio Methylene blue Methylenium ceruleum Methylthioninii chloridum Methylthioninium chloride •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methylene blue is an oxidation-reduction agent used for the treatment of pediatric and adult patients with acquired methemoglobinemia. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Mifepristone interact?

•Drug A: Abciximab •Drug B: Mifepristone •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Mifepristone is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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 medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful 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): Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol. •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 anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of a 20 mg oral dose is 69% •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): 98% (bound to plasma proteins, albumin and a 1-acid glycoprotein) •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. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Fecal: 83%; Renal: 9%. •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): 18 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Korlym, Mifegymiso •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mifepristone is a cortisol receptor blocker used to treat Cushing's syndrome, and to terminate pregnancies up to 70 days gestation.

Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Question: Does Abciximab and Mifepristone interact? Information: •Drug A: Abciximab •Drug B: Mifepristone •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Mifepristone is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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 medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful 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): Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol. •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 anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of a 20 mg oral dose is 69% •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): 98% (bound to plasma proteins, albumin and a 1-acid glycoprotein) •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. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Fecal: 83%; Renal: 9%. •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): 18 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Korlym, Mifegymiso •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mifepristone is a cortisol receptor blocker used to treat Cushing's syndrome, and to terminate pregnancies up to 70 days gestation. Output: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Does Abciximab and Milnacipran interact?

•Drug A: Abciximab •Drug B: Milnacipran •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Milnacipran is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia in patients that are 18 years old or above. While milnacipran may be used for the treatment of major depressive disorder (MDD), it is only recommended in adult patients who are 18 years old or above due to an increased risk for suicidal ideation, thinking, and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders. Some regional prescribing information notes that the use of the medication is specifically for the short-term symptomatic relief of MDD. Nevertheless, it is important to note that the regulatory approval of and/or indications listed here for milnacipran may or may not exist and/or vary greatly between regions and nations. •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): When utilized to treat fibromyalgia, the effect of milnacipran on the QTcF interval in patients was measured in a double-blind placebo-and positive-controlled parallel study in 88 healthy subjects using three to six times the recommended therapeutic dose for fibromyalgia at 600 mg/day. After baseline and placebo adjustment, the maximum mean QTcF change was 8 ms - an increase that is generally not considered to be clinically significant. Conversely, when used for treating major depressive disorder (MDD), non-clinical studies have shown that levomilnacipran binds with high affinity to the norepinephrine (NE) and serotonin (5-HT) transporters (Ki = 71-91 nM and 11 nM respectively at human transporters). Levomilnacipran inhibits the uptake of both NE and 5-HT in vitro and in vivo; preferentially inhibiting reuptake of NE over 5-HT by approximately 2-fold. Levomilnacipran does not directly affect the uptake of dopamine or other neurotransmitters. Levomilnacipran has no significant affinity for serotonergic (5-HT1-7), α- and β-adrenergic, muscarinic (M1-5), histamine (H1-4), dopamine (D1-5), opiate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors in vitro. Levomilnacipran has no significant affinity for Ca++, K+, Na+, and Cl– channels and does not inhibit the activity of human monoamine oxidases (MAO-A and MAO-B) or acetylcholinesterase. Moreover, in ECG studies with levomilnacipran used to treat MDD, although no clinically significant changes in QTcF interval (QTcF=QT/RR0.33) were noted, it appears that the agent can cause increases in heart rate and blood pressure. In particular, it appears that the maximum therapeutic dose of levomilnacipran at 120 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 20.2 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 3.8 to 7.2 mmHg and 6.1 to 8.1 mmHg, respectively. Alternatively, a supratherapeutic dose of 300 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 22.1 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 5.4 to 7.9 mmHg and 7.9 to 10.6 mmHg, respectively. •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 dual ability for milnacipran to inhibit the reuptake of both serotonin (5HT) and norepinephrine (NE) facilitates its treatment of both fibromyalgia and major depressive disorder (MDD). In particular, it is generally believed that 5HT and NE participate in the modulation of endogenous analgesic mechanisms by way of the descending inhibitory pain pathways in the brain and spinal cord. Although the specific mechanism of action remains unclear, some studies have proposed that low levels of 5HT may be associated with increased sensitivity to pain - a condition that could subsequently be improved by milnacipran's capacity to enhance the presence of 5HT by inhibiting its reuptake via serotonin transporters at synaptic clefts. Furthermore, in the CNS it is also generally believed that NE released from descending pathways can mitigate pain sensations via eliciting inhibitory effects on alpha-2A-adrenoceptors on central terminals of primary afferent nociceptors, by direct alpha-2-adrenergic action on pain-relay neurons, and by alpha-1-adrenoceptor-mediated activation of inhibitory interneurons. Such NE pain mitigation is consequently also enhanced by milnacipran's ability to enhance the presence of NE by inhibiting its reuptake via norepinephrine transporters at synaptic clefts. Concurrently, milnacipran's capacity to inhibit the reuptake of both 5HT and NE also facilitates its treatment of MDD. Given the monoamine hypothesis' assertion that decreased 5HT can be associated with anxiety, obsessions, compulsions, and decreased NE can result in lowered alertness, energy, attention, and general interest in life, it is proposed that milnacipran's basic activities as a serotonin and norepinephrine reuptake inhibitor could assist in treating such symptoms of MDD by increasing the presence of both 5HT and NE in the body by inhibiting their reuptake. •Absorption (Drug A): No absorption available •Absorption (Drug B): Racemic milnacipram demonstrates an absolute bioavailability of about 85-90% following oral administration. Maximum concentrations of the racemic agent are reached within 2-4 hours after oral dosing, and steady-state levels are obtained by 36-48 hours. Conversely, the relative bioavailability of levomilnacipram has been documented as 92%. The median time to peak concentration Tmax for levomilnacipram is about 6-8 hours after oral administration. After daily dosing of levomilnacipram 120 mg, the mean Cmax value is 341 ng/mL, and the mean steady-state AUC value is 5196 ng.h/mL. In general, the administration of either racemic milnacipram or levomilnacipram with food does not affect the medication's oral bioavailability. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution recorded for racemic milnacipran following a single intravenous dose to healthy subjects was approximately 400 L. Alternatively, levomilnacipran is widely distributed with an apparent volume of distribution of 387-473 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding determined for racemic milnacipran is 13%. Conversely, the plasma protein binding documented for levomilnacipran is 22% over a concentration range of 10 to 1000 ng/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): It has been determined that levomilnacipran undergoes desethylation and hydroxylation to generate desethyl levomilnacipran and p-hydroxy-levomilnacipran, respectively. Both oxidative metabolites undergo further conjugation with glucuronide to form the conjugate milnacipran carbamoyl-O-glucuronide. The desethylation is catalyzed primarily by CYP3A4 with minor contribution by CYP2C8, 2C19, 2D6, and 2J2. Additionally, it is the general understanding that there is no interconversion between the enantiomers of milnacipran in the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Levomilnacipran and its metabolites are eliminated primarily by renal excretion. Following oral administration of 14C-levomilnacipran solution, approximately 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran is the major metabolite excreted in the urine and accounted for approximately 18% of the dose. Other identifiable metabolites excreted in the urine are levomilnacipran glucuronide (4%), desethyl levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxy levomilnacipran (1%). •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 elimination half-life documented for racemic milnacipran is approximately 6-8 hours, where d-milnacipran has a longer elimination half-life of 8-10 hours compared to that of the l-enantionmer at 4-6 hours. Alternatively, the terminal elimination half-life determined specifically for levomilnacipran formulations is about 12 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total plasma clearance determined for milnacipran is approximately 40 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited clinical experience with milnacipran overdose in humans. In clinical trials, cases of acute ingestions up to 1000 mg daily were reported with none being fatal. In postmarketing experience, fatal outcomes have been reported for acute overdoses primarily involving multiple drugs but also with milnacipran only. The most common signs and symptoms of overdose included increased blood pressure, cardio-respiratory arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes. There are no adequate and well-controlled studies in pregnant women. In fact, milnacipram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SNRI class drugs like milnacipran or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. The effect of milnacipran on labor and delivery in humans is unknown. Milnacipran should be used during labor and delivery only if the potential benefits outweigh the potential risks. There are no adequate and well-controlled studies in nursing mothers. It is not known if milnacipran is excreted in human milk. Studies have shown that levomilnacipran is excreted into the milk of lactating rats. Subsequently, possible excretion into human milk possesses the potential for serious adverse reactions in nursing infants. As a consequence, breastfeeding by women treated with levomilnacipran should be considered only if the potential benefits outweigh the potential risks to the child. Milnacipran is not indicated for use in children under 18 years of age due to concerns over the potential for agitation-type emotional and behavioral changes, as well as suicidal ideation and/or behavior. SNRIs like milnacipran have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. Levomilnacipran was not mutagenic when evaluated in vitro in a bacterial mutagenicity study (Ames test) and not genotoxic in a mouse lymphoma study. It was not clastogenic in an in vivo micronucleus assay in rats. The potential effects of levomilnacipran on gonadal function, mating behavior, reproductive performance and early pregnancy were evaluated in rats at oral doses of 0, 10, 30, or 100 mg/kg/day. The NOAEL was 100 mg/kg/day based on reductions in body weight gain and food consumption. There were no levomilnacipran effects on male and female fertility parameters. In the rat and rabbit embryo/fetal development studies, decreases in maternal body weight gain and food consumption were noted. In the fetuses, increases in the incidence of ossification anomalies were noted but were of no toxicological significance. In both species, the NOAEL was determined to be 100 mg/kg/day, a dose which represents a rat or rabbit animal-to-human exposure margin of 9-fold and 4-fold, respectively relative to the human exposure from 120 mg/day of levomilnacipran. Material safety data for milnacipran has documented the LD50 oral value in the rat model as being 213 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Savella •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Midalcipran Milnacipran Milnacipranum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of fibromyalgia and a short-term treatment of major depressive disorder.

It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Milnacipran interact? Information: •Drug A: Abciximab •Drug B: Milnacipran •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Milnacipran is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia in patients that are 18 years old or above. While milnacipran may be used for the treatment of major depressive disorder (MDD), it is only recommended in adult patients who are 18 years old or above due to an increased risk for suicidal ideation, thinking, and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders. Some regional prescribing information notes that the use of the medication is specifically for the short-term symptomatic relief of MDD. Nevertheless, it is important to note that the regulatory approval of and/or indications listed here for milnacipran may or may not exist and/or vary greatly between regions and nations. •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): When utilized to treat fibromyalgia, the effect of milnacipran on the QTcF interval in patients was measured in a double-blind placebo-and positive-controlled parallel study in 88 healthy subjects using three to six times the recommended therapeutic dose for fibromyalgia at 600 mg/day. After baseline and placebo adjustment, the maximum mean QTcF change was 8 ms - an increase that is generally not considered to be clinically significant. Conversely, when used for treating major depressive disorder (MDD), non-clinical studies have shown that levomilnacipran binds with high affinity to the norepinephrine (NE) and serotonin (5-HT) transporters (Ki = 71-91 nM and 11 nM respectively at human transporters). Levomilnacipran inhibits the uptake of both NE and 5-HT in vitro and in vivo; preferentially inhibiting reuptake of NE over 5-HT by approximately 2-fold. Levomilnacipran does not directly affect the uptake of dopamine or other neurotransmitters. Levomilnacipran has no significant affinity for serotonergic (5-HT1-7), α- and β-adrenergic, muscarinic (M1-5), histamine (H1-4), dopamine (D1-5), opiate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors in vitro. Levomilnacipran has no significant affinity for Ca++, K+, Na+, and Cl– channels and does not inhibit the activity of human monoamine oxidases (MAO-A and MAO-B) or acetylcholinesterase. Moreover, in ECG studies with levomilnacipran used to treat MDD, although no clinically significant changes in QTcF interval (QTcF=QT/RR0.33) were noted, it appears that the agent can cause increases in heart rate and blood pressure. In particular, it appears that the maximum therapeutic dose of levomilnacipran at 120 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 20.2 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 3.8 to 7.2 mmHg and 6.1 to 8.1 mmHg, respectively. Alternatively, a supratherapeutic dose of 300 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 22.1 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 5.4 to 7.9 mmHg and 7.9 to 10.6 mmHg, respectively. •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 dual ability for milnacipran to inhibit the reuptake of both serotonin (5HT) and norepinephrine (NE) facilitates its treatment of both fibromyalgia and major depressive disorder (MDD). In particular, it is generally believed that 5HT and NE participate in the modulation of endogenous analgesic mechanisms by way of the descending inhibitory pain pathways in the brain and spinal cord. Although the specific mechanism of action remains unclear, some studies have proposed that low levels of 5HT may be associated with increased sensitivity to pain - a condition that could subsequently be improved by milnacipran's capacity to enhance the presence of 5HT by inhibiting its reuptake via serotonin transporters at synaptic clefts. Furthermore, in the CNS it is also generally believed that NE released from descending pathways can mitigate pain sensations via eliciting inhibitory effects on alpha-2A-adrenoceptors on central terminals of primary afferent nociceptors, by direct alpha-2-adrenergic action on pain-relay neurons, and by alpha-1-adrenoceptor-mediated activation of inhibitory interneurons. Such NE pain mitigation is consequently also enhanced by milnacipran's ability to enhance the presence of NE by inhibiting its reuptake via norepinephrine transporters at synaptic clefts. Concurrently, milnacipran's capacity to inhibit the reuptake of both 5HT and NE also facilitates its treatment of MDD. Given the monoamine hypothesis' assertion that decreased 5HT can be associated with anxiety, obsessions, compulsions, and decreased NE can result in lowered alertness, energy, attention, and general interest in life, it is proposed that milnacipran's basic activities as a serotonin and norepinephrine reuptake inhibitor could assist in treating such symptoms of MDD by increasing the presence of both 5HT and NE in the body by inhibiting their reuptake. •Absorption (Drug A): No absorption available •Absorption (Drug B): Racemic milnacipram demonstrates an absolute bioavailability of about 85-90% following oral administration. Maximum concentrations of the racemic agent are reached within 2-4 hours after oral dosing, and steady-state levels are obtained by 36-48 hours. Conversely, the relative bioavailability of levomilnacipram has been documented as 92%. The median time to peak concentration Tmax for levomilnacipram is about 6-8 hours after oral administration. After daily dosing of levomilnacipram 120 mg, the mean Cmax value is 341 ng/mL, and the mean steady-state AUC value is 5196 ng.h/mL. In general, the administration of either racemic milnacipram or levomilnacipram with food does not affect the medication's oral bioavailability. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution recorded for racemic milnacipran following a single intravenous dose to healthy subjects was approximately 400 L. Alternatively, levomilnacipran is widely distributed with an apparent volume of distribution of 387-473 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding determined for racemic milnacipran is 13%. Conversely, the plasma protein binding documented for levomilnacipran is 22% over a concentration range of 10 to 1000 ng/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): It has been determined that levomilnacipran undergoes desethylation and hydroxylation to generate desethyl levomilnacipran and p-hydroxy-levomilnacipran, respectively. Both oxidative metabolites undergo further conjugation with glucuronide to form the conjugate milnacipran carbamoyl-O-glucuronide. The desethylation is catalyzed primarily by CYP3A4 with minor contribution by CYP2C8, 2C19, 2D6, and 2J2. Additionally, it is the general understanding that there is no interconversion between the enantiomers of milnacipran in the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Levomilnacipran and its metabolites are eliminated primarily by renal excretion. Following oral administration of 14C-levomilnacipran solution, approximately 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran is the major metabolite excreted in the urine and accounted for approximately 18% of the dose. Other identifiable metabolites excreted in the urine are levomilnacipran glucuronide (4%), desethyl levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxy levomilnacipran (1%). •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 elimination half-life documented for racemic milnacipran is approximately 6-8 hours, where d-milnacipran has a longer elimination half-life of 8-10 hours compared to that of the l-enantionmer at 4-6 hours. Alternatively, the terminal elimination half-life determined specifically for levomilnacipran formulations is about 12 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total plasma clearance determined for milnacipran is approximately 40 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited clinical experience with milnacipran overdose in humans. In clinical trials, cases of acute ingestions up to 1000 mg daily were reported with none being fatal. In postmarketing experience, fatal outcomes have been reported for acute overdoses primarily involving multiple drugs but also with milnacipran only. The most common signs and symptoms of overdose included increased blood pressure, cardio-respiratory arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes. There are no adequate and well-controlled studies in pregnant women. In fact, milnacipram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SNRI class drugs like milnacipran or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. The effect of milnacipran on labor and delivery in humans is unknown. Milnacipran should be used during labor and delivery only if the potential benefits outweigh the potential risks. There are no adequate and well-controlled studies in nursing mothers. It is not known if milnacipran is excreted in human milk. Studies have shown that levomilnacipran is excreted into the milk of lactating rats. Subsequently, possible excretion into human milk possesses the potential for serious adverse reactions in nursing infants. As a consequence, breastfeeding by women treated with levomilnacipran should be considered only if the potential benefits outweigh the potential risks to the child. Milnacipran is not indicated for use in children under 18 years of age due to concerns over the potential for agitation-type emotional and behavioral changes, as well as suicidal ideation and/or behavior. SNRIs like milnacipran have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. Levomilnacipran was not mutagenic when evaluated in vitro in a bacterial mutagenicity study (Ames test) and not genotoxic in a mouse lymphoma study. It was not clastogenic in an in vivo micronucleus assay in rats. The potential effects of levomilnacipran on gonadal function, mating behavior, reproductive performance and early pregnancy were evaluated in rats at oral doses of 0, 10, 30, or 100 mg/kg/day. The NOAEL was 100 mg/kg/day based on reductions in body weight gain and food consumption. There were no levomilnacipran effects on male and female fertility parameters. In the rat and rabbit embryo/fetal development studies, decreases in maternal body weight gain and food consumption were noted. In the fetuses, increases in the incidence of ossification anomalies were noted but were of no toxicological significance. In both species, the NOAEL was determined to be 100 mg/kg/day, a dose which represents a rat or rabbit animal-to-human exposure margin of 9-fold and 4-fold, respectively relative to the human exposure from 120 mg/day of levomilnacipran. Material safety data for milnacipran has documented the LD50 oral value in the rat model as being 213 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Savella •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Midalcipran Milnacipran Milnacipranum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of fibromyalgia and a short-term treatment of major depressive disorder. Output: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Mirvetuximab soravtansine interact?

•Drug A: Abciximab •Drug B: Mirvetuximab soravtansine •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Mirvetuximab Soravtansine. •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 . •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): Mirvetuximab soravtansine is indicated for the treatment of adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Patients are selected for therapy based on an FDA-approved test. •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): There is an exposure-response relationship for mirvetuximab soravtansine-gynx. The increased exposure of mirvetuximab soravtansine-gynx was associated with a higher incidence of ocular adverse reactions and peripheral neuropathy grade 2 or higher. Mirvetuximab soravtansine-gynx did not cause large QTc increases (>10 msec) at the approved recommended dose. The use of mirvetuximab soravtansine-gynx has been associated with severe ocular adverse reactions, such as visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis. Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, as well as peripheral neuropathy, may also occur in patients treated with mirvetuximab soravtansine-gynx. Since mirvetuximab soravtansine-gynx contains DM4, a genotoxic compound, the use of this drug may cause embryo-fetal harm in pregnant women. •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): Mirvetuximab soravtansine-gynx is an antibody-drug conjugate (ADC) formed by three components: a chimeric IgG1 antibody against folate receptor alpha (FRα), the small molecule anti-tubulin agent DM4 (a maytansine derivative) and a sulfo-SPDB linker that joins DM4 to the mirvetuximab antibody. FRα is expressed on the cell surface and has a restricted distribution in normal tissues. However, abnormally high levels of FRα have been detected in serous and endometrioid epithelial ovarian cancer, endometrial adenocarcinoma, and non–small cell lung cancer of the adenocarcinoma subtype. In ovarian cancer patients, its expression is maintained in metastatic foci and recurrent carcinomas. Mirvetuximab soravtansine-gynx binds with high affinity to FRα and is then internalized through antigen-mediated endocytosis. Inside FRα-expressing tumor cells, DM4 is released via proteolytic cleavage. DM4 disrupts the microtubule network within the cell, leading to cell cycle arrest and apoptosis. Since DM4 is electrically neutral and lipophilic, it is able to diffuse across cell membranes and lead to the death of neighboring antigen-negative cells. This "bystander effect" is an important component of mirvetuximab soravtansine-gynx, allowing it to exert a cytotoxic effect even in cells that do not express FRα on their surface. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetic parameters of mirvetuximab soravtansine-gynx were evaluated in patients given a 6 mg/kg adjusted ideal body weight (AIBW) dose administered during the first treatment cycle (3 weeks). Mirvetuximab Soravtansine-gynx, the unconjugated DM4, and S-methyl-DM4 had a corresponding C max of 137.3 µg/mL, 4.11 ng/mL and 6.98 ng/mL, and a corresponding AUC tau of 20.65 h⋅mg/mL, 530 h⋅ng/mL and 1848 h⋅ng/mL. The peak concentration of mirvetuximab soravtansine-gynx was observed near the end of intravenous infusion, while DM4 and S-methyl-DM4 concentrations peaked 2 and 3 days after mirvetuximab soravtansine-gynx administration. After one treatment cycle, mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 reached steady-state concentrations. Following the repeated administration of mirvetuximab soravtansine-gynx, the accumulation of mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 were minimal. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mirvetuximab soravtansine-gynx has a steady-state volume of distribution of 2.63 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Based on in vitro studies, the plasma protein binding of the mirvetuximab soravtansine-gynx component DM4 and its metabolite S-methyl DM4 is higher than 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): After mirvetuximab soravtansine-gynx binds the folate receptor alpha (FRα) and is internalized via antigen-mediated endocytosis, the DM4 agent is released via proteolytic cleavage. The monoclonal antibody portion of this drug is expected to be metabolized by catabolic pathways into small peptides. Unconjugated DM4 is reduced and S-methylated to form S-methyl-DM4. DM4 and S-methyl-DM4 are the main circulating metabolites of mirvetuximab soravtansine-gynx and correspond to approximately 0.4% and 1.4% of mirvetuximab soravtansine-gynx AUCs. Both DM4 and S-methyl-DM4 undergo metabolism by CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mirvetuximab soravtansine-gynx metabolites S-methyl DM4 and DM4-sulfo-SPDB-lysine were detected in urine within 24 hours of infusion as the main 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): After the first dose, the geometric mean terminal phase half-life of mirvetuximab soravtansine-gynx is 4.8 days. The geometric mean terminal phase half-lives of the unconjugated DM4 and its metabolite, S-methyl-DM4, are 2.8 and 5.0 days, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total plasma clearance of mirvetuximab soravtansine-gynx is 18.9 mL/hour. The unconjugated DM4 has a total plasma clearance of 13.8 L/hour, while its metabolite, S-methyl-DM4, has a total plasma clearance of 4.3 L/hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding mirvetuximab soravtansine-gynx is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as ocular toxicity, pneumonitis and peripheral neuropathy. Symptomatic and supportive measures are recommended. Carcinogenicity studies with mirvetuximab soravtansine-gynx or DM4 have not been performed. An in vivo rat bone marrow micronucleus study showed that DM4 and its metabolite, S-methyl DM4, are clastogenic. DM4 and S-methyl DM4 did not show evidence of mutagenicity in the bacterial reverse mutation (Ames) assay. The effects of mirvetuximab soravtansine-gynx or DM4 on fertility studies have not been evaluated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Elahere •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Mirvetuximab soravtansine Mirvetuximab soravtansine-gynx •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mirvetuximab soravtansine is a folate receptor alpha-directed antibody and microtubule inhibitor conjugate used to treat folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Mirvetuximab soravtansine interact? Information: •Drug A: Abciximab •Drug B: Mirvetuximab soravtansine •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Mirvetuximab Soravtansine. •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 . •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): Mirvetuximab soravtansine is indicated for the treatment of adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Patients are selected for therapy based on an FDA-approved test. •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): There is an exposure-response relationship for mirvetuximab soravtansine-gynx. The increased exposure of mirvetuximab soravtansine-gynx was associated with a higher incidence of ocular adverse reactions and peripheral neuropathy grade 2 or higher. Mirvetuximab soravtansine-gynx did not cause large QTc increases (>10 msec) at the approved recommended dose. The use of mirvetuximab soravtansine-gynx has been associated with severe ocular adverse reactions, such as visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis. Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, as well as peripheral neuropathy, may also occur in patients treated with mirvetuximab soravtansine-gynx. Since mirvetuximab soravtansine-gynx contains DM4, a genotoxic compound, the use of this drug may cause embryo-fetal harm in pregnant women. •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): Mirvetuximab soravtansine-gynx is an antibody-drug conjugate (ADC) formed by three components: a chimeric IgG1 antibody against folate receptor alpha (FRα), the small molecule anti-tubulin agent DM4 (a maytansine derivative) and a sulfo-SPDB linker that joins DM4 to the mirvetuximab antibody. FRα is expressed on the cell surface and has a restricted distribution in normal tissues. However, abnormally high levels of FRα have been detected in serous and endometrioid epithelial ovarian cancer, endometrial adenocarcinoma, and non–small cell lung cancer of the adenocarcinoma subtype. In ovarian cancer patients, its expression is maintained in metastatic foci and recurrent carcinomas. Mirvetuximab soravtansine-gynx binds with high affinity to FRα and is then internalized through antigen-mediated endocytosis. Inside FRα-expressing tumor cells, DM4 is released via proteolytic cleavage. DM4 disrupts the microtubule network within the cell, leading to cell cycle arrest and apoptosis. Since DM4 is electrically neutral and lipophilic, it is able to diffuse across cell membranes and lead to the death of neighboring antigen-negative cells. This "bystander effect" is an important component of mirvetuximab soravtansine-gynx, allowing it to exert a cytotoxic effect even in cells that do not express FRα on their surface. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetic parameters of mirvetuximab soravtansine-gynx were evaluated in patients given a 6 mg/kg adjusted ideal body weight (AIBW) dose administered during the first treatment cycle (3 weeks). Mirvetuximab Soravtansine-gynx, the unconjugated DM4, and S-methyl-DM4 had a corresponding C max of 137.3 µg/mL, 4.11 ng/mL and 6.98 ng/mL, and a corresponding AUC tau of 20.65 h⋅mg/mL, 530 h⋅ng/mL and 1848 h⋅ng/mL. The peak concentration of mirvetuximab soravtansine-gynx was observed near the end of intravenous infusion, while DM4 and S-methyl-DM4 concentrations peaked 2 and 3 days after mirvetuximab soravtansine-gynx administration. After one treatment cycle, mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 reached steady-state concentrations. Following the repeated administration of mirvetuximab soravtansine-gynx, the accumulation of mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 were minimal. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mirvetuximab soravtansine-gynx has a steady-state volume of distribution of 2.63 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Based on in vitro studies, the plasma protein binding of the mirvetuximab soravtansine-gynx component DM4 and its metabolite S-methyl DM4 is higher than 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): After mirvetuximab soravtansine-gynx binds the folate receptor alpha (FRα) and is internalized via antigen-mediated endocytosis, the DM4 agent is released via proteolytic cleavage. The monoclonal antibody portion of this drug is expected to be metabolized by catabolic pathways into small peptides. Unconjugated DM4 is reduced and S-methylated to form S-methyl-DM4. DM4 and S-methyl-DM4 are the main circulating metabolites of mirvetuximab soravtansine-gynx and correspond to approximately 0.4% and 1.4% of mirvetuximab soravtansine-gynx AUCs. Both DM4 and S-methyl-DM4 undergo metabolism by CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mirvetuximab soravtansine-gynx metabolites S-methyl DM4 and DM4-sulfo-SPDB-lysine were detected in urine within 24 hours of infusion as the main 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): After the first dose, the geometric mean terminal phase half-life of mirvetuximab soravtansine-gynx is 4.8 days. The geometric mean terminal phase half-lives of the unconjugated DM4 and its metabolite, S-methyl-DM4, are 2.8 and 5.0 days, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total plasma clearance of mirvetuximab soravtansine-gynx is 18.9 mL/hour. The unconjugated DM4 has a total plasma clearance of 13.8 L/hour, while its metabolite, S-methyl-DM4, has a total plasma clearance of 4.3 L/hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding mirvetuximab soravtansine-gynx is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as ocular toxicity, pneumonitis and peripheral neuropathy. Symptomatic and supportive measures are recommended. Carcinogenicity studies with mirvetuximab soravtansine-gynx or DM4 have not been performed. An in vivo rat bone marrow micronucleus study showed that DM4 and its metabolite, S-methyl DM4, are clastogenic. DM4 and S-methyl DM4 did not show evidence of mutagenicity in the bacterial reverse mutation (Ames) assay. The effects of mirvetuximab soravtansine-gynx or DM4 on fertility studies have not been evaluated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Elahere •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Mirvetuximab soravtansine Mirvetuximab soravtansine-gynx •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mirvetuximab soravtansine is a folate receptor alpha-directed antibody and microtubule inhibitor conjugate used to treat folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Mitomycin interact?

•Drug A: Abciximab •Drug B: Mitomycin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mitomycin. •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. •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 malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, and urinary bladder. Also used as an adjunct to ab externo glaucoma surgery. Mitomycin is also indicated as a pyelocalyceal solution for the treatment of adults with low-grade upper tract urothelial cancer (LG-UTUC). •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): Mitomycin is one of the older chemotherapy drugs, which has been around and in use for decades. It is an antibiotic which has been shown to have antitumor activity. Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Mitomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. •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): Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent. Binding to DNA leads to cross-linking and inhibition of DNA synthesis and function. Mitomycin is cell cycle phase-nonspecific. •Absorption (Drug A): No absorption available •Absorption (Drug B): Erratic. •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): Primarily hepatic, some in various other tissues. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 10% of a dose of mitomycin is excreted unchanged 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): 8-48 min •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, mouse: LD 50 = 23 mg/kg; Oral, rat: LD 50 = 30 mg/kg. Symptoms of overdose include nausea and vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jelmyto, Mitosol, Mutamycin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ametycine Mitamycin Mitocin-C Mitomycin Mitomycin C Mitomycin-C •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mitomycin is an antimetabolite used as an adjunct to ab externo (outside approach) eye surgeries for the treatment of glaucoma and used as a chemotherapeutic agent for various malignancies.

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. The severity of the interaction is minor.

Question: Does Abciximab and Mitomycin interact? Information: •Drug A: Abciximab •Drug B: Mitomycin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mitomycin. •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. •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 malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, and urinary bladder. Also used as an adjunct to ab externo glaucoma surgery. Mitomycin is also indicated as a pyelocalyceal solution for the treatment of adults with low-grade upper tract urothelial cancer (LG-UTUC). •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): Mitomycin is one of the older chemotherapy drugs, which has been around and in use for decades. It is an antibiotic which has been shown to have antitumor activity. Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Mitomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. •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): Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent. Binding to DNA leads to cross-linking and inhibition of DNA synthesis and function. Mitomycin is cell cycle phase-nonspecific. •Absorption (Drug A): No absorption available •Absorption (Drug B): Erratic. •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): Primarily hepatic, some in various other tissues. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 10% of a dose of mitomycin is excreted unchanged 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): 8-48 min •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, mouse: LD 50 = 23 mg/kg; Oral, rat: LD 50 = 30 mg/kg. Symptoms of overdose include nausea and vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jelmyto, Mitosol, Mutamycin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ametycine Mitamycin Mitocin-C Mitomycin Mitomycin C Mitomycin-C •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mitomycin is an antimetabolite used as an adjunct to ab externo (outside approach) eye surgeries for the treatment of glaucoma and used as a chemotherapeutic agent for various malignancies. Output: 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. The severity of the interaction is minor.

Does Abciximab and Mitoxantrone interact?

•Drug A: Abciximab •Drug B: Mitoxantrone •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mitoxantrone. •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. •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 secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis •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): Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. •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): Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Poorly absorbed following oral administration •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1000 L/m2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 78% •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): 75 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 21.3 L/hr/m2 [Elderly patients with breast cancer receiving IV administration of 15-90 mg/m2] 28.3 L/hr/m2 [Non-elderly patients with nasopharyngeal carcinoma receiving IV administration of 15-90 mg/m2] 16.2 L/hr/m2 [Non-elderly patients with malignant lymphoma receiving IV administration of 15-90 mg/m2] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Severe leukopenia with infection. •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): Mitoxantrona Mitoxantrone Mitoxantronum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mitoxantrone is a chemotherapeutic agent used for the treatment of secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis.

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. The severity of the interaction is minor.

Question: Does Abciximab and Mitoxantrone interact? Information: •Drug A: Abciximab •Drug B: Mitoxantrone •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mitoxantrone. •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. •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 secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis •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): Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. •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): Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Poorly absorbed following oral administration •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1000 L/m2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 78% •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): 75 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 21.3 L/hr/m2 [Elderly patients with breast cancer receiving IV administration of 15-90 mg/m2] 28.3 L/hr/m2 [Non-elderly patients with nasopharyngeal carcinoma receiving IV administration of 15-90 mg/m2] 16.2 L/hr/m2 [Non-elderly patients with malignant lymphoma receiving IV administration of 15-90 mg/m2] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Severe leukopenia with infection. •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): Mitoxantrona Mitoxantrone Mitoxantronum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mitoxantrone is a chemotherapeutic agent used for the treatment of secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis. Output: 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. The severity of the interaction is minor.

Does Abciximab and Moclobemide interact?

•Drug A: Abciximab •Drug B: Moclobemide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Moclobemide is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 major depressive disorder and bipolar disorder. •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 selective, reversible inhibitor of monoamine oxidase (MAO) which increases the. Besides its presence in sympathetic nerves, there is an abundant evidence that MAO-A is localized in noradrenergic neurons in the locus coeruleus and MAO-B is closely associated with serotonergic neurons of the raphe nucleus. •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 moclobemide involves the selective, reversible inhibition of MAO-A. This inhibition leads to a decrease in the metabolism and destruction of monoamines in the neurotransmitters. This results in an increase in the monoamines, relieving depressive symptoms. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed from the gastrointestinal tract (> 95%). The presence of food reduces the rate but not the extent of absorption. Hepatic first-pass metabolism reduces bioavailability to about 56% following administration of one dose, but increases to 90% with steady-state dosing as a result of saturation of the first pass effect. Peak plasma concentrations are reached within 0.3 - 1 hours following oral administration with a terminal half-life of 1.6h. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1-1.5 L/Kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 50% (primarily 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): Moclobemide is almost completely metabolized in the liver by Cytochrome P450 2C19 and 2D6. Moclobemide is a substrate of CYP2C19. Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Moclobemide is almost completely 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): 1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of 30-78 L/h, mainly excreted in urine. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 (mouse) is 730mg/kg and LD50 (rat) is 1,300mg/kg. Signs of toxicity include hypertension, drowsiness, dizziness, confusion, tremors, headache, agitation, muscle rigidity and seizures. The effects of moclobemide alone in overdose are negligible, even with high volume ingestion. However, moclobemide overdose with a serotonergic agent (even in small, therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Manerix •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Moclobemid Moclobemida Moclobemide Moclobemidum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Moclobemide is a monoamine oxidase inhibitor used in the treatment of major depressive disorder and bipolar disorder.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Moclobemide interact? Information: •Drug A: Abciximab •Drug B: Moclobemide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Moclobemide is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 major depressive disorder and bipolar disorder. •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 selective, reversible inhibitor of monoamine oxidase (MAO) which increases the. Besides its presence in sympathetic nerves, there is an abundant evidence that MAO-A is localized in noradrenergic neurons in the locus coeruleus and MAO-B is closely associated with serotonergic neurons of the raphe nucleus. •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 moclobemide involves the selective, reversible inhibition of MAO-A. This inhibition leads to a decrease in the metabolism and destruction of monoamines in the neurotransmitters. This results in an increase in the monoamines, relieving depressive symptoms. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed from the gastrointestinal tract (> 95%). The presence of food reduces the rate but not the extent of absorption. Hepatic first-pass metabolism reduces bioavailability to about 56% following administration of one dose, but increases to 90% with steady-state dosing as a result of saturation of the first pass effect. Peak plasma concentrations are reached within 0.3 - 1 hours following oral administration with a terminal half-life of 1.6h. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1-1.5 L/Kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 50% (primarily 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): Moclobemide is almost completely metabolized in the liver by Cytochrome P450 2C19 and 2D6. Moclobemide is a substrate of CYP2C19. Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Moclobemide is almost completely 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): 1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of 30-78 L/h, mainly excreted in urine. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 (mouse) is 730mg/kg and LD50 (rat) is 1,300mg/kg. Signs of toxicity include hypertension, drowsiness, dizziness, confusion, tremors, headache, agitation, muscle rigidity and seizures. The effects of moclobemide alone in overdose are negligible, even with high volume ingestion. However, moclobemide overdose with a serotonergic agent (even in small, therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Manerix •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Moclobemid Moclobemida Moclobemide Moclobemidum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Moclobemide is a monoamine oxidase inhibitor used in the treatment of major depressive disorder and bipolar disorder. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Mogamulizumab interact?

•Drug A: Abciximab •Drug B: Mogamulizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Mogamulizumab. •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 . •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): Mogamulizumab is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one 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): This drug is a CC chemokine receptor 4 (CCR4) antagonist. It is a monoclonal antibody which blocks T cell proliferation, which leads to malignancy. CCR4 is a chemokine receptor that is preferentially expressed by Th2 and regulatory T (Treg) cells. In response to its ligands, CCL17 (TARC) and CCL22 (MDC), CCR4 promotes T-cell migration to extranodal sites, including the skin. •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): Mogamulizumab selectively binds to and inhibits the activity of CCR4, which may block CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, as well as chemokine-mediated angiogenesis. Additionally, this agent may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against CCR4-positive T cells. CCR4, a G-coupled-protein receptor for C-C chemokines such MIP-1, RANTES, TARC and MCP-1, is expressed on the surfaces of some types of T cells, endothelial cells, and certain types of neurons. CCR4, also known as CD194, may be overexpressed on adult T-cell lymphoma (ATL) and peripheral T-cell lymphoma (PTCL) cells. In addition to directly targeting malignant T cells expressing CCR4, mogamulizumab depletes Treg cells, an important therapeutic target in many human cancers because of their role in suppressing host antitumor immunity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following repeated dosing of the approved recommended dosage, steady-state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (Cmax,ss) is 32 (68%) μg/mL, the trough concentration (Cmin,ss) is 11 (239%) μg/mL, and AUCss is 5577 (125%) μg•hr/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central volume of distribution is 3.6 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): The terminal half-life is 17 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance is 12 mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common adverse reactions (reported in ≥20% of patients randomized to mogamulizumab) were rash (including drug eruption), infusion-related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain. Due to various adverse effects related to this drug, the adverse reactions have been categorized by organ system. Because of the risk of serious/fatal ADRs, patients administered mogamulizumab should be carefully monitored. Upper respiratory tract infection: This may occur due to decreased immunity following the administration of this drug. Monitor for signs of respiratory infection including fever, cough and shortness of breath. Dermatological: Patients must contact their healthcare provider immediately if they experience a new or worsening skin rash. Treatment should be temporarily interrupted for moderate or severe skin rashes and permanently discontinued for a life-threatening rash. Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of mogamulizumab. Rash (drug eruption) is one of the most common adverse reactions associated with mogamulizumab. Infusion Reactions: Patients must contact their healthcare provider immediately for signs or symptoms of infusion reactions. Treatment should be suspended for any infusion reaction and permanently discontinued for any life-threatening infusion reaction. Infections: Patients must contact their healthcare provider if they experience fever or other signs of infection. Infections should be monitored and treated promptly. Autoimmune Complications: Immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain- Barré syndrome. Patients must notify their healthcare provider of any history of autoimmune disease. Treatment should be suspended or permanently discontinued as appropriate. Fatal and life-threatening immune-mediated complications have been reported in recipients of this drug. Musculoskeletal pain: This drug may cause musculoskeletal pain. A note on complications of allogeneic hematopoietic stem cell transplantation: Patients must be aware of the possible risk of post-transplant complications when taking this agent. Patients should be monitored for severe acute graft-versus-host disease (GVHD) and steroid-refractory GVHD. Females of Reproductive Potential: Females who are able to become pregnant should use an effective method of birth control during treatment with Poteligeo and for at least three months after the last dose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Poteligeo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mogamulizumab is a monoclonal antibody used to treat relapsed or refractory mycosis fungoides or Sézary syndrome after attempting one other therapy.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Mogamulizumab interact? Information: •Drug A: Abciximab •Drug B: Mogamulizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Mogamulizumab. •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 . •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): Mogamulizumab is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one 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): This drug is a CC chemokine receptor 4 (CCR4) antagonist. It is a monoclonal antibody which blocks T cell proliferation, which leads to malignancy. CCR4 is a chemokine receptor that is preferentially expressed by Th2 and regulatory T (Treg) cells. In response to its ligands, CCL17 (TARC) and CCL22 (MDC), CCR4 promotes T-cell migration to extranodal sites, including the skin. •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): Mogamulizumab selectively binds to and inhibits the activity of CCR4, which may block CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, as well as chemokine-mediated angiogenesis. Additionally, this agent may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against CCR4-positive T cells. CCR4, a G-coupled-protein receptor for C-C chemokines such MIP-1, RANTES, TARC and MCP-1, is expressed on the surfaces of some types of T cells, endothelial cells, and certain types of neurons. CCR4, also known as CD194, may be overexpressed on adult T-cell lymphoma (ATL) and peripheral T-cell lymphoma (PTCL) cells. In addition to directly targeting malignant T cells expressing CCR4, mogamulizumab depletes Treg cells, an important therapeutic target in many human cancers because of their role in suppressing host antitumor immunity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following repeated dosing of the approved recommended dosage, steady-state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (Cmax,ss) is 32 (68%) μg/mL, the trough concentration (Cmin,ss) is 11 (239%) μg/mL, and AUCss is 5577 (125%) μg•hr/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central volume of distribution is 3.6 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): The terminal half-life is 17 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance is 12 mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common adverse reactions (reported in ≥20% of patients randomized to mogamulizumab) were rash (including drug eruption), infusion-related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain. Due to various adverse effects related to this drug, the adverse reactions have been categorized by organ system. Because of the risk of serious/fatal ADRs, patients administered mogamulizumab should be carefully monitored. Upper respiratory tract infection: This may occur due to decreased immunity following the administration of this drug. Monitor for signs of respiratory infection including fever, cough and shortness of breath. Dermatological: Patients must contact their healthcare provider immediately if they experience a new or worsening skin rash. Treatment should be temporarily interrupted for moderate or severe skin rashes and permanently discontinued for a life-threatening rash. Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of mogamulizumab. Rash (drug eruption) is one of the most common adverse reactions associated with mogamulizumab. Infusion Reactions: Patients must contact their healthcare provider immediately for signs or symptoms of infusion reactions. Treatment should be suspended for any infusion reaction and permanently discontinued for any life-threatening infusion reaction. Infections: Patients must contact their healthcare provider if they experience fever or other signs of infection. Infections should be monitored and treated promptly. Autoimmune Complications: Immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain- Barré syndrome. Patients must notify their healthcare provider of any history of autoimmune disease. Treatment should be suspended or permanently discontinued as appropriate. Fatal and life-threatening immune-mediated complications have been reported in recipients of this drug. Musculoskeletal pain: This drug may cause musculoskeletal pain. A note on complications of allogeneic hematopoietic stem cell transplantation: Patients must be aware of the possible risk of post-transplant complications when taking this agent. Patients should be monitored for severe acute graft-versus-host disease (GVHD) and steroid-refractory GVHD. Females of Reproductive Potential: Females who are able to become pregnant should use an effective method of birth control during treatment with Poteligeo and for at least three months after the last dose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Poteligeo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mogamulizumab is a monoclonal antibody used to treat relapsed or refractory mycosis fungoides or Sézary syndrome after attempting one other therapy. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Moroctocog alfa interact?

•Drug A: Abciximab •Drug B: Moroctocog alfa •Severity: MAJOR •Description: The therapeutic efficacy of Moroctocog 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. •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): Moroctocog alfa is indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to 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, which converts factor X to factor Xa to facilitate the 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). As factor VIII is the specific clotting factor deficient in patients with hemophilia A, replacement of clotting factor with Moroctocog alfa, also known as BDDrFVIII (B domain deleted recombinant factor VIII), is the cornerstone of the prevention and treatment of bleeding for this disorder. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax = 1.08±0.22 IU⋅hr/mL Cmax = 1.12 (±0.19) IU/mL •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mean steady-state volume of distribution = 65.1 (± 35.1) mL/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): 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): Mean terminal elimination half-life = 11.8 (± 5.1) hours Half-life = 11.2 ± 5.0 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean clearance = 4.21 (± 2.08) mL/h•kg Clearance = 4.51 ± 2.23 mL/h•kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Refacto AF, Xyntha •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Moroctocog alfa is a recombinant Factor VIII used to treat hemophilia A to control bleeding.

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. The severity of the interaction is major.

Question: Does Abciximab and Moroctocog alfa interact? Information: •Drug A: Abciximab •Drug B: Moroctocog alfa •Severity: MAJOR •Description: The therapeutic efficacy of Moroctocog 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. •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): Moroctocog alfa is indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to 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, which converts factor X to factor Xa to facilitate the 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). As factor VIII is the specific clotting factor deficient in patients with hemophilia A, replacement of clotting factor with Moroctocog alfa, also known as BDDrFVIII (B domain deleted recombinant factor VIII), is the cornerstone of the prevention and treatment of bleeding for this disorder. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax = 1.08±0.22 IU⋅hr/mL Cmax = 1.12 (±0.19) IU/mL •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mean steady-state volume of distribution = 65.1 (± 35.1) mL/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): 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): Mean terminal elimination half-life = 11.8 (± 5.1) hours Half-life = 11.2 ± 5.0 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean clearance = 4.21 (± 2.08) mL/h•kg Clearance = 4.51 ± 2.23 mL/h•kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Refacto AF, Xyntha •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Moroctocog alfa is a recombinant Factor VIII used to treat hemophilia A to control bleeding. Output: 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. The severity of the interaction is major.

Does Abciximab and Mosunetuzumab interact?

•Drug A: Abciximab •Drug B: Mosunetuzumab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mosunetuzumab. •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. •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): Mosunetuzumab as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic 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): Mosunetuzumab is an anti-CD20/CD3 bispecific antibody that leads to B-cell depletion (CD19 B-cell counts < 0.07 x 109/L) and hypogammaglobulinemia (IgG levels < 500 mg/dL). In patients with aggressive non-Hodgkin's lymphoma (NHL) treated with mosunetuzumab, the overall response rate (ORR) was 37.4%, and the complete remission (CR) rate was 19.5%, while patients with indolent NHL treated with mosunetuzumab had an ORR of 62.7% and a CR rate of 43.3%. The response to mosunetuzumab in a high-risk group of patients with progression of follicular lymphoma within 24 months after initiating frontline treatment (n=29) was also beneficial; the ORR was 75.9% and the CR rate was 55.2%. Patients treated with mosunetuzumab may develop cytokine release syndrome (CRS), including life-threatening reactions. CRS mainly occurred on days 1 and 15 of cycle 1. To avoid CRS, patients should receive corticosteroids, antipyretics and antihistamines prior to mosunetuzumab therapy. Serious infections such as pneumonia, bacteremia, and sepsis or septic shock have been reported in patients treated with mosunetuzumab, and caution should be exercised in patients with a history of recurring or chronic infections. Tumour flare and tumour lysis syndrome (TLS) have also been reported in patients treated with mosunetuzumab. •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): Mosunetuzumab is a full-length, humanized anti-CD20/CD3 bispecific antibody that targets CD20-expressing B-cells. Unlike B-cell-targeting monoclonal antibodies, such as rituximab, mosunetuzumab can recognize and bind two different targets, CD20 on cancer B-cells and CD3 on T-cells in a 1:1 ratio. Mosunetuzumab is a conditional agonist; the targeted killing of CD20-expressing B-cells is observed only when this drug is simultaneously bound to CD20 on B-cells and CD3 on T-cells. Mosunetuzumab recruits T-cells and leads to their activation by promoting the formation of an immunologic synapse between a target B-cell and a cytotoxic T-cell. The activation of T-cells leads to the directed release of perforin and granzymes through the immunologic synapsis, which ultimately induces B-cell lysis and cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Between 0.05 and 60 mg, mosunetuzumab follows a dose-proportional pharmacokinetic profile. The population pharmacokinetics of intravenous mosunetuzumab are described with a two-compartment pharmacokinetic model with time-dependent clearance. After two cycles of mosunetuzumab (42 days, given by intravenous infusion), patients reached a C max of 17.9 µg/mL at the end of dose of Cycle 2 Day 1. The average AUC of two cycles of mosunetuzumab was 126 µg⋅day/mL. In patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated with mosunetuzumab, serum concentration reached the C max at the end of the intravenous infusion and declined in a bi-exponential fashion. The steady-state values of mosunetuzumab were reached at cycle 4 (63 ‒ 84 days). Steady-state AUC and C max were 52.9 day⋅μg/mL and 7.02 μg/mL, respectively. Mosunetuzumab is expected to have a bioavailability close to 100% when given intravenously. In clinical trials, mosunetuzumab administered subcutaneously had a slow absorption rate and high bioavailability (>75%). The pharmacokinetics of mosunetuzumab was similar in Asian and non-Asian subjects. Compared to males, the steady-state clearance of mosunetuzumab in females is marginally lower (approximately 13%), and dose adjustment based on gender is not required. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated central volume of distribution for mosunetuzumab administered via intravenous infusion is 5.49 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Mosunetuzumab is a bispecific antibody; therefore, protein binding studies were not carried out. •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): Mosunetuzumab is a protein therapeutic; it is expected to be degraded into small peptides and amino acids via catabolic pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Since mosunetuzumab is an immunoglobulin G (IgG) antibody, it is expected to be mainly eliminated via intracellular catabolism. Hepatic or renal impairment is not expected to influence the elimination of mosunetuzumab. •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): Mosunetuzumab has a terminal half-life of 16.1 days, and an apparent half-life between 6 and 11 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean steady-state plateau clearance (CL ss ) of mosunetuzumab is 1.08 L/day, and its baseline clearance (CL base ) is 0.584 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In case of a mosunetuzumab overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted. Patients experiencing an overdose are at an increased risk of severe adverse effects such as cytokine release syndrome (CRS), febrile neutropenia, neutropenia and pneumonia. Preclinical single- and repeat-dose toxicity studies of up to 26 weeks in duration found that transient CRS was developed mostly after the first dose of mosunetuzumab. Findings suggest that this effect is pharmacologically-mediated and reversible. The effect of mosunetuzumab on male and female reproductive organs was evaluated in sexually mature cynomolgus monkeys given an intravenous infusion dose equivalent to the one recommended in patients. Up to 26 weeks, mosunetuzumab did not have an effect on male or female reproductive organs. Preclinical studies evaluating the effect of mosunetuzumab on developmental toxicity have not been conducted. Due to the low placental transfer of antibodies during the first trimester, mosunetuzumab is not expected to have a teratogenic effect. However, it can lead to a higher risk of opportunistic infections, which may cause fetal loss. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lunsumio •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mosunetuzumab is a humanized anti-CD20/CD3 bispecific antibody used to treat relapsed or refractory follicular lymphoma.

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. The severity of the interaction is minor.

Question: Does Abciximab and Mosunetuzumab interact? Information: •Drug A: Abciximab •Drug B: Mosunetuzumab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mosunetuzumab. •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. •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): Mosunetuzumab as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic 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): Mosunetuzumab is an anti-CD20/CD3 bispecific antibody that leads to B-cell depletion (CD19 B-cell counts < 0.07 x 109/L) and hypogammaglobulinemia (IgG levels < 500 mg/dL). In patients with aggressive non-Hodgkin's lymphoma (NHL) treated with mosunetuzumab, the overall response rate (ORR) was 37.4%, and the complete remission (CR) rate was 19.5%, while patients with indolent NHL treated with mosunetuzumab had an ORR of 62.7% and a CR rate of 43.3%. The response to mosunetuzumab in a high-risk group of patients with progression of follicular lymphoma within 24 months after initiating frontline treatment (n=29) was also beneficial; the ORR was 75.9% and the CR rate was 55.2%. Patients treated with mosunetuzumab may develop cytokine release syndrome (CRS), including life-threatening reactions. CRS mainly occurred on days 1 and 15 of cycle 1. To avoid CRS, patients should receive corticosteroids, antipyretics and antihistamines prior to mosunetuzumab therapy. Serious infections such as pneumonia, bacteremia, and sepsis or septic shock have been reported in patients treated with mosunetuzumab, and caution should be exercised in patients with a history of recurring or chronic infections. Tumour flare and tumour lysis syndrome (TLS) have also been reported in patients treated with mosunetuzumab. •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): Mosunetuzumab is a full-length, humanized anti-CD20/CD3 bispecific antibody that targets CD20-expressing B-cells. Unlike B-cell-targeting monoclonal antibodies, such as rituximab, mosunetuzumab can recognize and bind two different targets, CD20 on cancer B-cells and CD3 on T-cells in a 1:1 ratio. Mosunetuzumab is a conditional agonist; the targeted killing of CD20-expressing B-cells is observed only when this drug is simultaneously bound to CD20 on B-cells and CD3 on T-cells. Mosunetuzumab recruits T-cells and leads to their activation by promoting the formation of an immunologic synapse between a target B-cell and a cytotoxic T-cell. The activation of T-cells leads to the directed release of perforin and granzymes through the immunologic synapsis, which ultimately induces B-cell lysis and cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Between 0.05 and 60 mg, mosunetuzumab follows a dose-proportional pharmacokinetic profile. The population pharmacokinetics of intravenous mosunetuzumab are described with a two-compartment pharmacokinetic model with time-dependent clearance. After two cycles of mosunetuzumab (42 days, given by intravenous infusion), patients reached a C max of 17.9 µg/mL at the end of dose of Cycle 2 Day 1. The average AUC of two cycles of mosunetuzumab was 126 µg⋅day/mL. In patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated with mosunetuzumab, serum concentration reached the C max at the end of the intravenous infusion and declined in a bi-exponential fashion. The steady-state values of mosunetuzumab were reached at cycle 4 (63 ‒ 84 days). Steady-state AUC and C max were 52.9 day⋅μg/mL and 7.02 μg/mL, respectively. Mosunetuzumab is expected to have a bioavailability close to 100% when given intravenously. In clinical trials, mosunetuzumab administered subcutaneously had a slow absorption rate and high bioavailability (>75%). The pharmacokinetics of mosunetuzumab was similar in Asian and non-Asian subjects. Compared to males, the steady-state clearance of mosunetuzumab in females is marginally lower (approximately 13%), and dose adjustment based on gender is not required. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated central volume of distribution for mosunetuzumab administered via intravenous infusion is 5.49 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Mosunetuzumab is a bispecific antibody; therefore, protein binding studies were not carried out. •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): Mosunetuzumab is a protein therapeutic; it is expected to be degraded into small peptides and amino acids via catabolic pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Since mosunetuzumab is an immunoglobulin G (IgG) antibody, it is expected to be mainly eliminated via intracellular catabolism. Hepatic or renal impairment is not expected to influence the elimination of mosunetuzumab. •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): Mosunetuzumab has a terminal half-life of 16.1 days, and an apparent half-life between 6 and 11 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean steady-state plateau clearance (CL ss ) of mosunetuzumab is 1.08 L/day, and its baseline clearance (CL base ) is 0.584 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In case of a mosunetuzumab overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted. Patients experiencing an overdose are at an increased risk of severe adverse effects such as cytokine release syndrome (CRS), febrile neutropenia, neutropenia and pneumonia. Preclinical single- and repeat-dose toxicity studies of up to 26 weeks in duration found that transient CRS was developed mostly after the first dose of mosunetuzumab. Findings suggest that this effect is pharmacologically-mediated and reversible. The effect of mosunetuzumab on male and female reproductive organs was evaluated in sexually mature cynomolgus monkeys given an intravenous infusion dose equivalent to the one recommended in patients. Up to 26 weeks, mosunetuzumab did not have an effect on male or female reproductive organs. Preclinical studies evaluating the effect of mosunetuzumab on developmental toxicity have not been conducted. Due to the low placental transfer of antibodies during the first trimester, mosunetuzumab is not expected to have a teratogenic effect. However, it can lead to a higher risk of opportunistic infections, which may cause fetal loss. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lunsumio •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mosunetuzumab is a humanized anti-CD20/CD3 bispecific antibody used to treat relapsed or refractory follicular lymphoma. Output: 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. The severity of the interaction is minor.

Does Abciximab and Nabumetone interact?

•Drug A: Abciximab •Drug B: Nabumetone •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Nabumetone 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. •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: 1) Symptomatic relief in rheumatoid arthritis. 2) Symptomatic relief in osteoarthritis. •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): NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia. This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited. The anti-inflammatory effect of NSAIDs is mediated by preventing vasodilation, increases in vascular permeability, and the release of cytokines from endothelial cells. These three effects together prevent immunocompetent cells from migrating to the site of injury thereby preventing additional damage and inflammation due to activation of the immune system at the site of damage. PGs also modulate T-helper cell activation and differentiation, an activity which is thought to be of importance in arthritic conditions. The anti-pyretic effect of NSAIDs is mediated through preventing increases in temperature by prostaglandins (PGs) via the hypothalamus. Activation of this process by other inflammatory mediators relies upon subsequent action by PGs, therefore NSAIDs are able to reduce fever due to these mediators as well. The adverse effects of NSAIDs are related to their therapeutic effects. The same vasodilatory action which occurs in inflammation also serves to regulate blood flow to the kidneys through the afferent renal arteries. NSAIDs are widely known as nephrotoxic agents as the reduction in PGs produces vasoconstriction of these arteries resulting in reduced blood flow to the kidneys and a subsequent decline in renal function. Reductions in mucus and HCO 3 secretion in the stomach increases the risk of ulceration by limiting the protection mediated by PGs. Lastly, COX-2 selective agents like nabumetone can unbalance prothrombotic and antithrombotic prostanoid generation leading to increased platelet aggregation and increased risk of 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): Nabumetone's active metabolite, 6-MNA, is an inhibitor of both COX-1 and COX-2 although it exhibits some COX-2 selectivity. Inhibition of COX-1 and COX-2 reduces conversion of arachidonic acid to PGs and thromboxane (TXA 2 ). This reduction in prostanoid production is the common mechanism that mediates the effects of nambutone. PGE 2 is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE 2 activates the G q -coupled EP 1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE 2 also activates the EP 4 receptor, coupled to G s, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE 2 act via EP 3 to increase sensitivity to bradykinin and via EP 2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP 2 receptor which couples to G s. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI 2 is known to play a role via its G s -coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain. PGI 2 and PGE 2 contribute to acute inflammation via their IP and EP 2 receptors. Similarly to β adrenergic receptors these are G s -coupled and mediate vasodilation through the AC/PKA pathway. PGE 2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD 2 plays a role in the activation of endothelial cell release of cytokines through its DP 1 receptor. PGI 2 and PGE 2 modulate T-helper cell activation and differentiation through IP, EP 2, and EP 4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation. PGE 2 can cross the blood-brain barrier and act on excitatory G q EP 3 receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE 2 thereby reducing the activity of these neurons. The adverse effects of NSAIDs stem from the protective and regulatory roles of prostanoids which have been well-characterized. PGI 2 and PGE 2 regulate blood flow to the kidney by similar mechanisms to the vasodilation they produce in inflammation. Prevention of this regulation by NSAIDs produces vasoconstriction which limits renal function by reducing blood flow and the hydrostatic pressure which drives filtration. PGE 2 also regulates gastric protection via EP 3 receptors which are, in this location, coupled to G i which inhibits the AC/PKA pathway. This reduces the secretion of protons by H /K ATPase in parietal cells and increases the secretion of mucus and HCO 3 by superficial endothelial cells. Disruption of this protective action by NSAIDs lead to ulceration of the gastric mucosa. Lastly, disruption of PGI 2, which opposes platelet aggregation, generation by COX-2 selective agents leads to an imbalance with TXA 2 generated by COX-1, which promotes aggregation of platelets, leading to increased risk of thrombosis. Since nabumetone is somewhat COX-2 selective it is thought to promote this imbalance and increase thrombotic risk. •Absorption (Drug A): No absorption available •Absorption (Drug B): Nabumetone is well-absorbed from the GI tract and undergoes significant first pass metabolism resulting in approximately 35% being converted to the active metabolite, 6-MNA. Tmax for 6-MNA varies widely with a mean values of 3 and 11 hours reported in official product monographs, and described as 9-12 hours in published literature Administration with food increases Cmax by 33% and increases absorption rate. If formulated as a suspension the Cmax increases and the Tmax is reduced by 0.8 hours while the all other pharmacokinetic parameters remain unchanged. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The Vd of 6-MNA reported after administration of a single dose is 0.1-0.2 L/kg or approximately 5-10 L. Vdss reported in official product labeling is approximately 53 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 6-MNA is over 99% bound to plasma proteins, likely albumin. The unbound fraction is 0.1-0.2% and remains proportional in the dose range of 1000-2000mg •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): Nabumetone is reduced to 3-hydroxy nabumetone by the aldo-keto reductase-1C family and by corticosteroid 11-beta-dehydrogenase. It then undergoes oxidative cleavage by CYP1A2 to 6-MNA, the active metabolite. 6-MNA is eliminated by O-demethylation by CYP2C9 to 6-hydroxy-2-naphthylacetic acid (6-HNA). Both 6-MNA and 6-HNA are further converted to conjugates. Other metabolites are generated through a mix of ketone reduction and O-demethylation along with subsequent conjugation. Glucuronide conjugates of several metabolites have been found to become further conjugated to glycine residues. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Most drug is eliminated via hepatic metabolism with minimal to no parent drug detectable in the plasma. 80% of the dose is then excreted by the kidneys and 10% in the feces. It does not appear to undergo enterohepatic recirculation. •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): 6-MNA has a mean half-life of 24 hours with a range of 19-36 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 6-MNA has an apparent steady-state clearance of 20 - 30 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 Values Mouse: 4290 mg/kg (Oral), 2380 mg/kg (IP) Rat: 3880 mg/kg (Oral), 1520 mg/kg (IP), >10 g/kg (SC) Monkey: 3200 mg/kg (Oral) Overdose Signs and symptoms of nabumetone overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain. These are considered reversible with supportive care. GI bleeding, hypertension, acute kidney injury, respiratory depression, and coma are rare but can occur. No antidote exists for nabumetone overdose although administration of activated charcoal and/or induction of emesis can reduce absorption if the nabumetone dose was taken less than 4 hours prior. 6-MNA is cannot be cleared by dialysis. Carcinogenicity & Mutagenicity Nabumetone was not significantly carcinogenic in rats or mice studied over 2 years. Neither the Ames test nor mouse micronucleus test showed nabumetone or it's active metabolite, 6-MNA, to be mutagenic. Chromosomal abberation has been observed in cultured lymphocytes exposed to concentrations of 80 mcg/mL and higher of nabumetone or 6-MNA equivalent to the maximum recommended human dose. Reproductive Toxicity No adverse effects on fertility have been observed in male and female rats at doses of 320 mg/kg/day. ] No teratogenicity has been observed in pregnant rabbits or rats. Dystocia and delayed parturition have been noted in rats resulting in reduced survival of offspring. This has been attributed to the role of prostaglandins in uterine contraction. NSAIDs can also cause premature closure of the ductus ateriosus. Lactation 6-MNA has been detected in the milk of lactating rats. While no data is available in humans, 6-MNA is both highly protein bound and exists in its anionic form in circulation. For these reasons partitioning into breast milk is expected to be limited. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Relafen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Nabumeton Nabumetona Nabumétone Nabumetone Nabumetonum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nabumetone is an NSAID used to treat osteoarthritis and rheumatoid arthritis.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Nabumetone interact? Information: •Drug A: Abciximab •Drug B: Nabumetone •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Nabumetone 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. •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: 1) Symptomatic relief in rheumatoid arthritis. 2) Symptomatic relief in osteoarthritis. •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): NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia. This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited. The anti-inflammatory effect of NSAIDs is mediated by preventing vasodilation, increases in vascular permeability, and the release of cytokines from endothelial cells. These three effects together prevent immunocompetent cells from migrating to the site of injury thereby preventing additional damage and inflammation due to activation of the immune system at the site of damage. PGs also modulate T-helper cell activation and differentiation, an activity which is thought to be of importance in arthritic conditions. The anti-pyretic effect of NSAIDs is mediated through preventing increases in temperature by prostaglandins (PGs) via the hypothalamus. Activation of this process by other inflammatory mediators relies upon subsequent action by PGs, therefore NSAIDs are able to reduce fever due to these mediators as well. The adverse effects of NSAIDs are related to their therapeutic effects. The same vasodilatory action which occurs in inflammation also serves to regulate blood flow to the kidneys through the afferent renal arteries. NSAIDs are widely known as nephrotoxic agents as the reduction in PGs produces vasoconstriction of these arteries resulting in reduced blood flow to the kidneys and a subsequent decline in renal function. Reductions in mucus and HCO 3 secretion in the stomach increases the risk of ulceration by limiting the protection mediated by PGs. Lastly, COX-2 selective agents like nabumetone can unbalance prothrombotic and antithrombotic prostanoid generation leading to increased platelet aggregation and increased risk of 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): Nabumetone's active metabolite, 6-MNA, is an inhibitor of both COX-1 and COX-2 although it exhibits some COX-2 selectivity. Inhibition of COX-1 and COX-2 reduces conversion of arachidonic acid to PGs and thromboxane (TXA 2 ). This reduction in prostanoid production is the common mechanism that mediates the effects of nambutone. PGE 2 is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE 2 activates the G q -coupled EP 1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE 2 also activates the EP 4 receptor, coupled to G s, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE 2 act via EP 3 to increase sensitivity to bradykinin and via EP 2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP 2 receptor which couples to G s. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI 2 is known to play a role via its G s -coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain. PGI 2 and PGE 2 contribute to acute inflammation via their IP and EP 2 receptors. Similarly to β adrenergic receptors these are G s -coupled and mediate vasodilation through the AC/PKA pathway. PGE 2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD 2 plays a role in the activation of endothelial cell release of cytokines through its DP 1 receptor. PGI 2 and PGE 2 modulate T-helper cell activation and differentiation through IP, EP 2, and EP 4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation. PGE 2 can cross the blood-brain barrier and act on excitatory G q EP 3 receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE 2 thereby reducing the activity of these neurons. The adverse effects of NSAIDs stem from the protective and regulatory roles of prostanoids which have been well-characterized. PGI 2 and PGE 2 regulate blood flow to the kidney by similar mechanisms to the vasodilation they produce in inflammation. Prevention of this regulation by NSAIDs produces vasoconstriction which limits renal function by reducing blood flow and the hydrostatic pressure which drives filtration. PGE 2 also regulates gastric protection via EP 3 receptors which are, in this location, coupled to G i which inhibits the AC/PKA pathway. This reduces the secretion of protons by H /K ATPase in parietal cells and increases the secretion of mucus and HCO 3 by superficial endothelial cells. Disruption of this protective action by NSAIDs lead to ulceration of the gastric mucosa. Lastly, disruption of PGI 2, which opposes platelet aggregation, generation by COX-2 selective agents leads to an imbalance with TXA 2 generated by COX-1, which promotes aggregation of platelets, leading to increased risk of thrombosis. Since nabumetone is somewhat COX-2 selective it is thought to promote this imbalance and increase thrombotic risk. •Absorption (Drug A): No absorption available •Absorption (Drug B): Nabumetone is well-absorbed from the GI tract and undergoes significant first pass metabolism resulting in approximately 35% being converted to the active metabolite, 6-MNA. Tmax for 6-MNA varies widely with a mean values of 3 and 11 hours reported in official product monographs, and described as 9-12 hours in published literature Administration with food increases Cmax by 33% and increases absorption rate. If formulated as a suspension the Cmax increases and the Tmax is reduced by 0.8 hours while the all other pharmacokinetic parameters remain unchanged. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The Vd of 6-MNA reported after administration of a single dose is 0.1-0.2 L/kg or approximately 5-10 L. Vdss reported in official product labeling is approximately 53 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 6-MNA is over 99% bound to plasma proteins, likely albumin. The unbound fraction is 0.1-0.2% and remains proportional in the dose range of 1000-2000mg •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): Nabumetone is reduced to 3-hydroxy nabumetone by the aldo-keto reductase-1C family and by corticosteroid 11-beta-dehydrogenase. It then undergoes oxidative cleavage by CYP1A2 to 6-MNA, the active metabolite. 6-MNA is eliminated by O-demethylation by CYP2C9 to 6-hydroxy-2-naphthylacetic acid (6-HNA). Both 6-MNA and 6-HNA are further converted to conjugates. Other metabolites are generated through a mix of ketone reduction and O-demethylation along with subsequent conjugation. Glucuronide conjugates of several metabolites have been found to become further conjugated to glycine residues. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Most drug is eliminated via hepatic metabolism with minimal to no parent drug detectable in the plasma. 80% of the dose is then excreted by the kidneys and 10% in the feces. It does not appear to undergo enterohepatic recirculation. •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): 6-MNA has a mean half-life of 24 hours with a range of 19-36 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 6-MNA has an apparent steady-state clearance of 20 - 30 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 Values Mouse: 4290 mg/kg (Oral), 2380 mg/kg (IP) Rat: 3880 mg/kg (Oral), 1520 mg/kg (IP), >10 g/kg (SC) Monkey: 3200 mg/kg (Oral) Overdose Signs and symptoms of nabumetone overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain. These are considered reversible with supportive care. GI bleeding, hypertension, acute kidney injury, respiratory depression, and coma are rare but can occur. No antidote exists for nabumetone overdose although administration of activated charcoal and/or induction of emesis can reduce absorption if the nabumetone dose was taken less than 4 hours prior. 6-MNA is cannot be cleared by dialysis. Carcinogenicity & Mutagenicity Nabumetone was not significantly carcinogenic in rats or mice studied over 2 years. Neither the Ames test nor mouse micronucleus test showed nabumetone or it's active metabolite, 6-MNA, to be mutagenic. Chromosomal abberation has been observed in cultured lymphocytes exposed to concentrations of 80 mcg/mL and higher of nabumetone or 6-MNA equivalent to the maximum recommended human dose. Reproductive Toxicity No adverse effects on fertility have been observed in male and female rats at doses of 320 mg/kg/day. ] No teratogenicity has been observed in pregnant rabbits or rats. Dystocia and delayed parturition have been noted in rats resulting in reduced survival of offspring. This has been attributed to the role of prostaglandins in uterine contraction. NSAIDs can also cause premature closure of the ductus ateriosus. Lactation 6-MNA has been detected in the milk of lactating rats. While no data is available in humans, 6-MNA is both highly protein bound and exists in its anionic form in circulation. For these reasons partitioning into breast milk is expected to be limited. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Relafen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Nabumeton Nabumetona Nabumétone Nabumetone Nabumetonum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nabumetone is an NSAID used to treat osteoarthritis and rheumatoid arthritis. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Nadroparin interact?

•Drug A: Abciximab •Drug B: Nadroparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Nadroparin. •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. •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): Nadroparin is used for prophylaxis of thromboembolic disorders and general surgery in orthopedic surgery, treatment of deep vein thrombosis, prevention of clotting during hemodialysis and treatment of unstable angina and non-Q wave 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): Nadroparin is a low molecular weight heparin that is composed of a heterogeneous mixture of sulfated polysaccaride glycosaminoglycan chains. Th mean molecular weight is approximately 4300 daltons. The ratio of anti-Xa activity to anti-IIa is 3.5:1 whereas it is about 1:1 for heparin. Its use should be avoided in patients with a creatinine clearance less than 40mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH. •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 for nadroparin is similar to all other LMWHs. Like all LMWHs, nadroparin has a pentasaccharide sequence which binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 3.59L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Much lower compared to heparin, which has over 90% 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): Nadroparin is metabolized in the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nadroparin is eliminated via the kidneys through non-saturable mechanisms. •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 healthy patients, the half life is between 3.5hrs to 11.2hrs following subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of nadroparin is 21.4 +/- 7.0mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Osteopenia with extended use, skin necrosis, thrombocytosis, severe immunologically-mediated thrombocytopenia, eosinophilia (rare), calcinosis rarely occurs at the injection site, severe bleeding, transient elevation of liver transaminases. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fraxiparine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nadroparin is a low molecular weight heparin used for the prophylaxis of thrombotic events and deep vein thrombosis, and prevent unstable angina and non-Q-wave myocardial infarction.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Nadroparin interact? Information: •Drug A: Abciximab •Drug B: Nadroparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Nadroparin. •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. •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): Nadroparin is used for prophylaxis of thromboembolic disorders and general surgery in orthopedic surgery, treatment of deep vein thrombosis, prevention of clotting during hemodialysis and treatment of unstable angina and non-Q wave 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): Nadroparin is a low molecular weight heparin that is composed of a heterogeneous mixture of sulfated polysaccaride glycosaminoglycan chains. Th mean molecular weight is approximately 4300 daltons. The ratio of anti-Xa activity to anti-IIa is 3.5:1 whereas it is about 1:1 for heparin. Its use should be avoided in patients with a creatinine clearance less than 40mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH. •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 for nadroparin is similar to all other LMWHs. Like all LMWHs, nadroparin has a pentasaccharide sequence which binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 3.59L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Much lower compared to heparin, which has over 90% 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): Nadroparin is metabolized in the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nadroparin is eliminated via the kidneys through non-saturable mechanisms. •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 healthy patients, the half life is between 3.5hrs to 11.2hrs following subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of nadroparin is 21.4 +/- 7.0mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Osteopenia with extended use, skin necrosis, thrombocytosis, severe immunologically-mediated thrombocytopenia, eosinophilia (rare), calcinosis rarely occurs at the injection site, severe bleeding, transient elevation of liver transaminases. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fraxiparine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nadroparin is a low molecular weight heparin used for the prophylaxis of thrombotic events and deep vein thrombosis, and prevent unstable angina and non-Q-wave myocardial infarction. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Naproxen interact?

•Drug A: Abciximab •Drug B: Naproxen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Naproxen 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. •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): Naproxen is indicated for the management of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, tendinitis, bursitis, acute gout, primary dysmenorrhea, and for the relief of mild to moderate pain. Further, it is first-line therapy for osteoarthritis, acute gouty arthritis, dysmenorrhea, and musculoskeletal inflammation and pain. •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): Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood. Although naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control. A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use. Further, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs. Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers. •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): As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme. •Absorption (Drug A): No absorption available •Absorption (Drug B): Naproxen is available as a free acid and sodium salt. At comparable doses, (naproxen 500 mg = naproxen sodium 550 mg) they differ slightly in their rates of absorption, but otherwise they are therapeutically and pharmacologically equivalent. Naproxen sodium achieves a peak plasma concentration after 1 hour, while peak plasma concentration is observed after 2 hours with naproxen (free acid). There are no differences between the 2 forms in the post-absorption phase pharmacokinetics. The difference in initial absorption should be considered when treating acute pain, since naproxen sodium may offer a quicker onset of action. The mean Cmax for the various formulations (immediate release, enteric coated, controlled release etc.) of naproxen are comparable and range from 94 mcg/mL to 97.4 mcg/mL. In one pharmacokinetic study, the mean Tmax of naproxen 500 mg (immediate release) given every 12 hours over 5 days was 3 hours, compared to a mean Tmax of 5 hours for Naprelan 1000 mg (controlled release) given every 24 hours over 5 days. In this same study, the AUC 0-24hr was 1446mcgxhr/mL for naproxen immediate release and 1448 mcgxhr/mL for the controlled release formulation. A separate study comparing the pharmacokinetics of Naprosyn tablets and EC-Naprosyn observed the following values: Tmax and AUC 0-12hrs of EC-Naprosyn were 4 hours and 845 mcgxhr/mL respectively, and Tmax and AUC 0-12hrs values of Naprosyn were 1.9 hours and 767 mcgxhr/mL respectively. When given in combination with sumatriptan the Cmax of naproxen is roughly 36% lower compared to naproxen sodium 550 mg tablets, and the median Tmax is 5 hours. Based on the AUC and Cmax of naproxen, Vimovo (naproxen/esomeprazole combination product) and enteric-coated naproxen may be considered bioequivalent. Overall, naproxen is rapidly and completely absorbed when administered orally and rectally. Food may contribute to a delay in the absorption of orally administered naproxen, but will not affect the extent of absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Naproxen has a volume of distribution of 0.16 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Naproxen is highly protein bound with >99% of the drug bound to albumin at therapeutic levels. •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): Naproxen is heavily metabolized in the liver and undergoes both Phase I and Phase II metabolism. The first step involves demethylation of naproxen via CYP 1A2, 2C8, and 2C9. Both naproxen and desmethylnaproxen proceed to Phase II metabolism; however, desmethylnaproxen can form both acyl and phenolic glucoronide products, while naproxen only produces the acyl glucuronide. The acyl glucuronidation process involves UGT 1A1, 1A3, 1A6, 1A7, 1A9, 1A10 and 2B7, while phenolic glucuronidation is catalyzed by UGT 1A1, 1A7,1A9, and 1A10. Desmethylnaproxen also undergoes sulphation which is mediated by SULT 1A1, 1B1 and 1E1. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After oral administration, about 95% of naproxen and it's metabolites can be recovered in the urine with 66-92% recovered as conjugated metabolite and less than 1% recovered as naproxen or desmethylnaproxen. Less than 5% of naproxen is excreted in the 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 naproxen is reported to be 12-17 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Naproxen is cleared at a rate of 0.13 mL/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Although the over-the-counter (OTC) availability of naproxen provides convenience to patients, it also increases the likelihood of overdose. Thankfully, the extent of overdose is typically mild with adverse effects normally limited to drowsiness, lethargy, epigastric pain, nausea and vomiting. Although there is no antidote for naproxen overdose, symptoms will typically subside with appropriate supportive care. Naproxen is classified as Category B during the first 2 trimesters of pregnancy, and as Category D during the third trimester. Naproxen is contraindicated in the 3rd trimester since it increases the risk of premature closure of the fetal ductus arteriosus and should be avoided in pregnant women starting at 30 weeks gestation. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aleve, Aleve PM, Aleve-D, Anaprox, Naprelan, Naprosyn, Sallus, Sudafed Sinus & Pain, Treximet, Vimovo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-Naproxen Naprolag Naproxen Naproxène Naproxeno Naproxenum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Naproxen is an NSAID used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, tendinitis, bursitis, acute gout, primary dysmenorrhea, and mild to moderate pain.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Naproxen interact? Information: •Drug A: Abciximab •Drug B: Naproxen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Naproxen 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. •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): Naproxen is indicated for the management of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, tendinitis, bursitis, acute gout, primary dysmenorrhea, and for the relief of mild to moderate pain. Further, it is first-line therapy for osteoarthritis, acute gouty arthritis, dysmenorrhea, and musculoskeletal inflammation and pain. •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): Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood. Although naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control. A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use. Further, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs. Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers. •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): As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme. •Absorption (Drug A): No absorption available •Absorption (Drug B): Naproxen is available as a free acid and sodium salt. At comparable doses, (naproxen 500 mg = naproxen sodium 550 mg) they differ slightly in their rates of absorption, but otherwise they are therapeutically and pharmacologically equivalent. Naproxen sodium achieves a peak plasma concentration after 1 hour, while peak plasma concentration is observed after 2 hours with naproxen (free acid). There are no differences between the 2 forms in the post-absorption phase pharmacokinetics. The difference in initial absorption should be considered when treating acute pain, since naproxen sodium may offer a quicker onset of action. The mean Cmax for the various formulations (immediate release, enteric coated, controlled release etc.) of naproxen are comparable and range from 94 mcg/mL to 97.4 mcg/mL. In one pharmacokinetic study, the mean Tmax of naproxen 500 mg (immediate release) given every 12 hours over 5 days was 3 hours, compared to a mean Tmax of 5 hours for Naprelan 1000 mg (controlled release) given every 24 hours over 5 days. In this same study, the AUC 0-24hr was 1446mcgxhr/mL for naproxen immediate release and 1448 mcgxhr/mL for the controlled release formulation. A separate study comparing the pharmacokinetics of Naprosyn tablets and EC-Naprosyn observed the following values: Tmax and AUC 0-12hrs of EC-Naprosyn were 4 hours and 845 mcgxhr/mL respectively, and Tmax and AUC 0-12hrs values of Naprosyn were 1.9 hours and 767 mcgxhr/mL respectively. When given in combination with sumatriptan the Cmax of naproxen is roughly 36% lower compared to naproxen sodium 550 mg tablets, and the median Tmax is 5 hours. Based on the AUC and Cmax of naproxen, Vimovo (naproxen/esomeprazole combination product) and enteric-coated naproxen may be considered bioequivalent. Overall, naproxen is rapidly and completely absorbed when administered orally and rectally. Food may contribute to a delay in the absorption of orally administered naproxen, but will not affect the extent of absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Naproxen has a volume of distribution of 0.16 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Naproxen is highly protein bound with >99% of the drug bound to albumin at therapeutic levels. •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): Naproxen is heavily metabolized in the liver and undergoes both Phase I and Phase II metabolism. The first step involves demethylation of naproxen via CYP 1A2, 2C8, and 2C9. Both naproxen and desmethylnaproxen proceed to Phase II metabolism; however, desmethylnaproxen can form both acyl and phenolic glucoronide products, while naproxen only produces the acyl glucuronide. The acyl glucuronidation process involves UGT 1A1, 1A3, 1A6, 1A7, 1A9, 1A10 and 2B7, while phenolic glucuronidation is catalyzed by UGT 1A1, 1A7,1A9, and 1A10. Desmethylnaproxen also undergoes sulphation which is mediated by SULT 1A1, 1B1 and 1E1. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After oral administration, about 95% of naproxen and it's metabolites can be recovered in the urine with 66-92% recovered as conjugated metabolite and less than 1% recovered as naproxen or desmethylnaproxen. Less than 5% of naproxen is excreted in the 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 naproxen is reported to be 12-17 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Naproxen is cleared at a rate of 0.13 mL/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Although the over-the-counter (OTC) availability of naproxen provides convenience to patients, it also increases the likelihood of overdose. Thankfully, the extent of overdose is typically mild with adverse effects normally limited to drowsiness, lethargy, epigastric pain, nausea and vomiting. Although there is no antidote for naproxen overdose, symptoms will typically subside with appropriate supportive care. Naproxen is classified as Category B during the first 2 trimesters of pregnancy, and as Category D during the third trimester. Naproxen is contraindicated in the 3rd trimester since it increases the risk of premature closure of the fetal ductus arteriosus and should be avoided in pregnant women starting at 30 weeks gestation. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aleve, Aleve PM, Aleve-D, Anaprox, Naprelan, Naprosyn, Sallus, Sudafed Sinus & Pain, Treximet, Vimovo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-Naproxen Naprolag Naproxen Naproxène Naproxeno Naproxenum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Naproxen is an NSAID used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, tendinitis, bursitis, acute gout, primary dysmenorrhea, and mild to moderate pain. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Natalizumab interact?

•Drug A: Abciximab •Drug B: Natalizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Natalizumab. •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 . •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): Natalizumab is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. It is also indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn’s disease with evidence of inflammation who have had an inadequate response to or are unable to tolerate, conventional therapies and inhibitors of TNF-α. It is not to be used in combination with immunosuppressants or inhibitors of TNF-α. •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): Natalizumab is a disease-modifying drug that works to alleviate the symptoms of multiple sclerosis and Crohn’s disease by attenuating inflammation. A reduction in lesions was observed in patients with multiple sclerosis who received natalizumab. Natalizumab increases the number of circulating leukocytes, including lymphocytes, monocytes, basophils, and eosinophils; this effect is attributed to natalizumab inhibiting their transmigration out of the vascular space. Natalizumab does not affect the absolute count of circulating neutrophils. •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): Integrins are transmembrane receptors and adhesion molecules that facilitate the chemotaxis of leukocytes to inflammation sites. Made up of multiple subunits, α4 integrins form heterodimers with β-subunits to form functional molecules. During inflammation, endothelial cells lining blood vessels are activated by cytokines. There is increased expression of cell adhesion molecules on the vascular endothelium, such as vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), expressed on vascular endothelial cells of the gastrointestinal tract. These cell adhesion molecules act as ligands or counter-receptors for α4 integrin receptors expressed primarily on lymphocytes, monocytes, and eosinophils. The interaction between cell adhesion molecules and α4 integrin facilitates the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue, activation and proliferation of lymphocytes, and enhanced activity of local cytokines and chemokines. α4 integrin can also interact with extracellular matrix molecules such as fibronectin and osteopontin to further propagate inflammation. Natalizumab binds to the α4 subunit of α4β1 and α4β7 integrin receptors to block the α4-mediated adhesion of leukocytes to their counter-receptors. In vitro, natalizumab also blocks α4-mediated cell binding to osteopontin and an alternatively spliced domain of fibronectin, connecting segment-1 (CS-1). In vivo, natalizumab may further inhibit the interaction of α4-expressing leukocytes with their ligand(s) in the extracellular matrix and on parenchymal cells, thereby inhibiting further recruitment and inflammatory activity of activated immune cells. The specific mechanism(s) by which natalizumab exerts its effects in multiple sclerosis and Crohn’s disease have not been fully defined. Lesions in multiple sclerosis (MS) are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves the interaction between adhesion molecules on inflammatory cells and their counter-receptors expressed on endothelial cells lining blood vessels. Natalizumab blocks the molecular interaction of α4β1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain; thereby, natalizumab reduces leukocyte migration into brain parenchyma and reduces plaque formation associated with MS. The interaction of the α4β7 integrin with the endothelial receptor MAdCAM1 has been implicated as an important contributor to chronic inflammation in Crohn’s disease (CD). MAdCAM-1 is mainly expressed on gut endothelial cells and is critical in homing T lymphocytes to gut lymph tissue found in Peyer’s patches. Increased MAdCAM-1 expression is often observed at active inflammation sites in patients with CD, suggesting that MAdCAM-1 may be involved in the recruitment of leukocytes to the mucosa. The clinical effect of natalizumab in CD may, therefore, be secondary to the blockade of the molecular interaction of the α4ß7 integrin receptor with MAdCAM-1 expressed on the venular endothelium at inflammatory foci. VCAM-1 expression has been found to be upregulated on colonic endothelial cells in a mouse model of inflammatory bowel disease and appears to play a role in leukocyte recruitment to sites of inflammation; however, the role of VCAM-1 in CD is unclear. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD maximum observed serum concentration was 110 ± 52 mcg/mL. Mean average steady-state trough concentrations ranged from 23 mcg/mL to 29 mcg/mL. The observed time to steady-state was approximately 24 weeks after every four weeks of dosing. In patients with Crohn's Disease, the mean ± SD maximum observed serum concentration was 101 ± 34 mcg/mL. The mean ± SD average steady-state trough concentration was 10 ± 9 mcg/mL. The estimated time to steady-state was approximately 16 to 24 weeks after every four weeks of dosing. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD volume of distribution was 5.7 ± 1.9 L. In patients with Crohn's Disease, it was 5.2 ± 2.8 L. •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): No information is available. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No information is 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 the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD half-life was 11 ± 4 days. In patients with Crohn's Disease, it was 10 ± 7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD clearance was 16 ± 5 mL/hour. In patients with Crohn's Disease, it was 22 ± 22 mL/hour. Natalizumab clearance increased with body weight in a less-than-proportional manner. The presence of persistent anti-natalizumab antibodies increased natalizumab clearance approximately 3-fold. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information regarding the acute toxicity (LD 50 ) and overdosage of natalizumab. The safety of doses higher than 300 mg has not been adequately evaluated. The maximum amount of natalizumab that can be safely administered has not been determined. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tysabri •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Natalizumab is a monoclonal anti-integrin antibody used to treat Crohn's disease or multiple sclerosis.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Natalizumab interact? Information: •Drug A: Abciximab •Drug B: Natalizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Natalizumab. •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 . •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): Natalizumab is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. It is also indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn’s disease with evidence of inflammation who have had an inadequate response to or are unable to tolerate, conventional therapies and inhibitors of TNF-α. It is not to be used in combination with immunosuppressants or inhibitors of TNF-α. •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): Natalizumab is a disease-modifying drug that works to alleviate the symptoms of multiple sclerosis and Crohn’s disease by attenuating inflammation. A reduction in lesions was observed in patients with multiple sclerosis who received natalizumab. Natalizumab increases the number of circulating leukocytes, including lymphocytes, monocytes, basophils, and eosinophils; this effect is attributed to natalizumab inhibiting their transmigration out of the vascular space. Natalizumab does not affect the absolute count of circulating neutrophils. •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): Integrins are transmembrane receptors and adhesion molecules that facilitate the chemotaxis of leukocytes to inflammation sites. Made up of multiple subunits, α4 integrins form heterodimers with β-subunits to form functional molecules. During inflammation, endothelial cells lining blood vessels are activated by cytokines. There is increased expression of cell adhesion molecules on the vascular endothelium, such as vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), expressed on vascular endothelial cells of the gastrointestinal tract. These cell adhesion molecules act as ligands or counter-receptors for α4 integrin receptors expressed primarily on lymphocytes, monocytes, and eosinophils. The interaction between cell adhesion molecules and α4 integrin facilitates the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue, activation and proliferation of lymphocytes, and enhanced activity of local cytokines and chemokines. α4 integrin can also interact with extracellular matrix molecules such as fibronectin and osteopontin to further propagate inflammation. Natalizumab binds to the α4 subunit of α4β1 and α4β7 integrin receptors to block the α4-mediated adhesion of leukocytes to their counter-receptors. In vitro, natalizumab also blocks α4-mediated cell binding to osteopontin and an alternatively spliced domain of fibronectin, connecting segment-1 (CS-1). In vivo, natalizumab may further inhibit the interaction of α4-expressing leukocytes with their ligand(s) in the extracellular matrix and on parenchymal cells, thereby inhibiting further recruitment and inflammatory activity of activated immune cells. The specific mechanism(s) by which natalizumab exerts its effects in multiple sclerosis and Crohn’s disease have not been fully defined. Lesions in multiple sclerosis (MS) are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves the interaction between adhesion molecules on inflammatory cells and their counter-receptors expressed on endothelial cells lining blood vessels. Natalizumab blocks the molecular interaction of α4β1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain; thereby, natalizumab reduces leukocyte migration into brain parenchyma and reduces plaque formation associated with MS. The interaction of the α4β7 integrin with the endothelial receptor MAdCAM1 has been implicated as an important contributor to chronic inflammation in Crohn’s disease (CD). MAdCAM-1 is mainly expressed on gut endothelial cells and is critical in homing T lymphocytes to gut lymph tissue found in Peyer’s patches. Increased MAdCAM-1 expression is often observed at active inflammation sites in patients with CD, suggesting that MAdCAM-1 may be involved in the recruitment of leukocytes to the mucosa. The clinical effect of natalizumab in CD may, therefore, be secondary to the blockade of the molecular interaction of the α4ß7 integrin receptor with MAdCAM-1 expressed on the venular endothelium at inflammatory foci. VCAM-1 expression has been found to be upregulated on colonic endothelial cells in a mouse model of inflammatory bowel disease and appears to play a role in leukocyte recruitment to sites of inflammation; however, the role of VCAM-1 in CD is unclear. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD maximum observed serum concentration was 110 ± 52 mcg/mL. Mean average steady-state trough concentrations ranged from 23 mcg/mL to 29 mcg/mL. The observed time to steady-state was approximately 24 weeks after every four weeks of dosing. In patients with Crohn's Disease, the mean ± SD maximum observed serum concentration was 101 ± 34 mcg/mL. The mean ± SD average steady-state trough concentration was 10 ± 9 mcg/mL. The estimated time to steady-state was approximately 16 to 24 weeks after every four weeks of dosing. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD volume of distribution was 5.7 ± 1.9 L. In patients with Crohn's Disease, it was 5.2 ± 2.8 L. •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): No information is available. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No information is 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 the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD half-life was 11 ± 4 days. In patients with Crohn's Disease, it was 10 ± 7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following the repeat intravenous administration of a 300 mg dose of natalizumab in patients with multiple sclerosis, the mean ± SD clearance was 16 ± 5 mL/hour. In patients with Crohn's Disease, it was 22 ± 22 mL/hour. Natalizumab clearance increased with body weight in a less-than-proportional manner. The presence of persistent anti-natalizumab antibodies increased natalizumab clearance approximately 3-fold. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information regarding the acute toxicity (LD 50 ) and overdosage of natalizumab. The safety of doses higher than 300 mg has not been adequately evaluated. The maximum amount of natalizumab that can be safely administered has not been determined. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tysabri •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Natalizumab is a monoclonal anti-integrin antibody used to treat Crohn's disease or multiple sclerosis. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Necitumumab interact?

•Drug A: Abciximab •Drug B: Necitumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Necitumumab. •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 . •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): Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). It is not indicated for treatment of non-squamous NSCLC. •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): Necitumumab is an EGFR antagonist that functions by binding to epidermal growth factor receptor (EGFR) and preventing binding of its ligands, a process that is involved in cell proliferation, metastasis, angiogenesis, and malignant progression. Binding of necitumumab to EGFR induces receptor internalization and degradation. •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): Steady state volume of distribution is 7.0 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): Elimination half life is approximately 14 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): 14.1 mL/h •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The poor safety profile of necitumumab has been one of the major limitations of its use. Rigorous monitoring of the following adverse events is recommended for the use of this drug: cardiopulmonary arrest, hypomagnesia, venous and arterial thromboembolic events, dermatologic toxicities, and infusion-related reactions. Due to observations of increased toxicity and mortality in treatment of non-squamous NSCLC, necitumumab is only recommended for the treatment of squamous NSCLC in combination with cisplatin and gemcitabine. Animal studies suggest potential embryo-fetal toxicity. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Portrazza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Necitumumab is a monoclonal antibody used to treat metastatic squamous non-small cell lung cancer.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Necitumumab interact? Information: •Drug A: Abciximab •Drug B: Necitumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Necitumumab. •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 . •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): Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). It is not indicated for treatment of non-squamous NSCLC. •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): Necitumumab is an EGFR antagonist that functions by binding to epidermal growth factor receptor (EGFR) and preventing binding of its ligands, a process that is involved in cell proliferation, metastasis, angiogenesis, and malignant progression. Binding of necitumumab to EGFR induces receptor internalization and degradation. •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): Steady state volume of distribution is 7.0 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): Elimination half life is approximately 14 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): 14.1 mL/h •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The poor safety profile of necitumumab has been one of the major limitations of its use. Rigorous monitoring of the following adverse events is recommended for the use of this drug: cardiopulmonary arrest, hypomagnesia, venous and arterial thromboembolic events, dermatologic toxicities, and infusion-related reactions. Due to observations of increased toxicity and mortality in treatment of non-squamous NSCLC, necitumumab is only recommended for the treatment of squamous NSCLC in combination with cisplatin and gemcitabine. Animal studies suggest potential embryo-fetal toxicity. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Portrazza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Necitumumab is a monoclonal antibody used to treat metastatic squamous non-small cell lung cancer. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Nefazodone interact?

•Drug A: Abciximab •Drug B: Nefazodone •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Nefazodone is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 depression. •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): Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors. •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): Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT 2 ) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant. •Absorption (Drug A): No absorption available •Absorption (Drug B): Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.22 to 0.87 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Greater than 99% (in vitro, 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): Hepatic. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged 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): 2-4 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone. •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): Nefazodona Nefazodone Nefazodonum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nefazodone is an antidepressant used in the treatment of depression.

It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Nefazodone interact? Information: •Drug A: Abciximab •Drug B: Nefazodone •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Nefazodone is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 depression. •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): Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors. •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): Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT 2 ) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant. •Absorption (Drug A): No absorption available •Absorption (Drug B): Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.22 to 0.87 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Greater than 99% (in vitro, 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): Hepatic. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged 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): 2-4 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone. •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): Nefazodona Nefazodone Nefazodonum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nefazodone is an antidepressant used in the treatment of depression. Output: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Nelarabine interact?

•Drug A: Abciximab •Drug B: Nelarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Nelarabine. •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. •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): ARRANON is indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. •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): Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent. Since T lymphoblasts have a higher expression of deoxycytidine kinase, ara-G preferentially accumulates in T cells over B cells, thus showing higher toxicity to T lymphoblasts. •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): Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. As a nucleoside analog, Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Due to its intact 3'-OH group, ara-GTP can be incorporated into the growing DNA strand without absolute chain termination. Despite that, the inclusion of ara-GTP into DNA strand can impair proper DNA repair processes, although the exact mechanism is not well understood, leading to inhibition of DNA elongation, apoptosis, and cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration of nelarabine to adult patients with refractory leukemia or lymphoma, plasma ara-G C max values generally occurred at the end of the nelarabine infusion and were generally higher than nelarabine C max values, suggesting rapid and extensive conversion of nelarabine to ara-G. Mean plasma nelarabine and ara-G C max values were 5.0 ± 3.0 mcg/mL and 31.4 ± 5.6 mcg/mL, respectively, after a 1,500 mg/m nelarabine dose infused over 2 hours in adult patients. The area under the concentration-time curve (AUC) of ara-G is 37 times higher than that for nelarabine on Day 1 after nelarabine IV infusion of 1,500 mg/m dose (162 ± 49 mcg.h/mL versus 4.4 ± 2.2 mcg.h/mL, respectively). Comparable C max and AUC values were obtained for nelarabine between Days 1 and 5 at the nelarabine adult dosage of 1,500 mg/m, indicating that nelarabine does not accumulate after multiple dosing. There are not enough ara-G data to make a comparison between Day 1 and Day 5. After a nelarabine adult dose of 1,500 mg/m, intracellular C max for ara-GTP appeared within 3 to 25 hours on Day 1. Exposure (AUC) to intracellular ara-GTP was 532 times higher than that for nelarabine and 14 times higher than that for ara-G (2,339 ± 2,628 mcg.h/mL versus 4.4 ± 2.2 mcg.h/mL and 162 ± 49 mcg.h/mL, respectively). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Nelarabine and ara-G are extensively distributed throughout the body. For nelarabine, V ss values were 197 ± 216 L/m in adult patients. For ara-G, V ss /F values were 50 ± 24 L/m in adult patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Nelarabine and ara-G are not substantially bound to human plasma proteins (< 25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 µM. •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 principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine. In addition, some nelarabine is hydrolyzed to form methylguanine, which is O-demethylated to form guanine. Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid. Ring opening of uric acid followed by further oxidation results in the formation of allantoin. Ring opening of uric acid followed by further oxidation results in the formation of allantoin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nelarabine and ara-G are partially eliminated by the kidneys. Mean urinary excretion of nelarabine and ara-G was 6.6 ± 4.7% and 27 ± 15% of the administered dose, respectively, in 28 adult patients over the 24 hours after nelarabine infusion on Day 1. •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): Nelarabine and ara-G are rapidly eliminated from plasma with a mean half-life of 18 minutes and 3.2 hours, respectively, in adult patients. For pediatric patients, the half-life of nelarabine and ara-G are 13 minutes and 2 hours, respectively. Because the intracellular levels of ara-GTP were so prolonged, its elimination half-life could not be accurately estimated. •Clearance (Drug A): No clearance available •Clearance (Drug B): Renal clearance averaged 24 ± 23 L/h for nelarabine and 6.2 ± 5.0 L/h for ara-G in 21 adult patients. Combined Phase I pharmacokinetic data at nelarabine doses of 199 to 2,900 mg/m (n = 66 adult patients) indicate that the mean clearance (CL) of nelarabine is 197 ± 189 L/h/m on Day 1. The apparent clearance of ara-G (CL/F) is 10.5 ± 4.5 L/h/m on Day 1. For pediatric patients receiving at a dose of 104 to 2,900 mg/m, the combined Phase I pharmacokinetic data indicate that the mean clearance (CL) of nelarabine is 259 ± 409 L/h/m, 30% higher than in adult patients. The apparent clearance of ara-G on day 1 is also higher in pediatric patients than in adult patients, estimated to be 11.3 ± 4.2 L/h/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Arranon, Atriance •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Nelarabina Nelarabine Nelzarabine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nelarabine is a purine nucleoside analog and antineoplastic agent used for the treatment of with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma with inadequate clinical response to prior chemotherapeutic treatments.

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. The severity of the interaction is minor.

Question: Does Abciximab and Nelarabine interact? Information: •Drug A: Abciximab •Drug B: Nelarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Nelarabine. •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. •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): ARRANON is indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. •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): Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent. Since T lymphoblasts have a higher expression of deoxycytidine kinase, ara-G preferentially accumulates in T cells over B cells, thus showing higher toxicity to T lymphoblasts. •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): Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. As a nucleoside analog, Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Due to its intact 3'-OH group, ara-GTP can be incorporated into the growing DNA strand without absolute chain termination. Despite that, the inclusion of ara-GTP into DNA strand can impair proper DNA repair processes, although the exact mechanism is not well understood, leading to inhibition of DNA elongation, apoptosis, and cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration of nelarabine to adult patients with refractory leukemia or lymphoma, plasma ara-G C max values generally occurred at the end of the nelarabine infusion and were generally higher than nelarabine C max values, suggesting rapid and extensive conversion of nelarabine to ara-G. Mean plasma nelarabine and ara-G C max values were 5.0 ± 3.0 mcg/mL and 31.4 ± 5.6 mcg/mL, respectively, after a 1,500 mg/m nelarabine dose infused over 2 hours in adult patients. The area under the concentration-time curve (AUC) of ara-G is 37 times higher than that for nelarabine on Day 1 after nelarabine IV infusion of 1,500 mg/m dose (162 ± 49 mcg.h/mL versus 4.4 ± 2.2 mcg.h/mL, respectively). Comparable C max and AUC values were obtained for nelarabine between Days 1 and 5 at the nelarabine adult dosage of 1,500 mg/m, indicating that nelarabine does not accumulate after multiple dosing. There are not enough ara-G data to make a comparison between Day 1 and Day 5. After a nelarabine adult dose of 1,500 mg/m, intracellular C max for ara-GTP appeared within 3 to 25 hours on Day 1. Exposure (AUC) to intracellular ara-GTP was 532 times higher than that for nelarabine and 14 times higher than that for ara-G (2,339 ± 2,628 mcg.h/mL versus 4.4 ± 2.2 mcg.h/mL and 162 ± 49 mcg.h/mL, respectively). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Nelarabine and ara-G are extensively distributed throughout the body. For nelarabine, V ss values were 197 ± 216 L/m in adult patients. For ara-G, V ss /F values were 50 ± 24 L/m in adult patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Nelarabine and ara-G are not substantially bound to human plasma proteins (< 25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 µM. •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 principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine. In addition, some nelarabine is hydrolyzed to form methylguanine, which is O-demethylated to form guanine. Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid. Ring opening of uric acid followed by further oxidation results in the formation of allantoin. Ring opening of uric acid followed by further oxidation results in the formation of allantoin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nelarabine and ara-G are partially eliminated by the kidneys. Mean urinary excretion of nelarabine and ara-G was 6.6 ± 4.7% and 27 ± 15% of the administered dose, respectively, in 28 adult patients over the 24 hours after nelarabine infusion on Day 1. •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): Nelarabine and ara-G are rapidly eliminated from plasma with a mean half-life of 18 minutes and 3.2 hours, respectively, in adult patients. For pediatric patients, the half-life of nelarabine and ara-G are 13 minutes and 2 hours, respectively. Because the intracellular levels of ara-GTP were so prolonged, its elimination half-life could not be accurately estimated. •Clearance (Drug A): No clearance available •Clearance (Drug B): Renal clearance averaged 24 ± 23 L/h for nelarabine and 6.2 ± 5.0 L/h for ara-G in 21 adult patients. Combined Phase I pharmacokinetic data at nelarabine doses of 199 to 2,900 mg/m (n = 66 adult patients) indicate that the mean clearance (CL) of nelarabine is 197 ± 189 L/h/m on Day 1. The apparent clearance of ara-G (CL/F) is 10.5 ± 4.5 L/h/m on Day 1. For pediatric patients receiving at a dose of 104 to 2,900 mg/m, the combined Phase I pharmacokinetic data indicate that the mean clearance (CL) of nelarabine is 259 ± 409 L/h/m, 30% higher than in adult patients. The apparent clearance of ara-G on day 1 is also higher in pediatric patients than in adult patients, estimated to be 11.3 ± 4.2 L/h/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Arranon, Atriance •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Nelarabina Nelarabine Nelzarabine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nelarabine is a purine nucleoside analog and antineoplastic agent used for the treatment of with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma with inadequate clinical response to prior chemotherapeutic treatments. Output: 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. The severity of the interaction is minor.

Does Abciximab and Nilotinib interact?

•Drug A: Abciximab •Drug B: Nilotinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Nilotinib. •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. •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 potential treatment of various leukemias, including chronic myeloid leukemia (CML). •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): Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML). •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): Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN107 to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP1-like-1-PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN107 for myeloproliferative diseases characterised by these kinase fusions (Stover et al, 2005; Weisberg et al, 2005). AMN107 also inhibits the c-Kit receptor kinase, including the D816V-mutated variant of KIT, at pharmacologically achievable concentrations, supporting potential utility in the treatment of mastocytosis, and gastrointestinal stromal tumours (Weisberg et al, 2005; von Bubnoff et al, 2005; Gleixner et al, 2006). •Absorption (Drug A): No absorption available •Absorption (Drug B): Orally 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): 15 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): Tasigna •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nilotinib is a kinase inhibitor used for the chronic phase treatment of Chronic Myeloid Leukemia (CML) that is Philadelphia chromosome positive and for the treatment of CML that is resistant to therapy containing imatinib.

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. The severity of the interaction is minor.

Question: Does Abciximab and Nilotinib interact? Information: •Drug A: Abciximab •Drug B: Nilotinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Nilotinib. •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. •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 potential treatment of various leukemias, including chronic myeloid leukemia (CML). •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): Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML). •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): Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN107 to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP1-like-1-PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN107 for myeloproliferative diseases characterised by these kinase fusions (Stover et al, 2005; Weisberg et al, 2005). AMN107 also inhibits the c-Kit receptor kinase, including the D816V-mutated variant of KIT, at pharmacologically achievable concentrations, supporting potential utility in the treatment of mastocytosis, and gastrointestinal stromal tumours (Weisberg et al, 2005; von Bubnoff et al, 2005; Gleixner et al, 2006). •Absorption (Drug A): No absorption available •Absorption (Drug B): Orally 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): 15 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): Tasigna •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nilotinib is a kinase inhibitor used for the chronic phase treatment of Chronic Myeloid Leukemia (CML) that is Philadelphia chromosome positive and for the treatment of CML that is resistant to therapy containing imatinib. Output: 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. The severity of the interaction is minor.

Does Abciximab and Nimesulide interact?

•Drug A: Abciximab •Drug B: Nimesulide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Nimesulide 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. •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 acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. •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): Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics. •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 therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed following oral administration. •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): >97.5% •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): Hepatic. Extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Renal (50%), fecal (29%) •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): 1.8–4.7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral TDLO (human): 1.429 mg/kg; Oral TDLO (woman): 2 mg/kg; Oral LD50 (rat): 200 mg/kg; Oral LD50 (mouse): 392 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): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nimesulide is a cyclooxygenase 2 inhibitor used to treat acute pain and primary dysmenorrhea.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Nimesulide interact? Information: •Drug A: Abciximab •Drug B: Nimesulide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Nimesulide 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. •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 acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. •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): Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics. •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 therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed following oral administration. •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): >97.5% •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): Hepatic. Extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Renal (50%), fecal (29%) •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): 1.8–4.7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral TDLO (human): 1.429 mg/kg; Oral TDLO (woman): 2 mg/kg; Oral LD50 (rat): 200 mg/kg; Oral LD50 (mouse): 392 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): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nimesulide is a cyclooxygenase 2 inhibitor used to treat acute pain and primary dysmenorrhea. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Nintedanib interact?

•Drug A: Abciximab •Drug B: Nintedanib •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Nintedanib is combined with Abciximab. •Extended Description: Nintedanib is an inhibitor of vascular endothelial growth factor receptor (VEGFR), a class of medications that have been shown to increase the risk of hemorrhagic events. Concomitant use of these agents with other anticoagulants may increase the risk of bleeding. •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): Nintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF) and to slow declining pulmonary function in patients with systemic sclerosis-associated interstitial lung disease. It is also indicated for the treatment of chronic fibrosing interstitial lung diseases with a progressive phenotype. In the EU, under the brand name Vargatef, nintedanib is indicated in combination with docetaxel for the treatment of adult patients with metastatic, locally advanced, or locally recurrent non-small cell lung cancer of adenocarcinoma histology who have already tried 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): Nintedanib is a small molecule kinase inhibitor that inhibits upstream kinase activity to ultimately inhibit lung fibroblast proliferation and migration, as well as signalling pathways that promote the proliferation and survival of endothelial and perivascular cells in tumour tissues. Nintedanib poses a risk of drug-induced liver injury, especially within the first three months of therapy. Liver function tests should be conducted at baseline prior to beginning therapy, at regular intervals for the first three months of therapy, and as indicated thereafter in patients exhibiting symptoms of hepatic injury such as jaundice or right upper quadrant pain. It is not recommended to be used in patients with pre-existing moderate to severe hepatic impairment (Child Pugh class B or C). •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): Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells. In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of nintedanib is low at approximately 4.7%, likely owing to substantial first-pass metabolism and the effects of p-glycoprotein (P-gp) transporters. T max following oral administration is reached after approximately 2 hours in fasted patients and approximately 4 hours in fed patients, regardless of the food consumed. Administration of nintedanib following a high-fat, high-calorie meal resulted in an increase in C max by approximately 15% and an increase in AUC by approximately 20%. Age, body weight, and smoking status have been found to alter exposure to nintedanib, but these effects are not significant enough to warrant dose alterations. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Nintedanib appears to follow biphasic disposition kinetics - the observed volume of distribution following intravenous administration is 1050 L, indicating extensive distribution into peripheral tissues. In rats, nintedanib was shown to rapidly and homogeneously distribute into peripheral tissues with the exception of the CNS, suggestive of an inability of nintedanib to cross the blood-brain barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding of nintedanib is high, with a bound fraction of 97.8%. Albumin is thought to be the major binding 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): Nintedanib is predominantly metabolized via hydrolytic cleavage by esterases to its principle metabolite, BIBF 1202, which then undergoes glucuronidation via UGT enzymes in the intestines and liver (specifically UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10) to form BIBF 1202 glucuronide. The CYP450 enzyme system plays a minor role in nintedanib metabolism, with CYP3A4 believed to be the main contributor - the major CYP-dependent metabolite of nintedanib, a demethylated metabolite termed BIBF 1053, could not be detected in plasma during pharmacokinetic studies and was found only in small quantities in the feces (approximately 4% of total dose). CYP-dependent metabolism of nintedanib accounts for roughly 5% of total drug metabolism, as opposed to 25% for esterase cleavage. Other minor metabolites, M7 and M8, are found in very small quantities in the urine (0.03% and 0.01%, respectively), though their origin and relevance is currently unclear. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nintedanib is eliminated primarily via fecal and biliary excretion, with 93.4% of radio labelled nintedanib found in feces within 120 hours following administration. Renal clearance accounts for a small portion of nintedanib's elimination, approximately 0.65% of the total dose, and excretion of unchanged nintedanib 48 hours after oral and intravenous doses was 0.05% and 1.4%, 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 terminal elimination half-life of nintedanib is approximately 10-15 hours. In patients with idiopathic pulmonary fibrosis, the effective half-life of nintedanib has been estimated to be approximately 9.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Nintedanib is has a high total plasma clearance of approximately 1390 mL/min and a renal clearance of 20 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Experience with nintedanib overdose is limited, but patients who inadvertently received higher-than-intended doses during initial trials experienced adverse effects consistent with the known safety profile of nintedanib, for example elevated liver enzymes and significant gastrointestinal effects. There are no specific guidelines for the treatment of nintedanib overdose - in this case, therapy should be interrupted and general supportive measures employed as indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ofev, Vargatef •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Nintedanib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nintedanib is a triple angiokinase inhibitor indicated for the treatment of idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and in combination with docetaxel for non-small cell lung cancer.

Nintedanib is an inhibitor of vascular endothelial growth factor receptor (VEGFR), a class of medications that have been shown to increase the risk of hemorrhagic events. Concomitant use of these agents with other anticoagulants may increase the risk of bleeding. The severity of the interaction is moderate.

Question: Does Abciximab and Nintedanib interact? Information: •Drug A: Abciximab •Drug B: Nintedanib •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Nintedanib is combined with Abciximab. •Extended Description: Nintedanib is an inhibitor of vascular endothelial growth factor receptor (VEGFR), a class of medications that have been shown to increase the risk of hemorrhagic events. Concomitant use of these agents with other anticoagulants may increase the risk of bleeding. •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): Nintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF) and to slow declining pulmonary function in patients with systemic sclerosis-associated interstitial lung disease. It is also indicated for the treatment of chronic fibrosing interstitial lung diseases with a progressive phenotype. In the EU, under the brand name Vargatef, nintedanib is indicated in combination with docetaxel for the treatment of adult patients with metastatic, locally advanced, or locally recurrent non-small cell lung cancer of adenocarcinoma histology who have already tried 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): Nintedanib is a small molecule kinase inhibitor that inhibits upstream kinase activity to ultimately inhibit lung fibroblast proliferation and migration, as well as signalling pathways that promote the proliferation and survival of endothelial and perivascular cells in tumour tissues. Nintedanib poses a risk of drug-induced liver injury, especially within the first three months of therapy. Liver function tests should be conducted at baseline prior to beginning therapy, at regular intervals for the first three months of therapy, and as indicated thereafter in patients exhibiting symptoms of hepatic injury such as jaundice or right upper quadrant pain. It is not recommended to be used in patients with pre-existing moderate to severe hepatic impairment (Child Pugh class B or C). •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): Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells. In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of nintedanib is low at approximately 4.7%, likely owing to substantial first-pass metabolism and the effects of p-glycoprotein (P-gp) transporters. T max following oral administration is reached after approximately 2 hours in fasted patients and approximately 4 hours in fed patients, regardless of the food consumed. Administration of nintedanib following a high-fat, high-calorie meal resulted in an increase in C max by approximately 15% and an increase in AUC by approximately 20%. Age, body weight, and smoking status have been found to alter exposure to nintedanib, but these effects are not significant enough to warrant dose alterations. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Nintedanib appears to follow biphasic disposition kinetics - the observed volume of distribution following intravenous administration is 1050 L, indicating extensive distribution into peripheral tissues. In rats, nintedanib was shown to rapidly and homogeneously distribute into peripheral tissues with the exception of the CNS, suggestive of an inability of nintedanib to cross the blood-brain barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding of nintedanib is high, with a bound fraction of 97.8%. Albumin is thought to be the major binding 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): Nintedanib is predominantly metabolized via hydrolytic cleavage by esterases to its principle metabolite, BIBF 1202, which then undergoes glucuronidation via UGT enzymes in the intestines and liver (specifically UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10) to form BIBF 1202 glucuronide. The CYP450 enzyme system plays a minor role in nintedanib metabolism, with CYP3A4 believed to be the main contributor - the major CYP-dependent metabolite of nintedanib, a demethylated metabolite termed BIBF 1053, could not be detected in plasma during pharmacokinetic studies and was found only in small quantities in the feces (approximately 4% of total dose). CYP-dependent metabolism of nintedanib accounts for roughly 5% of total drug metabolism, as opposed to 25% for esterase cleavage. Other minor metabolites, M7 and M8, are found in very small quantities in the urine (0.03% and 0.01%, respectively), though their origin and relevance is currently unclear. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nintedanib is eliminated primarily via fecal and biliary excretion, with 93.4% of radio labelled nintedanib found in feces within 120 hours following administration. Renal clearance accounts for a small portion of nintedanib's elimination, approximately 0.65% of the total dose, and excretion of unchanged nintedanib 48 hours after oral and intravenous doses was 0.05% and 1.4%, 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 terminal elimination half-life of nintedanib is approximately 10-15 hours. In patients with idiopathic pulmonary fibrosis, the effective half-life of nintedanib has been estimated to be approximately 9.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Nintedanib is has a high total plasma clearance of approximately 1390 mL/min and a renal clearance of 20 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Experience with nintedanib overdose is limited, but patients who inadvertently received higher-than-intended doses during initial trials experienced adverse effects consistent with the known safety profile of nintedanib, for example elevated liver enzymes and significant gastrointestinal effects. There are no specific guidelines for the treatment of nintedanib overdose - in this case, therapy should be interrupted and general supportive measures employed as indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ofev, Vargatef •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Nintedanib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nintedanib is a triple angiokinase inhibitor indicated for the treatment of idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and in combination with docetaxel for non-small cell lung cancer. Output: Nintedanib is an inhibitor of vascular endothelial growth factor receptor (VEGFR), a class of medications that have been shown to increase the risk of hemorrhagic events. Concomitant use of these agents with other anticoagulants may increase the risk of bleeding. The severity of the interaction is moderate.

Does Abciximab and Nivolumab interact?

•Drug A: Abciximab •Drug B: Nivolumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Nivolumab. •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 . •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): Nivolumab is indicated to treat unresectable or metastatic melanoma, melanoma as adjuvant treatment, resectable or metastatic non-small cell lung cancer, small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, hepatocellular carcinoma, and esophageal cancer. The indication for classical Hodgkin lymphoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, and hepatocellular carcinoma were approved under accelerated approval based on the overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Nivolumab is also approved for the treatment of HER2-negative advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma when used in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen. In combination with relatlimab, nivolumab is indicated for the treatment of patients ≥12 years old with unresectable or metastatic melanoma. •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): Nivolumab blocks PD-1 inhibitory signalling to T-cells. It has a long duration of action as it is administered every 2-4 weeks. Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion-related adverse effects, complications of allogenic hematopoietic stem cell transplants, embryo-fetal toxicity. •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 ligands PD-L1 and PD-L2 bind to the PD-1 receptor on T-cells, inhibiting the action of these cells. Tumor cells express PD-L1 and PD-L2. Nivolumab binds to PD-1, preventing PD-L1 and PD-L2 from inhibiting the action of T-cells, restoring a patient's tumor-specific T-cell response. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pharmacokinetic studies have suggested that nivolumab presents linear pharmacokinetics with a dose-proportional increase in peak concentration and AUC. The time to peak plasma concentration ranges between 1-4 hours. The absorption pharmacokinetic properties respective to the administration of a dose of 10 mg/kg are reported to be Cmax, Tmax and AUC of 242 µg/kg, 2.99 hours and 68100 µg*h/mL respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady state when a dose of 10 mg/kg of nivolumab is administered is reported to be 91.1 mL/kg. At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information regarding the plasma protein binding of nivolumab. •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 have not been formal studies regarding the specific metabolism of nivolumab but as a human monoclonal antibody, it has been suggested to be degraded to small peptides and individual amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There have not been studies regarding the specific route of elimination of nivolumab. •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 of nivolumab is approximately 20 days with an elimination half life of 26.7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The estimated clearance rate of nivolumab is 9.4 mL/h. The clearance rate seems to be increased according to body weight. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses of nivolumab are not readily available. Common adverse effects include Rash, pruritus, cough, upper respiratory tract infection, and peripheral edema. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Opdivo, Opdualag •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nivolumab is a PD-1 blocking antibody used to treat melanoma, non small-cell lung cancer, renal cell cancer, head and neck cancer, and Hodgkin lymphoma.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Nivolumab interact? Information: •Drug A: Abciximab •Drug B: Nivolumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Nivolumab. •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 . •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): Nivolumab is indicated to treat unresectable or metastatic melanoma, melanoma as adjuvant treatment, resectable or metastatic non-small cell lung cancer, small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, hepatocellular carcinoma, and esophageal cancer. The indication for classical Hodgkin lymphoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, and hepatocellular carcinoma were approved under accelerated approval based on the overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Nivolumab is also approved for the treatment of HER2-negative advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma when used in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen. In combination with relatlimab, nivolumab is indicated for the treatment of patients ≥12 years old with unresectable or metastatic melanoma. •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): Nivolumab blocks PD-1 inhibitory signalling to T-cells. It has a long duration of action as it is administered every 2-4 weeks. Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion-related adverse effects, complications of allogenic hematopoietic stem cell transplants, embryo-fetal toxicity. •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 ligands PD-L1 and PD-L2 bind to the PD-1 receptor on T-cells, inhibiting the action of these cells. Tumor cells express PD-L1 and PD-L2. Nivolumab binds to PD-1, preventing PD-L1 and PD-L2 from inhibiting the action of T-cells, restoring a patient's tumor-specific T-cell response. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pharmacokinetic studies have suggested that nivolumab presents linear pharmacokinetics with a dose-proportional increase in peak concentration and AUC. The time to peak plasma concentration ranges between 1-4 hours. The absorption pharmacokinetic properties respective to the administration of a dose of 10 mg/kg are reported to be Cmax, Tmax and AUC of 242 µg/kg, 2.99 hours and 68100 µg*h/mL respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady state when a dose of 10 mg/kg of nivolumab is administered is reported to be 91.1 mL/kg. At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information regarding the plasma protein binding of nivolumab. •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 have not been formal studies regarding the specific metabolism of nivolumab but as a human monoclonal antibody, it has been suggested to be degraded to small peptides and individual amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There have not been studies regarding the specific route of elimination of nivolumab. •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 of nivolumab is approximately 20 days with an elimination half life of 26.7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The estimated clearance rate of nivolumab is 9.4 mL/h. The clearance rate seems to be increased according to body weight. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses of nivolumab are not readily available. Common adverse effects include Rash, pruritus, cough, upper respiratory tract infection, and peripheral edema. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Opdivo, Opdualag •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Nivolumab is a PD-1 blocking antibody used to treat melanoma, non small-cell lung cancer, renal cell cancer, head and neck cancer, and Hodgkin lymphoma. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Nomegestrol acetate interact?

•Drug A: Abciximab •Drug B: Nomegestrol acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Nomegestrol acetate is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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): Nomegestrol acetate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): No summary available

Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Question: Does Abciximab and Nomegestrol acetate interact? Information: •Drug A: Abciximab •Drug B: Nomegestrol acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Nomegestrol acetate is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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): Nomegestrol acetate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): No summary available Output: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Does Abciximab and Nonacog beta pegol interact?

•Drug A: Abciximab •Drug B: Nonacog beta pegol •Severity: MAJOR •Description: The therapeutic efficacy of Nonacog beta pegol 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. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found

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. The severity of the interaction is major.

Question: Does Abciximab and Nonacog beta pegol interact? Information: •Drug A: Abciximab •Drug B: Nonacog beta pegol •Severity: MAJOR •Description: The therapeutic efficacy of Nonacog beta pegol 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. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found Output: 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. The severity of the interaction is major.

Does Abciximab and Norethisterone interact?

•Drug A: Abciximab •Drug B: Norethisterone •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Norethisterone is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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): Norethisterone is indicated as an oral contraceptive when given as monotherapy or in combination with an estrogen component, such as ethinylestradiol or estradiol. In combination with an estrogen component, oral norethisterone is also indicated as a hormone replacement therapy in the treatment of postmenopausal osteoporosis and moderate-to-severe vasomotor symptoms arising from menopause. When applied via transdermal patch, the combination of norethisterone and estradiol is indicated for the treatment of hypoestrogenism, vulvovaginal atrophy, and moderate-severe vasomotor symptoms. Norethisterone, taken in combination with intramuscular leuprolide, is also indicated for the symptomatic treatment of endometriosis-related pain. •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): Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation. A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses. •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): On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes. Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system. Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration. Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation. Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development. When used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium. As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies. Norethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor. While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes). •Absorption (Drug A): No absorption available •Absorption (Drug B): The C max of norethisterone following oral administration of a single dose ranges from 5.39 to 7.36 ng/mL with a T max of 1-2 hours. AUC 0-24 values following single oral doses range from approximately 30 to 37 ng*hr/mL. The oral bioavailability of norethisterone is approximately 64%. When applied transdermally, norethisterone is well-absorbed through the skin, reaches steady-state concentrations within 24 hours, and has a C max ranging from 617 to 1060 pg/mL at steady state. Norethisterone is often formulated as norethisterone acetate, which is completely and rapidly deacetylated to norethisterone following oral administration - the disposition of norethisterone acetate is indistinguishable from that of orally administered norethisterone. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of norethisterone is approximately 4 L/kg. Sulfated metabolites of norethisterone, as well as small quantities of parent drug, have been shown to distribute into breast milk. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Norethisterone is 38% bound to sex hormone-binding globulin and 61% bound 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): Norethisterone is extensively metabolized, primarily in the liver, to a number of metabolites via partial and total reduction of its A-ring. The enzymes predominantly involved are 3α- and 3β-hydroxysteroid dehydrogenase (HSD) as well as 5α- and 5β-reductase. The 5α-reduced metabolites, including 5α-dihydronorethisterone and its derivatives, appear to carry biological activity while the 5β-reduced metabolites appear inactive. Norethisterone and its metabolites are also extensively conjugated - most of the plasmatic metabolites are sulfate conjugates, while most of the urinary metabolites are glucuronide conjugates. The major metabolites in plasma are a disulfate conjugate of 3α,5α-tetrahydronorethisterone and a monosulfate conjugate of 3α,5β-tetrahydronorethisterone, while the major metabolite(s) in the urine are comprised of glucuronide and/or sulfate conjugates of 3α,5β-tetrahydronorethisterone. Norethisterone has also been observed to undergo some degree of metabolism via the cytochrome P450 enzyme system, predominantly by CYP3A4 and, to a much lesser extent, by CYP2C19, CYP1A2, and CYP2A6. The metabolites generated by these reactions have not been fully characterized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following administration of radio-labeled norethisterone, slightly more than 50% of the administered dose was eliminated in the urine and 20-40% was eliminated in the 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 half-life of norethisterone has been variably estimated as 8-10 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of norethisterone has been estimated as 0.4 L/hr/kg, and the intrinsic clearance is approximately 73-81 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in mice 6 g/kg and the TDLo in human women is 42 mg/kg. There have been no reports of serious ill effects following overdose of oral contraceptives, including following ingestion by children. Symptoms of overdosage are likely to be consistent with the adverse effect profile of the contraceptive and may, therefore, include significant nausea and/or vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Activella 1/0.5 28 Day, Activelle, Alyacen 1/35, Alyacen 7/7/7, Amabelz 0.5/0.1 28 Day, Aranelle 28, Aurovela, Aurovela Fe, Aygestin, Balziva 28 Day, Blisovi 21 Fe 1.5/30 28 Day Pack, Blisovi 21 Fe 1/20 28 Day Pack, Blisovi 24 Fe 1/20 28 Day, Brevicon, Briellyn 28 Day, Camila 28 Day, Charlotte 24 Fe Chewable 28 Day, Combipatch, Cyclafem 1/35 28 Day, Cyclafem 7/7/7 28 Day, Cyonanz 28 Day, Dasetta 1/35 28 Day, Dasetta 7/7/7 28 Day, Deblitane 28 Day, Emzahh 28 Day, Errin 28 Day, Estalis, Etyqa 0.5/0.1 28 Day, Femcon Fe 28 Day, Femhrt 0.5/2.5 28 Day, Finzala 24 Fe Chewable 28 Day, Fyavolv, Gemmily 28 Day, Hailey 1.5/30 21 Day, Hailey 24 Fe 28 Day, Hailey Fe 1.5/30 28 Day, Hailey Fe 1/20 28 Day, Heather 28 Day, Incassia, Jencycla 28 Day, Jinteli, Junel 1.5/30 21 Day, Junel 1/20 21 Day, Junel Fe 1.5/30 28 Day, Junel Fe 1/20 28 Day, Junel Fe 24 1/20 28 Day, Kaitlib Fe 28 Day, Larin 1.5/30, Larin 1/20, Larin 24 Fe 1/20, Larin Fe 1.5/30, Larin Fe 1/20, Layolis Fe 28, Leena 28 Day, Lo Loestrin Fe 28 Day, Loestrin 1.5/30 21 Day, Loestrin 24 Fe 28 Day, Loestrin Fe 1/20 28 Day, Lolo, Lomedia 24 Fe, Lopreeza 1/0.5 28 Day, Lupaneta Pack 1-month, Lyleq 28 Day, Lyza, Melodetta 24 Fe Chewable 28 Day, Merzee 28 Day, Mibelas 24 Fe Chewable 28 Day, Microgestin 1.5/30 21 Day, Microgestin 1/20 21 Day, Microgestin 24 Fe 28 Day, Microgestin Fe 1.5/30 28 Day, Microgestin Fe 1/20 28 Day, Mimvey, Minastrin 24 Fe Chewable 28 Day, Myfembree, Necon 0.5/35 28 Day, Necon 1/35 28 Day, Necon 7/7/7 28 Day, Nexesta Fe 28 Day, Nora-BE 28 Day, Norlutate, Norlyda 28 Day, Norlyroc 28 Day, Nortrel 1/35 21 Day, Nortrel 1/35 28 Day, Nortrel 7/7/7 28 Day, Nylia 1/35 28 Day, Nylia 7/7/7 28 Day, Oriahnn 28 Day Kit, Ortho Micronor, Ortho Micronor 28 Day, Ortho-novum 7/7/7 28 Day, Philith 28 Day, Pirmella 1/35 28 Day, Pirmella 7/7/7 28 Day, Rhuzdah 28 Day, Select, Sharobel 28 Day, Synphasic, Tarina 24 Fe 1/20 28 Day, Tarina Fe 1/20 28 Day, Taysofy 28 Day, Taytulla 28 Day, Tilia Fe, Tri-legest 28 Day, Tulana 28 Day, Vyfemla 28 Day, Wera 28 Day, Wymzya Fe 28 Day, Zenchent •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 19-nor-ethindrone 19-norethisterone Norethindrone Norethisteron Noréthistérone Norethisterone Norethisteronum Noretisterona •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Norethisterone is a synthetic second-generation progestin used for contraception, prevention of endometrial hyperplasia in hormone replacement therapy, and in the treatment of other hormone-mediated illnesses such as endometriosis.

Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Question: Does Abciximab and Norethisterone interact? Information: •Drug A: Abciximab •Drug B: Norethisterone •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Norethisterone is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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): Norethisterone is indicated as an oral contraceptive when given as monotherapy or in combination with an estrogen component, such as ethinylestradiol or estradiol. In combination with an estrogen component, oral norethisterone is also indicated as a hormone replacement therapy in the treatment of postmenopausal osteoporosis and moderate-to-severe vasomotor symptoms arising from menopause. When applied via transdermal patch, the combination of norethisterone and estradiol is indicated for the treatment of hypoestrogenism, vulvovaginal atrophy, and moderate-severe vasomotor symptoms. Norethisterone, taken in combination with intramuscular leuprolide, is also indicated for the symptomatic treatment of endometriosis-related pain. •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): Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation. A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses. •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): On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes. Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system. Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration. Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation. Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development. When used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium. As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies. Norethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor. While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes). •Absorption (Drug A): No absorption available •Absorption (Drug B): The C max of norethisterone following oral administration of a single dose ranges from 5.39 to 7.36 ng/mL with a T max of 1-2 hours. AUC 0-24 values following single oral doses range from approximately 30 to 37 ng*hr/mL. The oral bioavailability of norethisterone is approximately 64%. When applied transdermally, norethisterone is well-absorbed through the skin, reaches steady-state concentrations within 24 hours, and has a C max ranging from 617 to 1060 pg/mL at steady state. Norethisterone is often formulated as norethisterone acetate, which is completely and rapidly deacetylated to norethisterone following oral administration - the disposition of norethisterone acetate is indistinguishable from that of orally administered norethisterone. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of norethisterone is approximately 4 L/kg. Sulfated metabolites of norethisterone, as well as small quantities of parent drug, have been shown to distribute into breast milk. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Norethisterone is 38% bound to sex hormone-binding globulin and 61% bound 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): Norethisterone is extensively metabolized, primarily in the liver, to a number of metabolites via partial and total reduction of its A-ring. The enzymes predominantly involved are 3α- and 3β-hydroxysteroid dehydrogenase (HSD) as well as 5α- and 5β-reductase. The 5α-reduced metabolites, including 5α-dihydronorethisterone and its derivatives, appear to carry biological activity while the 5β-reduced metabolites appear inactive. Norethisterone and its metabolites are also extensively conjugated - most of the plasmatic metabolites are sulfate conjugates, while most of the urinary metabolites are glucuronide conjugates. The major metabolites in plasma are a disulfate conjugate of 3α,5α-tetrahydronorethisterone and a monosulfate conjugate of 3α,5β-tetrahydronorethisterone, while the major metabolite(s) in the urine are comprised of glucuronide and/or sulfate conjugates of 3α,5β-tetrahydronorethisterone. Norethisterone has also been observed to undergo some degree of metabolism via the cytochrome P450 enzyme system, predominantly by CYP3A4 and, to a much lesser extent, by CYP2C19, CYP1A2, and CYP2A6. The metabolites generated by these reactions have not been fully characterized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following administration of radio-labeled norethisterone, slightly more than 50% of the administered dose was eliminated in the urine and 20-40% was eliminated in the 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 half-life of norethisterone has been variably estimated as 8-10 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of norethisterone has been estimated as 0.4 L/hr/kg, and the intrinsic clearance is approximately 73-81 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in mice 6 g/kg and the TDLo in human women is 42 mg/kg. There have been no reports of serious ill effects following overdose of oral contraceptives, including following ingestion by children. Symptoms of overdosage are likely to be consistent with the adverse effect profile of the contraceptive and may, therefore, include significant nausea and/or vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Activella 1/0.5 28 Day, Activelle, Alyacen 1/35, Alyacen 7/7/7, Amabelz 0.5/0.1 28 Day, Aranelle 28, Aurovela, Aurovela Fe, Aygestin, Balziva 28 Day, Blisovi 21 Fe 1.5/30 28 Day Pack, Blisovi 21 Fe 1/20 28 Day Pack, Blisovi 24 Fe 1/20 28 Day, Brevicon, Briellyn 28 Day, Camila 28 Day, Charlotte 24 Fe Chewable 28 Day, Combipatch, Cyclafem 1/35 28 Day, Cyclafem 7/7/7 28 Day, Cyonanz 28 Day, Dasetta 1/35 28 Day, Dasetta 7/7/7 28 Day, Deblitane 28 Day, Emzahh 28 Day, Errin 28 Day, Estalis, Etyqa 0.5/0.1 28 Day, Femcon Fe 28 Day, Femhrt 0.5/2.5 28 Day, Finzala 24 Fe Chewable 28 Day, Fyavolv, Gemmily 28 Day, Hailey 1.5/30 21 Day, Hailey 24 Fe 28 Day, Hailey Fe 1.5/30 28 Day, Hailey Fe 1/20 28 Day, Heather 28 Day, Incassia, Jencycla 28 Day, Jinteli, Junel 1.5/30 21 Day, Junel 1/20 21 Day, Junel Fe 1.5/30 28 Day, Junel Fe 1/20 28 Day, Junel Fe 24 1/20 28 Day, Kaitlib Fe 28 Day, Larin 1.5/30, Larin 1/20, Larin 24 Fe 1/20, Larin Fe 1.5/30, Larin Fe 1/20, Layolis Fe 28, Leena 28 Day, Lo Loestrin Fe 28 Day, Loestrin 1.5/30 21 Day, Loestrin 24 Fe 28 Day, Loestrin Fe 1/20 28 Day, Lolo, Lomedia 24 Fe, Lopreeza 1/0.5 28 Day, Lupaneta Pack 1-month, Lyleq 28 Day, Lyza, Melodetta 24 Fe Chewable 28 Day, Merzee 28 Day, Mibelas 24 Fe Chewable 28 Day, Microgestin 1.5/30 21 Day, Microgestin 1/20 21 Day, Microgestin 24 Fe 28 Day, Microgestin Fe 1.5/30 28 Day, Microgestin Fe 1/20 28 Day, Mimvey, Minastrin 24 Fe Chewable 28 Day, Myfembree, Necon 0.5/35 28 Day, Necon 1/35 28 Day, Necon 7/7/7 28 Day, Nexesta Fe 28 Day, Nora-BE 28 Day, Norlutate, Norlyda 28 Day, Norlyroc 28 Day, Nortrel 1/35 21 Day, Nortrel 1/35 28 Day, Nortrel 7/7/7 28 Day, Nylia 1/35 28 Day, Nylia 7/7/7 28 Day, Oriahnn 28 Day Kit, Ortho Micronor, Ortho Micronor 28 Day, Ortho-novum 7/7/7 28 Day, Philith 28 Day, Pirmella 1/35 28 Day, Pirmella 7/7/7 28 Day, Rhuzdah 28 Day, Select, Sharobel 28 Day, Synphasic, Tarina 24 Fe 1/20 28 Day, Tarina Fe 1/20 28 Day, Taysofy 28 Day, Taytulla 28 Day, Tilia Fe, Tri-legest 28 Day, Tulana 28 Day, Vyfemla 28 Day, Wera 28 Day, Wymzya Fe 28 Day, Zenchent •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 19-nor-ethindrone 19-norethisterone Norethindrone Norethisteron Noréthistérone Norethisterone Norethisteronum Noretisterona •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Norethisterone is a synthetic second-generation progestin used for contraception, prevention of endometrial hyperplasia in hormone replacement therapy, and in the treatment of other hormone-mediated illnesses such as endometriosis. Output: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Does Abciximab and Norgestrel interact?

•Drug A: Abciximab •Drug B: Norgestrel •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Norgestrel is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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): Norgestrel in combination with ethinyl estradiol is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. •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): Norgestrel (and more specifically the active stereoisomer levonorgestrel) binds to the progesterone and estrogen receptors within the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy. •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): Cryselle 28, Elinest 28 Day, Lo/ovral 28 Day, Low-ogestrel 28 Day, Turqoz 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): LD norgestrel Methylnorethindrone Norgestrel Norgestrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Norgestrel is a progestin used in combination with ethinyl estradiol for oral contraception and prevention of pregnancy in women.

Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Question: Does Abciximab and Norgestrel interact? Information: •Drug A: Abciximab •Drug B: Norgestrel •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Norgestrel is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •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): Norgestrel in combination with ethinyl estradiol is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. •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): Norgestrel (and more specifically the active stereoisomer levonorgestrel) binds to the progesterone and estrogen receptors within the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy. •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): Cryselle 28, Elinest 28 Day, Lo/ovral 28 Day, Low-ogestrel 28 Day, Turqoz 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): LD norgestrel Methylnorethindrone Norgestrel Norgestrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Norgestrel is a progestin used in combination with ethinyl estradiol for oral contraception and prevention of pregnancy in women. Output: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. The severity of the interaction is moderate.

Does Abciximab and Obeticholic acid interact?

•Drug A: Abciximab •Drug B: Obeticholic acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Obeticholic acid. •Extended Description: Antiplatelet agents may enhance the bleeding risk when administered with cholic acid due to the additive effects of both drugs. •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): Obeticholic acid is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. It is also used as a monotherapy in adults with PBC that are unable to tolerate UDCA. Obeticholic acid is currently being considered for FDA approval to treat fibrosis caused by non-alcoholic liver steatohepatitis (NASH), and is likely to be approved for this indication in 2020. •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 activation of the FXR by obeticholic acid acts to reduce the synthesis of bile acids, inflammation, and the resulting hepatic fibrosis. This may increase the survival of patients with PBC, but to date, an association between obeticholic acid and survival in PBC has not been established. •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): Primary biliary cirrhosis is an autoimmune process by which the bile ducts and liver are damaged progressively, leading to fibrosis and cirrhosis. Bile acids increase the risk of damage and fibrosis to the damaged bile ducts. Obeticholic acid is a potent agonist of the farnesoid X receptor, which serves to regulate the hepatic metabolism of bile and cholesterol. This drug acts by binding to the farnesoid X receptor (FXR), found in the nucleus of liver and intestinal cells, which in turn increases liver bile flow, suppressing its production and decreasing hepatocyte exposure to excess levels of bile with cholestasis. Cholestasis is a process that normally causes inflammation and cirrhosis of the liver. •Absorption (Drug A): No absorption available •Absorption (Drug B): Obeticholic acid is absorbed in the gastrointestinal tract. The Cmax of obeticholic acid occurs at approximately 1.5 hours after an oral dose and ranges from 28.8-53.7 ng/mL at doses of 5-10mg. The median Tmax for both the conjugates of obeticholic acid is about 10 hours. One product monograph reports a Tmax of 4.5h for both 5 and 10mg doses. The AUC ranged from 236.6-568.1 ng/h/mL with 5mg to 10 mg doses. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of obeticholic acid is 618 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Obeticholic acid and its metabolic conjugates are >99% 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): The metabolism of obeticholic acid occurs in the liver. Obeticholic acid is conjugated with glycine or taurine, followed by secretion into bile. The conjugates are then absorbed in the small intestine and then re-enter the liver via enterohepatic circulation. The intestinal microbiota in the ileum converts conjugated obeticholic acid in a deconjugated form that may be either reabsorbed or eliminated. Glycine conjugates account for 13.8% of the metabolites and taurine conjugates account for 12.3%. Another metabolite, 3-glucuronide, may also be formed, but displays little pharmacological activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 87% of an orally administered dose is accounted for in the feces. Less than 3% of the dose can be recovered 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 biological half-life of obeticholic acid is reported to be 24 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance information for obeticholic acid is not readily available in the literature. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for obeticholic acid is not readily available in the literature. The maximum documented exposure to obeticholic acid was 500 mg in healthy research volunteers. Doses of 250 mg have been administered to healthy volunteers for 12 consecutive days. Pruritus and reversible transaminase liver elevations were observed. In PBC patients who received 25mg daily to 50mg daily (2.5 to 5 times the maximum recommended dose), dose-dependent transaminase and bilirubin elevations, ascites, primary biliary cholangitis aggravation, and new-onset jaundice were reported. In the case of an overdose with obeticholic acid, clinical monitoring and supportive care should be offered as they are required. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ocaliva •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 6-alpha-ethylchenodeoxycholic acid 6-ECDCA 6-Ethyl-CDCA Obeticholic acid •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Obeticholic acid is a bile acid analog and farnesoid X receptor agonist used to treat primary biliary cholangitis in adult patients with inadequate clinical response or intolerance to UDCA.

Antiplatelet agents may enhance the bleeding risk when administered with cholic acid due to the additive effects of both drugs. The severity of the interaction is moderate.

Question: Does Abciximab and Obeticholic acid interact? Information: •Drug A: Abciximab •Drug B: Obeticholic acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Obeticholic acid. •Extended Description: Antiplatelet agents may enhance the bleeding risk when administered with cholic acid due to the additive effects of both drugs. •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): Obeticholic acid is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. It is also used as a monotherapy in adults with PBC that are unable to tolerate UDCA. Obeticholic acid is currently being considered for FDA approval to treat fibrosis caused by non-alcoholic liver steatohepatitis (NASH), and is likely to be approved for this indication in 2020. •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 activation of the FXR by obeticholic acid acts to reduce the synthesis of bile acids, inflammation, and the resulting hepatic fibrosis. This may increase the survival of patients with PBC, but to date, an association between obeticholic acid and survival in PBC has not been established. •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): Primary biliary cirrhosis is an autoimmune process by which the bile ducts and liver are damaged progressively, leading to fibrosis and cirrhosis. Bile acids increase the risk of damage and fibrosis to the damaged bile ducts. Obeticholic acid is a potent agonist of the farnesoid X receptor, which serves to regulate the hepatic metabolism of bile and cholesterol. This drug acts by binding to the farnesoid X receptor (FXR), found in the nucleus of liver and intestinal cells, which in turn increases liver bile flow, suppressing its production and decreasing hepatocyte exposure to excess levels of bile with cholestasis. Cholestasis is a process that normally causes inflammation and cirrhosis of the liver. •Absorption (Drug A): No absorption available •Absorption (Drug B): Obeticholic acid is absorbed in the gastrointestinal tract. The Cmax of obeticholic acid occurs at approximately 1.5 hours after an oral dose and ranges from 28.8-53.7 ng/mL at doses of 5-10mg. The median Tmax for both the conjugates of obeticholic acid is about 10 hours. One product monograph reports a Tmax of 4.5h for both 5 and 10mg doses. The AUC ranged from 236.6-568.1 ng/h/mL with 5mg to 10 mg doses. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of obeticholic acid is 618 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Obeticholic acid and its metabolic conjugates are >99% 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): The metabolism of obeticholic acid occurs in the liver. Obeticholic acid is conjugated with glycine or taurine, followed by secretion into bile. The conjugates are then absorbed in the small intestine and then re-enter the liver via enterohepatic circulation. The intestinal microbiota in the ileum converts conjugated obeticholic acid in a deconjugated form that may be either reabsorbed or eliminated. Glycine conjugates account for 13.8% of the metabolites and taurine conjugates account for 12.3%. Another metabolite, 3-glucuronide, may also be formed, but displays little pharmacological activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 87% of an orally administered dose is accounted for in the feces. Less than 3% of the dose can be recovered 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 biological half-life of obeticholic acid is reported to be 24 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance information for obeticholic acid is not readily available in the literature. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for obeticholic acid is not readily available in the literature. The maximum documented exposure to obeticholic acid was 500 mg in healthy research volunteers. Doses of 250 mg have been administered to healthy volunteers for 12 consecutive days. Pruritus and reversible transaminase liver elevations were observed. In PBC patients who received 25mg daily to 50mg daily (2.5 to 5 times the maximum recommended dose), dose-dependent transaminase and bilirubin elevations, ascites, primary biliary cholangitis aggravation, and new-onset jaundice were reported. In the case of an overdose with obeticholic acid, clinical monitoring and supportive care should be offered as they are required. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ocaliva •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 6-alpha-ethylchenodeoxycholic acid 6-ECDCA 6-Ethyl-CDCA Obeticholic acid •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Obeticholic acid is a bile acid analog and farnesoid X receptor agonist used to treat primary biliary cholangitis in adult patients with inadequate clinical response or intolerance to UDCA. Output: Antiplatelet agents may enhance the bleeding risk when administered with cholic acid due to the additive effects of both drugs. The severity of the interaction is moderate.

Does Abciximab and Obiltoxaximab interact?

•Drug A: Abciximab •Drug B: Obiltoxaximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Obiltoxaximab. •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 . •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): Investigated for use/treatment in anthrax exposure, bacterial infection, crohn's disease, and graft versus host 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): 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): ETI-204 is an affinity-enhanced, de-immunized antibody, which means that its ability to bind to its target pathogen has been strengthened and that elements that might cause an immune response have been removed. ETI-204 targets and binds to Protective Antigen, which prevents the anthrax toxins from binding to and entering the cells in the body, thereby preventing death. •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): Anthim •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Obiltoxaximab is a monoclonal antibody used for prophylaxis or treatment of inhalational anthrax.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Obiltoxaximab interact? Information: •Drug A: Abciximab •Drug B: Obiltoxaximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Obiltoxaximab. •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 . •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): Investigated for use/treatment in anthrax exposure, bacterial infection, crohn's disease, and graft versus host 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): 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): ETI-204 is an affinity-enhanced, de-immunized antibody, which means that its ability to bind to its target pathogen has been strengthened and that elements that might cause an immune response have been removed. ETI-204 targets and binds to Protective Antigen, which prevents the anthrax toxins from binding to and entering the cells in the body, thereby preventing death. •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): Anthim •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Obiltoxaximab is a monoclonal antibody used for prophylaxis or treatment of inhalational anthrax. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Obinutuzumab interact?

•Drug A: Abciximab •Drug B: Obinutuzumab •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Obinutuzumab. •Extended Description: Obinutuzumab has the potential to cause thrombocytopenia.1 When combined with antiplatelet agents, the risk of bleeding from obinutuzumab is increased. •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): Obinutuzumab is used as a combination treatment with chlorambucil to treat patients with untreated chronic lymphocytic leukemia. •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): Obinutuzumab is more potent than rituximab in depleting B-cells, antitumor activity, and tumor regression. •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 contrast to rituximab, which is a classic type I CD20 antibody, obinutuzumab binds to type II CD20 antibodies. This allows obinutuzumab to have a much higher induction of antibody-dependant cytotoxicity and a higher direct cytotoxic effect than the classic CD20 antibodies. •Absorption (Drug A): No absorption available •Absorption (Drug B): Obinutuzumab is administered intravenously, so its absorption is 100%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Obinutuzumab has a volume of distribution of about 3.8 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Obinutuzumab 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): Obinutuzumab is not metabolized by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The route of elimination of obinutuzumab was not indicated (FDA label). •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 obinutuzumab is 28.4 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of obinutuzumab is 0.09L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most serious toxicities observed with obinutuzumab are Hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML). HBV reactivation can occur with all anti-CD20 antibodies and can result in hepatic failure, fulminant hepatitis, and death. PML occurs as a result of JC virus infection and can be fatal as well. Other common but less serious adverse reactions include infusion reactions (pre-treat with glucocorticoids, acetaminophen, and anti-histamine to prevent this), neutropenia, thrombocytopenia, and Tumor Lysis Syndrome (TLS) (pre-treat patients, especially with a high lymphocyte count and/or a high tumor burden, with anti-hyperuricemics and hydration). It is also recommended to NOT administer live virus vaccinations prior to or during obinutuzumab treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gazyva •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Obinutuzumab is an antineoplastic CD20 antibody used to treat untreated chronic lymphocytic leukemia in combination with chlorambucil.

Obinutuzumab has the potential to cause thrombocytopenia.1 When combined with antiplatelet agents, the risk of bleeding from obinutuzumab is increased. The severity of the interaction is moderate.

Question: Does Abciximab and Obinutuzumab interact? Information: •Drug A: Abciximab •Drug B: Obinutuzumab •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Obinutuzumab. •Extended Description: Obinutuzumab has the potential to cause thrombocytopenia.1 When combined with antiplatelet agents, the risk of bleeding from obinutuzumab is increased. •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): Obinutuzumab is used as a combination treatment with chlorambucil to treat patients with untreated chronic lymphocytic leukemia. •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): Obinutuzumab is more potent than rituximab in depleting B-cells, antitumor activity, and tumor regression. •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 contrast to rituximab, which is a classic type I CD20 antibody, obinutuzumab binds to type II CD20 antibodies. This allows obinutuzumab to have a much higher induction of antibody-dependant cytotoxicity and a higher direct cytotoxic effect than the classic CD20 antibodies. •Absorption (Drug A): No absorption available •Absorption (Drug B): Obinutuzumab is administered intravenously, so its absorption is 100%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Obinutuzumab has a volume of distribution of about 3.8 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Obinutuzumab 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): Obinutuzumab is not metabolized by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The route of elimination of obinutuzumab was not indicated (FDA label). •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 obinutuzumab is 28.4 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of obinutuzumab is 0.09L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most serious toxicities observed with obinutuzumab are Hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML). HBV reactivation can occur with all anti-CD20 antibodies and can result in hepatic failure, fulminant hepatitis, and death. PML occurs as a result of JC virus infection and can be fatal as well. Other common but less serious adverse reactions include infusion reactions (pre-treat with glucocorticoids, acetaminophen, and anti-histamine to prevent this), neutropenia, thrombocytopenia, and Tumor Lysis Syndrome (TLS) (pre-treat patients, especially with a high lymphocyte count and/or a high tumor burden, with anti-hyperuricemics and hydration). It is also recommended to NOT administer live virus vaccinations prior to or during obinutuzumab treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gazyva •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Obinutuzumab is an antineoplastic CD20 antibody used to treat untreated chronic lymphocytic leukemia in combination with chlorambucil. Output: Obinutuzumab has the potential to cause thrombocytopenia.1 When combined with antiplatelet agents, the risk of bleeding from obinutuzumab is increased. The severity of the interaction is moderate.

Does Abciximab and Ocrelizumab interact?

•Drug A: Abciximab •Drug B: Ocrelizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ocrelizumab. •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 . •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): Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Ocrelizumab is also indicated for the treatment of primary progressive MS in adults. •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): Since ocrelizumab interferes with the CD20 assay, CD19+B-cells are used to assess B-cell counts after treatment. Fourteen days following infusion, a reduction in CD19+B-cell counts was observed. In clinical studies, B-cell counts rose above the lower limit of normal (LLN) or baseline counts between infusions of ocrelizumab at least once in 0.3% to 4.1% of patients. In a clinical study involving 51 patients, the time for B-cell counts to return to baseline or LLN ranged from 27 to 125 weeks, with a median time of 72 weeks after the last infusion. Within 2.5 years after the last infusion, B-cell counts returned to either baseline or LNN in 90% of patients treated with ocrelizumab. Since ocrelizumab is a recombinant humanized antibody, it is expected to be less immunogenic than rituximab, a chimeric antibody. Compared to the ocrelizumab pivotal trial, a rituximab phase II trial had a higher proportion of anti-drug antibodies, suggesting greater immunogenicity. However, caution should be exercised since these studies used different assay methods, and the association between anti-drug antibody development and infusion reactions has not been fully elucidated. The use of ocrelizumab can cause infusion reactions, and lead to a higher risk of respiratory tract infections and viral infections. Cases of progressive multifocal leukoencephalopathy (PML) and immune-mediated colitis have been reported in patients treated with ocrelizumab. Also, an increased risk of malignancy may exist. •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): Ocrelizumab is a recombinant humanized antibody that targets CD20, a glycosylated phosphoprotein expressed on the surface of different types of B-cells. CD20 can be found on pre-B cells, naïve and memory B-cells, and it is not expressed on hematopoietic stem B-cells, pro-B cells (precursors), or differentiated plasma cells. Therefore, by targeting CD20, ocrelizumab does not affect the concentration of IgG and IgM antibodies in blood or the cerebrospinal fluid. B-cells contribute to the pathogenesis of multiple sclerosis (MS) through the activation of proinflammatory T-cells and the secretion of proinflammatory cytokines. Also, B-cells may differentiate into plasma cells that produce autoantibodies directed against myelin, leading to the complement-mediated attack on the myelin sheath. By targeting CD20, ocrelizumab specifically depletes B-cells. While the exact mechanism of ocrelizumab leading to B-cell depletion is unknown, there are several proposed mechanisms. It has been suggested that upon cell surface binding to CD20-expressing B-cells, ocrelizumab promotes antibody-dependent cellular cytotoxicity and complement-mediated cell lysis while preserving the capacity for B-cell reconstitution and preexisting humoral immunity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ocrelizumab displays a two-compartment pharmacokinetic model with time-dependent clearance. The overall exposure at the steady-state (AUC over the 24 week dosing intervals) of ocrelizumab was 3,510 mcg/mL per day. Following the intravenous infusion of maintenance doses of 600 mg every 6 months in relapsing MS patients, the mean peak plasma concentration of ocrelizumab (C max ) was 212 mcg/mL. Following intravenous infusion of two 300 mg doses separated by 14 days every 6 months in patients with PPMS, C max was 141 mcg/mL. Ocrelizumab follows linear and dose proportional pharmacokinetics between 400 mg and 2000 mg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In a population pharmacokinetic estimate, the central volume of distribution of ocrelizumab was 2.78 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): As with other antibodies, ocrelizumab is expected to undergo nonspecific catabolism and broken into smaller peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies (mAb) such as ocrelizumab are too large to be filtered by the kidneys, and therefore, not eliminated in urine under normal conditions. If antibody fragments of low molecular weight are filtered, they are usually reabsorbed and metabolized in the proximal tubule. The peptides and amino acids produced by catabolism are recycled or used as an energy source. •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 elimination half-life of ocrelizumab was 26 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The constant clearance of ocrelizumab was 0.17 L/day, while the initial time-dependent clearance was 0.05 L/day. Peripheral volume and inter-compartment clearance were 2.68 L and 0.29 L/day, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding ocrelizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as immune-mediated colitis. Symptomatic and supportive measures are recommended. The carcinogenic and mutagenic potentials of ocrelizumab have not been evaluated. In monkeys given three loading doses of 15 or 75 mg/kg intravenously, followed by weekly doses of 20 or 100 mg/kg for 8 weeks (2-10 times the recommended human dose), ocrelizumab did not have effects on reproductive organs. No reproductive effects were detected on the estrus cycle of female monkeys given the same ocrelizumab regimen. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ocrevus •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ocrelizumab is a CD20 specific monoclonal antibody used to treat relapsing remitting multiple sclerosis.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Ocrelizumab interact? Information: •Drug A: Abciximab •Drug B: Ocrelizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ocrelizumab. •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 . •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): Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Ocrelizumab is also indicated for the treatment of primary progressive MS in adults. •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): Since ocrelizumab interferes with the CD20 assay, CD19+B-cells are used to assess B-cell counts after treatment. Fourteen days following infusion, a reduction in CD19+B-cell counts was observed. In clinical studies, B-cell counts rose above the lower limit of normal (LLN) or baseline counts between infusions of ocrelizumab at least once in 0.3% to 4.1% of patients. In a clinical study involving 51 patients, the time for B-cell counts to return to baseline or LLN ranged from 27 to 125 weeks, with a median time of 72 weeks after the last infusion. Within 2.5 years after the last infusion, B-cell counts returned to either baseline or LNN in 90% of patients treated with ocrelizumab. Since ocrelizumab is a recombinant humanized antibody, it is expected to be less immunogenic than rituximab, a chimeric antibody. Compared to the ocrelizumab pivotal trial, a rituximab phase II trial had a higher proportion of anti-drug antibodies, suggesting greater immunogenicity. However, caution should be exercised since these studies used different assay methods, and the association between anti-drug antibody development and infusion reactions has not been fully elucidated. The use of ocrelizumab can cause infusion reactions, and lead to a higher risk of respiratory tract infections and viral infections. Cases of progressive multifocal leukoencephalopathy (PML) and immune-mediated colitis have been reported in patients treated with ocrelizumab. Also, an increased risk of malignancy may exist. •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): Ocrelizumab is a recombinant humanized antibody that targets CD20, a glycosylated phosphoprotein expressed on the surface of different types of B-cells. CD20 can be found on pre-B cells, naïve and memory B-cells, and it is not expressed on hematopoietic stem B-cells, pro-B cells (precursors), or differentiated plasma cells. Therefore, by targeting CD20, ocrelizumab does not affect the concentration of IgG and IgM antibodies in blood or the cerebrospinal fluid. B-cells contribute to the pathogenesis of multiple sclerosis (MS) through the activation of proinflammatory T-cells and the secretion of proinflammatory cytokines. Also, B-cells may differentiate into plasma cells that produce autoantibodies directed against myelin, leading to the complement-mediated attack on the myelin sheath. By targeting CD20, ocrelizumab specifically depletes B-cells. While the exact mechanism of ocrelizumab leading to B-cell depletion is unknown, there are several proposed mechanisms. It has been suggested that upon cell surface binding to CD20-expressing B-cells, ocrelizumab promotes antibody-dependent cellular cytotoxicity and complement-mediated cell lysis while preserving the capacity for B-cell reconstitution and preexisting humoral immunity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ocrelizumab displays a two-compartment pharmacokinetic model with time-dependent clearance. The overall exposure at the steady-state (AUC over the 24 week dosing intervals) of ocrelizumab was 3,510 mcg/mL per day. Following the intravenous infusion of maintenance doses of 600 mg every 6 months in relapsing MS patients, the mean peak plasma concentration of ocrelizumab (C max ) was 212 mcg/mL. Following intravenous infusion of two 300 mg doses separated by 14 days every 6 months in patients with PPMS, C max was 141 mcg/mL. Ocrelizumab follows linear and dose proportional pharmacokinetics between 400 mg and 2000 mg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In a population pharmacokinetic estimate, the central volume of distribution of ocrelizumab was 2.78 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): As with other antibodies, ocrelizumab is expected to undergo nonspecific catabolism and broken into smaller peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies (mAb) such as ocrelizumab are too large to be filtered by the kidneys, and therefore, not eliminated in urine under normal conditions. If antibody fragments of low molecular weight are filtered, they are usually reabsorbed and metabolized in the proximal tubule. The peptides and amino acids produced by catabolism are recycled or used as an energy source. •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 elimination half-life of ocrelizumab was 26 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The constant clearance of ocrelizumab was 0.17 L/day, while the initial time-dependent clearance was 0.05 L/day. Peripheral volume and inter-compartment clearance were 2.68 L and 0.29 L/day, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding ocrelizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as immune-mediated colitis. Symptomatic and supportive measures are recommended. The carcinogenic and mutagenic potentials of ocrelizumab have not been evaluated. In monkeys given three loading doses of 15 or 75 mg/kg intravenously, followed by weekly doses of 20 or 100 mg/kg for 8 weeks (2-10 times the recommended human dose), ocrelizumab did not have effects on reproductive organs. No reproductive effects were detected on the estrus cycle of female monkeys given the same ocrelizumab regimen. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ocrevus •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ocrelizumab is a CD20 specific monoclonal antibody used to treat relapsing remitting multiple sclerosis. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Ofatumumab interact?

•Drug A: Abciximab •Drug B: Ofatumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ofatumumab. •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 . •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): Ofatumumab is indicated, in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate. In patients with recurrent or progressive CLL, ofatumumab is indicated for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. Ofatumumab is indicated for the treatment of patients with CLL refractory to fludarabine and alemtuzumab. Ofatumumab is also indicated for the treatment of adult patients with relapsing forms of multiple sclerosis, including active secondary progressive disease, clinically isolated syndrome, and relapsing-remitting 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): Ofatumumab works by binding to and blocking the action of CD-20, a molecule expressed on the surface of both healthy and leukemic B lymphocytes. In patients with previously untreated chronic lymphocytic leukemia (CLL), ofatumumab caused B-cell depletion in the peripheral blood after six months following the last dose. However, observable depletion of B cells in the peripheral blood does not directly correlate with the depletion of B-cells in solid organs or malignant tumours. In vitro, ofatumumab induces complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). •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): CD20 is expressed on normal pre-B lymphocytes and mature B lymphocytes, as well as malignant B lymphocytes. Numerous studies demonstrate that the depletion of B-cells can significantly alleviate symptoms of many forms of leukemia and lymphoma, which are malignancies associated with B-cell dysfunctions and high expression of CD20. Ofatumumab is an anti-CD20 monoclonal antibody that binds to the small and large extracellular loops of the CD20 molecule. The Fab domain of ofatumumab binds to CD20, and this drug-target interaction does not result in immediate shedding and internalization of CD20 from the plasma membrane of B lymphocytes. This allows ofatumumab to persist on the B lymphocyte cell surface for an extended period and recruit immunological molecules or FcR-expressing innate effectors, such as macrophages, that mediate immune effector functions with strong cytotoxic effects. These immune effector functions include complement-dependent cytotoxicity (CCD) and antibody-dependent cellular cytotoxicity (ADCC), which promote the lysis of malignant B-cells. Complement-dependent cytotoxicity (CDC) involves translocation of the CD20 molecule into lipid rafts, which are involved in cell signalling and receptor trafficking. The mechanism by which ofatumumab exerts a therapeutic effect in multiple sclerosis patients is unknown but is presumed to still occur as a consequence of its ability to bind CD20. •Absorption (Drug A): No absorption available •Absorption (Drug B): In one study consisting of patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, the Cmax was 94 μg/mL and the Tmax was 7.3 hours following the first infusion of 300 mg ofatumumab. Following subcutaneous injection, ofatumumab is thought to be absorbed primarily into the lymphatic system. Subcutaneous dosing of 20 mg every four weeks resulted in a mean AUC tau of 483 μg*h/mL and a mean steady-state C max of 1.43 μg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with CLL, the mean volume of distribution at steady-state was 5.8 L. Repeated subcutaneous dosing with 20 mg of ofatumumab resulted in a steady-state volume of distribution of 5.42 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is limited information on the serum protein binding profile of ofatumumab. •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): Like other monoclonal antibodies, ofatumumab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target‐mediated disposition pathway. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ofatumumab undergoes elimination by a target-independent route and a target (B cell)-mediated route, with a dose-dependent clearance in the dose range of 100 to 2000 mg. As ofatumumab causes B-cell depletion, the clearance of ofatumumab mediated by B-cells is decreased substantially after subsequent drug infusions. •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 patients with CLL, the mean half-life at steady state was 17.1 days. Similarly, in patients given ofatumumab subcutaneously, the steady-state elimination half-life was estimated at 16 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with CLL, the mean clearance at steady-state was 11.6 mL/hour. In patients administered ofatumumab subcutaneously in repeated 20 mg injections, the steady-state clearance following B-cell depletion was estimated to be 0.34 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information on overdose of ofatumumab. Ofatumumab may cause B-cell depletion in the fetus when administered in pregnant women. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Arzerra, Kesimpta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ofatumumab is an anti-CD20 antibody used for the treatment of chronic lymphocytic leukemia (CLL) in selected patients with certain treatment histories and responsiveness to anticancer medications.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Ofatumumab interact? Information: •Drug A: Abciximab •Drug B: Ofatumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ofatumumab. •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 . •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): Ofatumumab is indicated, in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate. In patients with recurrent or progressive CLL, ofatumumab is indicated for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. Ofatumumab is indicated for the treatment of patients with CLL refractory to fludarabine and alemtuzumab. Ofatumumab is also indicated for the treatment of adult patients with relapsing forms of multiple sclerosis, including active secondary progressive disease, clinically isolated syndrome, and relapsing-remitting 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): Ofatumumab works by binding to and blocking the action of CD-20, a molecule expressed on the surface of both healthy and leukemic B lymphocytes. In patients with previously untreated chronic lymphocytic leukemia (CLL), ofatumumab caused B-cell depletion in the peripheral blood after six months following the last dose. However, observable depletion of B cells in the peripheral blood does not directly correlate with the depletion of B-cells in solid organs or malignant tumours. In vitro, ofatumumab induces complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). •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): CD20 is expressed on normal pre-B lymphocytes and mature B lymphocytes, as well as malignant B lymphocytes. Numerous studies demonstrate that the depletion of B-cells can significantly alleviate symptoms of many forms of leukemia and lymphoma, which are malignancies associated with B-cell dysfunctions and high expression of CD20. Ofatumumab is an anti-CD20 monoclonal antibody that binds to the small and large extracellular loops of the CD20 molecule. The Fab domain of ofatumumab binds to CD20, and this drug-target interaction does not result in immediate shedding and internalization of CD20 from the plasma membrane of B lymphocytes. This allows ofatumumab to persist on the B lymphocyte cell surface for an extended period and recruit immunological molecules or FcR-expressing innate effectors, such as macrophages, that mediate immune effector functions with strong cytotoxic effects. These immune effector functions include complement-dependent cytotoxicity (CCD) and antibody-dependent cellular cytotoxicity (ADCC), which promote the lysis of malignant B-cells. Complement-dependent cytotoxicity (CDC) involves translocation of the CD20 molecule into lipid rafts, which are involved in cell signalling and receptor trafficking. The mechanism by which ofatumumab exerts a therapeutic effect in multiple sclerosis patients is unknown but is presumed to still occur as a consequence of its ability to bind CD20. •Absorption (Drug A): No absorption available •Absorption (Drug B): In one study consisting of patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, the Cmax was 94 μg/mL and the Tmax was 7.3 hours following the first infusion of 300 mg ofatumumab. Following subcutaneous injection, ofatumumab is thought to be absorbed primarily into the lymphatic system. Subcutaneous dosing of 20 mg every four weeks resulted in a mean AUC tau of 483 μg*h/mL and a mean steady-state C max of 1.43 μg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with CLL, the mean volume of distribution at steady-state was 5.8 L. Repeated subcutaneous dosing with 20 mg of ofatumumab resulted in a steady-state volume of distribution of 5.42 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is limited information on the serum protein binding profile of ofatumumab. •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): Like other monoclonal antibodies, ofatumumab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target‐mediated disposition pathway. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ofatumumab undergoes elimination by a target-independent route and a target (B cell)-mediated route, with a dose-dependent clearance in the dose range of 100 to 2000 mg. As ofatumumab causes B-cell depletion, the clearance of ofatumumab mediated by B-cells is decreased substantially after subsequent drug infusions. •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 patients with CLL, the mean half-life at steady state was 17.1 days. Similarly, in patients given ofatumumab subcutaneously, the steady-state elimination half-life was estimated at 16 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with CLL, the mean clearance at steady-state was 11.6 mL/hour. In patients administered ofatumumab subcutaneously in repeated 20 mg injections, the steady-state clearance following B-cell depletion was estimated to be 0.34 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information on overdose of ofatumumab. Ofatumumab may cause B-cell depletion in the fetus when administered in pregnant women. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Arzerra, Kesimpta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ofatumumab is an anti-CD20 antibody used for the treatment of chronic lymphocytic leukemia (CLL) in selected patients with certain treatment histories and responsiveness to anticancer medications. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Olaparib interact?

•Drug A: Abciximab •Drug B: Olaparib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Olaparib. •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. •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): Ovarian cancer Olaparib is indicated for the maintenance treatment of adults with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Olaparib is indicated in combination with bevacizumab for the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. Olaparib is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Breast cancer Olaparib is indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious g BRCA m human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious g BRCA m, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR) positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Pancreatic cancer Olaparib is indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Prostate cancer Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with a hormone agent, such as enzalutamide or abiraterone. It is also indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). •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): Olaparib is a cytotoxic and anti-tumour agent. Olaparib inhibits the growth of selective tumour cell lines in vitro and decreases tumour growth in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy. The drug exerts anti-tumour effects in cell lines and mouse tumour models with deficiencies in BRCA1/2, ATM, or other genes involved in the homologous recombination repair (HRR) of DNA damage and correlated with platinum response. In preclinical models of cancer, olaparib demonstrated anti-tumour activity when used alone, in combination with chemotherapeutic agents, or radiotherapy. Olaparib can act as a chemosensitizer to potentiate the cytotoxicity of DNA-damaging chemotherapeutic agents such as alkylating agents and platinum-based drugs. It can also act as a radiosensitizer by preventing PARP-mediated DNA repair. •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): Poly(ADP-ribose) polymerases (PARPs) are multifunctional enzymes comprising 17 members. They are involved in essential cellular functions, such as DNA transcription and DNA repair. PARPs recognize and repair cellular DNA damage, such as single-strand breaks (SSBs) and double-strand breaks (DSBs). Different DNA repair pathways exist to repair these DNA damages, including the base excision repair (BER) pathway for SSBs and BRCA-dependent homologous recombination for DSBs. Olaparib is a PARP inhibitor: while it acts on PARP1, PARP2, and PARP3, olaparib is a more selective competitive inhibitor of NAD at the catalytic site of PARP1 and PARP2. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of DSBs, which is the most toxic form of DNA damage. While BRCA-dependent homologous recombination can repair DSBs in normal cells, this repair pathway is defective in cells with BRCA1/2 mutations, such as certain tumour cells. Inhibition of PARP in cancer cells with BRCA mutations leads to genomic instability and apoptotic cell death. This end result is also referred to as synthetic lethality, a phenomenon where the combination of two defects - inhibition of PARP activity and loss of DSB repair by HR - that are otherwise benign when alone, lead to detrimental results. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, olaparib is rapidly absorbed. After administration of a single 300 mg dose of olaparib, the mean (CV%) C max was 5.4 μg/mL (32%) and AUC was 39.2 μg x h/mL (44%). The steady state C max and AUC following a dose of 300 mg twice daily was 7.6 μg/mL (35%) and 49.2 μg x h/mL (44%), respectively. T max is 1.5 hours. A high-fat and high-calorie meal may delay T max, but does not significantly alter the extent of olaparib absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (± standard deviation) apparent volume of distribution of olaparib is 158 ± 136 L following a single 300 mg dose. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding of olaparib is approximately 82% in vitro. In solutions of purified proteins, the olaparib fraction bound to albumin was approximately 56% and the fraction bound to alpha-1 acid glycoprotein was 29%. •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): Olaparib is metabolized by cytochrome P450 (CYP) 3A4/5 in vitro. Following an oral dose of radiolabeled olaparib to female patients, unchanged olaparib accounted for 70% of the circulating radioactivity in plasma. Olaparib undergoes oxidation reactions as well as subsequent glucuronide or sulfate conjugation. In humans, olaparib can also undergo hydrolysis, hydroxylation, and dehydrogenation. While up to 37 metabolites of olaparib were detected in plasma, urine, and feces, the majority of metabolites represent less than 1% of the total administered dose and they have not been fully characterized. The major circulating metabolites are a ring-opened piperazin-3-ol moiety and two mono-oxygenated metabolites. The pharmacodynamic activity of the metabolites is unknown. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following a single dose of radiolabeled olaparib, 86% of the dosed radioactivity was recovered within a seven-day collection period, mostly in the form of metabolites. About 44% of the drug was excreted via the urine and 42% of the dose was excreted via the feces. Following an oral dose of radiolabeled olaparib to female patients, the unchanged drug accounted for 15% and 6% of the radioactivity in urine and feces, 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): Following a single oral dose in patients with cancer, the mean terminal half-life was 6.10 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a single oral dose in patients with cancer, the mean apparent plasma clearance was 4.55 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is approximately 240-300 mg/kg. There is limited information regarding the overdose of olaparib. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lynparza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Olaparib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer.

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. The severity of the interaction is minor.

Question: Does Abciximab and Olaparib interact? Information: •Drug A: Abciximab •Drug B: Olaparib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Olaparib. •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. •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): Ovarian cancer Olaparib is indicated for the maintenance treatment of adults with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Olaparib is indicated in combination with bevacizumab for the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. Olaparib is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Breast cancer Olaparib is indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious g BRCA m human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious g BRCA m, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR) positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Pancreatic cancer Olaparib is indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Prostate cancer Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with a hormone agent, such as enzalutamide or abiraterone. It is also indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). •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): Olaparib is a cytotoxic and anti-tumour agent. Olaparib inhibits the growth of selective tumour cell lines in vitro and decreases tumour growth in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy. The drug exerts anti-tumour effects in cell lines and mouse tumour models with deficiencies in BRCA1/2, ATM, or other genes involved in the homologous recombination repair (HRR) of DNA damage and correlated with platinum response. In preclinical models of cancer, olaparib demonstrated anti-tumour activity when used alone, in combination with chemotherapeutic agents, or radiotherapy. Olaparib can act as a chemosensitizer to potentiate the cytotoxicity of DNA-damaging chemotherapeutic agents such as alkylating agents and platinum-based drugs. It can also act as a radiosensitizer by preventing PARP-mediated DNA repair. •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): Poly(ADP-ribose) polymerases (PARPs) are multifunctional enzymes comprising 17 members. They are involved in essential cellular functions, such as DNA transcription and DNA repair. PARPs recognize and repair cellular DNA damage, such as single-strand breaks (SSBs) and double-strand breaks (DSBs). Different DNA repair pathways exist to repair these DNA damages, including the base excision repair (BER) pathway for SSBs and BRCA-dependent homologous recombination for DSBs. Olaparib is a PARP inhibitor: while it acts on PARP1, PARP2, and PARP3, olaparib is a more selective competitive inhibitor of NAD at the catalytic site of PARP1 and PARP2. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of DSBs, which is the most toxic form of DNA damage. While BRCA-dependent homologous recombination can repair DSBs in normal cells, this repair pathway is defective in cells with BRCA1/2 mutations, such as certain tumour cells. Inhibition of PARP in cancer cells with BRCA mutations leads to genomic instability and apoptotic cell death. This end result is also referred to as synthetic lethality, a phenomenon where the combination of two defects - inhibition of PARP activity and loss of DSB repair by HR - that are otherwise benign when alone, lead to detrimental results. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, olaparib is rapidly absorbed. After administration of a single 300 mg dose of olaparib, the mean (CV%) C max was 5.4 μg/mL (32%) and AUC was 39.2 μg x h/mL (44%). The steady state C max and AUC following a dose of 300 mg twice daily was 7.6 μg/mL (35%) and 49.2 μg x h/mL (44%), respectively. T max is 1.5 hours. A high-fat and high-calorie meal may delay T max, but does not significantly alter the extent of olaparib absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (± standard deviation) apparent volume of distribution of olaparib is 158 ± 136 L following a single 300 mg dose. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding of olaparib is approximately 82% in vitro. In solutions of purified proteins, the olaparib fraction bound to albumin was approximately 56% and the fraction bound to alpha-1 acid glycoprotein was 29%. •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): Olaparib is metabolized by cytochrome P450 (CYP) 3A4/5 in vitro. Following an oral dose of radiolabeled olaparib to female patients, unchanged olaparib accounted for 70% of the circulating radioactivity in plasma. Olaparib undergoes oxidation reactions as well as subsequent glucuronide or sulfate conjugation. In humans, olaparib can also undergo hydrolysis, hydroxylation, and dehydrogenation. While up to 37 metabolites of olaparib were detected in plasma, urine, and feces, the majority of metabolites represent less than 1% of the total administered dose and they have not been fully characterized. The major circulating metabolites are a ring-opened piperazin-3-ol moiety and two mono-oxygenated metabolites. The pharmacodynamic activity of the metabolites is unknown. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following a single dose of radiolabeled olaparib, 86% of the dosed radioactivity was recovered within a seven-day collection period, mostly in the form of metabolites. About 44% of the drug was excreted via the urine and 42% of the dose was excreted via the feces. Following an oral dose of radiolabeled olaparib to female patients, the unchanged drug accounted for 15% and 6% of the radioactivity in urine and feces, 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): Following a single oral dose in patients with cancer, the mean terminal half-life was 6.10 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a single oral dose in patients with cancer, the mean apparent plasma clearance was 4.55 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is approximately 240-300 mg/kg. There is limited information regarding the overdose of olaparib. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lynparza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Olaparib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer. Output: 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. The severity of the interaction is minor.

Does Abciximab and Olaratumab interact?

•Drug A: Abciximab •Drug B: Olaratumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Olaratumab. •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 . •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): Olaratumab is indicated, in combination with doxorubicin, for the treatment of adult patients with advanced or mestastatic soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy 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): It exerts an anti-tumor activity in vivo and in vitro against selected sarcoma cells by inhibiting tumor growth by binding to PDGFR-alpha that is present on several types of cancer on transformed cells and in tumor stroma. Olaratumab antibody binding leads to inhibition of ligand-dependent signaling in PDGFR(alpha)-expressing tumor cells, as well as stromal cells in the tumor microenviroment that are dependent on PDGFR(alpha) signaling. When used in a combination therapy with doxorubicin, olaratumab improves progression-free survival in patients with advanced soft-tissue sarcoma. •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): Olaratumab blocks ligand-induced tumor cell proliferation, and inhibits receptor autophosphorylation and ligand-induced phosphorylation of the downstream signaling molecules protein kinase B (Akt) and mitogen-activated protein kinase. PDGFR signalling is a type of tyrosine kinase-mediated pathway that normally regulates cell growth, chemotaxis, and mesenchymal stem cell differentiation. It also promotes internalization of PDGFR thus alters the surface levels of PDGFR. •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): 7.7 L at steady state. •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. •Metabolism (Drug B): Mainly degraded nonspecifically by proteolytic enzymes •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): Estimated value of 11 days •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean value of 0.56L/day •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Infusion-related reactions may occur during or after the administration which include bronchospasm, flushing, hypotension, anaphylactic shock, or cardiac arrest. Olaratumab may cause embryo-fetal toxicity based on animal data and its mechanism of action. Other reported adverse effects include neutropenia, leukopenia, anemia, nausea and musculoskeletal pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lartruvo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Olaratumab is a platelet-derived growth factor receptor alpha blocking antibody used with doxorubicin to treat patients with certain types of soft tissue sarcoma (STS).

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 . The severity of the interaction is minor.

Question: Does Abciximab and Olaratumab interact? Information: •Drug A: Abciximab •Drug B: Olaratumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Olaratumab. •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 . •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): Olaratumab is indicated, in combination with doxorubicin, for the treatment of adult patients with advanced or mestastatic soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy 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): It exerts an anti-tumor activity in vivo and in vitro against selected sarcoma cells by inhibiting tumor growth by binding to PDGFR-alpha that is present on several types of cancer on transformed cells and in tumor stroma. Olaratumab antibody binding leads to inhibition of ligand-dependent signaling in PDGFR(alpha)-expressing tumor cells, as well as stromal cells in the tumor microenviroment that are dependent on PDGFR(alpha) signaling. When used in a combination therapy with doxorubicin, olaratumab improves progression-free survival in patients with advanced soft-tissue sarcoma. •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): Olaratumab blocks ligand-induced tumor cell proliferation, and inhibits receptor autophosphorylation and ligand-induced phosphorylation of the downstream signaling molecules protein kinase B (Akt) and mitogen-activated protein kinase. PDGFR signalling is a type of tyrosine kinase-mediated pathway that normally regulates cell growth, chemotaxis, and mesenchymal stem cell differentiation. It also promotes internalization of PDGFR thus alters the surface levels of PDGFR. •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): 7.7 L at steady state. •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. •Metabolism (Drug B): Mainly degraded nonspecifically by proteolytic enzymes •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): Estimated value of 11 days •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean value of 0.56L/day •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Infusion-related reactions may occur during or after the administration which include bronchospasm, flushing, hypotension, anaphylactic shock, or cardiac arrest. Olaratumab may cause embryo-fetal toxicity based on animal data and its mechanism of action. Other reported adverse effects include neutropenia, leukopenia, anemia, nausea and musculoskeletal pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lartruvo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Olaratumab is a platelet-derived growth factor receptor alpha blocking antibody used with doxorubicin to treat patients with certain types of soft tissue sarcoma (STS). Output: 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 . The severity of the interaction is minor.

Does Abciximab and Olive oil interact?

•Drug A: Abciximab •Drug B: Olive oil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Olive oil. •Extended Description: Olive oil has high vitamin K1 contents.1 Vitamin K1 serves as a vitamin required for blood coagulation,2 and may counteract the anticoagulant activity of vitamin K antagonists such as warfarin. However, there were no drug-interaction studies that examined the effect of soybean on the therapeutic efficacy of anticoagulant drugs. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found

Olive oil has high vitamin K1 contents.1 Vitamin K1 serves as a vitamin required for blood coagulation,2 and may counteract the anticoagulant activity of vitamin K antagonists such as warfarin. However, there were no drug-interaction studies that examined the effect of soybean on the therapeutic efficacy of anticoagulant drugs. The severity of the interaction is minor.

Question: Does Abciximab and Olive oil interact? Information: •Drug A: Abciximab •Drug B: Olive oil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Olive oil. •Extended Description: Olive oil has high vitamin K1 contents.1 Vitamin K1 serves as a vitamin required for blood coagulation,2 and may counteract the anticoagulant activity of vitamin K antagonists such as warfarin. However, there were no drug-interaction studies that examined the effect of soybean on the therapeutic efficacy of anticoagulant drugs. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found Output: Olive oil has high vitamin K1 contents.1 Vitamin K1 serves as a vitamin required for blood coagulation,2 and may counteract the anticoagulant activity of vitamin K antagonists such as warfarin. However, there were no drug-interaction studies that examined the effect of soybean on the therapeutic efficacy of anticoagulant drugs. The severity of the interaction is minor.

Does Abciximab and Olsalazine interact?

•Drug A: Abciximab •Drug B: Olsalazine •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Olsalazine 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. •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, olsalazine is indicated for the maintenance of remission of ulcerative colitis in adult patients who are intolerant to sulfasalazine. In Canada, it is used in the treatment of acute ulcerative colitis of mild to moderate severity, with or without the concomitant use of steroids. It is also indicated for the long-term maintenance of patients with ulcerative colitis in remission. •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): Olsalazine is an anti-inflammatory agent that blocks the production of cyclooxygenase (COX)-derived products of arachidonic acid metabolism. It works to alleviate inflammation in ulcerative colitis. Olsalazine was shown to decrease water and sodium absorption. While olsalazine is not expected to affect the motility and transit time of small intestines, it decreased small bowel transit time at high doses ranging from 60 to 120 mg/kg. In about 40% of the patients with ulcerative colitis, administration of olsalazine 1g daily was associated with a decrease in whole gut transit 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): Upon administration, the azo bond connecting two molecules of mesalamine (also known as 5-aminosalicylic acid or 5-ASA) is cleaved by azoreductase-containing bacteria in the colon. The two molecules of mesalamine are released to mediate therapeutic effects. The exact mechanism of action of olsalazine and its active moiety mesalamine in ulcerative colitis has not been elucidated; however, it is understood that mesalamine mediates an anti-inflammatory action on epithelial cells of the colon. The COX-derived (i.e., prostanoids such as prostaglandin E2) and lipoxygenase-derived products (i.e., leukotrienes [LTs] and hydroxyeicosatetraenoic acids [HETEs]) of arachidonic acid metabolism have been implicated in the pathogenesis and maintenance of inflammatory disorders, including ulcerative colitis and inflammatory bowel disease. Mesalamine may attenuate inflammation by blocking the COX enzyme and inhibiting prostaglandin production in the colon. Olsalazine was also shown to inhibit xanthine oxidase, an enzyme that generates oxygen-derived free radicals. Olsalazine may attenuate intestinal inflammation by limiting macrophage migration to inflamed intestinal mucosa: it was shown to inhibit in vitro migration of intestinal macrophages in response to leukotriene B 4. Olsalazine may also act as a free radical scavenger, and mesalazine may suppress fatty acid peroxidation. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration, olsalazine has limited systemic bioavailability, with less than 5% of the oral dose being absorbed. Based on oral and intravenous dosing studies, approximately 2.4% of a single 1 g oral dose is absorbed. Maximum serum concentrations of olsalazine appear after approximately one hour and, even after a 1 g single dose, are low (e.g., 1.6 to 6.2 µmol/L). Patients on daily doses of 1 g olsalazine for two to four years show a stable plasma concentration of olsalazine-S (3.3 to 12.4 µmol/L). Olsalazine-S accumulates to a steady state within two to three weeks. Serum concentrations of mesalamine are detected after four to eight hours. The peak levels of mesalamine after an oral dose of 1 g olsalazine are low (i.e., 0 to 4.3 µmol/L). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution determined in healthy volunteers is approximately 5L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Olsalazine and its metabolite olsalazine-S, are more than 99% bound to plasma proteins. Less than 1% of both olsalazine and olsalazine-S appears undissociated in plasma. It does not interfere with the protein binding of warfarin. Mesalamine (5-aminosalicylic acid, 5-ASA) and its metabolite, N-acetyl-5-ASA, are 74 and 81%, respectively, 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): Olsalazine is cleaved by colonic bacteria to release its active ingredient, mesalamine. Mesalamine can undergo acetylation to form N-acetyl-5-aminosalicylic acid (N-acetyl-5-ASA, Ac-5-ASA) by the colonic epithelium; however, the extent of acetylation depends on transit time. Approximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Olsalazine and its metabolites are excreted in the urine. Total recovery of oral 14C-labeled olsalazine in animals and humans ranges from 90 to 97%. Approximately 20% of the total mesalamine is recovered in the urine. Of the total mesalamine found in the urine, more than 90% is N-acetyl-5-ASA. Only small amounts of mesalamine are detected in the urine. The remaining mesalamine is partially acetylated and excreted in the feces. From fecal dialysis, the concentration of mesalamine in the colon following olsalazine has been calculated to be 18 to 49 mmol/L. The urinary recovery of olsalazine is below 1%. Less than 5% of an oral dose (0.25 to 2g) was recovered unchanged in the feces; however, more than 50% of the oral dose was excreted in feces as unchanged olsalazine when the whole gut transit time was decreased by approximately 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): Olsalazine has a very short serum half-life, approximately 0.9 hours. Olsalazine-S has a half-life of seven days due to slow dissociation from the protein binding site. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information available regarding acute toxicity (LD 50 ) of olsalazine. Symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe intoxication may lead to electrolyte and blood pH imbalance and potentially to organ damage. There is no antidote for olsalazine overdose; however, conventional therapy for salicylate toxicity, such as gastrointestinal tract decontamination, may be beneficial in acute overdosage. Overdose should be managed with proper medical care and appropriate supportive care, including the possible use of emesis, cathartics, and activated charcoal to prevent further absorption. Fluid and electrolyte imbalance may be managed with appropriate intravenous therapy and maintenance of adequate renal function. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dipentum •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Olsalazine is an anti-inflammatory aminosalicylate used in the treatment of inflammatory bowel disease and ulcerative colitis.

.Concurrent use of salicylates and anticoagulants may lead to increased anticoagulant activity and therefore an increased risk of bleeding, due to additive anticoagulant effects. The severity of the interaction is moderate.

Question: Does Abciximab and Olsalazine interact? Information: •Drug A: Abciximab •Drug B: Olsalazine •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Olsalazine 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. •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, olsalazine is indicated for the maintenance of remission of ulcerative colitis in adult patients who are intolerant to sulfasalazine. In Canada, it is used in the treatment of acute ulcerative colitis of mild to moderate severity, with or without the concomitant use of steroids. It is also indicated for the long-term maintenance of patients with ulcerative colitis in remission. •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): Olsalazine is an anti-inflammatory agent that blocks the production of cyclooxygenase (COX)-derived products of arachidonic acid metabolism. It works to alleviate inflammation in ulcerative colitis. Olsalazine was shown to decrease water and sodium absorption. While olsalazine is not expected to affect the motility and transit time of small intestines, it decreased small bowel transit time at high doses ranging from 60 to 120 mg/kg. In about 40% of the patients with ulcerative colitis, administration of olsalazine 1g daily was associated with a decrease in whole gut transit 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): Upon administration, the azo bond connecting two molecules of mesalamine (also known as 5-aminosalicylic acid or 5-ASA) is cleaved by azoreductase-containing bacteria in the colon. The two molecules of mesalamine are released to mediate therapeutic effects. The exact mechanism of action of olsalazine and its active moiety mesalamine in ulcerative colitis has not been elucidated; however, it is understood that mesalamine mediates an anti-inflammatory action on epithelial cells of the colon. The COX-derived (i.e., prostanoids such as prostaglandin E2) and lipoxygenase-derived products (i.e., leukotrienes [LTs] and hydroxyeicosatetraenoic acids [HETEs]) of arachidonic acid metabolism have been implicated in the pathogenesis and maintenance of inflammatory disorders, including ulcerative colitis and inflammatory bowel disease. Mesalamine may attenuate inflammation by blocking the COX enzyme and inhibiting prostaglandin production in the colon. Olsalazine was also shown to inhibit xanthine oxidase, an enzyme that generates oxygen-derived free radicals. Olsalazine may attenuate intestinal inflammation by limiting macrophage migration to inflamed intestinal mucosa: it was shown to inhibit in vitro migration of intestinal macrophages in response to leukotriene B 4. Olsalazine may also act as a free radical scavenger, and mesalazine may suppress fatty acid peroxidation. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration, olsalazine has limited systemic bioavailability, with less than 5% of the oral dose being absorbed. Based on oral and intravenous dosing studies, approximately 2.4% of a single 1 g oral dose is absorbed. Maximum serum concentrations of olsalazine appear after approximately one hour and, even after a 1 g single dose, are low (e.g., 1.6 to 6.2 µmol/L). Patients on daily doses of 1 g olsalazine for two to four years show a stable plasma concentration of olsalazine-S (3.3 to 12.4 µmol/L). Olsalazine-S accumulates to a steady state within two to three weeks. Serum concentrations of mesalamine are detected after four to eight hours. The peak levels of mesalamine after an oral dose of 1 g olsalazine are low (i.e., 0 to 4.3 µmol/L). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution determined in healthy volunteers is approximately 5L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Olsalazine and its metabolite olsalazine-S, are more than 99% bound to plasma proteins. Less than 1% of both olsalazine and olsalazine-S appears undissociated in plasma. It does not interfere with the protein binding of warfarin. Mesalamine (5-aminosalicylic acid, 5-ASA) and its metabolite, N-acetyl-5-ASA, are 74 and 81%, respectively, 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): Olsalazine is cleaved by colonic bacteria to release its active ingredient, mesalamine. Mesalamine can undergo acetylation to form N-acetyl-5-aminosalicylic acid (N-acetyl-5-ASA, Ac-5-ASA) by the colonic epithelium; however, the extent of acetylation depends on transit time. Approximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Olsalazine and its metabolites are excreted in the urine. Total recovery of oral 14C-labeled olsalazine in animals and humans ranges from 90 to 97%. Approximately 20% of the total mesalamine is recovered in the urine. Of the total mesalamine found in the urine, more than 90% is N-acetyl-5-ASA. Only small amounts of mesalamine are detected in the urine. The remaining mesalamine is partially acetylated and excreted in the feces. From fecal dialysis, the concentration of mesalamine in the colon following olsalazine has been calculated to be 18 to 49 mmol/L. The urinary recovery of olsalazine is below 1%. Less than 5% of an oral dose (0.25 to 2g) was recovered unchanged in the feces; however, more than 50% of the oral dose was excreted in feces as unchanged olsalazine when the whole gut transit time was decreased by approximately 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): Olsalazine has a very short serum half-life, approximately 0.9 hours. Olsalazine-S has a half-life of seven days due to slow dissociation from the protein binding site. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information available regarding acute toxicity (LD 50 ) of olsalazine. Symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe intoxication may lead to electrolyte and blood pH imbalance and potentially to organ damage. There is no antidote for olsalazine overdose; however, conventional therapy for salicylate toxicity, such as gastrointestinal tract decontamination, may be beneficial in acute overdosage. Overdose should be managed with proper medical care and appropriate supportive care, including the possible use of emesis, cathartics, and activated charcoal to prevent further absorption. Fluid and electrolyte imbalance may be managed with appropriate intravenous therapy and maintenance of adequate renal function. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dipentum •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Olsalazine is an anti-inflammatory aminosalicylate used in the treatment of inflammatory bowel disease and ulcerative colitis. Output: .Concurrent use of salicylates and anticoagulants may lead to increased anticoagulant activity and therefore an increased risk of bleeding, due to additive anticoagulant effects. The severity of the interaction is moderate.

Does Abciximab and Omacetaxine mepesuccinate interact?

•Drug A: Abciximab •Drug B: Omacetaxine mepesuccinate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Omacetaxine mepesuccinate. •Extended Description: Omacetaxine mepesuccinate therapy has been associated with drug-induced thrombocytopenia that may lead to bleeding events. Co-administration of omacetaxine mepesuccinate with drugs affecting hemostasis, including anticoagulants, may significantly increase the risk for bleeding and hemorrhage. •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 in patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML. •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 pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involved with protein synthesis inhibition and this leads to its antineoplastic activity. •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): Homoharringtonine inhibits protein synthesis by not directly binding to Bcr-Abl. It binds to the A-site cleft in the large ribosomal subunit, which affects chain elongation and prevents protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Homoharringtonine absorption was not quantified, but maximum concentration is reached after about 30 mins. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Homoharringtonine has a steady state Vd of 141 ± 93.4 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding is equal or less than 50%. •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): Homoharringtonine has undergoes little hepatic metabolism and is mostly metabolized to 4’-DMHHT by plasma esterase hydrolysis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main route of elimination for homoharringtonine is still unknown, but renal elimination is less than 15%. •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): Homoharringtonine has a half life of about 6 hours after subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance for homoharringtonine was not quantified. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most severe adverse effects after homoharringtonine administration are myelosuppression, bleeding, hyperglycemia, and fetal harm. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Synribo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1-[(1S,3aR,14bS)-2-Methoxy-1,5,6,8,9,14b-hexahydro-4H-cyclopenta[a][1,3]dioxolo[4,5-H]pyrrolo[2,1-b][3]benzazepin-1-yl] 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate CEPHALOTAXINE 4-METHYL (2R)-2-HYDROXY-2-(4-HYDROXY-4-METHYLPENTYL)BUTANEDIOATE (ESTER) CEPHALOTAXINE, 4-METHYL (2R)-2-HYDROXY-2-(4-HYDROXY-4-METHYLPENTYL)BUTANEDIOATE (ESTER) Homoharringtonin Homoharringtonine mepesuccinato de omacetaxina Omacetaxine mepesuccinate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omacetaxine mepesuccinate is a cephalotaxine used in the treatment of Chronic Myeloid Leukemia (CML) that is intolerant to or resistant to two or more tyrosine kinase inhibitors.

Omacetaxine mepesuccinate therapy has been associated with drug-induced thrombocytopenia that may lead to bleeding events. Co-administration of omacetaxine mepesuccinate with drugs affecting hemostasis, including anticoagulants, may significantly increase the risk for bleeding and hemorrhage. The severity of the interaction is moderate.

Question: Does Abciximab and Omacetaxine mepesuccinate interact? Information: •Drug A: Abciximab •Drug B: Omacetaxine mepesuccinate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Omacetaxine mepesuccinate. •Extended Description: Omacetaxine mepesuccinate therapy has been associated with drug-induced thrombocytopenia that may lead to bleeding events. Co-administration of omacetaxine mepesuccinate with drugs affecting hemostasis, including anticoagulants, may significantly increase the risk for bleeding and hemorrhage. •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 in patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML. •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 pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involved with protein synthesis inhibition and this leads to its antineoplastic activity. •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): Homoharringtonine inhibits protein synthesis by not directly binding to Bcr-Abl. It binds to the A-site cleft in the large ribosomal subunit, which affects chain elongation and prevents protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Homoharringtonine absorption was not quantified, but maximum concentration is reached after about 30 mins. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Homoharringtonine has a steady state Vd of 141 ± 93.4 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding is equal or less than 50%. •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): Homoharringtonine has undergoes little hepatic metabolism and is mostly metabolized to 4’-DMHHT by plasma esterase hydrolysis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main route of elimination for homoharringtonine is still unknown, but renal elimination is less than 15%. •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): Homoharringtonine has a half life of about 6 hours after subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance for homoharringtonine was not quantified. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most severe adverse effects after homoharringtonine administration are myelosuppression, bleeding, hyperglycemia, and fetal harm. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Synribo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1-[(1S,3aR,14bS)-2-Methoxy-1,5,6,8,9,14b-hexahydro-4H-cyclopenta[a][1,3]dioxolo[4,5-H]pyrrolo[2,1-b][3]benzazepin-1-yl] 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate CEPHALOTAXINE 4-METHYL (2R)-2-HYDROXY-2-(4-HYDROXY-4-METHYLPENTYL)BUTANEDIOATE (ESTER) CEPHALOTAXINE, 4-METHYL (2R)-2-HYDROXY-2-(4-HYDROXY-4-METHYLPENTYL)BUTANEDIOATE (ESTER) Homoharringtonin Homoharringtonine mepesuccinato de omacetaxina Omacetaxine mepesuccinate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omacetaxine mepesuccinate is a cephalotaxine used in the treatment of Chronic Myeloid Leukemia (CML) that is intolerant to or resistant to two or more tyrosine kinase inhibitors. Output: Omacetaxine mepesuccinate therapy has been associated with drug-induced thrombocytopenia that may lead to bleeding events. Co-administration of omacetaxine mepesuccinate with drugs affecting hemostasis, including anticoagulants, may significantly increase the risk for bleeding and hemorrhage. The severity of the interaction is moderate.

Does Abciximab and Omalizumab interact?

•Drug A: Abciximab •Drug B: Omalizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Omalizumab 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 . •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 an anti-IgE antibody indicated for: Moderate to severe persistent asthma in patients 6 years of age and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids Chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment •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): Omalizumab is a recombinant, humanized, monoclonal antibody against human immunoglobulin E (IgE) which treats the symptoms of asthma and chronic idiopathic urticaria by limiting the allergic response,. It inhibits the binding of IgE to receptors on mast cells and basophils, blocking the IgE-mediated secretion of inflammatory mediators from these cells. Mast cell activation and the release of mediators, in response to allergen exposure and IgE, results in a cascade of events. This cascade culminates in the activation of B-lymphocytes, T-lymphocytes, eosinophils, fibroblasts, smooth muscle cells, and the endothelium. This cellular interaction, as well as the release of cytokines, chemokines and growth factors and inflammatory remodeling of the airway results in chronic asthma. After 4 weeks of use of this medication in patients with chronic urticaria, it was found that rescue medication use was reduced significantly and quality of life improved. •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): When an environmental allergen first enters the body, is taken up by antigen-presenting cells (APCs). It is then processed, and presented to T and B immune cells. This is followed by the activation of B-lymphocyte and production of allergen-specific IgE. This IgE is then released by plasma cells (converted B lymphocytes) and is therefore available to bind to IgE receptors on several other cells. IgE binds to high-affinity (Fc€RI) and low-affinity (Fc€RII) receptors on multiple cells of the immune system. Following subsequent antigen exposure, cross-linking of the antigen occurs by several Fc€RI-bound IgE molecules on the surface of both basophils and mast cells. This leads to the activation of mast cells and histamine release, producing a wheal and other symptoms of urticaria. The following are explanations of the mechanism of action for both indications of this drug: Asthma Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of both mast cells and basophils. The reduction in surface-bound IgE on FcεRI-bearing cells limits the degree of release of mediators of the typical allergic response. Treatment with omalizumab also reduces the number of FcεRI receptors on basophils in atopic patients. Omalizumab binds to free IgE with a higher affinity than IgE itself binds to the high-affinity Fc€RI receptors found on basophils. Therefore, it decreases the availability of free IgE for binding. Omalizumab by itself does not bind to the Fc€RI receptors, nor does the drug bind to receptor-bound IgE. These binding characteristics allow omalizumab to neutralize the typical IgE-mediated responses without causing the degranulation of basophils or cross-linking with basophil-bound IgE. Chronic Idiopathic Urticaria Omalizumab binds to IgE and decreases free IgE levels. Subsequently, IgE receptors (FcεRI) on cells are down-regulated. The mechanism by which these effects of omalizumab result in an improvement of CIU symptoms is unclear. •Absorption (Drug A): No absorption available •Absorption (Drug B): After subcutaneous administration in pharmacokinetic studies, omalizumab was absorbed with a mean absolute bioavailability of 62%. After the administration of a single subcutanous dose in adult and adolescent patients with asthma, omalizumab was absorbed slowly. The peak serum concentrations peaked after an average of 7­-8 days. In patients with CIU, the peak serum concentration was reached at a similar time after a single SC dose. The pharmacokinetics of omalizumab was linear at doses which were higher than 0.5 mg/kg. In patients with asthma, after several doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after one dose. In patients with CIU, omalizumab showed linear pharmacokinetics in the dose range of 75 mg to 600 mg administered as a single subcutaneous dose. After repeated dosing from 75mg-300 mg every 4 weeks, trough serum concentrations of omalizumab increased proportionally with the dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of omalizumab in patients with asthma after subcutaneous administration was 78 ± 32 mL/kg. In patients with CIU, the distribution of omalizumab was similar to that in asthmatic patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are usually not required to have protein binding studies. •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, in general, are believed to be internalized in endothelial cells bound to the Fc receptor and rescued from metabolism by recycling. At a later time, they are degraded in the reticuloendothelial system to smaller peptides and amino acids, which can then be used for de-novo protein synthesis. Several factors may influence this process, however. These include factors related to the target antigen, antibody, and patient. The metabolism of omalizumab is determined by its IgG1 framework, and by its specific binding to IgE. The elimination of omalizumab is dose-dependent. The reticuloendothelial system and the liver are two sites of elimination for IgG (including degradation in the liver reticuloendothelial system and endothelial cells),. The omalizumab:IgE complexes are thought to be to cleared via interactions with Fc- gamma-Rs (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) at rates that are more rapid than that of IgG clearance. The relative clearance of free omalizumab, free IgE, and complexes is summarized as: free IgE clearance > > omalizumab:IgE clearance > omalizumab clearance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Liver elimination of IgG includes degradation in the liver reticuloendothelial system (RES) and endothelial cells. Intact IgG was also shown to be excreted in bile, in pharmacokinetic studies. •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 chronic idiopathic urticaria (CIU) patients, at steady state, based on population pharmacokinetics, omalizumab serum elimination half-life averaged 24 days. In asthmatic patients omalizumab serum elimination half-life averaged 26 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): In pharmacokinetic studies, the clearance of omalizumab involved IgG clearance as well as clearance by specific binding and complex formation with its target ligand, IgE,. The apparent clearance averaging 2.4 ± 1.1 mL/kg/day was measured in asthmatic patients. In chronic idiopathic urticaria (CIU) patients, at steady state, based on population pharmacokinetics, omalizumab apparent clearance averaged 240 mL/day (corresponding to 3.0 mL/kg/day for an 80 kg patient). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Anaphylaxis Anaphylaxis may occur rarely with this agent, either after the first dose or multiple doses,. Anaphylaxis presenting clinically as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported during and after this use of this drug. Therefore, close clinical monitoring should be performed during and shortly after administration. Maximum Dosage The maximum tolerated dosage of omalizumab has not yet been determined. Single intravenous (IV) doses of up to 4000 mg have been administered to patients without evidence of dose-limiting toxicity. The highest cumulative dose administered to patients was 44,000 mg over a 20 week time period, which was not associated with any toxicities. The use in Pregnancy The data with omalizumab use in pregnant women are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as omalizumab, are transported across the placenta in a linear fashion as a pregnancy progresses; therefore, potential effects on a fetus are likely to be greater in frequency during the second and third trimesters. In women with inadequately or moderately controlled asthma, the current evidence suggests that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small fetal size. The use During Breastfeeding There is no information regarding the presence of omalizumab in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for omalizumab and any potential adverse effects on the breastfed child from omalizumab or from the underlying maternal condition. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Xolair •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omalizumab is a monoclonal anti-immunoglobulin E antibody used in the treatment of severe asthma and chronic idiopathic urticaria.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Omalizumab interact? Information: •Drug A: Abciximab •Drug B: Omalizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Omalizumab 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 . •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 an anti-IgE antibody indicated for: Moderate to severe persistent asthma in patients 6 years of age and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids Chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment •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): Omalizumab is a recombinant, humanized, monoclonal antibody against human immunoglobulin E (IgE) which treats the symptoms of asthma and chronic idiopathic urticaria by limiting the allergic response,. It inhibits the binding of IgE to receptors on mast cells and basophils, blocking the IgE-mediated secretion of inflammatory mediators from these cells. Mast cell activation and the release of mediators, in response to allergen exposure and IgE, results in a cascade of events. This cascade culminates in the activation of B-lymphocytes, T-lymphocytes, eosinophils, fibroblasts, smooth muscle cells, and the endothelium. This cellular interaction, as well as the release of cytokines, chemokines and growth factors and inflammatory remodeling of the airway results in chronic asthma. After 4 weeks of use of this medication in patients with chronic urticaria, it was found that rescue medication use was reduced significantly and quality of life improved. •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): When an environmental allergen first enters the body, is taken up by antigen-presenting cells (APCs). It is then processed, and presented to T and B immune cells. This is followed by the activation of B-lymphocyte and production of allergen-specific IgE. This IgE is then released by plasma cells (converted B lymphocytes) and is therefore available to bind to IgE receptors on several other cells. IgE binds to high-affinity (Fc€RI) and low-affinity (Fc€RII) receptors on multiple cells of the immune system. Following subsequent antigen exposure, cross-linking of the antigen occurs by several Fc€RI-bound IgE molecules on the surface of both basophils and mast cells. This leads to the activation of mast cells and histamine release, producing a wheal and other symptoms of urticaria. The following are explanations of the mechanism of action for both indications of this drug: Asthma Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of both mast cells and basophils. The reduction in surface-bound IgE on FcεRI-bearing cells limits the degree of release of mediators of the typical allergic response. Treatment with omalizumab also reduces the number of FcεRI receptors on basophils in atopic patients. Omalizumab binds to free IgE with a higher affinity than IgE itself binds to the high-affinity Fc€RI receptors found on basophils. Therefore, it decreases the availability of free IgE for binding. Omalizumab by itself does not bind to the Fc€RI receptors, nor does the drug bind to receptor-bound IgE. These binding characteristics allow omalizumab to neutralize the typical IgE-mediated responses without causing the degranulation of basophils or cross-linking with basophil-bound IgE. Chronic Idiopathic Urticaria Omalizumab binds to IgE and decreases free IgE levels. Subsequently, IgE receptors (FcεRI) on cells are down-regulated. The mechanism by which these effects of omalizumab result in an improvement of CIU symptoms is unclear. •Absorption (Drug A): No absorption available •Absorption (Drug B): After subcutaneous administration in pharmacokinetic studies, omalizumab was absorbed with a mean absolute bioavailability of 62%. After the administration of a single subcutanous dose in adult and adolescent patients with asthma, omalizumab was absorbed slowly. The peak serum concentrations peaked after an average of 7­-8 days. In patients with CIU, the peak serum concentration was reached at a similar time after a single SC dose. The pharmacokinetics of omalizumab was linear at doses which were higher than 0.5 mg/kg. In patients with asthma, after several doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after one dose. In patients with CIU, omalizumab showed linear pharmacokinetics in the dose range of 75 mg to 600 mg administered as a single subcutaneous dose. After repeated dosing from 75mg-300 mg every 4 weeks, trough serum concentrations of omalizumab increased proportionally with the dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of omalizumab in patients with asthma after subcutaneous administration was 78 ± 32 mL/kg. In patients with CIU, the distribution of omalizumab was similar to that in asthmatic patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are usually not required to have protein binding studies. •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, in general, are believed to be internalized in endothelial cells bound to the Fc receptor and rescued from metabolism by recycling. At a later time, they are degraded in the reticuloendothelial system to smaller peptides and amino acids, which can then be used for de-novo protein synthesis. Several factors may influence this process, however. These include factors related to the target antigen, antibody, and patient. The metabolism of omalizumab is determined by its IgG1 framework, and by its specific binding to IgE. The elimination of omalizumab is dose-dependent. The reticuloendothelial system and the liver are two sites of elimination for IgG (including degradation in the liver reticuloendothelial system and endothelial cells),. The omalizumab:IgE complexes are thought to be to cleared via interactions with Fc- gamma-Rs (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) at rates that are more rapid than that of IgG clearance. The relative clearance of free omalizumab, free IgE, and complexes is summarized as: free IgE clearance > > omalizumab:IgE clearance > omalizumab clearance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Liver elimination of IgG includes degradation in the liver reticuloendothelial system (RES) and endothelial cells. Intact IgG was also shown to be excreted in bile, in pharmacokinetic studies. •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 chronic idiopathic urticaria (CIU) patients, at steady state, based on population pharmacokinetics, omalizumab serum elimination half-life averaged 24 days. In asthmatic patients omalizumab serum elimination half-life averaged 26 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): In pharmacokinetic studies, the clearance of omalizumab involved IgG clearance as well as clearance by specific binding and complex formation with its target ligand, IgE,. The apparent clearance averaging 2.4 ± 1.1 mL/kg/day was measured in asthmatic patients. In chronic idiopathic urticaria (CIU) patients, at steady state, based on population pharmacokinetics, omalizumab apparent clearance averaged 240 mL/day (corresponding to 3.0 mL/kg/day for an 80 kg patient). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Anaphylaxis Anaphylaxis may occur rarely with this agent, either after the first dose or multiple doses,. Anaphylaxis presenting clinically as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported during and after this use of this drug. Therefore, close clinical monitoring should be performed during and shortly after administration. Maximum Dosage The maximum tolerated dosage of omalizumab has not yet been determined. Single intravenous (IV) doses of up to 4000 mg have been administered to patients without evidence of dose-limiting toxicity. The highest cumulative dose administered to patients was 44,000 mg over a 20 week time period, which was not associated with any toxicities. The use in Pregnancy The data with omalizumab use in pregnant women are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as omalizumab, are transported across the placenta in a linear fashion as a pregnancy progresses; therefore, potential effects on a fetus are likely to be greater in frequency during the second and third trimesters. In women with inadequately or moderately controlled asthma, the current evidence suggests that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small fetal size. The use During Breastfeeding There is no information regarding the presence of omalizumab in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for omalizumab and any potential adverse effects on the breastfed child from omalizumab or from the underlying maternal condition. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Xolair •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omalizumab is a monoclonal anti-immunoglobulin E antibody used in the treatment of severe asthma and chronic idiopathic urticaria. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Omega-3 fatty acids interact?

•Drug A: Abciximab •Drug B: Omega-3 fatty acids •Severity: MODERATE •Description: Omega-3 fatty acids may increase the antiplatelet activities of Abciximab. •Extended Description: In vitro, fish oils containing omega-3 fatty acid competitively inhibit cyclo-oxygenase which decreases synthesis of thromboxane A2 from arachidonic acid (ARA) in platelets. The cyclo-oxygenase mediated generation of thromboxane A2 from ARA in platelets plays a vital role in blood coagulation. The concurrent administration of omega-3 fatty acids with antiplatelets may potentiate the bleeding risk normally associated with antiplatelet agents. •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): Provided as daily supplements. Aa preparation of omega-3-acid ethyl esters is licensed in UK for prevention of recurrent events after myocardial infarction in addition to treatment of hypertriglyceridaemia. •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): Omega-3 fatty acids are triglycerides that get broken down into smaller fatty acid units. They act to reduce plasma triglyceride levels however increase the cholesterol levels and are thought to possess potent antiarrythmic effects. Polyunsaturated fatty acids including eicosapentaenoic and docosahexaenoic acid mediate important cellular function such as inhibition of platelet function, prolongation of bleeding time, anti-inflammatory effects and reduction of plasma fibrinogen. Polyunsaturated fatty acids are components of the phospholipids that form the structures of the cell membranes and also serve as energy source. They form eicosanoids which are important signalling molecules with wide-ranging functions in the body's cardiovascular, pulmonary, immune and endocrine systems. DHA tends to exist in high concentrations in the retina, brain (via uptake by Mfsd2a as a transporter), and sperm. •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): Omega-3 fatty acids mediate anti-inflammatory effects and increased levels of EPA or DHA has shown to decrease the levels of PGE2 and 4 series-LT. Eicosapentaenoic acids compete with constitutive levels of arachidonic acid in cell membranes for the same desaturation enzymes and produce 3-series prostaglandins and thromboxanes, and 5-series leukotrienes which have low pro-inflammatory potential. The alteration in leukotriene biosynthesis due to higher concentration of omega-3 fatty acids compared to arachidonic acid underlies the anti-inflammatory effects. EPA and DHA also give rise to resolvins and related lipid signalling molecules such as protectins via cyclooxygenase and lipoxygenase pathways, which have anti-inflammatory effects. They inhibit transendothelial migration of neutrophils and inhibit TNF and IL-1β production. Omega-3 fatty acids also decrease adhesion molecule expression on leukocytes and on endothelial cells and decrease intercellular adhesive interactions. Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator-activated receptor (PPAR) gamma that regulates inflammatory gene expression and NFκB activation. PPAR alpha activation is also associated with induction of COX-2 expression. The role of EPA and DHA in reducing triglyceride levels include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal-beta-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity. They also may reduce triglyceride synthesis because they are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit esterification of other fatty acids. •Absorption (Drug A): No absorption available •Absorption (Drug B): After ingestion, dietary lipids are hydrolyzed in the intestinal lumen. The hydrolysis products—monoglycerides and free fatty acids—are then incorporated into bile-salt– containing micelles and absorbed into enterocytes, largely by passive diffusion. The absorption rate is about 95%. Within intestinal cells, free fatty acids are primarily incorporated into chylomicrons and enter the circulation via the lymphatic system where they are delivered to various tissues for metabolism, oxidation and storage. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Vd of EPA is aproximately 82L •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): ALA, DHA and EPA are metabolized and oxidized in the liver, which is the site of biosynthesis of n-3 fatty acid intermediates, synthesizing VLDL that transport fatty acids in the plasma to tissues. Major enzymes that generate lipid signalling molecules from EPA, DHA and ALA are lipoxygenases and cyclooxygenase. •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): Approximate half-life values in a compartmental study of ALA, EPA and DHA are 1h, 39-67h and 20h, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of EPA is approximately 757mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Some adverse effects experienced in patients include gastrointestinal disturbances such as vomiting and constipation, metabolic disorders and skin reactions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Animi-3 With Vitamin D, Vitafol-one •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): n-3 fatty acids Omega 3 fatty acids Omega-3 Omega-3 (n-3) polyunsaturated fatty acids Omega-3 acid Omega-3 fatty acid Omega-3 phospholipids Omega-3 polyunsaturates Phospholipids ω-3 fatty acids •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omega-3 fatty acids is an ingredient found in a variety of supplements and vitamins.

In vitro, fish oils containing omega-3 fatty acid competitively inhibit cyclo-oxygenase which decreases synthesis of thromboxane A2 from arachidonic acid (ARA) in platelets. The cyclo-oxygenase mediated generation of thromboxane A2 from ARA in platelets plays a vital role in blood coagulation. The concurrent administration of omega-3 fatty acids with antiplatelets may potentiate the bleeding risk normally associated with antiplatelet agents. The severity of the interaction is moderate.

Question: Does Abciximab and Omega-3 fatty acids interact? Information: •Drug A: Abciximab •Drug B: Omega-3 fatty acids •Severity: MODERATE •Description: Omega-3 fatty acids may increase the antiplatelet activities of Abciximab. •Extended Description: In vitro, fish oils containing omega-3 fatty acid competitively inhibit cyclo-oxygenase which decreases synthesis of thromboxane A2 from arachidonic acid (ARA) in platelets. The cyclo-oxygenase mediated generation of thromboxane A2 from ARA in platelets plays a vital role in blood coagulation. The concurrent administration of omega-3 fatty acids with antiplatelets may potentiate the bleeding risk normally associated with antiplatelet agents. •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): Provided as daily supplements. Aa preparation of omega-3-acid ethyl esters is licensed in UK for prevention of recurrent events after myocardial infarction in addition to treatment of hypertriglyceridaemia. •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): Omega-3 fatty acids are triglycerides that get broken down into smaller fatty acid units. They act to reduce plasma triglyceride levels however increase the cholesterol levels and are thought to possess potent antiarrythmic effects. Polyunsaturated fatty acids including eicosapentaenoic and docosahexaenoic acid mediate important cellular function such as inhibition of platelet function, prolongation of bleeding time, anti-inflammatory effects and reduction of plasma fibrinogen. Polyunsaturated fatty acids are components of the phospholipids that form the structures of the cell membranes and also serve as energy source. They form eicosanoids which are important signalling molecules with wide-ranging functions in the body's cardiovascular, pulmonary, immune and endocrine systems. DHA tends to exist in high concentrations in the retina, brain (via uptake by Mfsd2a as a transporter), and sperm. •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): Omega-3 fatty acids mediate anti-inflammatory effects and increased levels of EPA or DHA has shown to decrease the levels of PGE2 and 4 series-LT. Eicosapentaenoic acids compete with constitutive levels of arachidonic acid in cell membranes for the same desaturation enzymes and produce 3-series prostaglandins and thromboxanes, and 5-series leukotrienes which have low pro-inflammatory potential. The alteration in leukotriene biosynthesis due to higher concentration of omega-3 fatty acids compared to arachidonic acid underlies the anti-inflammatory effects. EPA and DHA also give rise to resolvins and related lipid signalling molecules such as protectins via cyclooxygenase and lipoxygenase pathways, which have anti-inflammatory effects. They inhibit transendothelial migration of neutrophils and inhibit TNF and IL-1β production. Omega-3 fatty acids also decrease adhesion molecule expression on leukocytes and on endothelial cells and decrease intercellular adhesive interactions. Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator-activated receptor (PPAR) gamma that regulates inflammatory gene expression and NFκB activation. PPAR alpha activation is also associated with induction of COX-2 expression. The role of EPA and DHA in reducing triglyceride levels include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal-beta-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity. They also may reduce triglyceride synthesis because they are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit esterification of other fatty acids. •Absorption (Drug A): No absorption available •Absorption (Drug B): After ingestion, dietary lipids are hydrolyzed in the intestinal lumen. The hydrolysis products—monoglycerides and free fatty acids—are then incorporated into bile-salt– containing micelles and absorbed into enterocytes, largely by passive diffusion. The absorption rate is about 95%. Within intestinal cells, free fatty acids are primarily incorporated into chylomicrons and enter the circulation via the lymphatic system where they are delivered to various tissues for metabolism, oxidation and storage. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Vd of EPA is aproximately 82L •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): ALA, DHA and EPA are metabolized and oxidized in the liver, which is the site of biosynthesis of n-3 fatty acid intermediates, synthesizing VLDL that transport fatty acids in the plasma to tissues. Major enzymes that generate lipid signalling molecules from EPA, DHA and ALA are lipoxygenases and cyclooxygenase. •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): Approximate half-life values in a compartmental study of ALA, EPA and DHA are 1h, 39-67h and 20h, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of EPA is approximately 757mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Some adverse effects experienced in patients include gastrointestinal disturbances such as vomiting and constipation, metabolic disorders and skin reactions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Animi-3 With Vitamin D, Vitafol-one •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): n-3 fatty acids Omega 3 fatty acids Omega-3 Omega-3 (n-3) polyunsaturated fatty acids Omega-3 acid Omega-3 fatty acid Omega-3 phospholipids Omega-3 polyunsaturates Phospholipids ω-3 fatty acids •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omega-3 fatty acids is an ingredient found in a variety of supplements and vitamins. Output: In vitro, fish oils containing omega-3 fatty acid competitively inhibit cyclo-oxygenase which decreases synthesis of thromboxane A2 from arachidonic acid (ARA) in platelets. The cyclo-oxygenase mediated generation of thromboxane A2 from ARA in platelets plays a vital role in blood coagulation. The concurrent administration of omega-3 fatty acids with antiplatelets may potentiate the bleeding risk normally associated with antiplatelet agents. The severity of the interaction is moderate.

Does Abciximab and Omega-3-acid ethyl esters interact?

•Drug A: Abciximab •Drug B: Omega-3-acid ethyl esters •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Omega-3-acid ethyl esters is combined with Abciximab. •Extended Description: Prolonged bleeding time was seen in some trials however formal clinical trials to determine the effect of omega-3-acid ethyl esters on anticoagulants have yet to be performed. •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): Omega-3-Acid Ethyl Esters capsules, USP are indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia (HTG). •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): Omega-3-acid ethyl esters reduce triglyceride production, increase fatty acid metabolism, inhibit the release of fatty acids, increase triglyceride clearance, and decrease production of very low density lipoprotein cholesterol(VLDL-C). •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): Omega-3-acid ethyl esters reduce triglyceride production by the liver but this mechanism is not well understood. Omega-3-acid ethyl esters inhibit acyl-CoA:1,2-diacylglycerol acyltransferase, reducing triglyceride synthesis and increasing paroxysmal beta-oxidation, which increases fatty aside metabolism. Omega-3-acid ethyl esters also inhibit the release of fatty acids by competing for enzymes involved in the synthesis of triglycerides, increase triglyceride clearance by increasing the activity of lipoprotein lipase, and decrease production of VLDL-C. •Absorption (Drug A): No absorption available •Absorption (Drug B): Omega-3-acid ethyl esters are rapidly hydrolysed to free fatty acids in the intestinal lumen which then become incorporated into phospholipids, cholesterol, and triglycerides so determination of bioavailability by serum concentration is not possible. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 82 ± 56L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Because omega-3-acid ethyl esters are rapidly hydrolysed and incorporated into other processes and structures, protein binding data is scarce. However, most of EPA is bound to plasma 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): Omega-3-acid ethyl esters are hydrolysed to free fatty acids in the intestinal lumen by pancreatic lipase. Once in enterocytes, the free fatty acids are packaged in chylomicrons which are released from cells into the circulation. Fatty acids then enter the liver where they can be incorporated into liver stores, incorporated into lipoprotein phospholipids, or oxidised for energy. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Includes oxidative catabolism to carbon dioxide and water •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): 79 hours ± 47 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 757 mL/h ± 283mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In rats, omega-3-acid ethyl esters are not mutagenic or clastogenic and do not lead to impairment of fertility. Safety in human pregnancy have not been performed, however an embryocidal effect was seen in rats force fed 7 times the maximum recommended human dose. The risk and benefit of treatment during pregnancy should be weighed before deciding on treatment. Animal studies in lactating rats have shown excretion of omega-3-acid ethyl esters at concentrations 6 to 14 times higher than in the serum of the mother, however the effects of this excretion on a mother or child have not been established. Safety and effectiveness in pediatric patients has not been established. There appear to be no differences in the safety and efficacy in patients above or below 60 years of age based on limited data. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lovaza, Omtryg •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omega-3-acid ethyl esters is a mixture of fatty acids used as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe hypertriglyceridemia.

Prolonged bleeding time was seen in some trials however formal clinical trials to determine the effect of omega-3-acid ethyl esters on anticoagulants have yet to be performed. The severity of the interaction is minor.

Question: Does Abciximab and Omega-3-acid ethyl esters interact? Information: •Drug A: Abciximab •Drug B: Omega-3-acid ethyl esters •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Omega-3-acid ethyl esters is combined with Abciximab. •Extended Description: Prolonged bleeding time was seen in some trials however formal clinical trials to determine the effect of omega-3-acid ethyl esters on anticoagulants have yet to be performed. •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): Omega-3-Acid Ethyl Esters capsules, USP are indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia (HTG). •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): Omega-3-acid ethyl esters reduce triglyceride production, increase fatty acid metabolism, inhibit the release of fatty acids, increase triglyceride clearance, and decrease production of very low density lipoprotein cholesterol(VLDL-C). •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): Omega-3-acid ethyl esters reduce triglyceride production by the liver but this mechanism is not well understood. Omega-3-acid ethyl esters inhibit acyl-CoA:1,2-diacylglycerol acyltransferase, reducing triglyceride synthesis and increasing paroxysmal beta-oxidation, which increases fatty aside metabolism. Omega-3-acid ethyl esters also inhibit the release of fatty acids by competing for enzymes involved in the synthesis of triglycerides, increase triglyceride clearance by increasing the activity of lipoprotein lipase, and decrease production of VLDL-C. •Absorption (Drug A): No absorption available •Absorption (Drug B): Omega-3-acid ethyl esters are rapidly hydrolysed to free fatty acids in the intestinal lumen which then become incorporated into phospholipids, cholesterol, and triglycerides so determination of bioavailability by serum concentration is not possible. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 82 ± 56L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Because omega-3-acid ethyl esters are rapidly hydrolysed and incorporated into other processes and structures, protein binding data is scarce. However, most of EPA is bound to plasma 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): Omega-3-acid ethyl esters are hydrolysed to free fatty acids in the intestinal lumen by pancreatic lipase. Once in enterocytes, the free fatty acids are packaged in chylomicrons which are released from cells into the circulation. Fatty acids then enter the liver where they can be incorporated into liver stores, incorporated into lipoprotein phospholipids, or oxidised for energy. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Includes oxidative catabolism to carbon dioxide and water •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): 79 hours ± 47 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 757 mL/h ± 283mL/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In rats, omega-3-acid ethyl esters are not mutagenic or clastogenic and do not lead to impairment of fertility. Safety in human pregnancy have not been performed, however an embryocidal effect was seen in rats force fed 7 times the maximum recommended human dose. The risk and benefit of treatment during pregnancy should be weighed before deciding on treatment. Animal studies in lactating rats have shown excretion of omega-3-acid ethyl esters at concentrations 6 to 14 times higher than in the serum of the mother, however the effects of this excretion on a mother or child have not been established. Safety and effectiveness in pediatric patients has not been established. There appear to be no differences in the safety and efficacy in patients above or below 60 years of age based on limited data. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lovaza, Omtryg •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Omega-3-acid ethyl esters is a mixture of fatty acids used as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe hypertriglyceridemia. Output: Prolonged bleeding time was seen in some trials however formal clinical trials to determine the effect of omega-3-acid ethyl esters on anticoagulants have yet to be performed. The severity of the interaction is minor.

Does Abciximab and Oxaliplatin interact?

•Drug A: Abciximab •Drug B: Oxaliplatin •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Oxaliplatin is combined with Abciximab. •Extended Description: In clinical trials, the incidence of hemorrhage was higher in patients taking oxaliplatin with fluorouracil/leucovorin. Therefore, the co-administration of oxaliplatin and anticoagulants can further increase the risk of hemorrhage. Particularly, prolonged prothrombin time and INR have been reported in patients receiving oxaliplatin with fluorouracil/leucovorin combination while also on anticoagulants. •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): Oxaliplatin, in combination with infusional fluorouracil and leucovorin, is indicated for the treatment of advanced colorectal cancer and adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor. •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 vivo studies have shown antitumor activities of oxaliplatin against colon carcinoma. In combination with fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models (HT29 [colon], GR [mammary], and L1210 [leukemia]). •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): Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both inter and intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. •Absorption (Drug A): No absorption available •Absorption (Drug B): The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. After a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m, pharmacokinetic parameters expressed as ultrafiltrable platinum was C max of 0.814 mcg/mL. Interpatient and intrapatient variability in ultrafiltrable platinum exposure (AUC 0-48hr ) assessed over 3 cycles was 23% and 6%, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m, the volume of distribution is 440 L.At the end of a 2-hour infusion, approximately 15% of the administered platinum is present in the systemic circulation. The remaining 85% is rapidly distributed into tissues or eliminated in the urine. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In patients, plasma protein binding of platinum is irreversible and is greater than 90%. The main binding proteins are albumin and gamma-globulins. Platinum also binds irreversibly and accumulates (approximately 2-fold) in erythrocytes, where it appears to have no relevant activity. No platinum accumulation was observed in plasma ultrafiltrate following 85 mg/m every two weeks. •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): Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation. There is no evidence of cytochrome P450-mediated metabolism in vitro. Up to 17 platinum-containing derivatives have been observed in plasma ultrafiltrate samples from patients, including several cytotoxic species (monochloro DACH platinum, dichloro DACH platinum, and monoaquo and diaquo DACH platinum) and a number of noncytotoxic, conjugated species. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of ELOXATIN, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%. •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 decline of ultrafilterable platinum levels following oxaliplatin administration is triphasic with two distribution phases: t1/2α; 0.43 hours and t1/2β; 16.8 hours. This is followed by a long terminal elimination phase that lasts 391 hours (t1/2γ). •Clearance (Drug A): No clearance available •Clearance (Drug B): Platinum was cleared from plasma at a rate (10-17 L/h) that was similar to or exceeded the average human glomerular filtration rate (GFR; 7.5 L/h). The renal clearance of ultrafiltrable platinum is significantly correlated with GFR. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The maximum dose of oxaliplatin that has been administered in a single infusion is 825 mg. Several cases of overdoses have been reported with oxaliplatin. Adverse reactions observed following an overdosage were grade 4 thrombocytopenia (less than 25,000/mm3) without bleeding, anemia, sensory neuropathy (including paresthesia, dysesthesia, laryngospasm, and facial muscle spasms), gastrointestinal disorders (including nausea, vomiting, stomatitis, flatulence, abdomen enlarged and grade 4 intestinal obstruction), grade 4 dehydration, dyspnea, wheezing, chest pain, respiratory failure, severe bradycardia, and death. Closely monitor patients suspected of receiving an overdose, including for the adverse reactions described above, and administer appropriate supportive treatment. Based on its direct interaction with DNA, ELOXATIN can cause fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriages related to the use of oxaliplatin. Reproductive toxicity studies demonstrated adverse effects on embryo-fetal development in rats at maternal doses that were below the recommended human dose based on body surface area. Advise a pregnant woman of the potential risk to a fetus. In the adjuvant treatment trial, 400 patients who received oxaliplatin with fluorouracil/leucovorin were greater than or equal to 65 years. The effect of oxaliplatin in patients greater than or equal to 65 years was not conclusive. Patients greater than or equal to 65 years receiving ELOXATIN experienced more diarrhea and grade 3-4 neutropenia (45% vs 39%) compared to patients less than 65 years. The AUC of unbound platinum in plasma ultrafiltrate was increased in patients with renal impairment. No dose reduction is recommended for patients with mild (creatinine clearance 50 to 79 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal impairment, calculated by Cockcroft-Gault equation. Reduce the dose of oxaliplatin in patients with severe renal impairment (creatinine clearance less than 30 mL/min). Long-term animal studies have not been performed to evaluate the carcinogenic potential of oxaliplatin. Oxaliplatin was not mutagenic to bacteria (Ames test) but was mutagenic to mammalian cells in vitro (L5178Y mouse lymphoma assay). Oxaliplatin was clastogenic both in vitro (chromosome aberration in human lymphocytes) and in vivo (mouse bone marrow micronucleus assay). In a fertility study, male rats were given oxaliplatin at 0, 0.5, 1, or 2 mg/kg/day for five days every 21 days for a total of three cycles prior to mating with females that received two cycles of oxaliplatin on the same schedule. A dose of 2 mg/kg/day (less than one-seventh the recommended human dose on a body surface area basis) did not affect the pregnancy rate but resulted in 97% postimplantation loss (increased early resorptions, decreased live fetuses, decreased live births), and delayed growth (decreased fetal weight). Testicular damage, characterized by degeneration, hypoplasia, and atrophy, was observed in dogs administered oxaliplatin at 0.75 mg/kg/day (approximately one-sixth of the recommended human dose on a body surface area basis) × 5 days every 28 days for three cycles. A no-effect level was not identified. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Oxaliplatin is a platinum based chemotherapy agent used to treat carcinoma of the colon or rectum or stage III colon cancer.

In clinical trials, the incidence of hemorrhage was higher in patients taking oxaliplatin with fluorouracil/leucovorin. Therefore, the co-administration of oxaliplatin and anticoagulants can further increase the risk of hemorrhage. Particularly, prolonged prothrombin time and INR have been reported in patients receiving oxaliplatin with fluorouracil/leucovorin combination while also on anticoagulants. The severity of the interaction is moderate.

Question: Does Abciximab and Oxaliplatin interact? Information: •Drug A: Abciximab •Drug B: Oxaliplatin •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Oxaliplatin is combined with Abciximab. •Extended Description: In clinical trials, the incidence of hemorrhage was higher in patients taking oxaliplatin with fluorouracil/leucovorin. Therefore, the co-administration of oxaliplatin and anticoagulants can further increase the risk of hemorrhage. Particularly, prolonged prothrombin time and INR have been reported in patients receiving oxaliplatin with fluorouracil/leucovorin combination while also on anticoagulants. •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): Oxaliplatin, in combination with infusional fluorouracil and leucovorin, is indicated for the treatment of advanced colorectal cancer and adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor. •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 vivo studies have shown antitumor activities of oxaliplatin against colon carcinoma. In combination with fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models (HT29 [colon], GR [mammary], and L1210 [leukemia]). •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): Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both inter and intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. •Absorption (Drug A): No absorption available •Absorption (Drug B): The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. After a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m, pharmacokinetic parameters expressed as ultrafiltrable platinum was C max of 0.814 mcg/mL. Interpatient and intrapatient variability in ultrafiltrable platinum exposure (AUC 0-48hr ) assessed over 3 cycles was 23% and 6%, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m, the volume of distribution is 440 L.At the end of a 2-hour infusion, approximately 15% of the administered platinum is present in the systemic circulation. The remaining 85% is rapidly distributed into tissues or eliminated in the urine. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In patients, plasma protein binding of platinum is irreversible and is greater than 90%. The main binding proteins are albumin and gamma-globulins. Platinum also binds irreversibly and accumulates (approximately 2-fold) in erythrocytes, where it appears to have no relevant activity. No platinum accumulation was observed in plasma ultrafiltrate following 85 mg/m every two weeks. •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): Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation. There is no evidence of cytochrome P450-mediated metabolism in vitro. Up to 17 platinum-containing derivatives have been observed in plasma ultrafiltrate samples from patients, including several cytotoxic species (monochloro DACH platinum, dichloro DACH platinum, and monoaquo and diaquo DACH platinum) and a number of noncytotoxic, conjugated species. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of ELOXATIN, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%. •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 decline of ultrafilterable platinum levels following oxaliplatin administration is triphasic with two distribution phases: t1/2α; 0.43 hours and t1/2β; 16.8 hours. This is followed by a long terminal elimination phase that lasts 391 hours (t1/2γ). •Clearance (Drug A): No clearance available •Clearance (Drug B): Platinum was cleared from plasma at a rate (10-17 L/h) that was similar to or exceeded the average human glomerular filtration rate (GFR; 7.5 L/h). The renal clearance of ultrafiltrable platinum is significantly correlated with GFR. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The maximum dose of oxaliplatin that has been administered in a single infusion is 825 mg. Several cases of overdoses have been reported with oxaliplatin. Adverse reactions observed following an overdosage were grade 4 thrombocytopenia (less than 25,000/mm3) without bleeding, anemia, sensory neuropathy (including paresthesia, dysesthesia, laryngospasm, and facial muscle spasms), gastrointestinal disorders (including nausea, vomiting, stomatitis, flatulence, abdomen enlarged and grade 4 intestinal obstruction), grade 4 dehydration, dyspnea, wheezing, chest pain, respiratory failure, severe bradycardia, and death. Closely monitor patients suspected of receiving an overdose, including for the adverse reactions described above, and administer appropriate supportive treatment. Based on its direct interaction with DNA, ELOXATIN can cause fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriages related to the use of oxaliplatin. Reproductive toxicity studies demonstrated adverse effects on embryo-fetal development in rats at maternal doses that were below the recommended human dose based on body surface area. Advise a pregnant woman of the potential risk to a fetus. In the adjuvant treatment trial, 400 patients who received oxaliplatin with fluorouracil/leucovorin were greater than or equal to 65 years. The effect of oxaliplatin in patients greater than or equal to 65 years was not conclusive. Patients greater than or equal to 65 years receiving ELOXATIN experienced more diarrhea and grade 3-4 neutropenia (45% vs 39%) compared to patients less than 65 years. The AUC of unbound platinum in plasma ultrafiltrate was increased in patients with renal impairment. No dose reduction is recommended for patients with mild (creatinine clearance 50 to 79 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal impairment, calculated by Cockcroft-Gault equation. Reduce the dose of oxaliplatin in patients with severe renal impairment (creatinine clearance less than 30 mL/min). Long-term animal studies have not been performed to evaluate the carcinogenic potential of oxaliplatin. Oxaliplatin was not mutagenic to bacteria (Ames test) but was mutagenic to mammalian cells in vitro (L5178Y mouse lymphoma assay). Oxaliplatin was clastogenic both in vitro (chromosome aberration in human lymphocytes) and in vivo (mouse bone marrow micronucleus assay). In a fertility study, male rats were given oxaliplatin at 0, 0.5, 1, or 2 mg/kg/day for five days every 21 days for a total of three cycles prior to mating with females that received two cycles of oxaliplatin on the same schedule. A dose of 2 mg/kg/day (less than one-seventh the recommended human dose on a body surface area basis) did not affect the pregnancy rate but resulted in 97% postimplantation loss (increased early resorptions, decreased live fetuses, decreased live births), and delayed growth (decreased fetal weight). Testicular damage, characterized by degeneration, hypoplasia, and atrophy, was observed in dogs administered oxaliplatin at 0.75 mg/kg/day (approximately one-sixth of the recommended human dose on a body surface area basis) × 5 days every 28 days for three cycles. A no-effect level was not identified. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Oxaliplatin is a platinum based chemotherapy agent used to treat carcinoma of the colon or rectum or stage III colon cancer. Output: In clinical trials, the incidence of hemorrhage was higher in patients taking oxaliplatin with fluorouracil/leucovorin. Therefore, the co-administration of oxaliplatin and anticoagulants can further increase the risk of hemorrhage. Particularly, prolonged prothrombin time and INR have been reported in patients receiving oxaliplatin with fluorouracil/leucovorin combination while also on anticoagulants. The severity of the interaction is moderate.

Does Abciximab and Oxaprozin interact?

•Drug A: Abciximab •Drug B: Oxaprozin •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Oxaprozin 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. •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 relieve the inflammation, swelling, stiffness, and joint pain associated with rheumatoid arthritis and osteoarthritis. •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): Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain. •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): Anti-inflammatory effects of Oxaprozin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Oxaprozin is a non-selective NSAID, with a cell assay system showing lower COX-2 selectivity implying higher COX-1 selectivity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oxaprozin is 95% absorbed after oral administration. Food may reduce the rate of absorption of oxaprozin, but the extent of absorption is unchanged. Antacids do not significantly affect the extent and rate of oxaprozin absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 11 to 17 L/70 kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): >99.5% bound 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): Hepatic. Ester and ether glucuronide are the major conjugated metabolites of oxaprozin, and do not have significant pharmacologic activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Oxaprozin is expected to be excreted in human milk based on its physical-chemical properties; however, the amount of oxaprozin excreted in breast milk has not been evaluated. Approximately 95% of oxaprozin is metabolized by the liver. Approximately 5% of the oxaprozin dose is excreted unchanged in the urine. Sixty-five percent (65%) of the dose is excreted in the urine and 35% in the feces as metabolite. Biliary excretion of unchanged oxaprozin is a minor pathway. Several oxaprozin metabolites have been identified in human urine or 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): 54.9 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, mouse: LD 50 = 1210 mg/kg; Oral, rabbit: LD 50 = 172 mg/kg; Oral, rat: LD 50 = 4470 mg/kg •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Coxanto, Daypro •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Oxaprozin is an NSAID used to treat osteoarthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Oxaprozin interact? Information: •Drug A: Abciximab •Drug B: Oxaprozin •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Oxaprozin 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. •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 relieve the inflammation, swelling, stiffness, and joint pain associated with rheumatoid arthritis and osteoarthritis. •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): Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain. •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): Anti-inflammatory effects of Oxaprozin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Oxaprozin is a non-selective NSAID, with a cell assay system showing lower COX-2 selectivity implying higher COX-1 selectivity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oxaprozin is 95% absorbed after oral administration. Food may reduce the rate of absorption of oxaprozin, but the extent of absorption is unchanged. Antacids do not significantly affect the extent and rate of oxaprozin absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 11 to 17 L/70 kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): >99.5% bound 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): Hepatic. Ester and ether glucuronide are the major conjugated metabolites of oxaprozin, and do not have significant pharmacologic activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Oxaprozin is expected to be excreted in human milk based on its physical-chemical properties; however, the amount of oxaprozin excreted in breast milk has not been evaluated. Approximately 95% of oxaprozin is metabolized by the liver. Approximately 5% of the oxaprozin dose is excreted unchanged in the urine. Sixty-five percent (65%) of the dose is excreted in the urine and 35% in the feces as metabolite. Biliary excretion of unchanged oxaprozin is a minor pathway. Several oxaprozin metabolites have been identified in human urine or 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): 54.9 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, mouse: LD 50 = 1210 mg/kg; Oral, rabbit: LD 50 = 172 mg/kg; Oral, rat: LD 50 = 4470 mg/kg •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Coxanto, Daypro •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Oxaprozin is an NSAID used to treat osteoarthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Paclitaxel interact?

•Drug A: Abciximab •Drug B: Paclitaxel •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Paclitaxel. •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. •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 in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer. •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): Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. •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): Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function. •Absorption (Drug A): No absorption available •Absorption (Drug B): When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng•h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 227 to 688 L/m^2 [apparent volume of distribution at steady-state, 24 hour infusion] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 89%-98% bound to plasma protein. The presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. •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. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered 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): When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h] 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h] 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h] 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Rat (ipr) LD 50 =32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Abraxane, Taxol •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): ABI-007 COMPONENT PACLITAXEL BENZENEPROPANOIC ACID, .BETA.-(BENZOYLAMINO)-.ALPHA.-HYDROXY-, (2AR,4S,4AS,6R,9S,11S,12S,12AR,12BS)-6,12B-BIS(ACETYLOXY)-12-(BENZOYLOXY)-2A,3,4,4A,5,6,9,10,11,12,12A,12B-DODECAHYDRO-4,11-DIHYDROXY-4A,8,13,13-TETRAMETHYL-5-OXO-7,11-METHANO-1H-CYCLODECA(3, liposomal encapsulated paclitaxel NAB-PACLITAXEL COMPONENT PACLITAXEL Nanoparticulate paclitaxel Paclitaxel paclitaxel protein-bound particles Paclitaxel protein-bound particles for injection suspension Taxol A •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Paclitaxel is a taxoid chemotherapeutic agent used as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast and lung cancer.

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. The severity of the interaction is minor.

Question: Does Abciximab and Paclitaxel interact? Information: •Drug A: Abciximab •Drug B: Paclitaxel •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Paclitaxel. •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. •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 in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer. •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): Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. •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): Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function. •Absorption (Drug A): No absorption available •Absorption (Drug B): When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng•h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 227 to 688 L/m^2 [apparent volume of distribution at steady-state, 24 hour infusion] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 89%-98% bound to plasma protein. The presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. •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. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered 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): When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h] 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h] 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h] 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Rat (ipr) LD 50 =32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Abraxane, Taxol •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): ABI-007 COMPONENT PACLITAXEL BENZENEPROPANOIC ACID, .BETA.-(BENZOYLAMINO)-.ALPHA.-HYDROXY-, (2AR,4S,4AS,6R,9S,11S,12S,12AR,12BS)-6,12B-BIS(ACETYLOXY)-12-(BENZOYLOXY)-2A,3,4,4A,5,6,9,10,11,12,12A,12B-DODECAHYDRO-4,11-DIHYDROXY-4A,8,13,13-TETRAMETHYL-5-OXO-7,11-METHANO-1H-CYCLODECA(3, liposomal encapsulated paclitaxel NAB-PACLITAXEL COMPONENT PACLITAXEL Nanoparticulate paclitaxel Paclitaxel paclitaxel protein-bound particles Paclitaxel protein-bound particles for injection suspension Taxol A •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Paclitaxel is a taxoid chemotherapeutic agent used as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast and lung cancer. Output: 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. The severity of the interaction is minor.

Does Abciximab and Padeliporfin interact?

•Drug A: Abciximab •Drug B: Padeliporfin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Padeliporfin. •Extended Description: Padeliporfin is a drug used in Vascular-Targeted Photodynamic therapy procedures. Patients with abnormal clotting may bleed excessively from the insertion of the needles required to position the fibres that guide the laser light. This may also cause bruising, blood in the urine and/or local pain. Abnormal clotting is not expected to affect how well the treatment works; however, it is recommended that drugs that affect clotting are stopped prior to and for the immediate period following the Vascular-Targeted Photodynamic therapy procedure. •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): Padeliporfin is indicated for the treatment of adults with previously untreated, unilateral, low-risk, adenocarcinoma of the prostate with a life expectancy greater than or equal to 10 years. Patients must meet the following criteria: clinical stage T1c or T2a; Gleason Score ≤ 6, based on high-resolution biopsy strategies; PSA ≤ 10 ng/mL; and 3 positive cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 positive cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 ng/mL/cm. •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): Padeliporfin mediates tumour-specific cytotoxicity. It works to destroy target cells through the release of reactive oxygen species in response to an exposure to laser light radiation delivered at a specific wavelength. Padeliporfin causes vascular shutdown and activation of an immune response in the target tissue. In preclinical studies in animal models, padeliporfin-mediated photosensitization caused occlusion of the full tumour vasculature in a few minutes of treatment. Padeliporfin remains confined within the circulation even at high doses with minimal extravasation: reactive oxygen species generated upon laser activation are contained in the vasculature and do not directly kill tumour 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): Vascular-targeted photodynamic therapy (VTP), or vascular targeted photochemotherapy, is a focal treatment for localized prostate cancer. VTP involves the process of light activation of photosensitizer localized in the target tissue, which produces reactive oxygen species that work to destroy target cells. Padeliporfin is retained within the vascular system. When activated with 753 nm wavelength laser light, padeliporfin triggers a photochemical reaction that generates oxygen radicals (hydroxyl radical, superoxide radical), thereby causing local hypoxia of the target tissue. Nitric oxide radicals are also released, resulting in transient arterial vasodilatation that triggers the release of the vasoconstrictor, endothelin-1. Rapid consumption of the nitric oxide radicals by oxygen radicals leads to the formation of reactive nitrogen species (RNS) including peroxynitrite, in parallel to arterial constriction. Impaired deformability enhances erythrocyte aggregability and formation of blood clots at the interface of the arterial supply of the target tissue, leading to occlusion of the tumour vasculature, or "vascular shutdown." This effect is enhanced by RNS-induced endothelial cell apoptosis and initiation of self-propagated tumour cells necrosis through peroxidation of their membrane. •Absorption (Drug A): No absorption available •Absorption (Drug B): After intravenous bolus injection at a dose of 6 mg/kg into healthy mice, the C max of padeliporfin was about 52 mg/L, with a T max of two minutes. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In healthy men receiving 1.25 to 15 mg/kg of padeliporfin di-potassium, the mean volume of distribution (V d ) ranged from 0.064 to 0.279 L/kg. In patients with localized prostate cancer treated with 2 and 4 mg/kg of padeliporfin di-potassium, the mean V d ranged from 0.09 to 0.10 L/kg. Upon administration, padeliporfin remain confined within the circulation even at high doses, with minimal extravasation to other tissues. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Padeliporfin di-potassium is 99% bound to human plasma proteins. Padeliporfin binds to high-density proteins, including serum albumin, but binds poorly to low-level density lipoproteins and high-density lipoproteins. •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 human liver microsomes and S9 fractions, padeliporfin underwent minimal metabolism. No metabolites of padeliporfin have been identified yet as a radiolabeled study has not been performed. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In healthy subjects, urinary excretion of padeliporfin was very low, accounting for less than 0.2% of the dose. Fecal elimination is a suspected predominant route 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 estimated half-life is 1.19 hrs ± 0.08 at 4 mg/kg of padeliporfin di-potassium. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following administration of 1.25-15 mg/kg of padeliporfin di-potassium in healthy men, clearance of padeliporfin di-potassium ranged from 0.0245 to 0.088 L/h/kg. In patients with localised prostate cancer treated with 4 mg/kg and 2 mg/kg of padeliporfin di-potassium, clearance was 0.04 L/h/kg and 0.06 L/h/kg, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information regarding the LD 50 of padeliporfin. There is limited clinical information on padeliporfin overdose. In clinical studies, healthy subjects were exposed to doses up to 15 mg/kg of padeliporfin di-potassium (corresponding to 13.73 mg/kg of padeliporfin) without light activation and 23 patients have been treated with 6 mg/kg of padeliporfin di-potassium (corresponding to 5.49 mg/kg of padeliporfin) without significant safety issues. However, prolonged photosensitization is possible and precautions against light exposure should be maintained for an additional 24 hours. An overdose of the laser light may increase the risk of undesirable extraprostatic necrosis. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Padeliporfin is a vascular-acting photosensitizer used to treat low-risk prostate cancer in adults.

Padeliporfin is a drug used in Vascular-Targeted Photodynamic therapy procedures. Patients with abnormal clotting may bleed excessively from the insertion of the needles required to position the fibres that guide the laser light. This may also cause bruising, blood in the urine and/or local pain. Abnormal clotting is not expected to affect how well the treatment works; however, it is recommended that drugs that affect clotting are stopped prior to and for the immediate period following the Vascular-Targeted Photodynamic therapy procedure. The severity of the interaction is moderate.

Question: Does Abciximab and Padeliporfin interact? Information: •Drug A: Abciximab •Drug B: Padeliporfin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Padeliporfin. •Extended Description: Padeliporfin is a drug used in Vascular-Targeted Photodynamic therapy procedures. Patients with abnormal clotting may bleed excessively from the insertion of the needles required to position the fibres that guide the laser light. This may also cause bruising, blood in the urine and/or local pain. Abnormal clotting is not expected to affect how well the treatment works; however, it is recommended that drugs that affect clotting are stopped prior to and for the immediate period following the Vascular-Targeted Photodynamic therapy procedure. •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): Padeliporfin is indicated for the treatment of adults with previously untreated, unilateral, low-risk, adenocarcinoma of the prostate with a life expectancy greater than or equal to 10 years. Patients must meet the following criteria: clinical stage T1c or T2a; Gleason Score ≤ 6, based on high-resolution biopsy strategies; PSA ≤ 10 ng/mL; and 3 positive cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 positive cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 ng/mL/cm. •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): Padeliporfin mediates tumour-specific cytotoxicity. It works to destroy target cells through the release of reactive oxygen species in response to an exposure to laser light radiation delivered at a specific wavelength. Padeliporfin causes vascular shutdown and activation of an immune response in the target tissue. In preclinical studies in animal models, padeliporfin-mediated photosensitization caused occlusion of the full tumour vasculature in a few minutes of treatment. Padeliporfin remains confined within the circulation even at high doses with minimal extravasation: reactive oxygen species generated upon laser activation are contained in the vasculature and do not directly kill tumour 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): Vascular-targeted photodynamic therapy (VTP), or vascular targeted photochemotherapy, is a focal treatment for localized prostate cancer. VTP involves the process of light activation of photosensitizer localized in the target tissue, which produces reactive oxygen species that work to destroy target cells. Padeliporfin is retained within the vascular system. When activated with 753 nm wavelength laser light, padeliporfin triggers a photochemical reaction that generates oxygen radicals (hydroxyl radical, superoxide radical), thereby causing local hypoxia of the target tissue. Nitric oxide radicals are also released, resulting in transient arterial vasodilatation that triggers the release of the vasoconstrictor, endothelin-1. Rapid consumption of the nitric oxide radicals by oxygen radicals leads to the formation of reactive nitrogen species (RNS) including peroxynitrite, in parallel to arterial constriction. Impaired deformability enhances erythrocyte aggregability and formation of blood clots at the interface of the arterial supply of the target tissue, leading to occlusion of the tumour vasculature, or "vascular shutdown." This effect is enhanced by RNS-induced endothelial cell apoptosis and initiation of self-propagated tumour cells necrosis through peroxidation of their membrane. •Absorption (Drug A): No absorption available •Absorption (Drug B): After intravenous bolus injection at a dose of 6 mg/kg into healthy mice, the C max of padeliporfin was about 52 mg/L, with a T max of two minutes. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In healthy men receiving 1.25 to 15 mg/kg of padeliporfin di-potassium, the mean volume of distribution (V d ) ranged from 0.064 to 0.279 L/kg. In patients with localized prostate cancer treated with 2 and 4 mg/kg of padeliporfin di-potassium, the mean V d ranged from 0.09 to 0.10 L/kg. Upon administration, padeliporfin remain confined within the circulation even at high doses, with minimal extravasation to other tissues. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Padeliporfin di-potassium is 99% bound to human plasma proteins. Padeliporfin binds to high-density proteins, including serum albumin, but binds poorly to low-level density lipoproteins and high-density lipoproteins. •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 human liver microsomes and S9 fractions, padeliporfin underwent minimal metabolism. No metabolites of padeliporfin have been identified yet as a radiolabeled study has not been performed. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In healthy subjects, urinary excretion of padeliporfin was very low, accounting for less than 0.2% of the dose. Fecal elimination is a suspected predominant route 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 estimated half-life is 1.19 hrs ± 0.08 at 4 mg/kg of padeliporfin di-potassium. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following administration of 1.25-15 mg/kg of padeliporfin di-potassium in healthy men, clearance of padeliporfin di-potassium ranged from 0.0245 to 0.088 L/h/kg. In patients with localised prostate cancer treated with 4 mg/kg and 2 mg/kg of padeliporfin di-potassium, clearance was 0.04 L/h/kg and 0.06 L/h/kg, respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information regarding the LD 50 of padeliporfin. There is limited clinical information on padeliporfin overdose. In clinical studies, healthy subjects were exposed to doses up to 15 mg/kg of padeliporfin di-potassium (corresponding to 13.73 mg/kg of padeliporfin) without light activation and 23 patients have been treated with 6 mg/kg of padeliporfin di-potassium (corresponding to 5.49 mg/kg of padeliporfin) without significant safety issues. However, prolonged photosensitization is possible and precautions against light exposure should be maintained for an additional 24 hours. An overdose of the laser light may increase the risk of undesirable extraprostatic necrosis. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Padeliporfin is a vascular-acting photosensitizer used to treat low-risk prostate cancer in adults. Output: Padeliporfin is a drug used in Vascular-Targeted Photodynamic therapy procedures. Patients with abnormal clotting may bleed excessively from the insertion of the needles required to position the fibres that guide the laser light. This may also cause bruising, blood in the urine and/or local pain. Abnormal clotting is not expected to affect how well the treatment works; however, it is recommended that drugs that affect clotting are stopped prior to and for the immediate period following the Vascular-Targeted Photodynamic therapy procedure. The severity of the interaction is moderate.

Does Abciximab and Palbociclib interact?

•Drug A: Abciximab •Drug B: Palbociclib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Palbociclib. •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. •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): Palbociclib is indicated in combination with letrozole as initial endocrine-based therapy for the treatment of human epidermal growth factor receptor type 2 (HER2)-negative and hormone receptor(HR)-positive tumors in adult patients with advanced/metastatic breast cancer. It is as well approved in combination with fulvestrant in patients with disease progression with prior endocrine therapy. In the official labeling, the use of palbociclib should be accompanied with either an aromatase inhibition, no restricted to letrozole, as initial endocrine-based therapy in postmenopausal women or in man. The breast cancer starts as a group of cancer cells that grow into and destroy the nearby breast tissue. This growth can spread into other parts of the body which is called metastasis. According to the location of the cancer cells, it can be categorized in ductal carcinoma and lobular carcinoma. However, other types of breast cancer include inflammatory breast cancer, Paget disease of the breast, triple negative breast cancer non-Hodgkin lymphoma and soft tissue sarcoma. In males, breast cancer is usually treated as the cases of postmenopausal women and almost all the cases are ductal 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): Due to its mechanism of action, palbociclib inhibits cell growth and suppresses DNA replication in retinoblastoma tumor suppressor gene (RB) proficient cancer cells. As expected, these RB cells present a significant increase in the proportion of cells in G1 state and the presence of palbociclib produces effective dephosphorylation of RB, reduce proliferation and induce senescence causing cell-cycle arrest. In vitro studies showed the potential for palbociclib to reduce cellular proliferation of estrogen receptor-positive breast cancer cell lines through the inhibition of the cell-cycle progression from G1 to S phase. In this study, it was demonstrated that the sensitivity of the cells significantly increased with the expression of RB1 and CCND1 and low expression of CDKN2A. As well, palbociclib, combined with antiestrogens, enhanced in vivo antitumor activity in estrogen receptor-positive breast cancer mouse models. In clinical trials, palbociclib, in combination with letrozole, was shown to significantly increase the progression-free survival (PFS) in patients with metastatic breast cancer without prior endocrine treatment. In the results, the PFS increased from 4.5 to 9.5 months with an overall response rate (ORR) of 24.6%. •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): Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that acts by binding to the ATP pocket with an IC50 in the range of 9-15 nmol/L. It is important to consider that it presents low to absent activity against other kinases. The CDK4/6 kinase is involved, with coregulatory partner cyclin D, in the G1-S transition. Hence, inhibition of this step prevents cell cycle progression in cells in whose this pathway is functioning. This step includes the pathways of the phosphorylation of retinoblastoma protein and the E2F family of transcription factors. •Absorption (Drug A): No absorption available •Absorption (Drug B): Palbociclib presents a linear pharmacokinetic profile and its peak plasma concentration was observed 6-12 hours after oral administration. The oral bioavailability is reported to be of 46% with a steady-state reached after 8 days and a median accumulation ratio of 2.4. The absorption of palbociclib is significantly reduced under fasting conditions and hence, food intake is recommended when this drug is administered. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean apparent distribution of palbociclib is 2583 L which suggests that palbociclib penetrates extensively into peripheral tissues. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binding of palbociclib to human plasma proteins in vitro accounts for approximately 85% 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): Palbociclib is mainly hepatically transformed. the metabolism is mainly performed by the activities of the cytochrome P450 isoenzyme 3A and the sulfotransferase 2A1. The metabolism of palbociclib is represented mainly by reactions of oxidation and sulfonation followed by acylation and glucuronidation as minor reactions. After its metabolism, palbociclib forms mainly inactive glucuronide and sulfamic acid conjugates. The major circulating metabolite, accounting for 1.5% of the dose in excreta is is the glucuronide conjugate. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main route of elimination of palbociclib is through feces after hepatic metabolism while renal clearance seems to play a minor role accounting only for 17.5% of the eliminated 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 mean plasma elimination half-life of palbociclib is 29 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean apparent oral clearance of palbociclib is of 63.1 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The reported oral Ld50 is of 100 mg/kg. In cases of overdosage, only supportive measures are considered. Palbociclib was showed to present clastogenic activities in in vitro and in vivo assays. As well, it has been reported to produce fetal harm due to its mechanism of action. Lastly, it was shown to increase the incidence of microglial cell tumors in the central nervous system at high doses. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ibrance •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Palbociclib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Palbociclib is an endocrine-based chemotherapeutic agent used in combination with other antineoplastic agents to treat HER2-negative and HR-positive advanced or metastatic breast cancer.

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. The severity of the interaction is minor.

Question: Does Abciximab and Palbociclib interact? Information: •Drug A: Abciximab •Drug B: Palbociclib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Palbociclib. •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. •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): Palbociclib is indicated in combination with letrozole as initial endocrine-based therapy for the treatment of human epidermal growth factor receptor type 2 (HER2)-negative and hormone receptor(HR)-positive tumors in adult patients with advanced/metastatic breast cancer. It is as well approved in combination with fulvestrant in patients with disease progression with prior endocrine therapy. In the official labeling, the use of palbociclib should be accompanied with either an aromatase inhibition, no restricted to letrozole, as initial endocrine-based therapy in postmenopausal women or in man. The breast cancer starts as a group of cancer cells that grow into and destroy the nearby breast tissue. This growth can spread into other parts of the body which is called metastasis. According to the location of the cancer cells, it can be categorized in ductal carcinoma and lobular carcinoma. However, other types of breast cancer include inflammatory breast cancer, Paget disease of the breast, triple negative breast cancer non-Hodgkin lymphoma and soft tissue sarcoma. In males, breast cancer is usually treated as the cases of postmenopausal women and almost all the cases are ductal 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): Due to its mechanism of action, palbociclib inhibits cell growth and suppresses DNA replication in retinoblastoma tumor suppressor gene (RB) proficient cancer cells. As expected, these RB cells present a significant increase in the proportion of cells in G1 state and the presence of palbociclib produces effective dephosphorylation of RB, reduce proliferation and induce senescence causing cell-cycle arrest. In vitro studies showed the potential for palbociclib to reduce cellular proliferation of estrogen receptor-positive breast cancer cell lines through the inhibition of the cell-cycle progression from G1 to S phase. In this study, it was demonstrated that the sensitivity of the cells significantly increased with the expression of RB1 and CCND1 and low expression of CDKN2A. As well, palbociclib, combined with antiestrogens, enhanced in vivo antitumor activity in estrogen receptor-positive breast cancer mouse models. In clinical trials, palbociclib, in combination with letrozole, was shown to significantly increase the progression-free survival (PFS) in patients with metastatic breast cancer without prior endocrine treatment. In the results, the PFS increased from 4.5 to 9.5 months with an overall response rate (ORR) of 24.6%. •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): Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that acts by binding to the ATP pocket with an IC50 in the range of 9-15 nmol/L. It is important to consider that it presents low to absent activity against other kinases. The CDK4/6 kinase is involved, with coregulatory partner cyclin D, in the G1-S transition. Hence, inhibition of this step prevents cell cycle progression in cells in whose this pathway is functioning. This step includes the pathways of the phosphorylation of retinoblastoma protein and the E2F family of transcription factors. •Absorption (Drug A): No absorption available •Absorption (Drug B): Palbociclib presents a linear pharmacokinetic profile and its peak plasma concentration was observed 6-12 hours after oral administration. The oral bioavailability is reported to be of 46% with a steady-state reached after 8 days and a median accumulation ratio of 2.4. The absorption of palbociclib is significantly reduced under fasting conditions and hence, food intake is recommended when this drug is administered. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean apparent distribution of palbociclib is 2583 L which suggests that palbociclib penetrates extensively into peripheral tissues. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binding of palbociclib to human plasma proteins in vitro accounts for approximately 85% 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): Palbociclib is mainly hepatically transformed. the metabolism is mainly performed by the activities of the cytochrome P450 isoenzyme 3A and the sulfotransferase 2A1. The metabolism of palbociclib is represented mainly by reactions of oxidation and sulfonation followed by acylation and glucuronidation as minor reactions. After its metabolism, palbociclib forms mainly inactive glucuronide and sulfamic acid conjugates. The major circulating metabolite, accounting for 1.5% of the dose in excreta is is the glucuronide conjugate. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main route of elimination of palbociclib is through feces after hepatic metabolism while renal clearance seems to play a minor role accounting only for 17.5% of the eliminated 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 mean plasma elimination half-life of palbociclib is 29 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean apparent oral clearance of palbociclib is of 63.1 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The reported oral Ld50 is of 100 mg/kg. In cases of overdosage, only supportive measures are considered. Palbociclib was showed to present clastogenic activities in in vitro and in vivo assays. As well, it has been reported to produce fetal harm due to its mechanism of action. Lastly, it was shown to increase the incidence of microglial cell tumors in the central nervous system at high doses. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ibrance •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Palbociclib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Palbociclib is an endocrine-based chemotherapeutic agent used in combination with other antineoplastic agents to treat HER2-negative and HR-positive advanced or metastatic breast cancer. Output: 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. The severity of the interaction is minor.

Does Abciximab and Palivizumab interact?

•Drug A: Abciximab •Drug B: Palivizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Palivizumab. •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 . •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 of respiratory diseases casued by respiratory syncytial virus. •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): Synagis exhibits neutralizing and fusion-inhibitory activity against Respiratory syncytial virus (RSV). These activities inhibit RSV replication or spread. Synagis is given to prevent the development of lower respiratory tract disease in pediatric patients. •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): Palivizumab binds to the fusion glycoprotein of RSV. This prevents its binding and uptake by host cellular 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): 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. •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): 18-20 days (in adults) •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): Synagis •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Palivizumab is a monoclonal anti respiratory syncytial virus F protein antibody used to prevent serious sequelae caused by respiratory syncytial virus infection in pediatric patients.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Palivizumab interact? Information: •Drug A: Abciximab •Drug B: Palivizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Palivizumab. •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 . •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 of respiratory diseases casued by respiratory syncytial virus. •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): Synagis exhibits neutralizing and fusion-inhibitory activity against Respiratory syncytial virus (RSV). These activities inhibit RSV replication or spread. Synagis is given to prevent the development of lower respiratory tract disease in pediatric patients. •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): Palivizumab binds to the fusion glycoprotein of RSV. This prevents its binding and uptake by host cellular 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): 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. •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): 18-20 days (in adults) •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): Synagis •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Palivizumab is a monoclonal anti respiratory syncytial virus F protein antibody used to prevent serious sequelae caused by respiratory syncytial virus infection in pediatric patients. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Panitumumab interact?

•Drug A: Abciximab •Drug B: Panitumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Panitumumab. •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 . •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 EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens. •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): Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases. Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration. Signal transduction through EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor 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): Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR. •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): 7.5 days (range: 4-11 days) •Clearance (Drug A): No clearance available •Clearance (Drug B): 4.9+/- 1.4 mL/kg/day [Following single-dose administrations of panitumumab as 1-hour infusions] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Panitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Vectibix •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Panitumumab •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Panitumumab is a recombinant humanized monoclonal antibody used to treat EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Panitumumab interact? Information: •Drug A: Abciximab •Drug B: Panitumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Panitumumab. •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 . •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 EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens. •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): Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases. Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration. Signal transduction through EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor 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): Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR. •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): 7.5 days (range: 4-11 days) •Clearance (Drug A): No clearance available •Clearance (Drug B): 4.9+/- 1.4 mL/kg/day [Following single-dose administrations of panitumumab as 1-hour infusions] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Panitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Vectibix •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Panitumumab •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Panitumumab is a recombinant humanized monoclonal antibody used to treat EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Pantothenic acid interact?

•Drug A: Abciximab •Drug B: Pantothenic acid •Severity: MAJOR •Description: The therapeutic efficacy of Pantothenic acid 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. •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): Studied for the treatment of many uses such as treatment of testicular torsion, diabetic ulceration, wound healing, acne, obesity, diabetic peripheral polyneuropathy. It has also been investigated for its hypolipidemic effects and as cholesterol lowering 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): Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate. Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively. Since pantothenic acid participates in a wide array of key biological roles, it may have numerous wide-ranging 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): Pantothenic acid is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dietary pantothenic acid is primarily in the form of CoA or ACP and must be converted into free pantothenic acid for absorption. CoA and ACP are hydrolyzed into 4'-phosphopantetheine which is then dephosphorylated into pantetheine and subsequently hydrolyzed again to free pantothenic acid by Pantetheinase in the intestinal lumen. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system with passive diffusion acting as a secondary pathway. As intake increases up to 10-fold absorption rate can decrease to as low as 10% due to transporter saturation. •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 Tolerable Upper Level Intake (UL) has been established for the vitamin. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Concept Ob, Irospan 24/6 Kit, Pregvit, Tandem Plus •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): D-pantothenic acid Pantothenate Vitamin B5 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pantothenic acid is a vitamin B5 found in various nutritional supplements.

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. The severity of the interaction is major.

Question: Does Abciximab and Pantothenic acid interact? Information: •Drug A: Abciximab •Drug B: Pantothenic acid •Severity: MAJOR •Description: The therapeutic efficacy of Pantothenic acid 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. •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): Studied for the treatment of many uses such as treatment of testicular torsion, diabetic ulceration, wound healing, acne, obesity, diabetic peripheral polyneuropathy. It has also been investigated for its hypolipidemic effects and as cholesterol lowering 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): Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate. Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively. Since pantothenic acid participates in a wide array of key biological roles, it may have numerous wide-ranging 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): Pantothenic acid is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dietary pantothenic acid is primarily in the form of CoA or ACP and must be converted into free pantothenic acid for absorption. CoA and ACP are hydrolyzed into 4'-phosphopantetheine which is then dephosphorylated into pantetheine and subsequently hydrolyzed again to free pantothenic acid by Pantetheinase in the intestinal lumen. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system with passive diffusion acting as a secondary pathway. As intake increases up to 10-fold absorption rate can decrease to as low as 10% due to transporter saturation. •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 Tolerable Upper Level Intake (UL) has been established for the vitamin. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Concept Ob, Irospan 24/6 Kit, Pregvit, Tandem Plus •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): D-pantothenic acid Pantothenate Vitamin B5 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pantothenic acid is a vitamin B5 found in various nutritional supplements. Output: 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. The severity of the interaction is major.

Does Abciximab and Parecoxib interact?

•Drug A: Abciximab •Drug B: Parecoxib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Parecoxib 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. •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 for short term perioperative pain control. •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): 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): Hepatic. Metabolized primarily via CYP3A4 and 2C9 to valdecoxib and propionic acid. •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): 22 minutes (parecoxib); 8 hours (valdecoxib) •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): Dynastat •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Parecoxib Parécoxib Parecoxibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Parecoxib is a selective COX-2 inhibitor and NSAID used for the short-term management of perioperative pain.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Parecoxib interact? Information: •Drug A: Abciximab •Drug B: Parecoxib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Parecoxib 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. •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 for short term perioperative pain control. •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): 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): Hepatic. Metabolized primarily via CYP3A4 and 2C9 to valdecoxib and propionic acid. •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): 22 minutes (parecoxib); 8 hours (valdecoxib) •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): Dynastat •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Parecoxib Parécoxib Parecoxibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Parecoxib is a selective COX-2 inhibitor and NSAID used for the short-term management of perioperative pain. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Parnaparin interact?

•Drug A: Abciximab •Drug B: Parnaparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Parnaparin. •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. •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 in the prevention and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of 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): 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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Parnaparin is a low molecular weight heparin (LMWH) used to prevent blood clots, specifically deep vein thrombosis.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Parnaparin interact? Information: •Drug A: Abciximab •Drug B: Parnaparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Parnaparin. •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. •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 in the prevention and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of 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): 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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Parnaparin is a low molecular weight heparin (LMWH) used to prevent blood clots, specifically deep vein thrombosis. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Paroxetine interact?

•Drug A: Abciximab •Drug B: Paroxetine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Paroxetine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Paroxetine is indicated for the management of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder. One form of paroxetine, commercially known as Brisdelle, is used to manage mild to moderate vasomotor symptoms of menopause. Off-label, paroxetine may be used for the treatment of premature ejaculation or irritable bowel syndrome (IBS). •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): Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake. The onset of action of paroxetine is reported to be approximately 6 weeks. Due its serotonergic activity, paroxetine, like other SSRI drugs, may potentiate serotonin syndrome. This risk is especially high when monoamine oxidase (MAO) inhibitors are given within 2 weeks of paroxetine administration. Upon cessation of MAO inhibitors, a 2-week interval before paroxetine administration is recommended. Do not coadminister these agents. •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): Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor. This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, including Citalopram, Fluoxetine, and Fluvoxamine. The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information, but may occur due to its effects on thermoregulation. Paroxetine shows a clinically insignificant affinity for adrenergic alpha-1 and alpha-2 receptors and β-adrenergic receptors, dopamine D1 and D2 receptors, histamine H1 receptors and serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. This drug shows some affinity for muscarinic cholinergic receptors and 5-H2B receptors. The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the 5-HT neurons. In rats, paroxetine activates 5-HT1A receptors when it is first administered, inhibiting the stimulation of the 5-HT neurons and subsequent release of serotonin at the synaptic cleft. •Absorption (Drug A): No absorption available •Absorption (Drug B): Paroxetine is readily absorbed from the gastrointestinal tract. Due to the first-pass metabolism, the bioavailability ranges from 30-60%. Cmax is attained 2 to 8 hours after an oral dose. Mean Tmax is 4.3 hours in healthy patients. The steady-state concentration of paroxetine is achieved within 7 to 14 days of oral therapy. In a pharmacokinetic study, AUC in healthy patients was 574 ng·h/mL and 1053 ng·h/mL in those with moderate renal impairment. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Paroxetine has a large volume of distribution and is found throughout the body, including in the central nervous system. Only 1% of the drug is found in the plasma. Paroxetine is found in the breast milk at concentrations similar to the concentrations found in plasma. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Paroxetine is 95% 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): Paroxetine metabolism occurs in the liver and is largely mediated by cytochrome CYP2D6 with contributions from CYP3A4 and possibly other cytochrome enzymes. Genetic polymorphisms of the CYP2D6 enzyme may alter the pharmacokinetics of this drug. Poor metabolizers may demonstrate increased adverse effects while rapid metabolizers may experience decreased therapeutic effects. The majority of a paroxetine dose is oxidized to a catechol metabolite that is subsequently converted to both glucuronide and sulfate metabolites via methylation and conjugation. In rat synaptosomes, the glucuronide and sulfate conjugates have been shown to thousands of times less potent than paroxetine itself. The metabolites of paroxetine are considered inactive. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 2/3 of a single paroxetine dose is found to be excreted in the urine and the remainder is found to be excreted in feces. Almost all of the dose is eliminated as metabolites; 3% is found to be excreted as unchanged paroxetine. About 64% of a 30 mg oral dose was found excreted in the urine, with 2% as the parent drug and 62% appearing as metabolites. Approximately 36% of the dose was found to be eliminated in the feces primarily as metabolites and less than 1% as the 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 mean elimination half-life of paroxetine is about 21 hours. In healthy young subjects, mean elimination half-life was found to be 17.3 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent oral clearance of paroxetine is 167 L/h. The clearance of paroxetine in patients with renal failure is significantly lower and dose adjustment may be required, despite the fact that it is mainly cleared by the liver. Dose adjustments may be required in hepatic impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The acute LD50 in mice and rats is 350 mg/kg. Overdose information The lowest dose of paroxetine reported to lead to a fatal outcome is approximately 400 mg. The largest reported paroxetine overdose from which a patient has survived and recovered is a dose of 2000 mg. Common manifestations in a paroxetine overdose include fatigue, fever, insomnia hypertension, tachycardia, nausea, vomiting, somnolence, tremor, dizziness, agitation, confusion, anxious symptoms, headache, insomnia, hyperhidrosis, dilated pupils, seizures, paresthesia, serotonin syndrome, involuntary muscle contraction, and change in mental status. It should be noted that in some cases, patients may have consumed alcohol in addition to taking an overdose of paroxetine. Some of these symptoms may also be seen with clinical use. There is no specific antidote to an overdose of paroxetine. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Paxil, Pexeva •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Paroxetina Paroxetine Paroxetinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Paroxetine is a selective serotonin reuptake inhibitor used to treat major depressive disorder, panic disorder, OCD, social phobia, generalized anxiety disorder, the vasomotor symptoms of menopause, and premenstrual dysphoric disorder.

It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Paroxetine interact? Information: •Drug A: Abciximab •Drug B: Paroxetine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Paroxetine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Paroxetine is indicated for the management of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder. One form of paroxetine, commercially known as Brisdelle, is used to manage mild to moderate vasomotor symptoms of menopause. Off-label, paroxetine may be used for the treatment of premature ejaculation or irritable bowel syndrome (IBS). •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): Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake. The onset of action of paroxetine is reported to be approximately 6 weeks. Due its serotonergic activity, paroxetine, like other SSRI drugs, may potentiate serotonin syndrome. This risk is especially high when monoamine oxidase (MAO) inhibitors are given within 2 weeks of paroxetine administration. Upon cessation of MAO inhibitors, a 2-week interval before paroxetine administration is recommended. Do not coadminister these agents. •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): Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor. This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, including Citalopram, Fluoxetine, and Fluvoxamine. The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information, but may occur due to its effects on thermoregulation. Paroxetine shows a clinically insignificant affinity for adrenergic alpha-1 and alpha-2 receptors and β-adrenergic receptors, dopamine D1 and D2 receptors, histamine H1 receptors and serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. This drug shows some affinity for muscarinic cholinergic receptors and 5-H2B receptors. The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the 5-HT neurons. In rats, paroxetine activates 5-HT1A receptors when it is first administered, inhibiting the stimulation of the 5-HT neurons and subsequent release of serotonin at the synaptic cleft. •Absorption (Drug A): No absorption available •Absorption (Drug B): Paroxetine is readily absorbed from the gastrointestinal tract. Due to the first-pass metabolism, the bioavailability ranges from 30-60%. Cmax is attained 2 to 8 hours after an oral dose. Mean Tmax is 4.3 hours in healthy patients. The steady-state concentration of paroxetine is achieved within 7 to 14 days of oral therapy. In a pharmacokinetic study, AUC in healthy patients was 574 ng·h/mL and 1053 ng·h/mL in those with moderate renal impairment. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Paroxetine has a large volume of distribution and is found throughout the body, including in the central nervous system. Only 1% of the drug is found in the plasma. Paroxetine is found in the breast milk at concentrations similar to the concentrations found in plasma. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Paroxetine is 95% 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): Paroxetine metabolism occurs in the liver and is largely mediated by cytochrome CYP2D6 with contributions from CYP3A4 and possibly other cytochrome enzymes. Genetic polymorphisms of the CYP2D6 enzyme may alter the pharmacokinetics of this drug. Poor metabolizers may demonstrate increased adverse effects while rapid metabolizers may experience decreased therapeutic effects. The majority of a paroxetine dose is oxidized to a catechol metabolite that is subsequently converted to both glucuronide and sulfate metabolites via methylation and conjugation. In rat synaptosomes, the glucuronide and sulfate conjugates have been shown to thousands of times less potent than paroxetine itself. The metabolites of paroxetine are considered inactive. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 2/3 of a single paroxetine dose is found to be excreted in the urine and the remainder is found to be excreted in feces. Almost all of the dose is eliminated as metabolites; 3% is found to be excreted as unchanged paroxetine. About 64% of a 30 mg oral dose was found excreted in the urine, with 2% as the parent drug and 62% appearing as metabolites. Approximately 36% of the dose was found to be eliminated in the feces primarily as metabolites and less than 1% as the 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 mean elimination half-life of paroxetine is about 21 hours. In healthy young subjects, mean elimination half-life was found to be 17.3 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent oral clearance of paroxetine is 167 L/h. The clearance of paroxetine in patients with renal failure is significantly lower and dose adjustment may be required, despite the fact that it is mainly cleared by the liver. Dose adjustments may be required in hepatic impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The acute LD50 in mice and rats is 350 mg/kg. Overdose information The lowest dose of paroxetine reported to lead to a fatal outcome is approximately 400 mg. The largest reported paroxetine overdose from which a patient has survived and recovered is a dose of 2000 mg. Common manifestations in a paroxetine overdose include fatigue, fever, insomnia hypertension, tachycardia, nausea, vomiting, somnolence, tremor, dizziness, agitation, confusion, anxious symptoms, headache, insomnia, hyperhidrosis, dilated pupils, seizures, paresthesia, serotonin syndrome, involuntary muscle contraction, and change in mental status. It should be noted that in some cases, patients may have consumed alcohol in addition to taking an overdose of paroxetine. Some of these symptoms may also be seen with clinical use. There is no specific antidote to an overdose of paroxetine. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Paxil, Pexeva •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Paroxetina Paroxetine Paroxetinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Paroxetine is a selective serotonin reuptake inhibitor used to treat major depressive disorder, panic disorder, OCD, social phobia, generalized anxiety disorder, the vasomotor symptoms of menopause, and premenstrual dysphoric disorder. Output: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Peginterferon alfa-2a interact?

•Drug A: Abciximab •Drug B: Peginterferon alfa-2a •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon alfa-2a. •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. •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): Peginterferon alfa-2a is indicated for the treatment of HCV in combination with other antiviral drugs in patients over 5 years of age with compensated liver disease. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies. Peginterferon alfa-2a is also indicated as a monotherapy for adult patients with HBeAg positive and HBeAg negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation. •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): Peginterferon alfa-2a induces the body's innate antiviral response. •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): Peginterferon alfa-2a is derived from recombinant human interferon's alfa-2a moeity. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peginterferon alfa-2a reaches peak plasma concentration 72-96 hours after subcutaneous administration. Trough concentrations at week 48 are approximately 2 fold higher than week 1. The peak to trough ratio at week 48 is 2. •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): The mean terminal half-life of peginterferon alfa-2a is 164 in a range of 84-353 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean systemic clearance of peginterferon alfa-2a is 94 milliliters per hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Peginterferon alfa-2a may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2a. Peginterferon alfa-2a may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2a causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2a. Peginterferon alfa-2a may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2a are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2a. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2a. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2a treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2a is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2a while pregant may result in delopmental abnormalities or death of the fetus. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pegasys •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Peginterferon alfa-2a Pegylated Interfeaon alfa-2A Pegylated interferon alfa-2a Pegylated interferon alpha-2a Pegylated-interferon alfa 2a •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Peginterferon alfa-2a is a modified form of recombinant human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses.

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. The severity of the interaction is minor.

Question: Does Abciximab and Peginterferon alfa-2a interact? Information: •Drug A: Abciximab •Drug B: Peginterferon alfa-2a •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon alfa-2a. •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. •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): Peginterferon alfa-2a is indicated for the treatment of HCV in combination with other antiviral drugs in patients over 5 years of age with compensated liver disease. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies. Peginterferon alfa-2a is also indicated as a monotherapy for adult patients with HBeAg positive and HBeAg negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation. •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): Peginterferon alfa-2a induces the body's innate antiviral response. •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): Peginterferon alfa-2a is derived from recombinant human interferon's alfa-2a moeity. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peginterferon alfa-2a reaches peak plasma concentration 72-96 hours after subcutaneous administration. Trough concentrations at week 48 are approximately 2 fold higher than week 1. The peak to trough ratio at week 48 is 2. •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): The mean terminal half-life of peginterferon alfa-2a is 164 in a range of 84-353 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean systemic clearance of peginterferon alfa-2a is 94 milliliters per hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Peginterferon alfa-2a may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2a. Peginterferon alfa-2a may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2a causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2a. Peginterferon alfa-2a may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2a are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2a. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2a. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2a treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2a is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2a while pregant may result in delopmental abnormalities or death of the fetus. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pegasys •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Peginterferon alfa-2a Pegylated Interfeaon alfa-2A Pegylated interferon alfa-2a Pegylated interferon alpha-2a Pegylated-interferon alfa 2a •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Peginterferon alfa-2a is a modified form of recombinant human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses. Output: 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. The severity of the interaction is minor.

Does Abciximab and Peginterferon alfa-2b interact?

•Drug A: Abciximab •Drug B: Peginterferon alfa-2b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon alfa-2b. •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. •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): Peginterferon alfa-2b is indicated for the treatment of HCV in combination with Ribavirin and a NS3/4A protease inhibitor for genotype 1 or without a NS3/4A protease inhibitor for genotypes 2-6. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies. It is also indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy. •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): Peginterferon alfa-2b inhibits viral replication in infected cells, suppresses cell proliferation, induces apoptosis, and exerts an anti-angiogenic effect. Exerts immunomodulatory effects such as enhancement of the phagocytic activity of macrophages, activation of NK cells, stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset. Also increases concentrations of effector proteins such as serum neopterin and 2'5' oligoadenylate synthetase, raises body temperature, and causes reversible decreases in leukocyte and platelet counts. •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): Peginterferon alfa-2b is derived from recombinant human interferon's alfa-2b moeity. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response. Peginterferon alfa-2b may also acitvate the nuclear factor κB pathway. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peginterferon alfa-2b reaches peak plasma concentration 15-44 hours after subcutaneous administration. The mean absorption half-life is 4.6 hours. After multiple doses the bioavailability of Peginterferon alfa-2b increases with trough concentrations at week 48 3-fold higher than those at week 4. •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): Renal elimination accounts for 30% of Peginterferon alfa-2b 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 mean half-life of elimination of Peginterferon alfa-2b is 40 hours in a range of 22-60 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The estimated apparent clearance of Peginterferon alfa-2b is 22 milliters per hour per kilogram. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Peginterferon alfa-2b may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2b. Peginterferon alfa-2b may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2b causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2b. Peginterferon alfa-2b may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2b are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2b. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2b. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2b treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2b is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2b while pregant may result in delopmental abnormalities or death of the fetus. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pegintron, Sylatron •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Peginterferon alfa-2b is a purified form of human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C, genital warts, and some cancers.

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. The severity of the interaction is minor.

Question: Does Abciximab and Peginterferon alfa-2b interact? Information: •Drug A: Abciximab •Drug B: Peginterferon alfa-2b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon alfa-2b. •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. •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): Peginterferon alfa-2b is indicated for the treatment of HCV in combination with Ribavirin and a NS3/4A protease inhibitor for genotype 1 or without a NS3/4A protease inhibitor for genotypes 2-6. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies. It is also indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy. •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): Peginterferon alfa-2b inhibits viral replication in infected cells, suppresses cell proliferation, induces apoptosis, and exerts an anti-angiogenic effect. Exerts immunomodulatory effects such as enhancement of the phagocytic activity of macrophages, activation of NK cells, stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset. Also increases concentrations of effector proteins such as serum neopterin and 2'5' oligoadenylate synthetase, raises body temperature, and causes reversible decreases in leukocyte and platelet counts. •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): Peginterferon alfa-2b is derived from recombinant human interferon's alfa-2b moeity. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response. Peginterferon alfa-2b may also acitvate the nuclear factor κB pathway. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peginterferon alfa-2b reaches peak plasma concentration 15-44 hours after subcutaneous administration. The mean absorption half-life is 4.6 hours. After multiple doses the bioavailability of Peginterferon alfa-2b increases with trough concentrations at week 48 3-fold higher than those at week 4. •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): Renal elimination accounts for 30% of Peginterferon alfa-2b 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 mean half-life of elimination of Peginterferon alfa-2b is 40 hours in a range of 22-60 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The estimated apparent clearance of Peginterferon alfa-2b is 22 milliters per hour per kilogram. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Peginterferon alfa-2b may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2b. Peginterferon alfa-2b may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2b causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2b. Peginterferon alfa-2b may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2b are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2b. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2b. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2b treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2b is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2b while pregant may result in delopmental abnormalities or death of the fetus. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pegintron, Sylatron •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Peginterferon alfa-2b is a purified form of human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C, genital warts, and some cancers. Output: 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. The severity of the interaction is minor.

Does Abciximab and Peginterferon beta-1a interact?

•Drug A: Abciximab •Drug B: Peginterferon beta-1a •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon beta-1a. •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. •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): Peginterferon beta-1a is indicated for the treatment of adult patients with relapsing forms of MS, including relapsing-remitting disease, clinically isolated syndrome, and active progressive secondary 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): Peginterferon beta-1a likely reduces MS relapses and the progression of disability and brain lesions associated with MS by reducing inflammation. Specifically, IFN-beta decreases antigen presentation and T-cell proliferation. In addition, it modifies cytokine and matrix metalloproteinase (MMP) expression while restoring suppressor function. •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 by which peginterferon beta-1a exerts its effects in patients with multiple sclerosis is unknown, however, it likely exerts its therapeutic actions by reducing inflammation. Through the binding of IFN-beta to its receptor, a cascade of transcriptional events occur, decreasing the inflammation that normally results in the progression of MS. Immune cells are the most likely target of therapeutic effects exerted by IFN-beta. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peginterferon beta-1a is almost completely absorbed after subcutaneous administration. After 125 microgram subcutaneous doses of peginterferon beta-1a to patient with MS, a Cmax of 280 pg/mL was reached between 1 and 1.5 days, and the AUC over a 14 day dosing interval was 34.8 ng.hr/mL. The AUC ranges from 23.5-29.5 ng ml h, according to one pharmacokinetic study of patients with MS. Impairment of renal function may alter the Cmax and AUC of interferon beta-1a. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of peginterferon beta-1a is about 481 L. One pharmacokinetic study of patients administered interferon beta-1a revealed a volume of distribution in the range of 248-726 L, depending on the week of treatment. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Protein binding information for peginterferon beta-1a is not readily available in the literature. •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): Peginterferon beta-1a is not extensively metabolized in the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Peginterferon beta-1a is mainly cleared through the kidneys. •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 peginterferon beta-1a is approximately 78 h in patients with MS, however, the half-life is highly variable and depends on duration of treatment and other factors. •Clearance (Drug A): No clearance available •Clearance (Drug B): The average steady state clearance of peginterferon beta-1a is about 4.1 L/h. One pharmacokinetic study revealed a clearance within the range of 3.68-7.89 L/h, depending on the week of treatment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for peginterferon beta-1a is not readily available in the literature. In clinical trials, no cases of overdoses occurred with the administration of interferon beta-1a at a dose of 75 μg administered subcutaneously 3 times a week. In a case report, a 38-year-old patient attempted suicide with about 6 or 7 pre-filled syringes containing 44 mug (12 MIU) of subcutaneous interferon beta-1a; symptoms were limited to malaise and skin erythema, which resolved within 24 hours with no intervention. Laboratory test results were unremarkable. In the case of an overdose with interferon-beta 1a, prescribing information suggests to contact the local poison control centre. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Plegridy •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Peginterferon beta-1a is an interferon beta used to treat relapsing forms of multiple sclerosis.

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. The severity of the interaction is minor.

Question: Does Abciximab and Peginterferon beta-1a interact? Information: •Drug A: Abciximab •Drug B: Peginterferon beta-1a •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon beta-1a. •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. •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): Peginterferon beta-1a is indicated for the treatment of adult patients with relapsing forms of MS, including relapsing-remitting disease, clinically isolated syndrome, and active progressive secondary 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): Peginterferon beta-1a likely reduces MS relapses and the progression of disability and brain lesions associated with MS by reducing inflammation. Specifically, IFN-beta decreases antigen presentation and T-cell proliferation. In addition, it modifies cytokine and matrix metalloproteinase (MMP) expression while restoring suppressor function. •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 by which peginterferon beta-1a exerts its effects in patients with multiple sclerosis is unknown, however, it likely exerts its therapeutic actions by reducing inflammation. Through the binding of IFN-beta to its receptor, a cascade of transcriptional events occur, decreasing the inflammation that normally results in the progression of MS. Immune cells are the most likely target of therapeutic effects exerted by IFN-beta. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peginterferon beta-1a is almost completely absorbed after subcutaneous administration. After 125 microgram subcutaneous doses of peginterferon beta-1a to patient with MS, a Cmax of 280 pg/mL was reached between 1 and 1.5 days, and the AUC over a 14 day dosing interval was 34.8 ng.hr/mL. The AUC ranges from 23.5-29.5 ng ml h, according to one pharmacokinetic study of patients with MS. Impairment of renal function may alter the Cmax and AUC of interferon beta-1a. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of peginterferon beta-1a is about 481 L. One pharmacokinetic study of patients administered interferon beta-1a revealed a volume of distribution in the range of 248-726 L, depending on the week of treatment. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Protein binding information for peginterferon beta-1a is not readily available in the literature. •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): Peginterferon beta-1a is not extensively metabolized in the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Peginterferon beta-1a is mainly cleared through the kidneys. •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 peginterferon beta-1a is approximately 78 h in patients with MS, however, the half-life is highly variable and depends on duration of treatment and other factors. •Clearance (Drug A): No clearance available •Clearance (Drug B): The average steady state clearance of peginterferon beta-1a is about 4.1 L/h. One pharmacokinetic study revealed a clearance within the range of 3.68-7.89 L/h, depending on the week of treatment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for peginterferon beta-1a is not readily available in the literature. In clinical trials, no cases of overdoses occurred with the administration of interferon beta-1a at a dose of 75 μg administered subcutaneously 3 times a week. In a case report, a 38-year-old patient attempted suicide with about 6 or 7 pre-filled syringes containing 44 mug (12 MIU) of subcutaneous interferon beta-1a; symptoms were limited to malaise and skin erythema, which resolved within 24 hours with no intervention. Laboratory test results were unremarkable. In the case of an overdose with interferon-beta 1a, prescribing information suggests to contact the local poison control centre. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Plegridy •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Peginterferon beta-1a is an interferon beta used to treat relapsing forms of multiple sclerosis. Output: 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. The severity of the interaction is minor.

Does Abciximab and Pembrolizumab interact?

•Drug A: Abciximab •Drug B: Pembrolizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Pembrolizumab. •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 . •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): Pembrolizumab is indicated for the following conditions: Melanoma for the treatment of patients with unresectable or metastatic melanoma (adult patients in the US and patients ≥12 years old in the EU) for the adjuvant treatment of adult and pediatric patients 12 years of age and older with Stage IIB, IIC, or III melanoma following complete resection Non-Small Cell Lung Cancer (NSCLC) in combination with pemetrexed and platinum-based chemotherapy as a first-line treatment for patients with metastatic nonsquamous NSCLC with no EGFR or ALK mutations in combination with carboplatin and paclitaxel as a first-line treatment for patients with metastatic squamous NSCLC as a monotherapy for the first-line treatment of NSCLC expressing PD-L1 with no EGFR or ALK mutations in patients with metastatic disease or stage III disease who are not candidates for surgery or chemoradiation as a monotherapy for the treatment of NSCLC expressing PD-L1 with disease progression on or after platinum-based chemotherapy - this includes patients with EGFR or ALK mutations, providing they have experienced disease progression on prior FDA-approved therapy for these aberrations in combination with platinum-based chemotherapy for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery Head and Neck Squamous Cell Cancer (HNSCC) in combination with fluorouracil and platinum-based chemotherapy as a first-line treatment for patients with metastatic or recurrent, unresectable HNSCC as a monotherapy for the first-line treatment of patients with metastatic or recurrent, unresectable HNSCC expressing PD-L1 as a monotherapy for the treatment of patients with metastatic or recurrent HNSCC with disease progression on or after platinum-based chemotherapy Classical Hodgkin Lymphoma (cHL) for the treatment of adult patients with relapsed or refractory cHL for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed following ≥2 lines of therapy Primary Mediastinal Large B-cell Lymphoma (PMBCL) for the treatment of adult and pediatric patients with refractory PMBCL, or PMBCL that has relapsed following ≥2 lines of therapy Urothelial Carcinoma for the treatment of locally advanced or metastatic urothelial carcinoma in patients ineligible for platinum-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-based chemotherapy or within 12 months of adjuvant/neoadjuvant platinum-based chemotherapy for the treatment of BCG vaccine -unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are not candidates for cystectomy for the treatment of locally advanced or metastatic urothelial carcinoma in combination with enfortumab vedotin in adult patients ineligible for platinum-based chemotherapy under the accelerated approval from the FDA Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient Cancer (dMMR) as a last-line therapy for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer Gastric Cancer in combination with trastuzumab, fluoropyrimidine-, and platinum-containing chemotherapy, as a first-line treatment for patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD -L1 (CPS ≥1) as determined by an FDA-approved test in combination with fluoropyrimidine - and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma Esophageal Cancer in combination with fluoropyrimidine- and platinum-based chemotherapy for the treatment of patients with locally advanced or metastatic esophageal or GEJ carcinoma who are not candidates for surgery or definitive chemoradiation as a monotherapy for the treatment of locally advanced or metastatic esophageal or GEJ carcinoma expressing PD-L1 in patients who are not candidates for surgery or definitive chemoradiation Cervical Cancer in combination with other chemotherapies, with or without bevacizumab, for the treatment of persistent, recurrent, or metastatic cervical cancer expressing PD-L1 as a monotherapy for the treatment of recurrent or metastatic cervical cancer expressing PD-L1 in patients who have experienced disease progression on or after previous chemotherapy in combination with chemoradiotherapy for the treatment of patients with FIGO 2014 Stage III -IVA cervical cancer Hepatocellular Carcinoma (HCC) as a monotherapy for the treatment of HCC in patients who have been previously treated with sorafenib Biliary Tract Cancer (BTC) in combination with gemcitabine and cisplatin for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer Merkel Cell Carcinoma (MCC) for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic MCC Renal Cell Carcinoma (RCC) in combination with either axitinib or lenvatinib as a first-line treatment for adult patients with advanced RCC for the adjuvant treatment of patients with RCC who are at an intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions Endometrial Carcinoma in combination with lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR who experience disease progression following prior systemic therapy and who are not candidates for surgery or radiation therapy as a monotherapy for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation Tumor Mutational Burden-High (TMB-H) Cancer as a last-line therapy for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H solid tumors that have progressed following prior treatment Cutaneous Squamous Cell Carcinoma (cSCC) for the treatment of patients with recurrent or metastatic sCC, or locally advanced sCC that is not curable with surgery or radiation therapy Triple-Negative Breast Cancer (TNBC) for the treatment of patients with high-risk early-stage TNBC, in combination with chemotherapy as a neoadjuvant treatment followed by continued use as a single adjuvant agent following surgery in combination with chemotherapy for the treatment of locally recurrent unresectable or metastatic TNBC expressing PD-L1 For all approved adult indications, pembrolizumab may be used for an additional 6 weeks at 400mg weekly. •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): Pembrolizumab exerts its pharmacologic effects by releasing PD-1 pathway-mediated inhibition of the immune response, which in turn improves the anti-tumor immune response. Due to its relatively broad mechanism of action, it is useful in the treatment of a wide variety of cancers. Pembrolizumab can cause immune-mediated adverse reactions - including hepatitis, nephritis, and pneumonitis - in any organ system or tissue. Careful monitoring of the patient (including laboratory evaluation of liver, kidney, and thyroid function) should occur at baseline and periodically throughout therapy to monitor for emerging immune-mediated 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): Pembrolizumab binds with high affinity to the cell surface receptor programmed cell death protein 1 (PD-1) and antagonizes its interaction with its known ligands PD-L1 and PD-L2. Under normal circumstances, the binding of the ligands of PD-1 to the receptor inhibits the TCR-mediated T-cell proliferation and cytokine production. This inhibitory signal appears to play a role in self-tolerance and collateral damage minimization after immune responses against a pathogen and maternal tolerance to fetal tissue. The binding of pembrolizumab to PD-1 prevents this inhibitory pathway, causing a physiological shift towards immune reactivity and enhancing tumor immunosurveillance and anti-tumor immune response. •Absorption (Drug A): No absorption available •Absorption (Drug B): Intravenously administered pembrolizumab is completely bioavailable. Steady-state is reached after approximately 16 weeks. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution of pembrolizumab is approximately 6 liters. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Pembrolizumab is not expected to 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): Pembrolizumab is catalyzed into smaller peptides and amino acids via general protein 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 of pembrolizumab is 22 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance is moderately lower at steady-state (195 mL/day) than after the first dose (252 mL/day), although this decrease is not clinically significant. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no data regarding overdosage with pembrolizumab. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Keytruda •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pembrolizumab is a PD-1 blocking antibody used to treat various types of cancer, including metastatic melanoma, non small-cell lung cancer, cervical cancer, head and neck cancer, and Hodgkin's lymphoma.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Pembrolizumab interact? Information: •Drug A: Abciximab •Drug B: Pembrolizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Pembrolizumab. •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 . •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): Pembrolizumab is indicated for the following conditions: Melanoma for the treatment of patients with unresectable or metastatic melanoma (adult patients in the US and patients ≥12 years old in the EU) for the adjuvant treatment of adult and pediatric patients 12 years of age and older with Stage IIB, IIC, or III melanoma following complete resection Non-Small Cell Lung Cancer (NSCLC) in combination with pemetrexed and platinum-based chemotherapy as a first-line treatment for patients with metastatic nonsquamous NSCLC with no EGFR or ALK mutations in combination with carboplatin and paclitaxel as a first-line treatment for patients with metastatic squamous NSCLC as a monotherapy for the first-line treatment of NSCLC expressing PD-L1 with no EGFR or ALK mutations in patients with metastatic disease or stage III disease who are not candidates for surgery or chemoradiation as a monotherapy for the treatment of NSCLC expressing PD-L1 with disease progression on or after platinum-based chemotherapy - this includes patients with EGFR or ALK mutations, providing they have experienced disease progression on prior FDA-approved therapy for these aberrations in combination with platinum-based chemotherapy for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery Head and Neck Squamous Cell Cancer (HNSCC) in combination with fluorouracil and platinum-based chemotherapy as a first-line treatment for patients with metastatic or recurrent, unresectable HNSCC as a monotherapy for the first-line treatment of patients with metastatic or recurrent, unresectable HNSCC expressing PD-L1 as a monotherapy for the treatment of patients with metastatic or recurrent HNSCC with disease progression on or after platinum-based chemotherapy Classical Hodgkin Lymphoma (cHL) for the treatment of adult patients with relapsed or refractory cHL for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed following ≥2 lines of therapy Primary Mediastinal Large B-cell Lymphoma (PMBCL) for the treatment of adult and pediatric patients with refractory PMBCL, or PMBCL that has relapsed following ≥2 lines of therapy Urothelial Carcinoma for the treatment of locally advanced or metastatic urothelial carcinoma in patients ineligible for platinum-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-based chemotherapy or within 12 months of adjuvant/neoadjuvant platinum-based chemotherapy for the treatment of BCG vaccine -unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are not candidates for cystectomy for the treatment of locally advanced or metastatic urothelial carcinoma in combination with enfortumab vedotin in adult patients ineligible for platinum-based chemotherapy under the accelerated approval from the FDA Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient Cancer (dMMR) as a last-line therapy for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer Gastric Cancer in combination with trastuzumab, fluoropyrimidine-, and platinum-containing chemotherapy, as a first-line treatment for patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD -L1 (CPS ≥1) as determined by an FDA-approved test in combination with fluoropyrimidine - and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma Esophageal Cancer in combination with fluoropyrimidine- and platinum-based chemotherapy for the treatment of patients with locally advanced or metastatic esophageal or GEJ carcinoma who are not candidates for surgery or definitive chemoradiation as a monotherapy for the treatment of locally advanced or metastatic esophageal or GEJ carcinoma expressing PD-L1 in patients who are not candidates for surgery or definitive chemoradiation Cervical Cancer in combination with other chemotherapies, with or without bevacizumab, for the treatment of persistent, recurrent, or metastatic cervical cancer expressing PD-L1 as a monotherapy for the treatment of recurrent or metastatic cervical cancer expressing PD-L1 in patients who have experienced disease progression on or after previous chemotherapy in combination with chemoradiotherapy for the treatment of patients with FIGO 2014 Stage III -IVA cervical cancer Hepatocellular Carcinoma (HCC) as a monotherapy for the treatment of HCC in patients who have been previously treated with sorafenib Biliary Tract Cancer (BTC) in combination with gemcitabine and cisplatin for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer Merkel Cell Carcinoma (MCC) for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic MCC Renal Cell Carcinoma (RCC) in combination with either axitinib or lenvatinib as a first-line treatment for adult patients with advanced RCC for the adjuvant treatment of patients with RCC who are at an intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions Endometrial Carcinoma in combination with lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR who experience disease progression following prior systemic therapy and who are not candidates for surgery or radiation therapy as a monotherapy for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation Tumor Mutational Burden-High (TMB-H) Cancer as a last-line therapy for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H solid tumors that have progressed following prior treatment Cutaneous Squamous Cell Carcinoma (cSCC) for the treatment of patients with recurrent or metastatic sCC, or locally advanced sCC that is not curable with surgery or radiation therapy Triple-Negative Breast Cancer (TNBC) for the treatment of patients with high-risk early-stage TNBC, in combination with chemotherapy as a neoadjuvant treatment followed by continued use as a single adjuvant agent following surgery in combination with chemotherapy for the treatment of locally recurrent unresectable or metastatic TNBC expressing PD-L1 For all approved adult indications, pembrolizumab may be used for an additional 6 weeks at 400mg weekly. •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): Pembrolizumab exerts its pharmacologic effects by releasing PD-1 pathway-mediated inhibition of the immune response, which in turn improves the anti-tumor immune response. Due to its relatively broad mechanism of action, it is useful in the treatment of a wide variety of cancers. Pembrolizumab can cause immune-mediated adverse reactions - including hepatitis, nephritis, and pneumonitis - in any organ system or tissue. Careful monitoring of the patient (including laboratory evaluation of liver, kidney, and thyroid function) should occur at baseline and periodically throughout therapy to monitor for emerging immune-mediated 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): Pembrolizumab binds with high affinity to the cell surface receptor programmed cell death protein 1 (PD-1) and antagonizes its interaction with its known ligands PD-L1 and PD-L2. Under normal circumstances, the binding of the ligands of PD-1 to the receptor inhibits the TCR-mediated T-cell proliferation and cytokine production. This inhibitory signal appears to play a role in self-tolerance and collateral damage minimization after immune responses against a pathogen and maternal tolerance to fetal tissue. The binding of pembrolizumab to PD-1 prevents this inhibitory pathway, causing a physiological shift towards immune reactivity and enhancing tumor immunosurveillance and anti-tumor immune response. •Absorption (Drug A): No absorption available •Absorption (Drug B): Intravenously administered pembrolizumab is completely bioavailable. Steady-state is reached after approximately 16 weeks. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution of pembrolizumab is approximately 6 liters. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Pembrolizumab is not expected to 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): Pembrolizumab is catalyzed into smaller peptides and amino acids via general protein 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 of pembrolizumab is 22 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance is moderately lower at steady-state (195 mL/day) than after the first dose (252 mL/day), although this decrease is not clinically significant. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no data regarding overdosage with pembrolizumab. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Keytruda •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pembrolizumab is a PD-1 blocking antibody used to treat various types of cancer, including metastatic melanoma, non small-cell lung cancer, cervical cancer, head and neck cancer, and Hodgkin's lymphoma. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Pemetrexed interact?

•Drug A: Abciximab •Drug B: Pemetrexed •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pemetrexed. •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. •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): Pemetrexed is indicated for the treatment of the following conditions: Non-squamous non-small cell lung cancer (NSCLC) in combination with pembrolizumab and platinum-based chemotherapy as initial treatment in metastatic disease where no EGFR or ALK genomic tumour aberrations exist in combination with cisplatin as initial treatment for locally advanced or metastatic disease as maintenance treatment for locally advanced or metastatic disease that has not progressed following four cycles of platinum-based chemotherapy recurrent metastatic disease following prior chemotherapy as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer Malignant pleural mesothelioma in combination with cisplatin for the initial treatment of patients with malignant pleural mesothelioma. In the US, it is reserved for patients whose disease is unresectable or otherwise not candidates for curative 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): Pemetrexed inhibited the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052) and showed synergistic effects when combined with cisplatin. Based on population pharmacodynamic analyses, the depth of the absolute neutrophil counts (ANC) nadir correlates with systemic exposure to pemetrexed and supplementation with folic acid and vitamin B12. There is no cumulative effect of pemetrexed exposure on ANC nadir over multiple treatment cycles. •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): Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetics of pemetrexed when pemetrexed was administered as a single agent in doses ranging from 0.2 to 838 mg/m infused over a 10-minute period have been evaluated in 426 cancer patients with a variety of solid tumors. Pemetrexed total systemic exposure (AUC) and maximum plasma concentration (C max ) increased proportionally with the increase in dose. The pharmacokinetics of pemetrexed did not change over multiple treatment cycles. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pemetrexed has a steady-state volume of distribution of 16.1 liters. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro studies indicated that pemetrexed is 81% 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): Pemetrexed is not metabolized to an appreciable extent by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pemetrexed is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration. In vitro studies indicated that pemetrexed is a substrate of OAT3 (organic anion transporter 3), a transporter that is involved in the active secretion of pemetrexed. •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 pemetrexed is 3.5 hours in patients with normal renal function (creatinine clearance of 90 mL/min). •Clearance (Drug A): No clearance available •Clearance (Drug B): The total systemic clearance of pemetrexed is 91.8 mL/min in patients with normal renal function (creatinine clearance of 90 mL/min). As renal function decreases, the clearance of pemetrexed decreases, and exposure (AUC) of pemetrexed increases. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alimta, Ciambra, Pemfexy, Pemrydi Rtu •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pemetrexed is a folate analog used to treat mesothelioma and non-small cell lung cancer.

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. The severity of the interaction is minor.

Question: Does Abciximab and Pemetrexed interact? Information: •Drug A: Abciximab •Drug B: Pemetrexed •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pemetrexed. •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. •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): Pemetrexed is indicated for the treatment of the following conditions: Non-squamous non-small cell lung cancer (NSCLC) in combination with pembrolizumab and platinum-based chemotherapy as initial treatment in metastatic disease where no EGFR or ALK genomic tumour aberrations exist in combination with cisplatin as initial treatment for locally advanced or metastatic disease as maintenance treatment for locally advanced or metastatic disease that has not progressed following four cycles of platinum-based chemotherapy recurrent metastatic disease following prior chemotherapy as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer Malignant pleural mesothelioma in combination with cisplatin for the initial treatment of patients with malignant pleural mesothelioma. In the US, it is reserved for patients whose disease is unresectable or otherwise not candidates for curative 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): Pemetrexed inhibited the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052) and showed synergistic effects when combined with cisplatin. Based on population pharmacodynamic analyses, the depth of the absolute neutrophil counts (ANC) nadir correlates with systemic exposure to pemetrexed and supplementation with folic acid and vitamin B12. There is no cumulative effect of pemetrexed exposure on ANC nadir over multiple treatment cycles. •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): Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetics of pemetrexed when pemetrexed was administered as a single agent in doses ranging from 0.2 to 838 mg/m infused over a 10-minute period have been evaluated in 426 cancer patients with a variety of solid tumors. Pemetrexed total systemic exposure (AUC) and maximum plasma concentration (C max ) increased proportionally with the increase in dose. The pharmacokinetics of pemetrexed did not change over multiple treatment cycles. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pemetrexed has a steady-state volume of distribution of 16.1 liters. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro studies indicated that pemetrexed is 81% 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): Pemetrexed is not metabolized to an appreciable extent by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pemetrexed is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration. In vitro studies indicated that pemetrexed is a substrate of OAT3 (organic anion transporter 3), a transporter that is involved in the active secretion of pemetrexed. •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 pemetrexed is 3.5 hours in patients with normal renal function (creatinine clearance of 90 mL/min). •Clearance (Drug A): No clearance available •Clearance (Drug B): The total systemic clearance of pemetrexed is 91.8 mL/min in patients with normal renal function (creatinine clearance of 90 mL/min). As renal function decreases, the clearance of pemetrexed decreases, and exposure (AUC) of pemetrexed increases. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alimta, Ciambra, Pemfexy, Pemrydi Rtu •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pemetrexed is a folate analog used to treat mesothelioma and non-small cell lung cancer. Output: 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. The severity of the interaction is minor.

Does Abciximab and Penicillamine interact?

•Drug A: Abciximab •Drug B: Penicillamine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Penicillamine. •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. •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 Wilson's disease, cystinuria and active rheumatoid arthritis. •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): Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in 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): Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): rapidly but incompletely •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% (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): Hepatic •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excretion is mainly renal, mainly as disulfides. •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 hour •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): Cuprimine, Depen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-3,3-dimethylcysteine D-penicillamine penicilamina Penicillamine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Penicillamine is a chelator used to treat Wilson's disease, cystinuria, and rheumatoid arthritis.

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. The severity of the interaction is minor.

Question: Does Abciximab and Penicillamine interact? Information: •Drug A: Abciximab •Drug B: Penicillamine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Penicillamine. •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. •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 Wilson's disease, cystinuria and active rheumatoid arthritis. •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): Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in 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): Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): rapidly but incompletely •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% (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): Hepatic •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excretion is mainly renal, mainly as disulfides. •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 hour •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): Cuprimine, Depen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-3,3-dimethylcysteine D-penicillamine penicilamina Penicillamine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Penicillamine is a chelator used to treat Wilson's disease, cystinuria, and rheumatoid arthritis. Output: 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. The severity of the interaction is minor.

Does Abciximab and Pentosan polysulfate interact?

•Drug A: Abciximab •Drug B: Pentosan polysulfate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Pentosan polysulfate is combined with Abciximab. •Extended Description: Pentosan polysulfate sodium itself is a weak blood thinner and has demonstrated to be associated with bleeding complications such as rectal hemorrhage, bruising, nosebleeds, and gum bleeding. Therefore, when taken with antiplatelet agents, bleeding risk is enhanced due to additive drug effects. •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 relief of bladder pain or discomfort associated with interstitial cystitis. •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): Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic 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): Pentosan polysulfate is a polymer of xylose hydrogen sulfate and contains two sulfate groups per carbohydrate monomer. It binds Fibroblast growth factors (FGFs) as well as other heparin-binding growth factors. It has been shown to interact also with the heparin-binding site of FGFR-1. It inhibits the growth of SW13 adrenocortical cells transfected with FGF-4 and tumorigenicity of MCF-7 breast carcinoma cells transfected with FGF-1 or FGF-4. •Absorption (Drug A): No absorption available •Absorption (Drug B): Slow •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): 4.8 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): Elmiron •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pentosan polysulfate is a sulfated pentosyl polysaccharide used to treat bladder pain and discomfort due to interstitial cystitis.

Pentosan polysulfate sodium itself is a weak blood thinner and has demonstrated to be associated with bleeding complications such as rectal hemorrhage, bruising, nosebleeds, and gum bleeding. Therefore, when taken with antiplatelet agents, bleeding risk is enhanced due to additive drug effects. The severity of the interaction is moderate.

Question: Does Abciximab and Pentosan polysulfate interact? Information: •Drug A: Abciximab •Drug B: Pentosan polysulfate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Pentosan polysulfate is combined with Abciximab. •Extended Description: Pentosan polysulfate sodium itself is a weak blood thinner and has demonstrated to be associated with bleeding complications such as rectal hemorrhage, bruising, nosebleeds, and gum bleeding. Therefore, when taken with antiplatelet agents, bleeding risk is enhanced due to additive drug effects. •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 relief of bladder pain or discomfort associated with interstitial cystitis. •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): Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic 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): Pentosan polysulfate is a polymer of xylose hydrogen sulfate and contains two sulfate groups per carbohydrate monomer. It binds Fibroblast growth factors (FGFs) as well as other heparin-binding growth factors. It has been shown to interact also with the heparin-binding site of FGFR-1. It inhibits the growth of SW13 adrenocortical cells transfected with FGF-4 and tumorigenicity of MCF-7 breast carcinoma cells transfected with FGF-1 or FGF-4. •Absorption (Drug A): No absorption available •Absorption (Drug B): Slow •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): 4.8 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): Elmiron •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pentosan polysulfate is a sulfated pentosyl polysaccharide used to treat bladder pain and discomfort due to interstitial cystitis. Output: Pentosan polysulfate sodium itself is a weak blood thinner and has demonstrated to be associated with bleeding complications such as rectal hemorrhage, bruising, nosebleeds, and gum bleeding. Therefore, when taken with antiplatelet agents, bleeding risk is enhanced due to additive drug effects. The severity of the interaction is moderate.

Does Abciximab and Pentostatin interact?

•Drug A: Abciximab •Drug B: Pentostatin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pentostatin. •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. •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 hairy cell leukaemia refractory to alpha interferon. •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): Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). •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): Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). •Absorption (Drug A): No absorption available •Absorption (Drug B): Not absorbed orally, crosses blood brain barrier. •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): 4% •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 hepatic, but only small amounts are metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In man, following a single dose of 4 mg/m2 of pentostatin infused over 5 minutes, approximately 90% of the dose was excreted in the urine as unchanged pentostatin and/or metabolites as measured by adenosine deaminase inhibitory activity. •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): 5.7 hours (with a range between 2.6 and 16 hrs) •Clearance (Drug A): No clearance available •Clearance (Drug B): 68 mL/min/m2 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nipent •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pentostatin is an adenosine deaminase inhibitor used to treat hairy cell leukemia.

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. The severity of the interaction is minor.

Question: Does Abciximab and Pentostatin interact? Information: •Drug A: Abciximab •Drug B: Pentostatin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pentostatin. •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. •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 hairy cell leukaemia refractory to alpha interferon. •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): Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). •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): Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). •Absorption (Drug A): No absorption available •Absorption (Drug B): Not absorbed orally, crosses blood brain barrier. •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): 4% •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 hepatic, but only small amounts are metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In man, following a single dose of 4 mg/m2 of pentostatin infused over 5 minutes, approximately 90% of the dose was excreted in the urine as unchanged pentostatin and/or metabolites as measured by adenosine deaminase inhibitory activity. •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): 5.7 hours (with a range between 2.6 and 16 hrs) •Clearance (Drug A): No clearance available •Clearance (Drug B): 68 mL/min/m2 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nipent •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pentostatin is an adenosine deaminase inhibitor used to treat hairy cell leukemia. Output: 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. The severity of the interaction is minor.

Does Abciximab and Pentoxifylline interact?

•Drug A: Abciximab •Drug B: Pentoxifylline •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Pentoxifylline. •Extended Description: There have been reports of bleeding or prolonged prothrombin time in patients treated with pentoxifylline even without anticoagulant treatment. The risk of bleeding is further increased when anticoagulants are administered. Some studies report a lack of pharmacodynamic effect resulting from this interaction, however, caution is nonetheless advised. •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): Pentoxifylline is indicated for the treatment of intermittent claudication in patients with chronic occlusive arterial disease. Pentoxifylline may improve limb function and reduce symptoms but cannot replace other therapies such as surgical bypass or removal of vascular obstructions. •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): Pentoxifylline, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, exhibits hemorheological, anti-oxidative, and anti-inflammatory properties and is traditionally indicated in the treatment of peripheral arterial disease (PAD). In PAD patients with concurrent cerebrovascular and coronary artery diseases, pentoxifylline treatment has occasionally been associated with angina, arrhythmia, and hypotension. Concurrent use with warfarin should be associated with more frequent monitoring of prothrombin times. Also, patients with risk factors complicated by hemorrhages, such as retinal bleeding, peptic ulceration, and recent surgery, should be monitored periodically for bleeding signs. •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): Patients with peripheral arterial disease (PAD) may suffer from intermittent claudication, exertional leg pain that resolves upon rest, which is underscored by a complex etiology including vascular dysfunction (reduced limb perfusion, angiogenesis, and microcirculatory flow), systemic inflammation, and skeletal muscle dysfunction. Pentoxifylline (PTX), (3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione) or 1-(5-oxohexyl)-3,7-­dimethylxanthine, is a methyl-xanthine derivative that acts to lower blood viscosity by increasing erythrocyte flexibility, reducing plasma fibrinogen, inhibiting neutrophil activation, and suppressing erythrocyte/platelet aggregation; it also has antioxidant and anti-inflammatory effects. Although the precise mechanism of action has yet to be elucidated, numerous studies have suggested several effects of PTX. The classical interpretation of PTX's broad effects is due to its ability to act, in vitro, as a non-specific cyclic-3',5'-phosphodiesterase (PDE) inhibitor at millimolar concentrations; specifically, it has been proposed that inhibition of PDE type III and IV isozymes leads to elevated cyclic adenosine monophosphate (cAMP) levels, which mediate diverse downstream effects. This view has been challenged, specifically by observing those plasma concentrations of PTX in routine clinical use are typically only around 1μM, far lower than those used to inhibit PDEs in vitro. Instead, several studies have suggested that PTX can modulate adenosine receptor function, specifically the Gα-coupled A2A receptor (A2AR). Whether PTX acts directly as an A2AR agonist is unclear, although it can clearly increase the response of A2AR to adenosine. A2AR activation activates adenylyl cyclase, which increases intracellular cAMP levels; this observation may explain PTX's ability to increase intracellular cAMP in a PDE-independent fashion. Elevated cAMP levels have numerous downstream effects. cAMP-mediated activation of protein kinase A (PKA) suppresses nuclear translocation of NF-κB, which suppresses transcription of pro-inflammatory cytokines such as tumour necrosis factor (TNF-α), interleukin-1 (IL-1), and IL-6 as well as TNF-induced molecules such as adhesion molecules (ICAM1 and VCAM1) and the C-reactive protein (CRP). PTX has also been shown to prevent the downstream phosphorylation of p38 MAPK and ERK, which are responsible for assembling the NADPH oxidase involved in the neutrophil oxidative burst. This effect is due to a PKA-independent decrease in Akt phosphorylation and a PKA-dependent decrease in phosphorylation of p38 MAPK and ERK. This transcriptional regulation at least partially explains the anti-inflammatory and anti-oxidative properties of PTX. Also, activated PKA can activate the cAMP response element-binding protein (CREB), which itself blocks SMAD-driven gene transcription, effectively disrupting transforming growth factor (TGF-β1) signalling. This results in lower levels of fibrinogenic molecules such as collagens, fibronectin, connective tissue growth factor, and alpha-smooth muscle actin. Hence, disruption of TGF-β1 signalling may explain the anti-fibrotic effects of PTX, including at least some of the decrease in blood viscosity. The picture is complicated by the observation that PTX metabolites M1, M4, and M5 have been shown to inhibit C5 Des Arg- and formyl-methionylleucylphenylalanine-induced superoxide production in neutrophils and M1 and M5 significantly contribute to PTX's observed hemorheological effects. Overall, PTX administration is associated with decreased pro-inflammatory molecules, an increase in anti-inflammatory molecules such as IL-10, and decreased production of fibrinogenic and cellular adhesion molecules. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral pentoxifylline (PTX) is almost completely absorbed but has low bioavailability of 20-30% due to extensive first-pass metabolism; three of the seven known metabolites, M1, M4, and M5 are present in plasma and appear soon after dosing. Single oral doses of 100, 200, and 400 mg of pentoxifylline in healthy males produced a mean t max of 0.29-0.41 h, a mean C max of 272-1607 ng/mL, and a mean AUC 0-∞ of 193-1229 ng*h/mL; corresponding ranges for metabolites 1, 4, and 5 were 0.72-1.15, 114-2753, and 189-7057. Single administration of a 400 mg extended-release tablet resulted in a heightened t max of 2.08 ± 1.16 h, lowered C max of 55.33 ± 22.04 ng/mL, and a comparable AUC 0-t of 516 ± 165 ng*h/mL; all these parameters were increased in cirrhotic patients. Smoking was associated with a decrease in the C max and AUC steady-state of metabolite M1 but did not dramatically affect the pharmacokinetic parameters of pentoxifylline or other measured metabolites. Renal impairment increases the mean C max, AUC, and ratio to parent compound AUC of metabolites M4 and M5, but has no significant effect on PTX or M1 pharmacokinetics. Finally, similar to cirrhotic patients, the C max and t max of PTX and its metabolites are increased in patients with varying degrees of chronic heart failure. Overall, metabolites M1 and M5 exhibit plasma concentrations roughly five and eight times greater than PTX, respectively. PTX and M1 pharmacokinetics are approximately dose-dependent, while those of M5 are not. Food intake before PTX ingestion delays time to peak plasma concentrations but not overall absorption. Extended-release forms of PTX extend the t max to between two and four hours but also serves to ameliorate peaks and troughs in plasma concentration over time. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pentoxifylline has a volume of distribution of 4.15 ± 0.85 following a single intravenous 100 mg dose in healthy subjects. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Pentoxifylline is approximately 45% bound to erythrocyte membranes. •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): Pentoxifylline (PTX) metabolism is incompletely understood. There are seven known metabolites (M1 through M7), although only M1, M4, and M5 are detected in plasma at appreciable levels, following the general pattern M5 > M1 > PTX > M4. As PTX apparent clearance is higher than hepatic blood flow and the AUC ratio of M1 to PTX is not appreciably different in cirrhotic patients, it is clear that erythrocytes are the main site of PTX-M1 interconversion. However, the reaction likely occurs in the liver as well. PTX is reduced in an NADPH-dependent manner by unknown an unidentified carbonyl reductase to form either lisofylline (the (R)-M1 enantiomer) or (S)-M1; the reaction is stereoselective, producing (S)-M1 exclusively in liver cytosol, 85% (S)-M1 in liver microsomes, and a ratio of 0.010-0.025 R:S-M1 after IV or oral dosing in humans. Although both (R)- and (S)-M1 can be oxidized back into PTX, (R)-M1 can also give rise to M2 and M3 in liver microsomes. In vitro studies suggest that CYP1A2 is at least partly responsible for the conversion of lisofylline ((R)-M1) back into PTX. Unlike the reversible oxidation/reduction of PTX and its M1 metabolites, M4 and M5 are formed via irreversible oxidation of PTX in the liver. Studies in mice recapitulating the PTX-ciprofloxacin drug reaction suggest that CYP1A2 is responsible for the formation of M6 from PTX and of M7 from M1, both through de-methylation at position 7. In general, metabolites M2, M3, and M6 are formed at very low levels in mammals. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pentoxifylline is eliminated almost entirely in the urine and predominantly as M5, which accounts for between 57 and 65 percent of the administered dose. Smaller amounts of M4 are recovered, while M1 and the parent compound account for less than 1% of the recovered dose. The fecal route accounts for less than 4% of the 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): Overall, pentoxifylline has an elimination half-life of between 0.39 and 0.84 hours, while its primary metabolites have elimination half-lives of between 0.96 and 1.61 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pentoxifylline given as a single 100 mg intravenous infusion has a clearance of 3.62 ± 0.75 L/h/kg in healthy subjects, which decreased to 1.44 ± 0.46 L/h/kg in cirrhotic patients. In another study, the apparent clearance of either 300 or 600 mg of pentoxifylline given intravenously (median and range) was 4.2 (2.8-6.3) and 4.1 (2.3-4.6) L/min, respectively. It is important to note that, due to the reversible extra-hepatic metabolism of the parent compound and metabolite 1, the true clearance of pentoxifylline may be even higher than the measured values. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdoses of pentoxifylline have been reported with symptoms including agitation, fever, flushing, hypotension, convulsions, somnolence, and loss of consciousness beginning 4-5 hours following ingestion and lasting up to 12 hours. Symptomatic treatment is recommended, specifically pertaining to maintaining proper respiration, blood pressure, and controlling convulsions. Activated charcoal may prove useful in absorbing excess pentoxifylline in overdose cases. Patients have recovered from overdose even at doses as high as 80 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): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pentoxifylline is a methylxanthine derivative used to treat intermittent claudication caused by chronic occlusive arterial disease of the limbs.

There have been reports of bleeding or prolonged prothrombin time in patients treated with pentoxifylline even without anticoagulant treatment. The risk of bleeding is further increased when anticoagulants are administered. Some studies report a lack of pharmacodynamic effect resulting from this interaction, however, caution is nonetheless advised. The severity of the interaction is moderate.

Question: Does Abciximab and Pentoxifylline interact? Information: •Drug A: Abciximab •Drug B: Pentoxifylline •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Pentoxifylline. •Extended Description: There have been reports of bleeding or prolonged prothrombin time in patients treated with pentoxifylline even without anticoagulant treatment. The risk of bleeding is further increased when anticoagulants are administered. Some studies report a lack of pharmacodynamic effect resulting from this interaction, however, caution is nonetheless advised. •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): Pentoxifylline is indicated for the treatment of intermittent claudication in patients with chronic occlusive arterial disease. Pentoxifylline may improve limb function and reduce symptoms but cannot replace other therapies such as surgical bypass or removal of vascular obstructions. •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): Pentoxifylline, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, exhibits hemorheological, anti-oxidative, and anti-inflammatory properties and is traditionally indicated in the treatment of peripheral arterial disease (PAD). In PAD patients with concurrent cerebrovascular and coronary artery diseases, pentoxifylline treatment has occasionally been associated with angina, arrhythmia, and hypotension. Concurrent use with warfarin should be associated with more frequent monitoring of prothrombin times. Also, patients with risk factors complicated by hemorrhages, such as retinal bleeding, peptic ulceration, and recent surgery, should be monitored periodically for bleeding signs. •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): Patients with peripheral arterial disease (PAD) may suffer from intermittent claudication, exertional leg pain that resolves upon rest, which is underscored by a complex etiology including vascular dysfunction (reduced limb perfusion, angiogenesis, and microcirculatory flow), systemic inflammation, and skeletal muscle dysfunction. Pentoxifylline (PTX), (3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione) or 1-(5-oxohexyl)-3,7-­dimethylxanthine, is a methyl-xanthine derivative that acts to lower blood viscosity by increasing erythrocyte flexibility, reducing plasma fibrinogen, inhibiting neutrophil activation, and suppressing erythrocyte/platelet aggregation; it also has antioxidant and anti-inflammatory effects. Although the precise mechanism of action has yet to be elucidated, numerous studies have suggested several effects of PTX. The classical interpretation of PTX's broad effects is due to its ability to act, in vitro, as a non-specific cyclic-3',5'-phosphodiesterase (PDE) inhibitor at millimolar concentrations; specifically, it has been proposed that inhibition of PDE type III and IV isozymes leads to elevated cyclic adenosine monophosphate (cAMP) levels, which mediate diverse downstream effects. This view has been challenged, specifically by observing those plasma concentrations of PTX in routine clinical use are typically only around 1μM, far lower than those used to inhibit PDEs in vitro. Instead, several studies have suggested that PTX can modulate adenosine receptor function, specifically the Gα-coupled A2A receptor (A2AR). Whether PTX acts directly as an A2AR agonist is unclear, although it can clearly increase the response of A2AR to adenosine. A2AR activation activates adenylyl cyclase, which increases intracellular cAMP levels; this observation may explain PTX's ability to increase intracellular cAMP in a PDE-independent fashion. Elevated cAMP levels have numerous downstream effects. cAMP-mediated activation of protein kinase A (PKA) suppresses nuclear translocation of NF-κB, which suppresses transcription of pro-inflammatory cytokines such as tumour necrosis factor (TNF-α), interleukin-1 (IL-1), and IL-6 as well as TNF-induced molecules such as adhesion molecules (ICAM1 and VCAM1) and the C-reactive protein (CRP). PTX has also been shown to prevent the downstream phosphorylation of p38 MAPK and ERK, which are responsible for assembling the NADPH oxidase involved in the neutrophil oxidative burst. This effect is due to a PKA-independent decrease in Akt phosphorylation and a PKA-dependent decrease in phosphorylation of p38 MAPK and ERK. This transcriptional regulation at least partially explains the anti-inflammatory and anti-oxidative properties of PTX. Also, activated PKA can activate the cAMP response element-binding protein (CREB), which itself blocks SMAD-driven gene transcription, effectively disrupting transforming growth factor (TGF-β1) signalling. This results in lower levels of fibrinogenic molecules such as collagens, fibronectin, connective tissue growth factor, and alpha-smooth muscle actin. Hence, disruption of TGF-β1 signalling may explain the anti-fibrotic effects of PTX, including at least some of the decrease in blood viscosity. The picture is complicated by the observation that PTX metabolites M1, M4, and M5 have been shown to inhibit C5 Des Arg- and formyl-methionylleucylphenylalanine-induced superoxide production in neutrophils and M1 and M5 significantly contribute to PTX's observed hemorheological effects. Overall, PTX administration is associated with decreased pro-inflammatory molecules, an increase in anti-inflammatory molecules such as IL-10, and decreased production of fibrinogenic and cellular adhesion molecules. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral pentoxifylline (PTX) is almost completely absorbed but has low bioavailability of 20-30% due to extensive first-pass metabolism; three of the seven known metabolites, M1, M4, and M5 are present in plasma and appear soon after dosing. Single oral doses of 100, 200, and 400 mg of pentoxifylline in healthy males produced a mean t max of 0.29-0.41 h, a mean C max of 272-1607 ng/mL, and a mean AUC 0-∞ of 193-1229 ng*h/mL; corresponding ranges for metabolites 1, 4, and 5 were 0.72-1.15, 114-2753, and 189-7057. Single administration of a 400 mg extended-release tablet resulted in a heightened t max of 2.08 ± 1.16 h, lowered C max of 55.33 ± 22.04 ng/mL, and a comparable AUC 0-t of 516 ± 165 ng*h/mL; all these parameters were increased in cirrhotic patients. Smoking was associated with a decrease in the C max and AUC steady-state of metabolite M1 but did not dramatically affect the pharmacokinetic parameters of pentoxifylline or other measured metabolites. Renal impairment increases the mean C max, AUC, and ratio to parent compound AUC of metabolites M4 and M5, but has no significant effect on PTX or M1 pharmacokinetics. Finally, similar to cirrhotic patients, the C max and t max of PTX and its metabolites are increased in patients with varying degrees of chronic heart failure. Overall, metabolites M1 and M5 exhibit plasma concentrations roughly five and eight times greater than PTX, respectively. PTX and M1 pharmacokinetics are approximately dose-dependent, while those of M5 are not. Food intake before PTX ingestion delays time to peak plasma concentrations but not overall absorption. Extended-release forms of PTX extend the t max to between two and four hours but also serves to ameliorate peaks and troughs in plasma concentration over time. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pentoxifylline has a volume of distribution of 4.15 ± 0.85 following a single intravenous 100 mg dose in healthy subjects. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Pentoxifylline is approximately 45% bound to erythrocyte membranes. •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): Pentoxifylline (PTX) metabolism is incompletely understood. There are seven known metabolites (M1 through M7), although only M1, M4, and M5 are detected in plasma at appreciable levels, following the general pattern M5 > M1 > PTX > M4. As PTX apparent clearance is higher than hepatic blood flow and the AUC ratio of M1 to PTX is not appreciably different in cirrhotic patients, it is clear that erythrocytes are the main site of PTX-M1 interconversion. However, the reaction likely occurs in the liver as well. PTX is reduced in an NADPH-dependent manner by unknown an unidentified carbonyl reductase to form either lisofylline (the (R)-M1 enantiomer) or (S)-M1; the reaction is stereoselective, producing (S)-M1 exclusively in liver cytosol, 85% (S)-M1 in liver microsomes, and a ratio of 0.010-0.025 R:S-M1 after IV or oral dosing in humans. Although both (R)- and (S)-M1 can be oxidized back into PTX, (R)-M1 can also give rise to M2 and M3 in liver microsomes. In vitro studies suggest that CYP1A2 is at least partly responsible for the conversion of lisofylline ((R)-M1) back into PTX. Unlike the reversible oxidation/reduction of PTX and its M1 metabolites, M4 and M5 are formed via irreversible oxidation of PTX in the liver. Studies in mice recapitulating the PTX-ciprofloxacin drug reaction suggest that CYP1A2 is responsible for the formation of M6 from PTX and of M7 from M1, both through de-methylation at position 7. In general, metabolites M2, M3, and M6 are formed at very low levels in mammals. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pentoxifylline is eliminated almost entirely in the urine and predominantly as M5, which accounts for between 57 and 65 percent of the administered dose. Smaller amounts of M4 are recovered, while M1 and the parent compound account for less than 1% of the recovered dose. The fecal route accounts for less than 4% of the 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): Overall, pentoxifylline has an elimination half-life of between 0.39 and 0.84 hours, while its primary metabolites have elimination half-lives of between 0.96 and 1.61 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pentoxifylline given as a single 100 mg intravenous infusion has a clearance of 3.62 ± 0.75 L/h/kg in healthy subjects, which decreased to 1.44 ± 0.46 L/h/kg in cirrhotic patients. In another study, the apparent clearance of either 300 or 600 mg of pentoxifylline given intravenously (median and range) was 4.2 (2.8-6.3) and 4.1 (2.3-4.6) L/min, respectively. It is important to note that, due to the reversible extra-hepatic metabolism of the parent compound and metabolite 1, the true clearance of pentoxifylline may be even higher than the measured values. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdoses of pentoxifylline have been reported with symptoms including agitation, fever, flushing, hypotension, convulsions, somnolence, and loss of consciousness beginning 4-5 hours following ingestion and lasting up to 12 hours. Symptomatic treatment is recommended, specifically pertaining to maintaining proper respiration, blood pressure, and controlling convulsions. Activated charcoal may prove useful in absorbing excess pentoxifylline in overdose cases. Patients have recovered from overdose even at doses as high as 80 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): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pentoxifylline is a methylxanthine derivative used to treat intermittent claudication caused by chronic occlusive arterial disease of the limbs. Output: There have been reports of bleeding or prolonged prothrombin time in patients treated with pentoxifylline even without anticoagulant treatment. The risk of bleeding is further increased when anticoagulants are administered. Some studies report a lack of pharmacodynamic effect resulting from this interaction, however, caution is nonetheless advised. The severity of the interaction is moderate.

Does Abciximab and Pertuzumab interact?

•Drug A: Abciximab •Drug B: Pertuzumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Pertuzumab. •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 . •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): Pertuzumab is indicated for intravenous administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. It is also indicated in combination with trastuzumab and other chemotherapies for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early-stage breast cancer as part of a complete treatment regimen and as adjuvant treatment in patients with HER2-positive early-stage breast cancer at high risk of recurrence. Pertuzumab is also indicated for subcutaneous injection - in combination with trastuzumab and hyaluronidase - in the treatment of HER2-positive breast cancers in adults. •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): Pertuzumab exerts its antineoplastic effects by binding to and inhibiting the activity of HER2, an oncogene that has been implicated in the formation of numerous cancers. As with other therapeutic monoclonal antibodies, pertuzumab has a relatively long duration of action necessitating dosing every 3 weeks. Drugs that block HER2 activity, including pertuzumab, have been implicated in the development of cardiotoxicity (specifically left ventricular dysfunction) - a baseline assessment of left ventricular ejection fraction (LVEF) should be conducted prior to beginning therapy with pertuzumab and at regular intervals throughout therapy to ensure LVEF remains within normal limits. Consider indefinite suspension of therapy if LVEF declines and does not improve. •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): Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase receptor that plays an integral role in cell proliferation, differentiation, and survival. HER2 becomes active following dimerization with another HER2 receptor, another member of the HER protein family (e.g. HER3), or with a ligand - this dimer then phosphorylates and activates numerous intracellular signaling proteins, initiating signal transduction via pathways that include the Ras/mitogen-activated protein kinase pathway, the phosphatidylinositol 3' kinase (PI3K)/Akt pathway, and then Janus kinases/signal transducer and activator transcription pathway. HER2 is also a known oncogene - it is overexpressed or gene-amplified (i.e. HER2-positive) in approximately 20% of breast cancers and these cancers carry a generally poorer prognosis than HER2-negative breast cancers. Pertuzumab targets the extracellular dimerization domain (subdomain II) of HER2, thereby inhibiting ligand-initiated intracellular signaling via the MAP kinase and PI3K pathways. Inhibition of these pathways results in inhibition of cell growth and the initiation of apoptosis, respectively. Pertuzumab also appears to mediate antibody-dependent cell-mediated cytotoxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Intravenously administered pertuzumab, given as a loading dose of 840mg followed by a maintenance dose of 420mg every 3 weeks, reaches steady-state concentration following the first maintenance dose. In its subcutaneous formulation, in combination with [hylauronidase], the absolute bioavailability of pertuzumab is approximately 0.7 and the median T max is 4 days. This subcutaneous formulation leverages the benefits of co-administration with hyaluronidase - this enzyme breaks down hylauronic acid, thereby decreasing the viscosity of the extracellular matrix (ECM) and allowing for greater bioavailability with subcutaneous administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The average steady-state volume of distribution following intravenous administration is 3.53 - 7.5 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 metabolism of pertuzumab has not been studied directly. Monoclonal antibodies are typically subject to catabolism to smaller peptides and proteins prior to elimination. •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 median half-life of pertuzumab was determined to be 18 days based on a population pharmacokinetic analysis. •Clearance (Drug A): No clearance available •Clearance (Drug B): The median clearance of pertuzumab was determined to be 0.24 L/day based on a population pharmacokinetic analysis. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no data regarding overdose of pertuzumab. Single doses higher than 25 mg/kg have not been tested. Symptoms of overdose are likely to be consistent with pertuzumab's adverse effect profile, and may therefore involve significant diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and/or peripheral neuropathy. Pertuzumab has been associated with the development of left ventricular dysfunction (i.e. cardiotoxicity) that may be exacerbated in instances of overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Perjeta, Perjeta-Herceptin, Phesgo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pertuzumab is an antineoplastic agent used in the treatment of HER2-positive metastatic breast cancer in combination with other antineoplastic agents.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Pertuzumab interact? Information: •Drug A: Abciximab •Drug B: Pertuzumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Pertuzumab. •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 . •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): Pertuzumab is indicated for intravenous administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. It is also indicated in combination with trastuzumab and other chemotherapies for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early-stage breast cancer as part of a complete treatment regimen and as adjuvant treatment in patients with HER2-positive early-stage breast cancer at high risk of recurrence. Pertuzumab is also indicated for subcutaneous injection - in combination with trastuzumab and hyaluronidase - in the treatment of HER2-positive breast cancers in adults. •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): Pertuzumab exerts its antineoplastic effects by binding to and inhibiting the activity of HER2, an oncogene that has been implicated in the formation of numerous cancers. As with other therapeutic monoclonal antibodies, pertuzumab has a relatively long duration of action necessitating dosing every 3 weeks. Drugs that block HER2 activity, including pertuzumab, have been implicated in the development of cardiotoxicity (specifically left ventricular dysfunction) - a baseline assessment of left ventricular ejection fraction (LVEF) should be conducted prior to beginning therapy with pertuzumab and at regular intervals throughout therapy to ensure LVEF remains within normal limits. Consider indefinite suspension of therapy if LVEF declines and does not improve. •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): Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase receptor that plays an integral role in cell proliferation, differentiation, and survival. HER2 becomes active following dimerization with another HER2 receptor, another member of the HER protein family (e.g. HER3), or with a ligand - this dimer then phosphorylates and activates numerous intracellular signaling proteins, initiating signal transduction via pathways that include the Ras/mitogen-activated protein kinase pathway, the phosphatidylinositol 3' kinase (PI3K)/Akt pathway, and then Janus kinases/signal transducer and activator transcription pathway. HER2 is also a known oncogene - it is overexpressed or gene-amplified (i.e. HER2-positive) in approximately 20% of breast cancers and these cancers carry a generally poorer prognosis than HER2-negative breast cancers. Pertuzumab targets the extracellular dimerization domain (subdomain II) of HER2, thereby inhibiting ligand-initiated intracellular signaling via the MAP kinase and PI3K pathways. Inhibition of these pathways results in inhibition of cell growth and the initiation of apoptosis, respectively. Pertuzumab also appears to mediate antibody-dependent cell-mediated cytotoxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Intravenously administered pertuzumab, given as a loading dose of 840mg followed by a maintenance dose of 420mg every 3 weeks, reaches steady-state concentration following the first maintenance dose. In its subcutaneous formulation, in combination with [hylauronidase], the absolute bioavailability of pertuzumab is approximately 0.7 and the median T max is 4 days. This subcutaneous formulation leverages the benefits of co-administration with hyaluronidase - this enzyme breaks down hylauronic acid, thereby decreasing the viscosity of the extracellular matrix (ECM) and allowing for greater bioavailability with subcutaneous administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The average steady-state volume of distribution following intravenous administration is 3.53 - 7.5 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 metabolism of pertuzumab has not been studied directly. Monoclonal antibodies are typically subject to catabolism to smaller peptides and proteins prior to elimination. •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 median half-life of pertuzumab was determined to be 18 days based on a population pharmacokinetic analysis. •Clearance (Drug A): No clearance available •Clearance (Drug B): The median clearance of pertuzumab was determined to be 0.24 L/day based on a population pharmacokinetic analysis. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no data regarding overdose of pertuzumab. Single doses higher than 25 mg/kg have not been tested. Symptoms of overdose are likely to be consistent with pertuzumab's adverse effect profile, and may therefore involve significant diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and/or peripheral neuropathy. Pertuzumab has been associated with the development of left ventricular dysfunction (i.e. cardiotoxicity) that may be exacerbated in instances of overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Perjeta, Perjeta-Herceptin, Phesgo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pertuzumab is an antineoplastic agent used in the treatment of HER2-positive metastatic breast cancer in combination with other antineoplastic agents. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Phenelzine interact?

•Drug A: Abciximab •Drug B: Phenelzine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Phenelzine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Phenelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy. Atypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression. Neurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category. A nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living. •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 elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings. Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia. •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 basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Phenelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase. •Absorption (Drug A): No absorption available •Absorption (Drug B): Phenelzine is rapidly absorbed from the gastrointestinal tract. The decay of the drug action is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of monoamine oxidase. The mean Cmax is 19.8 ng/ml and it occurs after 43 minutes of dose administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of phenelzine is hard to determine as drugs from this kind penetrate the CNS very well into the tissue where their activity is desired. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Unchanged phenelzine presents a high protein binding which reduced its bioavailability. •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): For the metabolic studies, it is assumed that phenelzine is acetylated. Some of the metabolites of phenelzine are phenylacetic acid, 2-phenylethylamine and 4-hydroxyphenylacetic acid as major metabolites and N-acetyl-phenelzine as a minor metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of the administered dose is mainly composed of the phenelzine metabolites, phenylacetic acid and parahydroxyphenylacetic acid that constitute 79% of the dose found in the urine in the first 96 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): After administration phenelzine presents a very short half-life of 11.6 hours in humans. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Phenelzine, as must of the monoamine oxidase inhibitors, can cause transient, mild and asymptomatic aminotransferase elevations. It has also been reported to be associated with cases of liver injury after 1-3 months of treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nardil •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Phenelzine is a monoamine oxidase inhibitor used to treat atypical, nonendogenous, or neurotic depression.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Phenelzine interact? Information: •Drug A: Abciximab •Drug B: Phenelzine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Phenelzine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Phenelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy. Atypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression. Neurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category. A nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living. •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 elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings. Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia. •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 basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Phenelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase. •Absorption (Drug A): No absorption available •Absorption (Drug B): Phenelzine is rapidly absorbed from the gastrointestinal tract. The decay of the drug action is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of monoamine oxidase. The mean Cmax is 19.8 ng/ml and it occurs after 43 minutes of dose administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of phenelzine is hard to determine as drugs from this kind penetrate the CNS very well into the tissue where their activity is desired. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Unchanged phenelzine presents a high protein binding which reduced its bioavailability. •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): For the metabolic studies, it is assumed that phenelzine is acetylated. Some of the metabolites of phenelzine are phenylacetic acid, 2-phenylethylamine and 4-hydroxyphenylacetic acid as major metabolites and N-acetyl-phenelzine as a minor metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of the administered dose is mainly composed of the phenelzine metabolites, phenylacetic acid and parahydroxyphenylacetic acid that constitute 79% of the dose found in the urine in the first 96 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): After administration phenelzine presents a very short half-life of 11.6 hours in humans. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Phenelzine, as must of the monoamine oxidase inhibitors, can cause transient, mild and asymptomatic aminotransferase elevations. It has also been reported to be associated with cases of liver injury after 1-3 months of treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nardil •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Phenelzine is a monoamine oxidase inhibitor used to treat atypical, nonendogenous, or neurotic depression. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Phenprocoumon interact?

•Drug A: Abciximab •Drug B: Phenprocoumon •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Phenprocoumon. •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. •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 for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). •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): Phenprocoumon, a coumarin anticoagulant, thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as phenprocoumon have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. •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): Phenprocoumon 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 proteins, 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. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results 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): Bioavailability is close to 100% •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): Phenprocoumon is stereoselectively metabolized by hepatic microsomal enzymes (cytochrome P-450) to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites. Cytochrome P450 2C9 is the principal form of human liver P-450 responsible for 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): 5-6 days •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): 50=500 mg/kg. Symptoms of overdose includes suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries). •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): Fenprocumon Fenprocumone Phenprocoumarol Phenprocoumarole Phenprocoumon Phenprocoumone Phenprocoumonum Phenprocumone •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Phenprocoumon is an anticoagulant drug used for the prevention of thrombosis.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Phenprocoumon interact? Information: •Drug A: Abciximab •Drug B: Phenprocoumon •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Phenprocoumon. •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. •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 for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). •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): Phenprocoumon, a coumarin anticoagulant, thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as phenprocoumon have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. •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): Phenprocoumon 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 proteins, 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. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results 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): Bioavailability is close to 100% •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): Phenprocoumon is stereoselectively metabolized by hepatic microsomal enzymes (cytochrome P-450) to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites. Cytochrome P450 2C9 is the principal form of human liver P-450 responsible for 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): 5-6 days •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): 50=500 mg/kg. Symptoms of overdose includes suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries). •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): Fenprocumon Fenprocumone Phenprocoumarol Phenprocoumarole Phenprocoumon Phenprocoumone Phenprocoumonum Phenprocumone •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Phenprocoumon is an anticoagulant drug used for the prevention of thrombosis. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Phenylalanine interact?

•Drug A: Abciximab •Drug B: Phenylalanine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Phenylalanine. •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. •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): L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic 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): Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory. •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 supposed antidepressant effects of L-phenylalanine may be due to its role as a precursor in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorbed from the small intestine by a sodium dependent active transport process. •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): Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver. •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): L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aminosyn II 7 %, Sulfite-free, Aminosyn-PF 7%, Clinimix 2.75/5, Clinimix E 2.75/5, Clinisol 15, Freamine 6.9, Freamine III 10, Hepatamine 8, Nephramine, Olimel, Periolimel, Plenamine, Premasol, Primene, Procalamine 3, Prosol, Travasol 10, Trophamine 10 % •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fenilalanina L-Phenylalanine Phenylalanine Phenylalaninum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Phenylalanine is an amino acid commonly found as a component of total parenteral nutrition.

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. The severity of the interaction is minor.

Question: Does Abciximab and Phenylalanine interact? Information: •Drug A: Abciximab •Drug B: Phenylalanine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Phenylalanine. •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. •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): L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic 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): Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory. •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 supposed antidepressant effects of L-phenylalanine may be due to its role as a precursor in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorbed from the small intestine by a sodium dependent active transport process. •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): Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver. •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): L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aminosyn II 7 %, Sulfite-free, Aminosyn-PF 7%, Clinimix 2.75/5, Clinimix E 2.75/5, Clinisol 15, Freamine 6.9, Freamine III 10, Hepatamine 8, Nephramine, Olimel, Periolimel, Plenamine, Premasol, Primene, Procalamine 3, Prosol, Travasol 10, Trophamine 10 % •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fenilalanina L-Phenylalanine Phenylalanine Phenylalaninum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Phenylalanine is an amino acid commonly found as a component of total parenteral nutrition. Output: 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. The severity of the interaction is minor.

Does Abciximab and Piroxicam interact?

•Drug A: Abciximab •Drug B: Piroxicam •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Piroxicam 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. •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 osteoarthritis and rheumatoid arthritis. •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): Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis. •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 antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed following oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.14 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): Renal •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Piroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Piroxicam is excreted into human 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): 30 to 86 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 drowsiness, nausea, stomach pain, and/or vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Feldene •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Piroxicam Piroxicam betadex Piroxicamum Pyroxycam •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Piroxicam is an NSAID used to treat the symptoms of osteoarthritis and rheumatoid arthritis.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Piroxicam interact? Information: •Drug A: Abciximab •Drug B: Piroxicam •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Piroxicam 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. •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 osteoarthritis and rheumatoid arthritis. •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): Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis. •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 antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed following oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.14 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): Renal •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Piroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Piroxicam is excreted into human 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): 30 to 86 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 drowsiness, nausea, stomach pain, and/or vomiting. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Feldene •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Piroxicam Piroxicam betadex Piroxicamum Pyroxycam •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Piroxicam is an NSAID used to treat the symptoms of osteoarthritis and rheumatoid arthritis. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Pirtobrutinib interact?

•Drug A: Abciximab •Drug B: Pirtobrutinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pirtobrutinib. •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. •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): Pirtobrutinib is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK 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): Pirtobrutinib is a non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) with more than 300-fold selectivity for BTK over 98% of other kinases. In vivo murine studies suggest that pirtobrutinib has an efficacy similar to ibrutinib with BTK wild-type tumor cells but an improved efficacy in BTK Cys481 mutant cells. Pirtobrutinib has shown efficacy against different B-cell malignancies and is effective in patients that are intolerant of irreversible BTK inhibitors or have developed a disease resistant to these covalent inhibitors. At the recommended dosage of 200 mg once daily, pirtobrutinib trough concentrations exceeded the BTK IC 96. In healthy subjects given a single 900 mg dose (concentration 2 times higher than the steady state at the recommended dosage), pirtobrutinib did not have a clinically meaningful effect on the change in QTcF interval, and there was no relationship between pirtobrutinib exposure and change in QTc interval. The use of pirtobrutinib may lead to fatal and serious infections, hemorrhage, cytopenias, atrial fibrillation and atrial flutter. Patients should also be warned about the development of second primary malignancies. •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): Bruton’s tyrosine kinase (BTK) is a tyrosine kinase located in the cytoplasm that is recruited to the cytoplasm upon activation. In B-cells, BTK participates in the activation of B-cell antigen receptor (BCR) signaling and cytokine receptor pathways, both critical for B-cell development, function, adhesion and migration. Therefore, the inhibition of BTK is a valuable target for the treatment of B-cell cancers. Pirtobrutinib binds to Bruton’s tyrosine kinase (BTK) in a non-covalent manner and inhibits its activity. Unlike other BTK inhibitors that bind covalently to the active site of BTK, the inhibitory activity of pirtobrutinib is maintained even in the presence of mutations in this region, such as the presence of Cys481. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation. •Absorption (Drug A): No absorption available •Absorption (Drug B): With single oral doses between 300 mg and 800 mg (1.5 to 4 times the approved recommended dose) and once daily doses between 25 mg and 300 mg (0.125 to 1.5 times the recommended dose), pirtobrutinib follows a dose-proportional pharmacokinetic profile. Within 5 days of once-daily dosing, pirtobrutinib reached steady-state concentration, with an accumulation ratio of 1.63 based on AUC after 200 mg dosages. With the recommended dose, pirtobrutinib has a steady-state AUC and C max of 91300 h⋅ng/mL and 6460 ng/mL, respectively. On day 8 of cycle 1, pirtobrutinib had an AUC 0-24 of 81800 h⋅ng/mL and a C max of 3670 ng/mL. After approximately 2 hours, pirtobrutinib reaches peak plasma concentration (t max ). After a single oral dose of 200 mg, pirtobrutinib reaches an absolute bioavailability of 85.5%. The administration of a high-fat, high-calorie meal to healthy subjects did not have a clinically significant effect on the pharmacokinetics of pirtobrutinib. A high-fat meal decreased the C max of pirtobrutinib by 23%, delayed t max by 1 hour and had no effects on the AUC. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pirtobrutinib has an apparent central volume of distribution of 32.8 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The human protein binding of pirtobrutinib is 96%, independent of in vitro concentration. Pirtobrutinib has a blood-to-plasma ratio of 0.79. •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 studies suggest that pirtobrutinib is mainly metabolized by CYP3A4 and direct glucuronidation by UGT1A8 and UGT1A9. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pirtobrutinib is mainly excreted in urine and feces. In healthy subjects given a single dose of 200 mg of radiolabeled pirtobrutinib, 57% of the dose was recovered in urine (10% unchanged), and 37% was recovered in feces (18% unchanged). •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): Pirtobrutinib has an effective half-life of approximately 19 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pirtobrutinib has an apparent clearance of 2.02 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding pirtobrutinib is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hemorrhage, cytopenias, atrial fibrillation and atrial flutter. Symptomatic and supportive measures are recommended. In vivo carcinogenicity studies have not been conducted with pirtobrutinib. A bacterial mutagenicity (Ames) assay found that pirtobrutinib was not mutagenic, and in vitro micronucleus assays using human peripheral blood lymphocytes found that pirtobrutinib was aneugenic. Up to 2000 mg/kg, pirtobrutinib was not genotoxic in an in vivo rat bone marrow micronucleus assay. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jaypirca •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pirtobrutinib is a kinase inhibitor used to treat relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy.

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. The severity of the interaction is minor.

Question: Does Abciximab and Pirtobrutinib interact? Information: •Drug A: Abciximab •Drug B: Pirtobrutinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pirtobrutinib. •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. •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): Pirtobrutinib is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK 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): Pirtobrutinib is a non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) with more than 300-fold selectivity for BTK over 98% of other kinases. In vivo murine studies suggest that pirtobrutinib has an efficacy similar to ibrutinib with BTK wild-type tumor cells but an improved efficacy in BTK Cys481 mutant cells. Pirtobrutinib has shown efficacy against different B-cell malignancies and is effective in patients that are intolerant of irreversible BTK inhibitors or have developed a disease resistant to these covalent inhibitors. At the recommended dosage of 200 mg once daily, pirtobrutinib trough concentrations exceeded the BTK IC 96. In healthy subjects given a single 900 mg dose (concentration 2 times higher than the steady state at the recommended dosage), pirtobrutinib did not have a clinically meaningful effect on the change in QTcF interval, and there was no relationship between pirtobrutinib exposure and change in QTc interval. The use of pirtobrutinib may lead to fatal and serious infections, hemorrhage, cytopenias, atrial fibrillation and atrial flutter. Patients should also be warned about the development of second primary malignancies. •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): Bruton’s tyrosine kinase (BTK) is a tyrosine kinase located in the cytoplasm that is recruited to the cytoplasm upon activation. In B-cells, BTK participates in the activation of B-cell antigen receptor (BCR) signaling and cytokine receptor pathways, both critical for B-cell development, function, adhesion and migration. Therefore, the inhibition of BTK is a valuable target for the treatment of B-cell cancers. Pirtobrutinib binds to Bruton’s tyrosine kinase (BTK) in a non-covalent manner and inhibits its activity. Unlike other BTK inhibitors that bind covalently to the active site of BTK, the inhibitory activity of pirtobrutinib is maintained even in the presence of mutations in this region, such as the presence of Cys481. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation. •Absorption (Drug A): No absorption available •Absorption (Drug B): With single oral doses between 300 mg and 800 mg (1.5 to 4 times the approved recommended dose) and once daily doses between 25 mg and 300 mg (0.125 to 1.5 times the recommended dose), pirtobrutinib follows a dose-proportional pharmacokinetic profile. Within 5 days of once-daily dosing, pirtobrutinib reached steady-state concentration, with an accumulation ratio of 1.63 based on AUC after 200 mg dosages. With the recommended dose, pirtobrutinib has a steady-state AUC and C max of 91300 h⋅ng/mL and 6460 ng/mL, respectively. On day 8 of cycle 1, pirtobrutinib had an AUC 0-24 of 81800 h⋅ng/mL and a C max of 3670 ng/mL. After approximately 2 hours, pirtobrutinib reaches peak plasma concentration (t max ). After a single oral dose of 200 mg, pirtobrutinib reaches an absolute bioavailability of 85.5%. The administration of a high-fat, high-calorie meal to healthy subjects did not have a clinically significant effect on the pharmacokinetics of pirtobrutinib. A high-fat meal decreased the C max of pirtobrutinib by 23%, delayed t max by 1 hour and had no effects on the AUC. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pirtobrutinib has an apparent central volume of distribution of 32.8 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The human protein binding of pirtobrutinib is 96%, independent of in vitro concentration. Pirtobrutinib has a blood-to-plasma ratio of 0.79. •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 studies suggest that pirtobrutinib is mainly metabolized by CYP3A4 and direct glucuronidation by UGT1A8 and UGT1A9. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Pirtobrutinib is mainly excreted in urine and feces. In healthy subjects given a single dose of 200 mg of radiolabeled pirtobrutinib, 57% of the dose was recovered in urine (10% unchanged), and 37% was recovered in feces (18% unchanged). •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): Pirtobrutinib has an effective half-life of approximately 19 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pirtobrutinib has an apparent clearance of 2.02 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding pirtobrutinib is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hemorrhage, cytopenias, atrial fibrillation and atrial flutter. Symptomatic and supportive measures are recommended. In vivo carcinogenicity studies have not been conducted with pirtobrutinib. A bacterial mutagenicity (Ames) assay found that pirtobrutinib was not mutagenic, and in vitro micronucleus assays using human peripheral blood lymphocytes found that pirtobrutinib was aneugenic. Up to 2000 mg/kg, pirtobrutinib was not genotoxic in an in vivo rat bone marrow micronucleus assay. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jaypirca •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pirtobrutinib is a kinase inhibitor used to treat relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy. Output: 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. The severity of the interaction is minor.

Does Abciximab and Polatuzumab vedotin interact?

•Drug A: Abciximab •Drug B: Polatuzumab vedotin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Polatuzumab 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 . •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): Polatuzumab vedotin is used in combination with bendamustine and rituximab to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies. In Canada, this indication is approved for patients who are not eligible for autologous stem cell transplant and have received at least one prior therapy. Polatuzumab vedotin is also used in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) to treat adult patients with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high-grade B-cell lymphoma, Epstein-Barr virus-positive (EBV+) DLBCL NOS, and T-cell/histiocyte rich LBCL. •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): Polatuzumab vedotin is an anti-cancer agent that works to cause apoptosis in malignant B cells. In vitro, it exerted cytotoxic effects on most diffuse large B-cell lymphoma (DLBCL) cell lines: this effect was consistent across cell lines, regardless of the cell-of-origin subtypes and whether they harboured mutations in the CD79B gene or not. In mouse xenograft models, polatuzumab vedotin caused apoptosis and reduced proliferation of mature CD79b+ B-cell NHL cell lines. Polatuzumab vedotin can cause immunosuppression, including neutropenia and thrombocytopenia. •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): Polatuzumab vedotin is an antibody-drug conjugate consisting of a CD79b-directed antibody, a microtubule-disrupting agent called monomethyl auristatin E (MMAE), and a cleavable linker that holds the components together. CD79 is a heterodimer composed of CD79a and CD79b. Responsible for signal transduction, CD79 forms a complex with the B cell receptor (BCR) and is almost exclusively expressed on B cells, including malignant B cells. Most importantly, CD79b gained increasing attention as a promising therapeutic target as it plays an essential role in BCR expression, transport, and functions such as B cell proliferation and differentiation. Once the antibody component binds to CD79b, polatuzumab vedotin is internalized, and lysosomal proteases cleave the linker to release MMAE in the cell. MMAE is a microtubule-disrupting anti-mitotic agent that exerts cytotoxic effects against malignant B cells. It binds to microtubules, inhibits mitosis by interfering with tubulin and tubulin polymerization, and induces apoptosis in dividing B cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): After the first polatuzumab vedotin dose of 1.8 mg/kg, the mean (± SD) C max of antibody-conjugated MMAE and unconjugated MMAE were 803 (± 233) ng/mL and 6.82 (± 4.73) ng/mL, respectively. The mean AUC inf of antibody-conjugated MMAE and unconjugated MMAE were 1860 (± 966) day x ng/mL and 52.3 (± 18.0) day x ng/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated central volume of distribution of polatuzumab vedotin based on population PK analysis is 3.15 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): MMAE is 71% to 77% bound to plasma proteins. Its blood-to-plasma ratio is 0.79 to 0.98, in vitro. •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): Polatuzumab vedotin is expected to undergo catabolism into small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites. MMAE is metabolized by CYP3A4/5. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Polatuzumab vedotin is predominantly excreted in feces, as well as in urine to some extent. •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 polatuzumab vedotin is approximately 12 days (95% CI: 8.1 to 19.5 days) at Cycle 6. The terminal half-life of unconjugated MMAE is approximately four days after the first dose of polatuzumab vedotin. •Clearance (Drug A): No clearance available •Clearance (Drug B): The predicted clearance of polatuzumab vedotin is 0.9 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses and LD 50 are not readily available. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Polivy •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Polatuzumab vedotin is a CD79b antibody conjugate indicated to treat different types of large B-cell lymphoma.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Polatuzumab vedotin interact? Information: •Drug A: Abciximab •Drug B: Polatuzumab vedotin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Polatuzumab 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 . •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): Polatuzumab vedotin is used in combination with bendamustine and rituximab to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies. In Canada, this indication is approved for patients who are not eligible for autologous stem cell transplant and have received at least one prior therapy. Polatuzumab vedotin is also used in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) to treat adult patients with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high-grade B-cell lymphoma, Epstein-Barr virus-positive (EBV+) DLBCL NOS, and T-cell/histiocyte rich LBCL. •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): Polatuzumab vedotin is an anti-cancer agent that works to cause apoptosis in malignant B cells. In vitro, it exerted cytotoxic effects on most diffuse large B-cell lymphoma (DLBCL) cell lines: this effect was consistent across cell lines, regardless of the cell-of-origin subtypes and whether they harboured mutations in the CD79B gene or not. In mouse xenograft models, polatuzumab vedotin caused apoptosis and reduced proliferation of mature CD79b+ B-cell NHL cell lines. Polatuzumab vedotin can cause immunosuppression, including neutropenia and thrombocytopenia. •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): Polatuzumab vedotin is an antibody-drug conjugate consisting of a CD79b-directed antibody, a microtubule-disrupting agent called monomethyl auristatin E (MMAE), and a cleavable linker that holds the components together. CD79 is a heterodimer composed of CD79a and CD79b. Responsible for signal transduction, CD79 forms a complex with the B cell receptor (BCR) and is almost exclusively expressed on B cells, including malignant B cells. Most importantly, CD79b gained increasing attention as a promising therapeutic target as it plays an essential role in BCR expression, transport, and functions such as B cell proliferation and differentiation. Once the antibody component binds to CD79b, polatuzumab vedotin is internalized, and lysosomal proteases cleave the linker to release MMAE in the cell. MMAE is a microtubule-disrupting anti-mitotic agent that exerts cytotoxic effects against malignant B cells. It binds to microtubules, inhibits mitosis by interfering with tubulin and tubulin polymerization, and induces apoptosis in dividing B cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): After the first polatuzumab vedotin dose of 1.8 mg/kg, the mean (± SD) C max of antibody-conjugated MMAE and unconjugated MMAE were 803 (± 233) ng/mL and 6.82 (± 4.73) ng/mL, respectively. The mean AUC inf of antibody-conjugated MMAE and unconjugated MMAE were 1860 (± 966) day x ng/mL and 52.3 (± 18.0) day x ng/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated central volume of distribution of polatuzumab vedotin based on population PK analysis is 3.15 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): MMAE is 71% to 77% bound to plasma proteins. Its blood-to-plasma ratio is 0.79 to 0.98, in vitro. •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): Polatuzumab vedotin is expected to undergo catabolism into small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites. MMAE is metabolized by CYP3A4/5. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Polatuzumab vedotin is predominantly excreted in feces, as well as in urine to some extent. •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 polatuzumab vedotin is approximately 12 days (95% CI: 8.1 to 19.5 days) at Cycle 6. The terminal half-life of unconjugated MMAE is approximately four days after the first dose of polatuzumab vedotin. •Clearance (Drug A): No clearance available •Clearance (Drug B): The predicted clearance of polatuzumab vedotin is 0.9 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses and LD 50 are not readily available. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Polivy •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Polatuzumab vedotin is a CD79b antibody conjugate indicated to treat different types of large B-cell lymphoma. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Polythiazide interact?

•Drug A: Abciximab •Drug B: Polythiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Polythiazide. •Extended Description: The efficacy of oral anticoagulants may be reduced by the concomitant use of thiazide diuretics.2 The evidence for this interaction is conflicting.1 •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): Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure. •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): As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure •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): As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. •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): Minizide, Renese, Renese-R •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Polythiazide is a thiazide diuretic used in the management of hypertension and treatment of edema.

The efficacy of oral anticoagulants may be reduced by the concomitant use of thiazide diuretics.2 The evidence for this interaction is conflicting.1 The severity of the interaction is minor.

Question: Does Abciximab and Polythiazide interact? Information: •Drug A: Abciximab •Drug B: Polythiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Polythiazide. •Extended Description: The efficacy of oral anticoagulants may be reduced by the concomitant use of thiazide diuretics.2 The evidence for this interaction is conflicting.1 •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): Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure. •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): As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure •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): As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. •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): Minizide, Renese, Renese-R •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Polythiazide is a thiazide diuretic used in the management of hypertension and treatment of edema. Output: The efficacy of oral anticoagulants may be reduced by the concomitant use of thiazide diuretics.2 The evidence for this interaction is conflicting.1 The severity of the interaction is minor.

Does Abciximab and Pomalidomide interact?

•Drug A: Abciximab •Drug B: Pomalidomide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pomalidomide. •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. •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): Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and have demonstrated disease progression on or within 60 days of completion of the last therapy. It is also indicated for the treatment of Kaposi's sarcoma (KS) in AIDS patients who have failed highly active antiretroviral therapy (HAART) and for the treatment of KS in HIV-negative patients. •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): Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times). •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): Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mean apparent volume of distribution (Vd/F), steady-state = 62 - 138 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 12-44% protein bound. It is not concentration dependent. •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): Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, 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): Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance = 7-10 L/hour •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Imnovid, Pomalyst •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pomalidomide is a thalidomide analogue used in combination with dexamethasone to treat patients with multiple myeloma.

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. The severity of the interaction is minor.

Question: Does Abciximab and Pomalidomide interact? Information: •Drug A: Abciximab •Drug B: Pomalidomide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Pomalidomide. •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. •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): Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and have demonstrated disease progression on or within 60 days of completion of the last therapy. It is also indicated for the treatment of Kaposi's sarcoma (KS) in AIDS patients who have failed highly active antiretroviral therapy (HAART) and for the treatment of KS in HIV-negative patients. •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): Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times). •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): Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mean apparent volume of distribution (Vd/F), steady-state = 62 - 138 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 12-44% protein bound. It is not concentration dependent. •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): Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, 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): Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance = 7-10 L/hour •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Imnovid, Pomalyst •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Pomalidomide is a thalidomide analogue used in combination with dexamethasone to treat patients with multiple myeloma. Output: 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. The severity of the interaction is minor.

Does Abciximab and Ponatinib interact?

•Drug A: Abciximab •Drug B: Ponatinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ponatinib. •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. •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): Ponatinib is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor 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): 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): Ponatinib is a multi-target kinase inhibitor. Its primary cellular target is the Bcr-Abl tyrosine kinase protein which is constitutively active and promotes the progression of CML. This protein arises from the fused Bcr and Abl gene- what is commonly known as the Philadelphia chromosome. Ponatinib is unique in that it is especially useful in the treatment of resistant CML because it inhibits the tyrosine kinase activity of Abl and T315I mutant kinases. The T315I mutation confers resistance in cells as it prevents other Bcr-Abl inhibitors from binding to the Abl kinase. Other targets that ponatinib inhibits are members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. A decrease in tumour size expressing native or T315I mutant BCR-ABL have been observed in rats. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of ponatinib is unknown. Peak concentrations of ponatinib are observed within 6 hours after Iclusig oral administration. Food does not affect absorption of food. The aqueous solubility of ponatinib is pH dependent, with higher pH resulting in lower solubility. When 45 mg of ponatinib is given to cancer patients, the pharmacokinetic parameters are as follows: Cmax = 73 ng/mL; AUC = 1253 ng•hr/mL; •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After oral administration of 45 mg ponatinib once daily for 28 days in cancer patients, the steady state volume of distribution is 1223 L. Ponatinib is a weak substrate for P-gp and ABCG2. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): > 99% 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): At least 64% of a ponatinib dose undergoes phase I and phase II metabolism. CYP3A4 and to a lesser extent CYP2C8, CYP2D6 and CYP3A5 are involved in the phase I metabolism of ponatinib in vitro. Ponatinib is also metabolized by esterases and/or amidases. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ponatinib is mainly eliminated via feces. Following a single oral dose of [14C]-labeled ponatinib, approximately 87% of the radioactive dose is recovered in the feces and approximately 5% 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): After oral administration of 45 mg ponatinib once daily for 28 days in cancer patients, the terminal elimination half-life is 24 hours (range of 12 - 66 hours). •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common non-hematologic adverse reactions (≥ 20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Iclusig •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ponatinib is a kinase inhibitor used to treat patients with various types of chronic myeloid leukemia (CML).

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. The severity of the interaction is minor.

Question: Does Abciximab and Ponatinib interact? Information: •Drug A: Abciximab •Drug B: Ponatinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ponatinib. •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. •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): Ponatinib is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor 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): 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): Ponatinib is a multi-target kinase inhibitor. Its primary cellular target is the Bcr-Abl tyrosine kinase protein which is constitutively active and promotes the progression of CML. This protein arises from the fused Bcr and Abl gene- what is commonly known as the Philadelphia chromosome. Ponatinib is unique in that it is especially useful in the treatment of resistant CML because it inhibits the tyrosine kinase activity of Abl and T315I mutant kinases. The T315I mutation confers resistance in cells as it prevents other Bcr-Abl inhibitors from binding to the Abl kinase. Other targets that ponatinib inhibits are members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. A decrease in tumour size expressing native or T315I mutant BCR-ABL have been observed in rats. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of ponatinib is unknown. Peak concentrations of ponatinib are observed within 6 hours after Iclusig oral administration. Food does not affect absorption of food. The aqueous solubility of ponatinib is pH dependent, with higher pH resulting in lower solubility. When 45 mg of ponatinib is given to cancer patients, the pharmacokinetic parameters are as follows: Cmax = 73 ng/mL; AUC = 1253 ng•hr/mL; •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After oral administration of 45 mg ponatinib once daily for 28 days in cancer patients, the steady state volume of distribution is 1223 L. Ponatinib is a weak substrate for P-gp and ABCG2. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): > 99% 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): At least 64% of a ponatinib dose undergoes phase I and phase II metabolism. CYP3A4 and to a lesser extent CYP2C8, CYP2D6 and CYP3A5 are involved in the phase I metabolism of ponatinib in vitro. Ponatinib is also metabolized by esterases and/or amidases. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ponatinib is mainly eliminated via feces. Following a single oral dose of [14C]-labeled ponatinib, approximately 87% of the radioactive dose is recovered in the feces and approximately 5% 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): After oral administration of 45 mg ponatinib once daily for 28 days in cancer patients, the terminal elimination half-life is 24 hours (range of 12 - 66 hours). •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common non-hematologic adverse reactions (≥ 20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Iclusig •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ponatinib is a kinase inhibitor used to treat patients with various types of chronic myeloid leukemia (CML). Output: 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. The severity of the interaction is minor.

Does Abciximab and Potassium Iodide interact?

•Drug A: Abciximab •Drug B: Potassium Iodide •Severity: MODERATE •Description: Potassium Iodide 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): Potassium Iodide is oral antithyroid agent used in the prevention of radioactive iodine uptake into the thyroid gland during a nuclear radiation emergency. Potassium Iodide may be used as an adjunct to other antithyroid agents in the treatment of hyperthyroidism and thyrotoxicosis and preoperatively to induce thyroid involution. •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): It works in the thyroid gland. By inhibiting thyroid hormone synthesis and release, thyroid gland vascularity is reduced, thyroid gland tissue becomes firmer, thyroid cell size is reduced, follicular colloid reaccumulates, and bound iodine levels increase. As a protectant following radiation exposure, KI blocks the uptake of radioactive iodine isotopes by the thyroid gland thereby minimizing the risk of radiation-induced thyroid neoplasms. •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): Iosat, Pregvit, Thyrosafe, Thyroshield, Xylocaine With Epinephrine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Kaliumiodid Potasio ioduro Potassium Iodide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Potassium Iodide is an oral antithyroid agent used for the prevention of radioactive iodine uptake into the thyroid gland during a nuclear radiation emergency.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Potassium Iodide interact? Information: •Drug A: Abciximab •Drug B: Potassium Iodide •Severity: MODERATE •Description: Potassium Iodide 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): Potassium Iodide is oral antithyroid agent used in the prevention of radioactive iodine uptake into the thyroid gland during a nuclear radiation emergency. Potassium Iodide may be used as an adjunct to other antithyroid agents in the treatment of hyperthyroidism and thyrotoxicosis and preoperatively to induce thyroid involution. •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): It works in the thyroid gland. By inhibiting thyroid hormone synthesis and release, thyroid gland vascularity is reduced, thyroid gland tissue becomes firmer, thyroid cell size is reduced, follicular colloid reaccumulates, and bound iodine levels increase. As a protectant following radiation exposure, KI blocks the uptake of radioactive iodine isotopes by the thyroid gland thereby minimizing the risk of radiation-induced thyroid neoplasms. •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): Iosat, Pregvit, Thyrosafe, Thyroshield, Xylocaine With Epinephrine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Kaliumiodid Potasio ioduro Potassium Iodide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Potassium Iodide is an oral antithyroid agent used for the prevention of radioactive iodine uptake into the thyroid gland during a nuclear radiation emergency. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Pozelimab interact?

•Drug A: Abciximab •Drug B: Pozelimab •Severity: MODERATE •Description: The serum concentration of Pozelimab can be decreased when it is combined with Abciximab. •Extended Description: Since pozelimab is an IgG4 antibody, co-administration of pozelimab with other immunoglobulins-based products can interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies, thus decreasing the serum concentration of pozelimab. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found

Since pozelimab is an IgG4 antibody, co-administration of pozelimab with other immunoglobulins-based products can interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies, thus decreasing the serum concentration of pozelimab. The severity of the interaction is moderate.

Question: Does Abciximab and Pozelimab interact? Information: •Drug A: Abciximab •Drug B: Pozelimab •Severity: MODERATE •Description: The serum concentration of Pozelimab can be decreased when it is combined with Abciximab. •Extended Description: Since pozelimab is an IgG4 antibody, co-administration of pozelimab with other immunoglobulins-based products can interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies, thus decreasing the serum concentration of pozelimab. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found Output: Since pozelimab is an IgG4 antibody, co-administration of pozelimab with other immunoglobulins-based products can interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies, thus decreasing the serum concentration of pozelimab. The severity of the interaction is moderate.

Does Abciximab and Prasugrel interact?

•Drug A: Abciximab •Drug B: Prasugrel •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Prasugrel. •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. •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 in combination with acetylsalicylic acid (ASA) to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI). May be used in patients with unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) who are to be managed with PCI. Prasugrel is not recommended in patients 75 years of age or greater, those that weigh<60kg, and patients with a history of stroke or transient ischemic attack due to increased risk of fatal and intracranial 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): Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 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): Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel. •Absorption (Drug A): No absorption available •Absorption (Drug B): 79% or greater of the dose is absorbed after oral administration. Absorption and metabolism occur rapidly and peak plasma concentrations (C max ) are reached approximately 30 minutes following oral administration. Administration with a high fat, high calorie meal did not affect the AUC of the active metabolite in healthy individuals, but the C max was decreased by ~49% and the T max was increased to 0.5 to 1.5 hours. Prasugrel may be administered with or without food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 44-68L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 98% of the active metabolite was bound to human serum albumin in a 4% buffered solution. The major inactive metabolites are also highly 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): Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to thiolactone by human carboxylesterase (hCE) 2. This intermediate is further metabolized to its active metabolite, R-138727, in a single step by cytochrome P450 enzymes in the liver (primarily CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19). The active metabolite is further metabolized by S-methylation or cysteine conjugation to two inactive metabolites. Unlike clopidogrel, transformation of prasugrel to its active metabolite does not appear to be affected by cytochrome P450 polymorphisms. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 68% of the orally administered dose is excreted in urine and 27% in the feces, as inactive metabolites. The active metabolite is not expected to be removed by dialysis. •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 active metabolite has an elimination half-life of about 7.4 hours (range 2-15 hours). •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance = 112 - 166 L/hr •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 (rat) 1,000 - 2,000 mg/kg; LD50 (rabbit) > 1,000 mg/kg •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Effient, Efient •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Prasugrel is a P2Y12 platelet inhibitor used to reduce risk of thrombotic cardiovascular events in unstable angina or non-ST-elevation myocardial infarction (NSTEMI), and in patients with STEMI when managed with either primary or delayed PCI.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Prasugrel interact? Information: •Drug A: Abciximab •Drug B: Prasugrel •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Prasugrel. •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. •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 in combination with acetylsalicylic acid (ASA) to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI). May be used in patients with unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) who are to be managed with PCI. Prasugrel is not recommended in patients 75 years of age or greater, those that weigh<60kg, and patients with a history of stroke or transient ischemic attack due to increased risk of fatal and intracranial 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): Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 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): Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel. •Absorption (Drug A): No absorption available •Absorption (Drug B): 79% or greater of the dose is absorbed after oral administration. Absorption and metabolism occur rapidly and peak plasma concentrations (C max ) are reached approximately 30 minutes following oral administration. Administration with a high fat, high calorie meal did not affect the AUC of the active metabolite in healthy individuals, but the C max was decreased by ~49% and the T max was increased to 0.5 to 1.5 hours. Prasugrel may be administered with or without food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 44-68L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 98% of the active metabolite was bound to human serum albumin in a 4% buffered solution. The major inactive metabolites are also highly 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): Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to thiolactone by human carboxylesterase (hCE) 2. This intermediate is further metabolized to its active metabolite, R-138727, in a single step by cytochrome P450 enzymes in the liver (primarily CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19). The active metabolite is further metabolized by S-methylation or cysteine conjugation to two inactive metabolites. Unlike clopidogrel, transformation of prasugrel to its active metabolite does not appear to be affected by cytochrome P450 polymorphisms. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 68% of the orally administered dose is excreted in urine and 27% in the feces, as inactive metabolites. The active metabolite is not expected to be removed by dialysis. •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 active metabolite has an elimination half-life of about 7.4 hours (range 2-15 hours). •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance = 112 - 166 L/hr •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 (rat) 1,000 - 2,000 mg/kg; LD50 (rabbit) > 1,000 mg/kg •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Effient, Efient •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Prasugrel is a P2Y12 platelet inhibitor used to reduce risk of thrombotic cardiovascular events in unstable angina or non-ST-elevation myocardial infarction (NSTEMI), and in patients with STEMI when managed with either primary or delayed PCI. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Procaine interact?

•Drug A: Abciximab •Drug B: Procaine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Procaine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 as a local anesthetic primarily in oral 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): Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into 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): Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex. •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): Hydrolysis by plasma esterases to PABA •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): With normal kidney function, the drug is excreted rapidly by tubular 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): 7.7 minutes •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): Novocain •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Novocaine Procaina Procaine Procainum Vitamin H3 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Procaine is a local anesthetic used for anesthesia, peripheral nerve block, and spinal nerve block.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Procaine interact? Information: •Drug A: Abciximab •Drug B: Procaine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Procaine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 as a local anesthetic primarily in oral 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): Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into 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): Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex. •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): Hydrolysis by plasma esterases to PABA •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): With normal kidney function, the drug is excreted rapidly by tubular 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): 7.7 minutes •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): Novocain •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Novocaine Procaina Procaine Procainum Vitamin H3 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Procaine is a local anesthetic used for anesthesia, peripheral nerve block, and spinal nerve block. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Procarbazine interact?

•Drug A: Abciximab •Drug B: Procarbazine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Procarbazine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's 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): Procarbazine 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 inhibits their correct utilization by base pairing and causes a miscoding of DNA. Procarbazine is cell-phase specific for the S phase of cell division. •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 mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA. •Absorption (Drug A): No absorption available •Absorption (Drug B): Procarbazine is rapidly and completely 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): 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): Procarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO 2 and CH 4 and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic acid, which is excreted 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): 10 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =785 mg/kg (orally in rats) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Matulane •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Procarbazin Procarbazina Procarbazine Procarbazinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Procarbazine is an antineoplastic agent indicated for the treatment of stage III and stage IV Hodgkin's disease in combination with other chemotherapeutic agents.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Procarbazine interact? Information: •Drug A: Abciximab •Drug B: Procarbazine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Procarbazine is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's 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): Procarbazine 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 inhibits their correct utilization by base pairing and causes a miscoding of DNA. Procarbazine is cell-phase specific for the S phase of cell division. •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 mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA. •Absorption (Drug A): No absorption available •Absorption (Drug B): Procarbazine is rapidly and completely 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): 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): Procarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO 2 and CH 4 and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic acid, which is excreted 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): 10 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =785 mg/kg (orally in rats) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Matulane •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Procarbazin Procarbazina Procarbazine Procarbazinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Procarbazine is an antineoplastic agent indicated for the treatment of stage III and stage IV Hodgkin's disease in combination with other chemotherapeutic agents. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Progesterone interact?

•Drug A: Abciximab •Drug B: Progesterone •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Progesterone. •Extended Description: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. •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): Gelatinized capsules The gelatinized capsules are indicated for use in the prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea. Vaginal gel Progesterone gel (8%) is indicated as progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency. The lower concentration progesterone gel (4%) is used in the treatment of secondary amenorrhea, with the use of the 8% concentration if there is no therapeutic response to the 4% gel. Vaginal insert This form is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women. Injection (intramuscular) This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. Tablets, contraceptive The tablet form of progesterone in contraceptive formulations is indicated for the prevention of pregnancy. •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): Progesterone, depending on concentration and dosage form, and timing of exposure may have several pharmacodynamic effects. These actions, according, to various preparations, are listed below: General effects Progesterone is the main hormone of the corpus luteum and the placenta. It acts on the uterus by changing the proliferative phase to the secretory phase of the endometrium (inner mucous lining of the uterus). This hormone, stimulated by a hormone called luteinizing hormone (LH) is the main hormone during the secretory phase to prepare the corpus luteum and the endometrium for implantation of a fertilized ovum. As the luteal phase concludes, the progesterone hormone sends negative feedback to the anterior pituitary gland in the brain to decrease FSH (follicle stimulating hormone) and LH (luteinizing hormone) levels. This prevents ovulation and maturation of oocytes (immature egg cells). The endometrium then prepares for pregnancy by increasing its vascularity (blood vessels) and stimulating mucous secretion. This process occurs by progesterone stimulating the endometrium to decrease endometrial proliferation, leading to a decreased uterine lining thickness, developing more complex uterine glands, collecting energy in the form of glycogen, and providing more uterine blood vessel surface area suitable for supporting a growing embryo. As opposed to cervical mucous changes observed during the proliferative phase and ovulation, progesterone decreases and thickens the cervical mucus, rendering it less elastic. This change occurs because the fertilization time period has passed, and a specific consistency of mucous amenable to sperm entry is no longer required. Gelatinized capsules Progesterone capsules are an oral dosage form of micronized progesterone which, chemically identical to progesterone of ovarian origin. Progesterone capsules have all the properties of endogenous progesterone with induction of a secretory phase endometrium with gestagenic, antiestrogenic, slightly antiandrogenic and anti-aldosterone effects. Progesterone opposes the effects of estrogen on the uterus, and is beneficial in women with unopposed estrogen exposure, which carries an increased risk of malignancy. Vaginal gel and vaginal insert The gel preparation mimics the effects of naturally occurring progesterone. In the presence of adequate levels of estrogen, progesterone converts a proliferative endometrium into secretory endometrium. This means that the endometrium changes from a growing and thickening stage into a subsequent preparation stage for pregnancy, which involves further preparatory changes. Progesterone is necessary for the development of decidual tissue (specialized tissue amenable to supporting a possible pregnancy). Progesterone is required to increase endometrial receptivity for the implantation of a fertilized embryo. Once an embryo is implanted, progesterone helps to maintain the pregnancy. Injection (intramuscular) Intramuscularly injected progesterone increases serum progesterone and aids in the prevention of endometrial tissue overgrowth due to unopposed estrogen (which leads to abnormal uterine bleeding and sometimes uterine cancer),. In the absence or deficiency of progesterone, the endometrium continually proliferates, eventually outgrowing its limited blood supply, shedding incompletely, and leading to abnormal and/or profuse bleeding as well as malignancy. Tablets, contraceptive Progesterone-only contraceptive tablets prevent conception by suppressing ovulation in about half of users, causing a thickening of cervical mucus to inhibit sperm movement, lowering the midcycle LH and FSH hormone peaks, slowing the movement of the ovum through the fallopian tubes, and causing secretory changes in the endometrium as described above. •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): Progesterone binds and activates its nuclear receptor, PR, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy. Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy. Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately 0.5%. The typical failure rate, however, is estimated to be approximately 5%, due to late or missed pills. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral micronized capsules Following oral administration of progesterone in the micronized soft-gelatin capsule formulation, peak serum concentration was achieved in the first 3 hours. The absolute bioavailability of micronized progesterone is unknown at this time. In postmenopausal women, serum progesterone concentration increased in a dose-proportional and linear fashion after multiple doses of progesterone capsules, ranging from 100 mg/day to 300 mg/day. IM administration After intramuscular (IM) administration of 10 mg of progesterone in oil, the maximum plasma concentrations were achieved in about 8 hours post-injection and plasma concentrations stayed above baseline for approximately 24 hours post-injection. Injections of 10, 25, and 50 mg lead to geometric mean values for maximum plasma concentration (CMAX) of 7, 28, and 50 ng/mL, respectively. Progesterone administered by the intramuscular (IM) route avoids significant first-pass hepatic metabolism. As a result, endometrial tissue concentrations of progesterone achieved with IM administration are higher when compared with oral administration. Despite this, the highest concentrations of progesterone in endometrial tissue are reached with vaginal administration. Note on oral contraceptive tablet absorption Serum progestin levels peak about 2 hours after oral administration of progesterone-only contraceptive tablets, followed by rapid distribution and elimination. By 24 hours after drug administration, serum levels remain near the baseline, making efficacy dependent upon strict adherence to the dosing schedule. Large variations in serum progesterone levels occur among individuals. Progestin-only administration leads to lower steady-state serum progestin levels and a shorter elimination half-life than concurrent administration with estrogens. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): When administered vaginally, progesterone is well absorbed by uterine endometrial tissue, and a small percentage is distributed into the systemic circulation. The amount of progesterone in the systemic circulation appears to be of minimal importance, especially when implantation, pregnancy, and live birth outcomes appear similar for intramuscular and vaginal administration of progesterone. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 96%-99% bound to serum proteins, primarily to serum albumin (50%-54%) and transcortin (43%-48%). •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): Progesterone is mainly metabolized by the liver. After oral administration, the major plasma metabolites found are 20 a hydroxy-Δ4 a-prenolone and 5 a-dihydroprogesterone. Some progesterone metabolites are found excreted in the bile and these metabolites may be deconjugated and subsequently metabolized in the gut by reduction, dehydroxylation, and epimerization. The major plasma and urinary metabolites are comparable to those found during the physiological progesterone secretion of the corpus luteum. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Progesterone metabolites are excreted mainly by the kidneys. Urinary elimination is observed for 95% of patients in the form of glycuroconjugated metabolites, primarily 3 a, 5 ß–pregnanediol ( pregnandiol ). The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the urine and bile. Progesterone metabolites, excreted in the bile, may undergo enterohepatic recycling or may be found excreted in the 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): Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes (progesterone gel). Progesterone, administered orally, has a short serum half-life (approximately 5 minutes). It is rapidly metabolized to 17-hydroxyprogesterone during its first pass through the liver. •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance 1367 ± 348 (50mg of progesterone administered by vaginal insert once daily). 106 ± 15 L/h (50mg/mL IM injection once daily). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Intraperitoneal LD50 (rat): 327 mg/kg. Use in pregnancy Only forms of progesterone that are indicated on product labeling for pregnancy should be used. Some forms of progesterone should not be used in pregnancy,. Refer to individual product monographs for information regarding use in pregnancy. Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. Studies of infant growth and development that have been conducted have not demonstrated significant adverse effects, however, these studies are few in number. It is therefore advisable to rule out suspected pregnancy before starting any hormonal contraceptive. Effects on fertility Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until cessation. The progesterone contraceptive should not be used during pregnancy. Carcinogenicity Progesterone has been shown to induce or promote the formation of ovarian, uterine, mammary, and genital tract tumors in animals. The clinical relevance of these findings is unknown. Certain epidemiological studies of patients using oral contraceptives have reported an increased relative risk of developing breast cancer, especially at a younger age and associated with a longer duration of use. These studies have mainly involved combined oral contraceptives, and therefore, it is unknown whether this risk is attributable to progestins, estrogens, or a combination of both. At this time, there is insufficient data to determine whether the use of progestin-only contraceptives increases the risk in a similar way to combined contraceptives. A meta-analysis of 54 studies showed a small increase in the frequency of breast cancer diagnosis for women who were currently using combined oral contraceptives, or had used them within the past 10 years. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of hormone use. Women with breast cancer should not use oral contraceptives, as there is no sufficient data to fully establish or negate the risk of cancer with hormonal contraceptive use. Use in breastfeeding Progesterone has been detected in the milk of nursing mothers,. No adverse effects, in general, have been found on breastfeeding ability or on the health, growth, or development of the growing infant. Despite this, isolated post-marketing cases of decreased milk production have been reported. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bijuva, Crinone, Endometrin, Prochieve, Prometrium •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-Progesterone 17alpha-Progesterone Agolutin Akrolutin Corpus Luteum Hormone Gelbkörperhormon Luteohormone Lutogynon Progesteron Progesterona Progestérone Progesterone Progesteronum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Progesterone is a hormone used for a variety of functions, including contraception, control of abnormal uterine bleeding, maintenance of pregnancy, and prevention of endometrial hyperplasia.

Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. The severity of the interaction is moderate.

Question: Does Abciximab and Progesterone interact? Information: •Drug A: Abciximab •Drug B: Progesterone •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Progesterone. •Extended Description: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. •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): Gelatinized capsules The gelatinized capsules are indicated for use in the prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea. Vaginal gel Progesterone gel (8%) is indicated as progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency. The lower concentration progesterone gel (4%) is used in the treatment of secondary amenorrhea, with the use of the 8% concentration if there is no therapeutic response to the 4% gel. Vaginal insert This form is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women. Injection (intramuscular) This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. Tablets, contraceptive The tablet form of progesterone in contraceptive formulations is indicated for the prevention of pregnancy. •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): Progesterone, depending on concentration and dosage form, and timing of exposure may have several pharmacodynamic effects. These actions, according, to various preparations, are listed below: General effects Progesterone is the main hormone of the corpus luteum and the placenta. It acts on the uterus by changing the proliferative phase to the secretory phase of the endometrium (inner mucous lining of the uterus). This hormone, stimulated by a hormone called luteinizing hormone (LH) is the main hormone during the secretory phase to prepare the corpus luteum and the endometrium for implantation of a fertilized ovum. As the luteal phase concludes, the progesterone hormone sends negative feedback to the anterior pituitary gland in the brain to decrease FSH (follicle stimulating hormone) and LH (luteinizing hormone) levels. This prevents ovulation and maturation of oocytes (immature egg cells). The endometrium then prepares for pregnancy by increasing its vascularity (blood vessels) and stimulating mucous secretion. This process occurs by progesterone stimulating the endometrium to decrease endometrial proliferation, leading to a decreased uterine lining thickness, developing more complex uterine glands, collecting energy in the form of glycogen, and providing more uterine blood vessel surface area suitable for supporting a growing embryo. As opposed to cervical mucous changes observed during the proliferative phase and ovulation, progesterone decreases and thickens the cervical mucus, rendering it less elastic. This change occurs because the fertilization time period has passed, and a specific consistency of mucous amenable to sperm entry is no longer required. Gelatinized capsules Progesterone capsules are an oral dosage form of micronized progesterone which, chemically identical to progesterone of ovarian origin. Progesterone capsules have all the properties of endogenous progesterone with induction of a secretory phase endometrium with gestagenic, antiestrogenic, slightly antiandrogenic and anti-aldosterone effects. Progesterone opposes the effects of estrogen on the uterus, and is beneficial in women with unopposed estrogen exposure, which carries an increased risk of malignancy. Vaginal gel and vaginal insert The gel preparation mimics the effects of naturally occurring progesterone. In the presence of adequate levels of estrogen, progesterone converts a proliferative endometrium into secretory endometrium. This means that the endometrium changes from a growing and thickening stage into a subsequent preparation stage for pregnancy, which involves further preparatory changes. Progesterone is necessary for the development of decidual tissue (specialized tissue amenable to supporting a possible pregnancy). Progesterone is required to increase endometrial receptivity for the implantation of a fertilized embryo. Once an embryo is implanted, progesterone helps to maintain the pregnancy. Injection (intramuscular) Intramuscularly injected progesterone increases serum progesterone and aids in the prevention of endometrial tissue overgrowth due to unopposed estrogen (which leads to abnormal uterine bleeding and sometimes uterine cancer),. In the absence or deficiency of progesterone, the endometrium continually proliferates, eventually outgrowing its limited blood supply, shedding incompletely, and leading to abnormal and/or profuse bleeding as well as malignancy. Tablets, contraceptive Progesterone-only contraceptive tablets prevent conception by suppressing ovulation in about half of users, causing a thickening of cervical mucus to inhibit sperm movement, lowering the midcycle LH and FSH hormone peaks, slowing the movement of the ovum through the fallopian tubes, and causing secretory changes in the endometrium as described above. •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): Progesterone binds and activates its nuclear receptor, PR, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy. Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy. Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately 0.5%. The typical failure rate, however, is estimated to be approximately 5%, due to late or missed pills. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral micronized capsules Following oral administration of progesterone in the micronized soft-gelatin capsule formulation, peak serum concentration was achieved in the first 3 hours. The absolute bioavailability of micronized progesterone is unknown at this time. In postmenopausal women, serum progesterone concentration increased in a dose-proportional and linear fashion after multiple doses of progesterone capsules, ranging from 100 mg/day to 300 mg/day. IM administration After intramuscular (IM) administration of 10 mg of progesterone in oil, the maximum plasma concentrations were achieved in about 8 hours post-injection and plasma concentrations stayed above baseline for approximately 24 hours post-injection. Injections of 10, 25, and 50 mg lead to geometric mean values for maximum plasma concentration (CMAX) of 7, 28, and 50 ng/mL, respectively. Progesterone administered by the intramuscular (IM) route avoids significant first-pass hepatic metabolism. As a result, endometrial tissue concentrations of progesterone achieved with IM administration are higher when compared with oral administration. Despite this, the highest concentrations of progesterone in endometrial tissue are reached with vaginal administration. Note on oral contraceptive tablet absorption Serum progestin levels peak about 2 hours after oral administration of progesterone-only contraceptive tablets, followed by rapid distribution and elimination. By 24 hours after drug administration, serum levels remain near the baseline, making efficacy dependent upon strict adherence to the dosing schedule. Large variations in serum progesterone levels occur among individuals. Progestin-only administration leads to lower steady-state serum progestin levels and a shorter elimination half-life than concurrent administration with estrogens. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): When administered vaginally, progesterone is well absorbed by uterine endometrial tissue, and a small percentage is distributed into the systemic circulation. The amount of progesterone in the systemic circulation appears to be of minimal importance, especially when implantation, pregnancy, and live birth outcomes appear similar for intramuscular and vaginal administration of progesterone. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 96%-99% bound to serum proteins, primarily to serum albumin (50%-54%) and transcortin (43%-48%). •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): Progesterone is mainly metabolized by the liver. After oral administration, the major plasma metabolites found are 20 a hydroxy-Δ4 a-prenolone and 5 a-dihydroprogesterone. Some progesterone metabolites are found excreted in the bile and these metabolites may be deconjugated and subsequently metabolized in the gut by reduction, dehydroxylation, and epimerization. The major plasma and urinary metabolites are comparable to those found during the physiological progesterone secretion of the corpus luteum. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Progesterone metabolites are excreted mainly by the kidneys. Urinary elimination is observed for 95% of patients in the form of glycuroconjugated metabolites, primarily 3 a, 5 ß–pregnanediol ( pregnandiol ). The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the urine and bile. Progesterone metabolites, excreted in the bile, may undergo enterohepatic recycling or may be found excreted in the 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): Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes (progesterone gel). Progesterone, administered orally, has a short serum half-life (approximately 5 minutes). It is rapidly metabolized to 17-hydroxyprogesterone during its first pass through the liver. •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance 1367 ± 348 (50mg of progesterone administered by vaginal insert once daily). 106 ± 15 L/h (50mg/mL IM injection once daily). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Intraperitoneal LD50 (rat): 327 mg/kg. Use in pregnancy Only forms of progesterone that are indicated on product labeling for pregnancy should be used. Some forms of progesterone should not be used in pregnancy,. Refer to individual product monographs for information regarding use in pregnancy. Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. Studies of infant growth and development that have been conducted have not demonstrated significant adverse effects, however, these studies are few in number. It is therefore advisable to rule out suspected pregnancy before starting any hormonal contraceptive. Effects on fertility Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until cessation. The progesterone contraceptive should not be used during pregnancy. Carcinogenicity Progesterone has been shown to induce or promote the formation of ovarian, uterine, mammary, and genital tract tumors in animals. The clinical relevance of these findings is unknown. Certain epidemiological studies of patients using oral contraceptives have reported an increased relative risk of developing breast cancer, especially at a younger age and associated with a longer duration of use. These studies have mainly involved combined oral contraceptives, and therefore, it is unknown whether this risk is attributable to progestins, estrogens, or a combination of both. At this time, there is insufficient data to determine whether the use of progestin-only contraceptives increases the risk in a similar way to combined contraceptives. A meta-analysis of 54 studies showed a small increase in the frequency of breast cancer diagnosis for women who were currently using combined oral contraceptives, or had used them within the past 10 years. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of hormone use. Women with breast cancer should not use oral contraceptives, as there is no sufficient data to fully establish or negate the risk of cancer with hormonal contraceptive use. Use in breastfeeding Progesterone has been detected in the milk of nursing mothers,. No adverse effects, in general, have been found on breastfeeding ability or on the health, growth, or development of the growing infant. Despite this, isolated post-marketing cases of decreased milk production have been reported. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bijuva, Crinone, Endometrin, Prochieve, Prometrium •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-Progesterone 17alpha-Progesterone Agolutin Akrolutin Corpus Luteum Hormone Gelbkörperhormon Luteohormone Lutogynon Progesteron Progesterona Progestérone Progesterone Progesteronum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Progesterone is a hormone used for a variety of functions, including contraception, control of abnormal uterine bleeding, maintenance of pregnancy, and prevention of endometrial hyperplasia. Output: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. The severity of the interaction is moderate.

Does Abciximab and Propylthiouracil interact?

•Drug A: Abciximab •Drug B: Propylthiouracil •Severity: MODERATE •Description: Propylthiouracil 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): Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's 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): Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole. •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): Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed following oral administration. •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): 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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, 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): 2 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat: LD 50 = 1250 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): 6-Propylthiouracil Propiltiouracilo Propylthiouracil Propylthiouracile Propylthiouracilum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Propylthiouracil is a thiourea antithyroid agent used to treat hyperthyroidism.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Propylthiouracil interact? Information: •Drug A: Abciximab •Drug B: Propylthiouracil •Severity: MODERATE •Description: Propylthiouracil 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): Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's 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): Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole. •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): Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed following oral administration. •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): 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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, 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): 2 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat: LD 50 = 1250 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): 6-Propylthiouracil Propiltiouracilo Propylthiouracil Propylthiouracile Propylthiouracilum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Propylthiouracil is a thiourea antithyroid agent used to treat hyperthyroidism. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Protein C interact?

•Drug A: Abciximab •Drug B: Protein C •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Protein C. •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. •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): Protein C concentrate is indicated for pediatric and adult patients with severe congenital protein C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. It is also found as a component of some prothrombin complex concentrate (i.e. Factor IX Complex (Human) ) formulations, such as Kcentra. •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 clinical studies, the intravenous administration of Protein C Concentrate demonstrated a temporary increase, within approximately half an hour of administration, in plasma levels of APC. Replacement of protein C in protein C-deficient patients is expected to control or, if given prophylactically, to prevent thrombotic complications. •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): Protein C is an endogenously occurring plasma protein that plays a key role within the coagulation cascade. Also known as blood coagulation factor XIV, Protein C is a zymogen, or enzyme precursor, of a vitamin K-dependent anticoagulant glycoprotein (serine protease) that is synthesized in the liver. It is converted by the thrombin/thrombomodulin-complex on the endothelial cell surface to Activated Protein C (APC). Once in its activated form, APC functions as a serine protease with potent anticoagulant effects, especially in the presence of its cofactor protein S. APC exerts its effect by inactivating essential components of the coagulation cascade (specifically factors V and VIII), which leads to a decrease in thrombin formation, and therefore a reduction in clot formation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax = 110 IU/dL Tmax = 0.50 hr •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Volume of distribution at steady state = 0.74 dL/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): 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): Initial half life = 7.8 hr Terminal half life = 9.9 hr •Clearance (Drug A): No clearance available •Clearance (Drug B): CL = 0.0533 dL/kg/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): Balfaxar, Beriplex, Ceprotin, Kcentra, Octaplex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Protein C is a medication used to treat protein C deficiency leading to purpura fulminans or coumarin-induced skin necrosis.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Protein C interact? Information: •Drug A: Abciximab •Drug B: Protein C •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Protein C. •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. •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): Protein C concentrate is indicated for pediatric and adult patients with severe congenital protein C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. It is also found as a component of some prothrombin complex concentrate (i.e. Factor IX Complex (Human) ) formulations, such as Kcentra. •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 clinical studies, the intravenous administration of Protein C Concentrate demonstrated a temporary increase, within approximately half an hour of administration, in plasma levels of APC. Replacement of protein C in protein C-deficient patients is expected to control or, if given prophylactically, to prevent thrombotic complications. •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): Protein C is an endogenously occurring plasma protein that plays a key role within the coagulation cascade. Also known as blood coagulation factor XIV, Protein C is a zymogen, or enzyme precursor, of a vitamin K-dependent anticoagulant glycoprotein (serine protease) that is synthesized in the liver. It is converted by the thrombin/thrombomodulin-complex on the endothelial cell surface to Activated Protein C (APC). Once in its activated form, APC functions as a serine protease with potent anticoagulant effects, especially in the presence of its cofactor protein S. APC exerts its effect by inactivating essential components of the coagulation cascade (specifically factors V and VIII), which leads to a decrease in thrombin formation, and therefore a reduction in clot formation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax = 110 IU/dL Tmax = 0.50 hr •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Volume of distribution at steady state = 0.74 dL/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): 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): Initial half life = 7.8 hr Terminal half life = 9.9 hr •Clearance (Drug A): No clearance available •Clearance (Drug B): CL = 0.0533 dL/kg/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): Balfaxar, Beriplex, Ceprotin, Kcentra, Octaplex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Protein C is a medication used to treat protein C deficiency leading to purpura fulminans or coumarin-induced skin necrosis. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Quinidine interact?

•Drug A: Abciximab •Drug B: Quinidine •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Quinidine. •Extended Description: Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. •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): Quinidine is indicated for the management and prophylactic therapy of atrial fibrillation/flutter, as well as the suppression of recurrent documented ventricular arrhythmias. It is also used in the treatment of Brugada syndrome, short QT syndrome and idiopathic ventricular fibrillation.. •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): Quinidine is an antimalarial schizonticide, and a class Ia antiarrhythmic agent used to interrupt or prevent reentrant arrhythmias and arrhythmias due to increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia. In most patients, quinidine can lead to an increase in the sinus rate. Quinidine also causes a marked prolongation of the QT interval in a dose-related manner, acts peripherally as an α-adrenergic antagonist, and has anticholinergic and negative inotropic activity. The QT interval prolongation caused by quinidine can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such as torsades de pointes. The risk of torsades is increased by bradycardia, hypokalemia, hypomagnesemia or high serum levels of quinidine. However, this type of rhythm disturbance may appear in the absence of any of them. Patients treated with quinidine may also be at risk of a paradoxical increase in ventricular rate in atrial flutter/fibrillation, and patients with sick sinus syndrome treated with quinidine may develop marked sinus node depression and bradycardia. •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): Quinidine has a complex electrophysiological profile that has not been fully elucidated. The antiarrhythmic actions of this drug are mediated through effects on sodium channels in Purkinje fibers. Quinidine blocks the rapid sodium channel (I Na ), decreasing the phase zero of rapid depolarization of the action potential. Quinidine also reduces repolarizing K currents (I Kr, I Ks ), the inward rectifier potassium current (I K1 ), and the transient outward potassium current I to, as well as the L-type calcium current I Ca and the late I Na inward current. The reduction of these currents leads to the prolongation of the action potential duration. By shortening the plateau but prolonging late depolarization, quinidine facilitates the formation of early afterdepolarisation (EAD). Additionally, in patients with malaria, quinidine acts primarily as an intra-erythrocytic schizonticide, and is gametocidal to Plasmodium vivax and P. malariae, but not to P. falciparum. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of quinidine sulfate is approximately 70%, but it ranges from 45% to 100%. The less-than-complete quinidine sulfate bioavailability is a result of first-pass metabolism in the liver. In contrast, the absolute bioavailability of quinidine gluconate ranges from 70% to 80%, and relative to quinidine sulfate, quinidine from quinidine gluconate has a bioavailability of 1.03. The t max of quinidine sulfate extended-release tablets is approximately 6 h, while the t max of quinidine gluconate goes from 3 to 5 h. The peak serum concentration reached with immediate-release quinidine sulfate is delayed for about an hour when taken with food. Furthermore, the ingestion of grapefruit juice may decrease the rate of absorption of quinidine. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Quinidine has a volume of distribution of 2-3 L/kg in healthy young adults, 0.5 L/kg in patients with congestive heart failure, and 3-5 L/kg in patients with liver cirrhosis. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): From 6.5 to 16.2 µmol/L, 80 to 88% of quinidine is bound to plasma proteins, mainly α1-acid glycoprotein and albumin. This fraction is lower in pregnant women, and it may be as low as 50 to 70% in infants and neonates. •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): Quinidine is mainly metabolized in the liver by cytochrome P450 enzymes, specifically CYP3A4. The major metabolite of quinidine is 3-hydroxy-quinidine, which has a volume of distribution larger than quinidine and an elimination half-life of about 12 hours. Non-clinical and clinical studies suggest that 3-hydroxy-quinidine has approximately half the antiarrhythmic activity of quinidine; therefore, this metabolite is partly responsible for the effects detected with the chronic use of quinidine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of quinidine is achieved by the renal excretion of the unchanged drug (15 to 40% of total clearance) and its hepatic biotransformation to a variety of metabolites (60 to 85% of total clearance). When urine has a pH lower than 7, 20% of administered quinidine appears in urine unchanged. However, this proportion decreases to as little as 5% as it becomes more alkaline. The renal clearance of quinidine involves both glomerular filtration and active tubular secretion, moderated by pH-dependent tubular reabsorption. •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 quinidine is 6-8 hours in adults and 3-4 hours in pediatric patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of quinidine ranges from 3 to 5 mL/min/kg in adults. In pediatric patients, quinidine clearance may be two or three times as rapid. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Quinidine overdoses have been well described. The ingestion of 5 g of quinidine resulted in the death of a toddler, while an adolescent was reported to survive after ingesting 8 g of quinidine. A 16-month that ingested quinidine tablets developed a concretion of bezoar in the stomach, which led to non-declining toxic levels of quinidine. A gastric aspirate revealed that quinidine levels were 50 times higher than the ones detected in plasma. In cases of massive overdose, it may be appropriate to perform an endoscopy. Acute quinidine overdoses are characterized by ventricular arrhythmias and hypotension. Other signs and symptoms of quinidine overdose may include vomiting, diarrhea, tinnitus, high-frequency hearing loss, vertigo, blurred vision, diplopia, photophobia, headache, confusion and delirium. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nuedexta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (8R,9S)-Quinidine beta-Quinine Chinidin Chinidinum CIN-QUIN Conchinin Conquinine Pitayine Quinidina •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Quinidine is a medication used to restore normal sinus rhythm, treat atrial fibrillation and flutter, and treat ventricular arrhythmias.

Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. The severity of the interaction is moderate.

Question: Does Abciximab and Quinidine interact? Information: •Drug A: Abciximab •Drug B: Quinidine •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Quinidine. •Extended Description: Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. •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): Quinidine is indicated for the management and prophylactic therapy of atrial fibrillation/flutter, as well as the suppression of recurrent documented ventricular arrhythmias. It is also used in the treatment of Brugada syndrome, short QT syndrome and idiopathic ventricular fibrillation.. •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): Quinidine is an antimalarial schizonticide, and a class Ia antiarrhythmic agent used to interrupt or prevent reentrant arrhythmias and arrhythmias due to increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia. In most patients, quinidine can lead to an increase in the sinus rate. Quinidine also causes a marked prolongation of the QT interval in a dose-related manner, acts peripherally as an α-adrenergic antagonist, and has anticholinergic and negative inotropic activity. The QT interval prolongation caused by quinidine can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such as torsades de pointes. The risk of torsades is increased by bradycardia, hypokalemia, hypomagnesemia or high serum levels of quinidine. However, this type of rhythm disturbance may appear in the absence of any of them. Patients treated with quinidine may also be at risk of a paradoxical increase in ventricular rate in atrial flutter/fibrillation, and patients with sick sinus syndrome treated with quinidine may develop marked sinus node depression and bradycardia. •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): Quinidine has a complex electrophysiological profile that has not been fully elucidated. The antiarrhythmic actions of this drug are mediated through effects on sodium channels in Purkinje fibers. Quinidine blocks the rapid sodium channel (I Na ), decreasing the phase zero of rapid depolarization of the action potential. Quinidine also reduces repolarizing K currents (I Kr, I Ks ), the inward rectifier potassium current (I K1 ), and the transient outward potassium current I to, as well as the L-type calcium current I Ca and the late I Na inward current. The reduction of these currents leads to the prolongation of the action potential duration. By shortening the plateau but prolonging late depolarization, quinidine facilitates the formation of early afterdepolarisation (EAD). Additionally, in patients with malaria, quinidine acts primarily as an intra-erythrocytic schizonticide, and is gametocidal to Plasmodium vivax and P. malariae, but not to P. falciparum. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of quinidine sulfate is approximately 70%, but it ranges from 45% to 100%. The less-than-complete quinidine sulfate bioavailability is a result of first-pass metabolism in the liver. In contrast, the absolute bioavailability of quinidine gluconate ranges from 70% to 80%, and relative to quinidine sulfate, quinidine from quinidine gluconate has a bioavailability of 1.03. The t max of quinidine sulfate extended-release tablets is approximately 6 h, while the t max of quinidine gluconate goes from 3 to 5 h. The peak serum concentration reached with immediate-release quinidine sulfate is delayed for about an hour when taken with food. Furthermore, the ingestion of grapefruit juice may decrease the rate of absorption of quinidine. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Quinidine has a volume of distribution of 2-3 L/kg in healthy young adults, 0.5 L/kg in patients with congestive heart failure, and 3-5 L/kg in patients with liver cirrhosis. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): From 6.5 to 16.2 µmol/L, 80 to 88% of quinidine is bound to plasma proteins, mainly α1-acid glycoprotein and albumin. This fraction is lower in pregnant women, and it may be as low as 50 to 70% in infants and neonates. •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): Quinidine is mainly metabolized in the liver by cytochrome P450 enzymes, specifically CYP3A4. The major metabolite of quinidine is 3-hydroxy-quinidine, which has a volume of distribution larger than quinidine and an elimination half-life of about 12 hours. Non-clinical and clinical studies suggest that 3-hydroxy-quinidine has approximately half the antiarrhythmic activity of quinidine; therefore, this metabolite is partly responsible for the effects detected with the chronic use of quinidine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of quinidine is achieved by the renal excretion of the unchanged drug (15 to 40% of total clearance) and its hepatic biotransformation to a variety of metabolites (60 to 85% of total clearance). When urine has a pH lower than 7, 20% of administered quinidine appears in urine unchanged. However, this proportion decreases to as little as 5% as it becomes more alkaline. The renal clearance of quinidine involves both glomerular filtration and active tubular secretion, moderated by pH-dependent tubular reabsorption. •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 quinidine is 6-8 hours in adults and 3-4 hours in pediatric patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of quinidine ranges from 3 to 5 mL/min/kg in adults. In pediatric patients, quinidine clearance may be two or three times as rapid. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Quinidine overdoses have been well described. The ingestion of 5 g of quinidine resulted in the death of a toddler, while an adolescent was reported to survive after ingesting 8 g of quinidine. A 16-month that ingested quinidine tablets developed a concretion of bezoar in the stomach, which led to non-declining toxic levels of quinidine. A gastric aspirate revealed that quinidine levels were 50 times higher than the ones detected in plasma. In cases of massive overdose, it may be appropriate to perform an endoscopy. Acute quinidine overdoses are characterized by ventricular arrhythmias and hypotension. Other signs and symptoms of quinidine overdose may include vomiting, diarrhea, tinnitus, high-frequency hearing loss, vertigo, blurred vision, diplopia, photophobia, headache, confusion and delirium. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nuedexta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (8R,9S)-Quinidine beta-Quinine Chinidin Chinidinum CIN-QUIN Conchinin Conquinine Pitayine Quinidina •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Quinidine is a medication used to restore normal sinus rhythm, treat atrial fibrillation and flutter, and treat ventricular arrhythmias. Output: Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. The severity of the interaction is moderate.

Does Abciximab and Quinine interact?

•Drug A: Abciximab •Drug B: Quinine •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Quinine. •Extended Description: Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. •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 malaria and leg cramps •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): Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine. •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 theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself. •Absorption (Drug A): No absorption available •Absorption (Drug B): 76 - 88% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1.43 ± 0.18 L/kg [Healthy Pediatric Controls] 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients] 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 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): Hepatic, over 80% metabolized by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged 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): Approximately 18 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.17 L/h/kg [healthy] 0.09 L/h/kg [patients with uncomplicated malaria] 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal] 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal] Oral cl=0.06 L/h/kg [elderly subjects] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Quinine induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Qualaquin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (8S,9R)-quinine 6'-Methoxycinchonidine Chinin Chinine Chininum Quinina Quinine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Quinine is an alkaloid used to treat uncomplicated Plasmodium falciparum malaria.

Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. The severity of the interaction is moderate.

Question: Does Abciximab and Quinine interact? Information: •Drug A: Abciximab •Drug B: Quinine •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Quinine. •Extended Description: Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. •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 malaria and leg cramps •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): Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine. •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 theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself. •Absorption (Drug A): No absorption available •Absorption (Drug B): 76 - 88% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1.43 ± 0.18 L/kg [Healthy Pediatric Controls] 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients] 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 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): Hepatic, over 80% metabolized by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged 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): Approximately 18 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.17 L/h/kg [healthy] 0.09 L/h/kg [patients with uncomplicated malaria] 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal] 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal] Oral cl=0.06 L/h/kg [elderly subjects] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Quinine induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Qualaquin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (8S,9R)-quinine 6'-Methoxycinchonidine Chinin Chinine Chininum Quinina Quinine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Quinine is an alkaloid used to treat uncomplicated Plasmodium falciparum malaria. Output: Quinine has the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and thus, it can enhance the action of other anticoagulants. The severity of the interaction is moderate.

Does Abciximab and Raltitrexed interact?

•Drug A: Abciximab •Drug B: Raltitrexed •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Raltitrexed. •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. •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 malignant neoplasm of colon and rectum •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): Raltitrexed belongs to a group of medicines known as antimetabolites. It is used to treat cancer of the colon and rectum. It may also be used to treat other kinds of cancer, as determined by your doctor. Raltitrexed blocks an enzyme needed by the cell to live. This interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by raltitrexed, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. •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): Raltitrexed is an antineoplastic Agents and folic acid antagonists. Raltitrexed inhibits thymidylate synthase (TS) leading to DNA fragmentation and cell death. It is transported into cells via a reduced folate carrier. Inside the cell Raltitrexed is extensively polyglutamated, which enhances thymidylate synthase inhibitory power and duration. Inhibition of this enzyme results in decreased synthesis of thymidine triphosphate which is required for DNA 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): >93% •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): Raltitrexed is transported into cells via a reduced folate carrier. Inside the cell it is extensively polyglutamated by the enzyme folyl polyglutamate synthetase to polyglutamate forms. •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): 198 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Side effects include pale skin, troubled breathing, unusual bleeding or bruising, unusual tiredness or weakness, black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, shortness of breath, sore throat, sores, ulcers, or white spots on lips or in mouth, swollen glands, increase in bowel movements, loose stools, soft stools. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tomudex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Raltitrexed is a folate analog thymidylate synthase inhibitor used in the treatment of advanced colorectal cancer.

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. The severity of the interaction is minor.

Question: Does Abciximab and Raltitrexed interact? Information: •Drug A: Abciximab •Drug B: Raltitrexed •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Raltitrexed. •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. •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 malignant neoplasm of colon and rectum •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): Raltitrexed belongs to a group of medicines known as antimetabolites. It is used to treat cancer of the colon and rectum. It may also be used to treat other kinds of cancer, as determined by your doctor. Raltitrexed blocks an enzyme needed by the cell to live. This interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by raltitrexed, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. •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): Raltitrexed is an antineoplastic Agents and folic acid antagonists. Raltitrexed inhibits thymidylate synthase (TS) leading to DNA fragmentation and cell death. It is transported into cells via a reduced folate carrier. Inside the cell Raltitrexed is extensively polyglutamated, which enhances thymidylate synthase inhibitory power and duration. Inhibition of this enzyme results in decreased synthesis of thymidine triphosphate which is required for DNA 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): >93% •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): Raltitrexed is transported into cells via a reduced folate carrier. Inside the cell it is extensively polyglutamated by the enzyme folyl polyglutamate synthetase to polyglutamate forms. •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): 198 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Side effects include pale skin, troubled breathing, unusual bleeding or bruising, unusual tiredness or weakness, black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, shortness of breath, sore throat, sores, ulcers, or white spots on lips or in mouth, swollen glands, increase in bowel movements, loose stools, soft stools. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tomudex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Raltitrexed is a folate analog thymidylate synthase inhibitor used in the treatment of advanced colorectal cancer. Output: 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. The severity of the interaction is minor.

Does Abciximab and Ramucirumab interact?

•Drug A: Abciximab •Drug B: Ramucirumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ramucirumab. •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 . •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): Ramucirumab is indicated for the treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel for patients who progress after prior fluoropyrimidine- or platinum-containing chemotherapy. It is indicated, in combination with erlotinib, for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor exon 19 deletions or exon 21 (L858R) point mutations. It is also indicated in combination with docetaxel for the treatment of metastatic non-small cell lung cancer in patients who have progressed following prior platinum-based chemotherapy. Patients who have EGFR or ALK genomic aberrations should also have disease progression following FDA-approved therapy for these aberrations. Ramucirumab, in combination with FOLFIRI ( folinic acid, fluorouracil, and irinotecan ), is indicated for the treatment of metastatic colorectal cancer in patients who have progressed following therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Lastly, ramucirumab is indicated for the treatment of hepatocellular carcinoma in patients with an alpha-fetoprotein level ≥400 ng/mL and have previously been treated with sorafenib. •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): Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial 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): 5.5 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): 15 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.014 L/hour •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ramucirumab packaging includes warnings for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforation, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy syndrome. The most common reactions observed in single-agent-treated patients at a rate of >10% and >2% higher than placebo were hypertension and diarrhea. The most common adverse reactions observed in patients treated with ramucirumab plus paclitaxel at a rate of of >30% and >2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cyramza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ramucirumab is an antineoplastic agent and direct VEGFR2 (vascular endothelial growth factor receptor 2) antagonist that blocks the binding of natural VEGF ligands, which are secreted by solid tumors to promote angiogenesis and enhance tumor blood supply.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Ramucirumab interact? Information: •Drug A: Abciximab •Drug B: Ramucirumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ramucirumab. •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 . •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): Ramucirumab is indicated for the treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel for patients who progress after prior fluoropyrimidine- or platinum-containing chemotherapy. It is indicated, in combination with erlotinib, for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor exon 19 deletions or exon 21 (L858R) point mutations. It is also indicated in combination with docetaxel for the treatment of metastatic non-small cell lung cancer in patients who have progressed following prior platinum-based chemotherapy. Patients who have EGFR or ALK genomic aberrations should also have disease progression following FDA-approved therapy for these aberrations. Ramucirumab, in combination with FOLFIRI ( folinic acid, fluorouracil, and irinotecan ), is indicated for the treatment of metastatic colorectal cancer in patients who have progressed following therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Lastly, ramucirumab is indicated for the treatment of hepatocellular carcinoma in patients with an alpha-fetoprotein level ≥400 ng/mL and have previously been treated with sorafenib. •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): Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial 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): 5.5 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): 15 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.014 L/hour •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ramucirumab packaging includes warnings for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforation, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy syndrome. The most common reactions observed in single-agent-treated patients at a rate of >10% and >2% higher than placebo were hypertension and diarrhea. The most common adverse reactions observed in patients treated with ramucirumab plus paclitaxel at a rate of of >30% and >2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cyramza •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ramucirumab is an antineoplastic agent and direct VEGFR2 (vascular endothelial growth factor receptor 2) antagonist that blocks the binding of natural VEGF ligands, which are secreted by solid tumors to promote angiogenesis and enhance tumor blood supply. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Ranibizumab interact?

•Drug A: Abciximab •Drug B: Ranibizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ranibizumab. •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 . •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): Ranibizumab injection for intravitreal use is indicated to treat Neovascular (wet) Age-related Macular Degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization by the FDA. Ranibizumab injection for intravitreal use via ocular implant is used to treat Neovascular (wet) Age-related Macular Degeneration (AMD) in patients who have responded to at least two intravitreal injections of a VEGF inhibitor. In Canada, ranibizumab is approved to treat adult patients with neovascular (wet) age-related macular degeneration (AMD) and visual impairment due to diabetic macular edema, macular edema secondary to retinal vein occlusion, choroidal neovascularisation (CNV) secondary to pathologic myopia (PM), and choroidal neovascularisation (CNV) secondary to ocular conditions other than AMD or PM, including but not limited to angioid streaks, postinflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy. In Europe, ranibizumab is also approved for the treatment of similar ophthalmological conditions, including neovascular (wet) age-related macular degeneration (AMD), visual impairment due to diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), and visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO) or choroidal neovascularisation (CNV) for adults and retinopathy of prematurity (ROP) with zone I (stage 1+, 2+, 3 or 3+), zone II (stage 3+) or AP-ROP (aggressive posterior ROP) disease for preterm infants. •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): Ranibizumab is a vascular endothelial growth factor (VEGF-A) inhibitor used to manage ocular diseases with abnormal angiogenesis. It inhibits the formation of new blood vessels or neovascularization. Ultimately, ranibizumab works to slow down the loss of vision and causes significant visual improvement in patients with ocular degenerative disorders, such as age-related macular degeneration. It can also reduce retinal thickness. As ranibizumab has one binding site for VEGF, two drug molecules bind to one VEGF dimer. Ranibizumab lacks the Fc region of an antibody, which may prevent the drug from causing intraocular inflammation following intravitreal injection. •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 pathogenesis of neovascular eye diseases is not fully understood; however, vascular endothelial growth factor-A (VEGF-A) has been implicated in the development of clinical manifestations, such as choroidal neovascularization. Neovascularization is characterized by aberrated proliferation of abnormal vessels in the choroid capillary matrix. As a member of the VEGF family, VEGF-A is a key regulator of vascular permeability and angiogenesis; thus, it has been studied as a therapeutic target for the treatment of a wide array of neovascular eye diseases, including neovascular (wet) age-related macular degeneration (AMD) and diabetic retinopathy. For example, increased VEGF-A levels in the vitreous were shown in patients with neovascular age-related macular degeneration. Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody directed against human VEGF-A. Ranibizumab binds to VEGF-A with high affinity as well as its biologically active forms, such as VEGF165, VEGF121, and VEGF110. Notably, VEGF165 is the most predominant isoform in the human eye that promotes ocular neovascularization. VEGF165 enhances vascular permeability, inhibits apoptosis, and causes endothelial-cell mobilization from the bone marrow and differentiation for angiogenesis. Ranibizumab binds to the receptor-binding site of VEGF-A, preventing it from binding to its receptors - VEGFR1 and VEGFR2 - that are expressed on the surface of endothelial cells. Ranibizumab thereby attenuates endothelial cell proliferation, vascular leakage, and new blood vessel formation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ranibizumab rapidly penetrates through the retina to reach the choroid after intravitreal injection. Following monthly intravitreal administration of 0.5 mg ranibizumab in patients with neovascular (wet) age-related macular degeneration, the mean C max (±SD) was 1.7 (± 1.1) ng/mL. Following an implant insertion, the mean (±SD) C max of ranibizumab was 0.48 (±0.17) ng/mL and median T max was 26 days, with a range of one to 89 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of the central compartment (Vd/F) is 2.77 L. Ranibizumab is not shown to accumulate in serum. Due to its small size from lacking the Fc region of an antibody, ranibizumab achieves enhanced diffusion into the retina and choroid. •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): The metabolism of ranibizumab has not been studied. Since it is a monoclonal antibody fragment, ranibizumab is expected to undergo catabolism. •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): The estimated average vitreous elimination half-life is approximately nine days following intravitreal injection. The half-life of ranibizumab implant is approximately 25 weeks. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with retinal vein occlusion or diabetic macular edema, the apparent clearance (CL/F) of ranibizumab was 24.8 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information available regarding the LD 50 values of ranibizumab. There is also limited clinical experience of ranibizumab overdose: concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients, with no additional unexpected adverse reactions that were observed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Byooviz, Cimerli, Lucentis, Susvimo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ranibizumab is a recombinant humanized monoclonal antibody and VEGF-A antagonist used for the management of macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Ranibizumab interact? Information: •Drug A: Abciximab •Drug B: Ranibizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ranibizumab. •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 . •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): Ranibizumab injection for intravitreal use is indicated to treat Neovascular (wet) Age-related Macular Degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization by the FDA. Ranibizumab injection for intravitreal use via ocular implant is used to treat Neovascular (wet) Age-related Macular Degeneration (AMD) in patients who have responded to at least two intravitreal injections of a VEGF inhibitor. In Canada, ranibizumab is approved to treat adult patients with neovascular (wet) age-related macular degeneration (AMD) and visual impairment due to diabetic macular edema, macular edema secondary to retinal vein occlusion, choroidal neovascularisation (CNV) secondary to pathologic myopia (PM), and choroidal neovascularisation (CNV) secondary to ocular conditions other than AMD or PM, including but not limited to angioid streaks, postinflammatory retinochoroidopathy, central serous chorioretinopathy or idiopathic chorioretinopathy. In Europe, ranibizumab is also approved for the treatment of similar ophthalmological conditions, including neovascular (wet) age-related macular degeneration (AMD), visual impairment due to diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), and visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO) or choroidal neovascularisation (CNV) for adults and retinopathy of prematurity (ROP) with zone I (stage 1+, 2+, 3 or 3+), zone II (stage 3+) or AP-ROP (aggressive posterior ROP) disease for preterm infants. •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): Ranibizumab is a vascular endothelial growth factor (VEGF-A) inhibitor used to manage ocular diseases with abnormal angiogenesis. It inhibits the formation of new blood vessels or neovascularization. Ultimately, ranibizumab works to slow down the loss of vision and causes significant visual improvement in patients with ocular degenerative disorders, such as age-related macular degeneration. It can also reduce retinal thickness. As ranibizumab has one binding site for VEGF, two drug molecules bind to one VEGF dimer. Ranibizumab lacks the Fc region of an antibody, which may prevent the drug from causing intraocular inflammation following intravitreal injection. •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 pathogenesis of neovascular eye diseases is not fully understood; however, vascular endothelial growth factor-A (VEGF-A) has been implicated in the development of clinical manifestations, such as choroidal neovascularization. Neovascularization is characterized by aberrated proliferation of abnormal vessels in the choroid capillary matrix. As a member of the VEGF family, VEGF-A is a key regulator of vascular permeability and angiogenesis; thus, it has been studied as a therapeutic target for the treatment of a wide array of neovascular eye diseases, including neovascular (wet) age-related macular degeneration (AMD) and diabetic retinopathy. For example, increased VEGF-A levels in the vitreous were shown in patients with neovascular age-related macular degeneration. Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody directed against human VEGF-A. Ranibizumab binds to VEGF-A with high affinity as well as its biologically active forms, such as VEGF165, VEGF121, and VEGF110. Notably, VEGF165 is the most predominant isoform in the human eye that promotes ocular neovascularization. VEGF165 enhances vascular permeability, inhibits apoptosis, and causes endothelial-cell mobilization from the bone marrow and differentiation for angiogenesis. Ranibizumab binds to the receptor-binding site of VEGF-A, preventing it from binding to its receptors - VEGFR1 and VEGFR2 - that are expressed on the surface of endothelial cells. Ranibizumab thereby attenuates endothelial cell proliferation, vascular leakage, and new blood vessel formation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ranibizumab rapidly penetrates through the retina to reach the choroid after intravitreal injection. Following monthly intravitreal administration of 0.5 mg ranibizumab in patients with neovascular (wet) age-related macular degeneration, the mean C max (±SD) was 1.7 (± 1.1) ng/mL. Following an implant insertion, the mean (±SD) C max of ranibizumab was 0.48 (±0.17) ng/mL and median T max was 26 days, with a range of one to 89 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of the central compartment (Vd/F) is 2.77 L. Ranibizumab is not shown to accumulate in serum. Due to its small size from lacking the Fc region of an antibody, ranibizumab achieves enhanced diffusion into the retina and choroid. •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): The metabolism of ranibizumab has not been studied. Since it is a monoclonal antibody fragment, ranibizumab is expected to undergo catabolism. •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): The estimated average vitreous elimination half-life is approximately nine days following intravitreal injection. The half-life of ranibizumab implant is approximately 25 weeks. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with retinal vein occlusion or diabetic macular edema, the apparent clearance (CL/F) of ranibizumab was 24.8 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information available regarding the LD 50 values of ranibizumab. There is also limited clinical experience of ranibizumab overdose: concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients, with no additional unexpected adverse reactions that were observed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Byooviz, Cimerli, Lucentis, Susvimo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ranibizumab is a recombinant humanized monoclonal antibody and VEGF-A antagonist used for the management of macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Rasagiline interact?

•Drug A: Abciximab •Drug B: Rasagiline •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Rasagiline is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa. •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): Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications. •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 mechanisms of action of rasagiline is unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline's beneficial effects seen in models of dopaminergic motor dysfunction. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 87 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/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): Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway. After oral administration of 14C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted 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): Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Azilect •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Rasagilina Rasagiline •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rasagiline is an irreversible inhibitor of monoamine oxidase used for the symptomatic management of idiopathic Parkinson's disease as initial monotherapy and as adjunct therapy to levodopa.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Rasagiline interact? Information: •Drug A: Abciximab •Drug B: Rasagiline •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Rasagiline is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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 signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa. •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): Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications. •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 mechanisms of action of rasagiline is unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline's beneficial effects seen in models of dopaminergic motor dysfunction. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 87 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/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): Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway. After oral administration of 14C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted 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): Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Azilect •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Rasagilina Rasagiline •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rasagiline is an irreversible inhibitor of monoamine oxidase used for the symptomatic management of idiopathic Parkinson's disease as initial monotherapy and as adjunct therapy to levodopa. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Ravulizumab interact?

•Drug A: Abciximab •Drug B: Ravulizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ravulizumab. •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 . •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): Ravulizumab is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH). It is also indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). However, the FDA advises against the use of ravulizumab for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). Ravulizumab is also indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. It is indicated for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. The European Commission approved ravulizumab for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) in adults and children with a body weight of 10 kg or more with the following conditions: hemolysis with clinical symptoms indicative of high disease activity or clinically stable after having been treated with eculizumab for at least the past six months. Ravulizumab is also indicated for the treatment of hemolytic uremic syndrome (aHUS) in patients with a body weight of 10 kg or more who are either complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab. •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): Ravulizumab is a potent long-acting complement inhibitor of C5, which is a key complement protein involved in inflammatory and thrombotic pathways. It has a long duration of action and fast onset of action. In a clinical study of adult and pediatric patients with paroxysmal nocturnal hemoglobinuria, completion inhibition of free C5 - determined as the serum concentration of less than 0.5 mcg/mL - was observed by the end of the first ravulizumab infusion: this effect was sustained throughout the entire 26-week treatment period. In patients with atypical hemolytic uremic syndrome, inhibition of C5 was observed in 93% of the patients in the study. C5 inhibition by ravulizumab is exposure-dependent. •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): Complement system activation plays an important role in innate and acquired immunity. Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. It is caused by a genetic mutation, leading to complement-mediated hemolysis and deficiencies in glycosylphosphatidylinositol (GPI)-linked proteins such as those involved in fibrinolysis. Atypical hemolytic uraemic syndrome (aHUS) is a type of thrombotic microangiopathy also caused by complement dysregulation. It is associated with thrombocytopenia, microangiopathic hemolytic anemia, and end-organ damage. Myasthenia gravis, an autoimmune neuromuscular disease, also involves the immune system aberrantly attacking the muscles, causing progressive muscle damage. Ravulizumab inhibits the terminal complement pathway by binding to C5 with high affinity: this inhibits the cleavage of C5 to C5a, which is a pro-inflammatory and pro-thrombotic anaphylatoxin, and C5b, an initiating subunit of the terminal complement complex (C5b-9), which promotes cell lysis. Since the generation of C5b is blocked, the formation of C5b-9 is also inhibited by ravulizumab. Ravulizumab inhibits terminal complement-mediated intravascular hemolysis in patients with PNH and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. By blocking the complement system, ravulizumab ameliorates the extent of inflammatory and immune responses that play a role in the pathophysiology of myasthenia gravis. •Absorption (Drug A): No absorption available •Absorption (Drug B): In children with paroxysmal nocturnal hemoglobinuria who are complement inhibitor-naïve, the mean C max was 733 mcg/mL following the loading dose and 1490 mcg/mL following the maintenance dose. In children who were previously treated with eculizumab, the mean C max was 885 mcg/mL following the loading dose and 1705 mcg/mL following the maintenance dose. In adults with paroxysmal nocturnal hemoglobinuria who are complement inhibitor-naïve, the mean C max was 771 mcg/mL following the loading dose and 1379 mcg/mL following the maintenance dose. In adults who were previously treated with eculizumab, the mean C max was 843 mcg/mL following the loading dose and 1386 mcg/mL following the maintenance dose. In children with atypical hemolytic uremic syndrome and a body weight of less than 20 kg, the mean C max was 656 mcg/mL following the loading dose and 1467 mcg/mL following the maintenance dose. In children with a body weight ranging from 20 to 40 kg, the mean C max was 600 mcg/mL following the loading dose and 1863 mcg/mL following the maintenance dose. In adults with a body weight greater than 40 kg, the mean C max was 754 mcg/mL following the loading dose and 1458 mcg/mL following the maintenance dose. T max is expected at the end of infusion (EOI) or soon after EOI. Therapeutic steady-state drug concentrations are reached after the first dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (%CV) volume of distribution at steady state was 5.30 (17.9) L in patients with paroxysmal nocturnal hemoglobinuria and 5.22 (35.4) L in patients with atypical hemolytic uremic syndrome. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information on the protein binding of ravulizumab. •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): Ravulizumab is expected to be metabolized in the same manner as any endogenous immunoglobulin gamma monoclonal antibody: it undergoes degradation into small peptides and amino acids via catabolic pathways. Ravulizumab contains only natural occurring amino acids and has no known active metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is no information on the route of elimination of ravulizumab. •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 (%CV) terminal elimination half-life of ravulizumab is 49.6 (18.3) days in patients with paroxysmal nocturnal hemoglobinuria and 51.8 (31.3) days in patients with atypical hemolytic uremic syndrome. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (%CV) clearance of ravulizumab is 0.08 (28.1) L/day in patients with paroxysmal nocturnal hemoglobinuria and 0.08 (53.3) L/day in patients with atypical hemolytic uremic syndrome. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information on the LD 50 value of ravulizumab. No case of ravulizumab overdose has been reported to date. Patients who experience overdose should have immediate interruption of their infusion and be closely monitored. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ultomiris •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ravulizumab is a monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and myasthenia gravis.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Ravulizumab interact? Information: •Drug A: Abciximab •Drug B: Ravulizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ravulizumab. •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 . •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): Ravulizumab is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH). It is also indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). However, the FDA advises against the use of ravulizumab for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). Ravulizumab is also indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. It is indicated for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. The European Commission approved ravulizumab for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) in adults and children with a body weight of 10 kg or more with the following conditions: hemolysis with clinical symptoms indicative of high disease activity or clinically stable after having been treated with eculizumab for at least the past six months. Ravulizumab is also indicated for the treatment of hemolytic uremic syndrome (aHUS) in patients with a body weight of 10 kg or more who are either complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab. •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): Ravulizumab is a potent long-acting complement inhibitor of C5, which is a key complement protein involved in inflammatory and thrombotic pathways. It has a long duration of action and fast onset of action. In a clinical study of adult and pediatric patients with paroxysmal nocturnal hemoglobinuria, completion inhibition of free C5 - determined as the serum concentration of less than 0.5 mcg/mL - was observed by the end of the first ravulizumab infusion: this effect was sustained throughout the entire 26-week treatment period. In patients with atypical hemolytic uremic syndrome, inhibition of C5 was observed in 93% of the patients in the study. C5 inhibition by ravulizumab is exposure-dependent. •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): Complement system activation plays an important role in innate and acquired immunity. Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. It is caused by a genetic mutation, leading to complement-mediated hemolysis and deficiencies in glycosylphosphatidylinositol (GPI)-linked proteins such as those involved in fibrinolysis. Atypical hemolytic uraemic syndrome (aHUS) is a type of thrombotic microangiopathy also caused by complement dysregulation. It is associated with thrombocytopenia, microangiopathic hemolytic anemia, and end-organ damage. Myasthenia gravis, an autoimmune neuromuscular disease, also involves the immune system aberrantly attacking the muscles, causing progressive muscle damage. Ravulizumab inhibits the terminal complement pathway by binding to C5 with high affinity: this inhibits the cleavage of C5 to C5a, which is a pro-inflammatory and pro-thrombotic anaphylatoxin, and C5b, an initiating subunit of the terminal complement complex (C5b-9), which promotes cell lysis. Since the generation of C5b is blocked, the formation of C5b-9 is also inhibited by ravulizumab. Ravulizumab inhibits terminal complement-mediated intravascular hemolysis in patients with PNH and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. By blocking the complement system, ravulizumab ameliorates the extent of inflammatory and immune responses that play a role in the pathophysiology of myasthenia gravis. •Absorption (Drug A): No absorption available •Absorption (Drug B): In children with paroxysmal nocturnal hemoglobinuria who are complement inhibitor-naïve, the mean C max was 733 mcg/mL following the loading dose and 1490 mcg/mL following the maintenance dose. In children who were previously treated with eculizumab, the mean C max was 885 mcg/mL following the loading dose and 1705 mcg/mL following the maintenance dose. In adults with paroxysmal nocturnal hemoglobinuria who are complement inhibitor-naïve, the mean C max was 771 mcg/mL following the loading dose and 1379 mcg/mL following the maintenance dose. In adults who were previously treated with eculizumab, the mean C max was 843 mcg/mL following the loading dose and 1386 mcg/mL following the maintenance dose. In children with atypical hemolytic uremic syndrome and a body weight of less than 20 kg, the mean C max was 656 mcg/mL following the loading dose and 1467 mcg/mL following the maintenance dose. In children with a body weight ranging from 20 to 40 kg, the mean C max was 600 mcg/mL following the loading dose and 1863 mcg/mL following the maintenance dose. In adults with a body weight greater than 40 kg, the mean C max was 754 mcg/mL following the loading dose and 1458 mcg/mL following the maintenance dose. T max is expected at the end of infusion (EOI) or soon after EOI. Therapeutic steady-state drug concentrations are reached after the first dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (%CV) volume of distribution at steady state was 5.30 (17.9) L in patients with paroxysmal nocturnal hemoglobinuria and 5.22 (35.4) L in patients with atypical hemolytic uremic syndrome. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information on the protein binding of ravulizumab. •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): Ravulizumab is expected to be metabolized in the same manner as any endogenous immunoglobulin gamma monoclonal antibody: it undergoes degradation into small peptides and amino acids via catabolic pathways. Ravulizumab contains only natural occurring amino acids and has no known active metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is no information on the route of elimination of ravulizumab. •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 (%CV) terminal elimination half-life of ravulizumab is 49.6 (18.3) days in patients with paroxysmal nocturnal hemoglobinuria and 51.8 (31.3) days in patients with atypical hemolytic uremic syndrome. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (%CV) clearance of ravulizumab is 0.08 (28.1) L/day in patients with paroxysmal nocturnal hemoglobinuria and 0.08 (53.3) L/day in patients with atypical hemolytic uremic syndrome. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information on the LD 50 value of ravulizumab. No case of ravulizumab overdose has been reported to date. Patients who experience overdose should have immediate interruption of their infusion and be closely monitored. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ultomiris •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ravulizumab is a monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and myasthenia gravis. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Raxibacumab interact?

•Drug A: Abciximab •Drug B: Raxibacumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Raxibacumab. •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 . •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): Raxibacumab is indicated for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or 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): 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): Raxibacumab is a monoclonal antibody that binds free PA with an affinity equilibrium dissociation constant (Kd) of 2.78 ± 0.9 nM. Raxibacumab inhibits the binding of PA to its cellular receptors, preventing the intracellular entry of the anthrax lethal factor and edema factor, the enzymatic toxin components responsible for the pathogenic effects of anthrax toxin. It does not have direct antibacterial activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Raxibacumab does not cross the blood-brain-barrier. When a single IV dose of 40 mg/kg was administered to healthy, male and female human subjects, the pharmacokinetic parameters are as follows: Cmax = 1020.3 ± 140.6 mcg/mL; AUCinf = 15845.8 ± 4333.5 mcg·day/mL. Bioavailability is also dependent on site of injection. When administered to the vastus lateralis, the bioavailability is 71-85%. When administered to the gluteus maximus, the bioavailability is 50-54%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Steady state volume of distribution exceeded plasma volume. This suggests that there is some distribution into the tissues. •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): Mean terminal elimination half-lives of raxibacumab are as follows: IM dose = 15-19 days; IV dose = 16-19 days •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance values were much smaller than the glomerular filtration rate indicating that there is virtually no renal clearance of raxibacumab. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequently reported adverse reactions were rash, pain in extremity, pruritus, and somnolence. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Raxibacumab is a monoclonal antibody used in conjunction with an antibacterial regimen to treat patients with inhalational anthrax caused by Bacillus anthracis and for prophylaxis of inhalational anthrax when appropriate.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Raxibacumab interact? Information: •Drug A: Abciximab •Drug B: Raxibacumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Raxibacumab. •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 . •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): Raxibacumab is indicated for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or 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): 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): Raxibacumab is a monoclonal antibody that binds free PA with an affinity equilibrium dissociation constant (Kd) of 2.78 ± 0.9 nM. Raxibacumab inhibits the binding of PA to its cellular receptors, preventing the intracellular entry of the anthrax lethal factor and edema factor, the enzymatic toxin components responsible for the pathogenic effects of anthrax toxin. It does not have direct antibacterial activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Raxibacumab does not cross the blood-brain-barrier. When a single IV dose of 40 mg/kg was administered to healthy, male and female human subjects, the pharmacokinetic parameters are as follows: Cmax = 1020.3 ± 140.6 mcg/mL; AUCinf = 15845.8 ± 4333.5 mcg·day/mL. Bioavailability is also dependent on site of injection. When administered to the vastus lateralis, the bioavailability is 71-85%. When administered to the gluteus maximus, the bioavailability is 50-54%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Steady state volume of distribution exceeded plasma volume. This suggests that there is some distribution into the tissues. •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): Mean terminal elimination half-lives of raxibacumab are as follows: IM dose = 15-19 days; IV dose = 16-19 days •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance values were much smaller than the glomerular filtration rate indicating that there is virtually no renal clearance of raxibacumab. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequently reported adverse reactions were rash, pain in extremity, pruritus, and somnolence. •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 •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Raxibacumab is a monoclonal antibody used in conjunction with an antibacterial regimen to treat patients with inhalational anthrax caused by Bacillus anthracis and for prophylaxis of inhalational anthrax when appropriate. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Reslizumab interact?

•Drug A: Abciximab •Drug B: Reslizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Reslizumab. •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 . •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 add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype. •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 reduction in blood eosinophil counts was observed in clinical studies following an initial infusion of 3 mg/kg reslizumab and was maintained through 52 weeks of treatment with no signs of tachyphylaxis. Greater reductions of blood eosinophils were observed in subjects with higher reslizumab serum concentrations. This effect was independent of the presence of treatment-emergent anti-reslizumab antibodies. •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): Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm. IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow. IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface. Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma. Reslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface. By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation. •Absorption (Drug A): No absorption available •Absorption (Drug B): The peak serum concentrations of reslizumab were typically observed at the end of the infusion with the serum concentrations gradually declining from the peak in a biphasic manner. Following multiple doses, serum concentrations of reslizumab accumulated approximately 1.5 to 1.9-fold. Interindividual variability in peak and overall exposure across healthy individuals, patients with asthma, and other populations in pharmacokinetic studies was around 20-30%. Systemic exposure to reslizumab appeared to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The approximate volume of distribution of reslizumab is 5L, suggesting minimal distribution to the extravascular tissues. •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): Like other monoclonal antibodies, reslizumab is assumed to undergo enzymatic proteolysis into smaller peptides and amino acids. As reslizumab bind to the target, it is not expected to undergo a target-mediated clearance. •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 is approximately 24 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Reslizumab clearance was approximately 7 mL/hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Single doses of up to 732 mg have been administered intravenously to subjects in clinical trials without evidence of dose-related toxicities. There is no specific treatment for an overdose with reslizumab. If the event of an overdose, the patient should be treated supportively with appropriate monitoring as necessary. Based on the findings of a 6-month bioassay, reslizumab showed no evidence of carcinogenicity. In a fertility study, administration of reslizumab to parental mice at doses up to 50 mg/kg (approximately 6 times the MRHD on an AUC basis) had no effects on male or female mating or fertility. The malignancy risk of reslizumab in humans with effects on tumor growth is not yet established. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cinqair •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Reslizumab is an IL-5 antagonist used as an add-on maintenance treatment of patients with severe eosinophilic asthma in adults.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Reslizumab interact? Information: •Drug A: Abciximab •Drug B: Reslizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Reslizumab. •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 . •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 add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype. •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 reduction in blood eosinophil counts was observed in clinical studies following an initial infusion of 3 mg/kg reslizumab and was maintained through 52 weeks of treatment with no signs of tachyphylaxis. Greater reductions of blood eosinophils were observed in subjects with higher reslizumab serum concentrations. This effect was independent of the presence of treatment-emergent anti-reslizumab antibodies. •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): Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm. IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow. IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface. Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma. Reslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface. By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation. •Absorption (Drug A): No absorption available •Absorption (Drug B): The peak serum concentrations of reslizumab were typically observed at the end of the infusion with the serum concentrations gradually declining from the peak in a biphasic manner. Following multiple doses, serum concentrations of reslizumab accumulated approximately 1.5 to 1.9-fold. Interindividual variability in peak and overall exposure across healthy individuals, patients with asthma, and other populations in pharmacokinetic studies was around 20-30%. Systemic exposure to reslizumab appeared to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The approximate volume of distribution of reslizumab is 5L, suggesting minimal distribution to the extravascular tissues. •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): Like other monoclonal antibodies, reslizumab is assumed to undergo enzymatic proteolysis into smaller peptides and amino acids. As reslizumab bind to the target, it is not expected to undergo a target-mediated clearance. •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 is approximately 24 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Reslizumab clearance was approximately 7 mL/hour. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Single doses of up to 732 mg have been administered intravenously to subjects in clinical trials without evidence of dose-related toxicities. There is no specific treatment for an overdose with reslizumab. If the event of an overdose, the patient should be treated supportively with appropriate monitoring as necessary. Based on the findings of a 6-month bioassay, reslizumab showed no evidence of carcinogenicity. In a fertility study, administration of reslizumab to parental mice at doses up to 50 mg/kg (approximately 6 times the MRHD on an AUC basis) had no effects on male or female mating or fertility. The malignancy risk of reslizumab in humans with effects on tumor growth is not yet established. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cinqair •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Reslizumab is an IL-5 antagonist used as an add-on maintenance treatment of patients with severe eosinophilic asthma in adults. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Reteplase interact?

•Drug A: Abciximab •Drug B: Reteplase •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Reteplase. •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. •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 lysis of acute pulmonary emboli, intracoronary emboli, and management of 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): Reteplase cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction. •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): Reteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic 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): 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): Retavase •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Reteplase is a purified form of human tissue plasminogen activator used in the emergency treatment of myocardial infarction, ischemic stroke, and pulmonary emboli.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Reteplase interact? Information: •Drug A: Abciximab •Drug B: Reteplase •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Reteplase. •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. •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 lysis of acute pulmonary emboli, intracoronary emboli, and management of 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): Reteplase cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. This helps eliminate blood clots or arterial blockages that cause myocardial infarction. •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): Reteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic 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): 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): Retavase •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Reteplase is a purified form of human tissue plasminogen activator used in the emergency treatment of myocardial infarction, ischemic stroke, and pulmonary emboli. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Risankizumab interact?

•Drug A: Abciximab •Drug B: Risankizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Risankizumab. •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 . •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): Risankizumab is indicated to treat: moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. active psoriatic arthritis in adults. In Canada and Europe, it may be used alone or in combination with a conventional non-biologic disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate). moderately to severely active Crohn's disease in adults. In Canada, it is used in patients who have had an inadequate response, intolerance, or demonstrated dependence on corticosteroids; or an inadequate response, intolerance, or loss of response to immunomodulators or biologic 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): Risankizumab works to suppress the inflammatory effects of interleukin (IL)-23. It inhibits the release of pro-inflammatory cytokines and chemokines. In vitro, risankizumab blocked IL-17 production; however, risankizumab does not actually bind to IL-17. •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 (IL)-23 is a pro-inflammatory cytokine implicated in various chronic inflammatory disorders, such as plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-23 binds to the IL-23 receptor to activate the IL-23/Th17 axis, which is responsible for mediating T cell-mediated immune responses and inflammation. The IL-23/Th17 axis triggers the differentiation of Th-17 and Th-22 cells and induces the release of inflammatory cytokines and chemokines such as IL-17. While the IL-23/Th17 axis serves a critical role in protection against pathogens, it is also involved in chronic, autoimmune, inflammatory disorders. IL-23 is made up of two subunits, p19 and p40: p19 is specific to IL-23 and p40 is present on both IL-12 and IL-23. Risankizumab binds to the p19 subunit of IL-23 with high affinity and neutralizes it, thereby preventing its interaction with the IL-23 receptor and activation of IL-23 signalling cascades. •Absorption (Drug A): No absorption available •Absorption (Drug B): Drug plasma concentrations increased dose-proportionally after subcutaneous administration of a single dose over the dose range from 18 mg to 360 mg and intravenous administration over a dose range from 200 mg to 1800 mg via a 3-hour infusion. In patients with plaque psoriasis who received a subcutaneous dose of 150 mg risankizumab, steady-state peak concentration (C max ) and trough concentration (C trough ) were 12 mcg/mL and 2 mcg/mL, respectively. In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every 8 weeks thereafter, the median Cmax and Ctrough are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8-12; and the steady state median Cmax and Ctrough are estimated to be 14.0 mcg/mL and 4.1 mcg/mL, respectively for 180 mg or 28.0 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg, during Weeks 40-48. The absolute bioavailability of risankizumab was approximately 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, C max was reached by 3 to 14 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease. •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): The metabolic pathway of risankizumab has not been fully characterized. As a humanized IgG1 monoclonal antibody, it is likely to be catabolized into small peptides and amino acids in the same way as endogenous IgG. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtration in the kidneys or to be excreted as an intact molecule 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 terminal elimination half-life was approximately 28 days in patients with plaque psoriasis and 21 days in patients with Crohn’s disease. •Clearance (Drug A): No clearance available •Clearance (Drug B): The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) in patients with plaque psoriasis and 0.30 L/day (34%) in patients with Crohn’s disease. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The NOAEL was 50 mg/kg in monkeys following intravenous or subcutaneous administration. There is no information available regarding the overdose of risankizumab. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Skyrizi 150 Mg Dose Pack •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Risankizumab is an interleukin-23 antagonist used to treat plaque psoriasis, psoriatic arthritis, and Crohn's disease in adults.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Risankizumab interact? Information: •Drug A: Abciximab •Drug B: Risankizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Risankizumab. •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 . •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): Risankizumab is indicated to treat: moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. active psoriatic arthritis in adults. In Canada and Europe, it may be used alone or in combination with a conventional non-biologic disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate). moderately to severely active Crohn's disease in adults. In Canada, it is used in patients who have had an inadequate response, intolerance, or demonstrated dependence on corticosteroids; or an inadequate response, intolerance, or loss of response to immunomodulators or biologic 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): Risankizumab works to suppress the inflammatory effects of interleukin (IL)-23. It inhibits the release of pro-inflammatory cytokines and chemokines. In vitro, risankizumab blocked IL-17 production; however, risankizumab does not actually bind to IL-17. •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 (IL)-23 is a pro-inflammatory cytokine implicated in various chronic inflammatory disorders, such as plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-23 binds to the IL-23 receptor to activate the IL-23/Th17 axis, which is responsible for mediating T cell-mediated immune responses and inflammation. The IL-23/Th17 axis triggers the differentiation of Th-17 and Th-22 cells and induces the release of inflammatory cytokines and chemokines such as IL-17. While the IL-23/Th17 axis serves a critical role in protection against pathogens, it is also involved in chronic, autoimmune, inflammatory disorders. IL-23 is made up of two subunits, p19 and p40: p19 is specific to IL-23 and p40 is present on both IL-12 and IL-23. Risankizumab binds to the p19 subunit of IL-23 with high affinity and neutralizes it, thereby preventing its interaction with the IL-23 receptor and activation of IL-23 signalling cascades. •Absorption (Drug A): No absorption available •Absorption (Drug B): Drug plasma concentrations increased dose-proportionally after subcutaneous administration of a single dose over the dose range from 18 mg to 360 mg and intravenous administration over a dose range from 200 mg to 1800 mg via a 3-hour infusion. In patients with plaque psoriasis who received a subcutaneous dose of 150 mg risankizumab, steady-state peak concentration (C max ) and trough concentration (C trough ) were 12 mcg/mL and 2 mcg/mL, respectively. In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every 8 weeks thereafter, the median Cmax and Ctrough are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8-12; and the steady state median Cmax and Ctrough are estimated to be 14.0 mcg/mL and 4.1 mcg/mL, respectively for 180 mg or 28.0 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg, during Weeks 40-48. The absolute bioavailability of risankizumab was approximately 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, C max was reached by 3 to 14 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease. •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): The metabolic pathway of risankizumab has not been fully characterized. As a humanized IgG1 monoclonal antibody, it is likely to be catabolized into small peptides and amino acids in the same way as endogenous IgG. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtration in the kidneys or to be excreted as an intact molecule 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 terminal elimination half-life was approximately 28 days in patients with plaque psoriasis and 21 days in patients with Crohn’s disease. •Clearance (Drug A): No clearance available •Clearance (Drug B): The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) in patients with plaque psoriasis and 0.30 L/day (34%) in patients with Crohn’s disease. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The NOAEL was 50 mg/kg in monkeys following intravenous or subcutaneous administration. There is no information available regarding the overdose of risankizumab. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Skyrizi 150 Mg Dose Pack •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Risankizumab is an interleukin-23 antagonist used to treat plaque psoriasis, psoriatic arthritis, and Crohn's disease in adults. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Rituximab interact?

•Drug A: Abciximab •Drug B: Rituximab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Rituximab. •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. •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): Rituximab is indicated for the treatment of adult patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s Lymphoma (NHL) as a single agent. Also, it is indicated for the treatment of adult patients with previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. Additionally, rituximab is indicated for the treatment of adult patients with non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; and previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens. Rituximab, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL). In combination with methotrexate, rituximab is indicated for the treatment of adult patients with moderately-to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. Additionally, rituximab, in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA). RITUXAN (rituximab injection for intravenous use) is indicated for the treatment of pediatric patients aged 6 months and older with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or mature B-cell acute leukemia (B-AL) in combination with chemotherapy; as well as the treatment of adult patients with moderate to severe pemphigus vulgaris. These indications for RITUXAN are not included in the labels of rituximab biosimilar products (rituximab-arrx, rituximab-abbs, rituximab-pvvr). The combination product RITUXAN HYCELA (rituximab and hyaluronidase human injection, for subcutaneous use) is not indicated for the treatment of non-malignant conditions. •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): Rituximab is a chimeric murine/human monoclonal antibody that binds to the CD20 antigen. CD20 is predominantly expressed on the surface of pre-B and mature B-lymphocytes, allowing rituximab to target and promote lysis in this specific type of cells.. In Non-Hodgkin's Lymphoma patients, rituximab treatment depleted circulating and tissue-based B-cells. In a study that included 166 patients, CD19-positive B-cells were depleted within three weeks, and in 83% of patients, cell depletion lasted up to 6-9 months. B-cell levels started to recover at approximately 6 months and returned to normal 12 months after treatment was completed. Approximately 14% of Non-Hodgkin's Lymphoma patients had IgM or IgG serum levels below the normal range. Most rheumatoid arthritis (RA) patients treated with rituximab showed a near-complete depletion of peripheral B lymphocytes within 2 weeks after the first dose. Peripheral B-cell depletion was sustained for at least 6 months, and in approximately 4% of RA patients, peripheral B-cell depletion was sustained for more than 3 years after a single course of rituximab treatment. Total IgG, IgA, and, more specifically, IgM levels were lower 24 weeks after the first cycle of rituximab treatment (2.8%, 0.8% and 10% below the lower limit of normal, respectively). However, the clinical consequences of this decrease in immunoglobulin levels in RA patients are not clear at this time. Treatment with rituximab in patients with RA was also associated with a decreased level of inflammation markers. In patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) treated with rituximab, CD19 B-cells in peripheral blood were depleted to less than 10 cells/μl after the first two infusions. By month 6, approximately 84% of patients had the same level of peripheral blood CD19 B-cells, and by month 12, 81% of patients demonstrated signs of B-cell return with counts >10 cells/μL. By Month 18, the majority of patients (87%) had counts >10 cells/μL. •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): Rituximab is a monoclonal antibody that targets CD20, an antigen expressed on the surface of pre-B and mature B-lymphocytes. About 85% of non-Hodgkin’s lymphoma (NHL) cases are B-cell lymphomas, characterized by the high expression of CD19, CD20 and CD22 cell surface antigens. CD20 is involved in cell cycle regulation, apoptosis and calcium signaling. By targeting CD20, rituximab promotes cell lysis while sparing hematopoietic and plasma cells without this surface antigen. It has been suggested that cell lysis mechanisms triggered by rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Rituximab is part of the immunoglobulin G1 (IgG1) subclass of antibodies, and is formed by a murine variable region (Fab region) and a human constant region (Fc region). The Fab region gives rituximab its specificity for CD20, while the Fc region interacts with cell surface receptors to activate the immune system, leading to the depletion of circulating B lymphocytes. In regards to the mechanism of action in rheumatoid arthritis (RA), B-cells are thought to play a role in the pathogenesis of RA and the associated condition of chronic synovitis. B-cells may act at various sites in the autoimmune/inflammatory process through the production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and the production of proinflammatory cytokines. The administration of rituximab in this condition has resulted in significant clinical and symptomatic improvements. Rituximab is also indicated for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two conditions characterized by the presence of circulating antineutrophil cytoplasmic antibodies and increased B-cell activity. It has been suggested that rituximab depletes CD20 B-cells at a higher rate in GPA and MPA patients with high levels of Fc receptor-like 5 (FCRL5). •Absorption (Drug A): No absorption available •Absorption (Drug B): Rituximab follows a linear pharmacokinetic model. In patients with non-Hodgkin’s lymphoma (NHL) administered 4 doses of 375 mg/m of rituximab (IV) weekly, detectable levels were observed 3-6 months after treatment completion. The pharmacokinetic profile of rituximab administered in combination with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy was similar to the one observed when administered alone. In patients with rheumatoid arthritis (RA) administered 2 doses of 500 mg of rituximab, the C max of the first and second infusions were 157 (SD ± 46) and 183 (SD ± 55) mcg/mL. In patients administered 2 doses of 1,000 mg of rituximab, the C max of the first and second infusions were 318 (SD ± 86) and 381 (SD ± 98) mcg/mL. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, the AUC 0-180 was 9787 µg/mL⋅day (range from 4838 to 20446 µg/mL⋅day). In adult patients given the same dose, the AUC 0-180 of rituximab was 10302 µg/mL⋅day (range from 3653 to 21874 µg/mL⋅day). The bioavailability of rituximab administered intravenously is expected to be close to 100%. Compared to rituximab administered intravenously, the bioavailability of RITUXAN HYCELA, a combination product of rituximab and hyaluronidase (human recombinant), is 64.6% in patients with follicular lymphoma and 63.4% in patients with chronic lymphocytic leukemia (CLL). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the volume of distribution of rituximab is 3.1 L. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, the volume of distribution was 2.28 L (range from 1.43 to 3.17 L). In adult patients given the same dose, the volume of distribution was 3.12 L (range from 2.42 to 3.91 L). In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab on days 1, 15, 168, and 182, the volume of distribution was 3.49 L (range from 2.48 to 5.22 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): As a monoclonal antibody, rituximab is expected to be metabolized by proteases throughout the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies (mAb) such as rituximab trigger the formation of antidrug antibodies (ADAs) that form ADA-mAb immune complexes. The endogenous elimination of these immune complexes is mediated by the reticuloendothelial system, most likely via fragment crystallizable-gamma (Fcγ)-mediated endocytosis. •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 patients with non-Hodgkin's lymphoma (NHL) treated with rituximab once a week or once every three weeks (n=298), the median terminal elimination half-life was 22 days (range of 6.1-52 days). In patients with chronic lymphocytic leukemia (CLL) treated with rituximab (n=21), the estimated median terminal half-life was 32 days (range of 14-62 days). Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the mean terminal elimination half-life of rituximab is 18.0 days. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, the terminal half-life was 22 days (range from 11 to 42 days). In adult patients given the same dose, the terminal half-life was 25 days (range from 11 to 52 days). In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab, the terminal half-life was 21.1 days (range from 9.3 to 36.2 days) in the first infusion cycle (days 1 and 15), and 26.2 days (range from 16.4 to 42.8 days) in the second infusion cycle (days 168 and 182). •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with non-Hodgkin’s lymphoma (NHL), those with higher CD19-positive cell counts or larger measurable tumor lesions at pretreatment had higher rituximab clearance. Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the clearance of rituximab is 0.335 L/day. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, clearance was 0.222 L/day (range from 0.0996 to 0.381 L/day). In adult patients given the same dose, clearance was 0.279 L/day (range from 0.113 to 0.653 L/day). In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab, clearance was 0.30 L/day (range from 0.16 to 1.51 L/day) in the first infusion cycle (days 1 and 15), and 0.24 L/day (range from 0.13 to 0.45 L/day) in the second infusion cycle (days 168 and 182). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding rituximab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as fatal infusion-related reactions and severe mucocutaneous reactions. Symptomatic and supportive measures are recommended. No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of rituximab or to determine potential effects on fertility in males or females. The maximum tolerated dose of rituximab in mice administered intraperitoneally is higher than 100 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): MabThera, Riabni, Rituxan, Rituxan Hycela, Ruxience, Truxima •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rituximab is a monoclonal anti-CD20 antibody used to treat non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Wegener's granulomatosis, pemphigus vulgaris, and rheumatoid arthritis.

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. The severity of the interaction is minor.

Question: Does Abciximab and Rituximab interact? Information: •Drug A: Abciximab •Drug B: Rituximab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Rituximab. •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. •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): Rituximab is indicated for the treatment of adult patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s Lymphoma (NHL) as a single agent. Also, it is indicated for the treatment of adult patients with previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. Additionally, rituximab is indicated for the treatment of adult patients with non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; and previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens. Rituximab, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL). In combination with methotrexate, rituximab is indicated for the treatment of adult patients with moderately-to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. Additionally, rituximab, in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA). RITUXAN (rituximab injection for intravenous use) is indicated for the treatment of pediatric patients aged 6 months and older with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or mature B-cell acute leukemia (B-AL) in combination with chemotherapy; as well as the treatment of adult patients with moderate to severe pemphigus vulgaris. These indications for RITUXAN are not included in the labels of rituximab biosimilar products (rituximab-arrx, rituximab-abbs, rituximab-pvvr). The combination product RITUXAN HYCELA (rituximab and hyaluronidase human injection, for subcutaneous use) is not indicated for the treatment of non-malignant conditions. •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): Rituximab is a chimeric murine/human monoclonal antibody that binds to the CD20 antigen. CD20 is predominantly expressed on the surface of pre-B and mature B-lymphocytes, allowing rituximab to target and promote lysis in this specific type of cells.. In Non-Hodgkin's Lymphoma patients, rituximab treatment depleted circulating and tissue-based B-cells. In a study that included 166 patients, CD19-positive B-cells were depleted within three weeks, and in 83% of patients, cell depletion lasted up to 6-9 months. B-cell levels started to recover at approximately 6 months and returned to normal 12 months after treatment was completed. Approximately 14% of Non-Hodgkin's Lymphoma patients had IgM or IgG serum levels below the normal range. Most rheumatoid arthritis (RA) patients treated with rituximab showed a near-complete depletion of peripheral B lymphocytes within 2 weeks after the first dose. Peripheral B-cell depletion was sustained for at least 6 months, and in approximately 4% of RA patients, peripheral B-cell depletion was sustained for more than 3 years after a single course of rituximab treatment. Total IgG, IgA, and, more specifically, IgM levels were lower 24 weeks after the first cycle of rituximab treatment (2.8%, 0.8% and 10% below the lower limit of normal, respectively). However, the clinical consequences of this decrease in immunoglobulin levels in RA patients are not clear at this time. Treatment with rituximab in patients with RA was also associated with a decreased level of inflammation markers. In patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) treated with rituximab, CD19 B-cells in peripheral blood were depleted to less than 10 cells/μl after the first two infusions. By month 6, approximately 84% of patients had the same level of peripheral blood CD19 B-cells, and by month 12, 81% of patients demonstrated signs of B-cell return with counts >10 cells/μL. By Month 18, the majority of patients (87%) had counts >10 cells/μL. •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): Rituximab is a monoclonal antibody that targets CD20, an antigen expressed on the surface of pre-B and mature B-lymphocytes. About 85% of non-Hodgkin’s lymphoma (NHL) cases are B-cell lymphomas, characterized by the high expression of CD19, CD20 and CD22 cell surface antigens. CD20 is involved in cell cycle regulation, apoptosis and calcium signaling. By targeting CD20, rituximab promotes cell lysis while sparing hematopoietic and plasma cells without this surface antigen. It has been suggested that cell lysis mechanisms triggered by rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Rituximab is part of the immunoglobulin G1 (IgG1) subclass of antibodies, and is formed by a murine variable region (Fab region) and a human constant region (Fc region). The Fab region gives rituximab its specificity for CD20, while the Fc region interacts with cell surface receptors to activate the immune system, leading to the depletion of circulating B lymphocytes. In regards to the mechanism of action in rheumatoid arthritis (RA), B-cells are thought to play a role in the pathogenesis of RA and the associated condition of chronic synovitis. B-cells may act at various sites in the autoimmune/inflammatory process through the production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and the production of proinflammatory cytokines. The administration of rituximab in this condition has resulted in significant clinical and symptomatic improvements. Rituximab is also indicated for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two conditions characterized by the presence of circulating antineutrophil cytoplasmic antibodies and increased B-cell activity. It has been suggested that rituximab depletes CD20 B-cells at a higher rate in GPA and MPA patients with high levels of Fc receptor-like 5 (FCRL5). •Absorption (Drug A): No absorption available •Absorption (Drug B): Rituximab follows a linear pharmacokinetic model. In patients with non-Hodgkin’s lymphoma (NHL) administered 4 doses of 375 mg/m of rituximab (IV) weekly, detectable levels were observed 3-6 months after treatment completion. The pharmacokinetic profile of rituximab administered in combination with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy was similar to the one observed when administered alone. In patients with rheumatoid arthritis (RA) administered 2 doses of 500 mg of rituximab, the C max of the first and second infusions were 157 (SD ± 46) and 183 (SD ± 55) mcg/mL. In patients administered 2 doses of 1,000 mg of rituximab, the C max of the first and second infusions were 318 (SD ± 86) and 381 (SD ± 98) mcg/mL. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, the AUC 0-180 was 9787 µg/mL⋅day (range from 4838 to 20446 µg/mL⋅day). In adult patients given the same dose, the AUC 0-180 of rituximab was 10302 µg/mL⋅day (range from 3653 to 21874 µg/mL⋅day). The bioavailability of rituximab administered intravenously is expected to be close to 100%. Compared to rituximab administered intravenously, the bioavailability of RITUXAN HYCELA, a combination product of rituximab and hyaluronidase (human recombinant), is 64.6% in patients with follicular lymphoma and 63.4% in patients with chronic lymphocytic leukemia (CLL). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the volume of distribution of rituximab is 3.1 L. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, the volume of distribution was 2.28 L (range from 1.43 to 3.17 L). In adult patients given the same dose, the volume of distribution was 3.12 L (range from 2.42 to 3.91 L). In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab on days 1, 15, 168, and 182, the volume of distribution was 3.49 L (range from 2.48 to 5.22 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): As a monoclonal antibody, rituximab is expected to be metabolized by proteases throughout the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies (mAb) such as rituximab trigger the formation of antidrug antibodies (ADAs) that form ADA-mAb immune complexes. The endogenous elimination of these immune complexes is mediated by the reticuloendothelial system, most likely via fragment crystallizable-gamma (Fcγ)-mediated endocytosis. •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 patients with non-Hodgkin's lymphoma (NHL) treated with rituximab once a week or once every three weeks (n=298), the median terminal elimination half-life was 22 days (range of 6.1-52 days). In patients with chronic lymphocytic leukemia (CLL) treated with rituximab (n=21), the estimated median terminal half-life was 32 days (range of 14-62 days). Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the mean terminal elimination half-life of rituximab is 18.0 days. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, the terminal half-life was 22 days (range from 11 to 42 days). In adult patients given the same dose, the terminal half-life was 25 days (range from 11 to 52 days). In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab, the terminal half-life was 21.1 days (range from 9.3 to 36.2 days) in the first infusion cycle (days 1 and 15), and 26.2 days (range from 16.4 to 42.8 days) in the second infusion cycle (days 168 and 182). •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with non-Hodgkin’s lymphoma (NHL), those with higher CD19-positive cell counts or larger measurable tumor lesions at pretreatment had higher rituximab clearance. Based on a pharmacokinetic analysis that included 2005 patients with rheumatoid arthritis (RA), the clearance of rituximab is 0.335 L/day. In pediatric patients (6-17 years old) with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) given four doses of 375 mg/m of rituximab intravenously once a week, clearance was 0.222 L/day (range from 0.0996 to 0.381 L/day). In adult patients given the same dose, clearance was 0.279 L/day (range from 0.113 to 0.653 L/day). In patients with pemphigus vulgaris given an intravenous infusion of 1000 mg of rituximab, clearance was 0.30 L/day (range from 0.16 to 1.51 L/day) in the first infusion cycle (days 1 and 15), and 0.24 L/day (range from 0.13 to 0.45 L/day) in the second infusion cycle (days 168 and 182). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding rituximab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as fatal infusion-related reactions and severe mucocutaneous reactions. Symptomatic and supportive measures are recommended. No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of rituximab or to determine potential effects on fertility in males or females. The maximum tolerated dose of rituximab in mice administered intraperitoneally is higher than 100 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): MabThera, Riabni, Rituxan, Rituxan Hycela, Ruxience, Truxima •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rituximab is a monoclonal anti-CD20 antibody used to treat non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Wegener's granulomatosis, pemphigus vulgaris, and rheumatoid arthritis. Output: 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. The severity of the interaction is minor.

Does Abciximab and Rivaroxaban interact?

•Drug A: Abciximab •Drug B: Rivaroxaban •Severity: MAJOR •Description: Abciximab may increase the anticoagulant activities of Rivaroxaban. •Extended Description: Concomitant use of rivaroxaban with drugs affecting hemostasis, including other anticoagulants, leads to an additive effect on anti-factor Xa activity of ribaroxavan and increases the risk of bleeding. •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): Rivaroxaban is indicated for the prevention of venous thromboembolic events (VTE) in patients who have undergone total hips replacements and total knee replacement surgery; prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE); to reduce risk of recurrent DVT and/or PE. Rivaroxaban is also indicated, in combination with aspirin, for reducing the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Its use is also not recommended in those with severe renal impairment (<30mL/min). Rivaroxaban is also indicated for the treatment and prevention of VTE in pediatric patients (from birth to 18 years of age) and for thromboprophylaxis in pediatric patients ≥2 years old with congenital heart disease following the Fontan procedure. •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): Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban. •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): Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, rivaroxaban is rapidly absorbed and reaches peak plasma concentration in 2-4 hours. Bioavailability of the 10 mg dose is >80%. However, the 15-20 mg dose have a lower bioavailability if taken in the fasted state and consequently should be taken with food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady state Vd is 50 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding is about 92% to 95% •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 two-thirds of the dose is metabolized. It is metabolized by CYP3A4, CYP3A5, CYP2J2 and CYP-independant mechanisms •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately two-thirds of rivaroxaban is excreted into urine (via active tubular secretion in which approximately 36% as unchanged drug and 30% as inactive metabolism). The remaining third of the administered dose is excreted via feces in which 7% is in the form of unchanged drug and 21% as inactive 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): The terminal half life is 5-9 hours in adults and 11-13 hours in the elderly. •Clearance (Drug A): No clearance available •Clearance (Drug B): Systemic clearance is approximately 10 L/h, so rivaroxaban is considered a drug with low clearance. Renal clearance is ~3-4 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Excessive bleeding. Overdosages should be treated using activated charcoal and supportive measures such as mechanical compression and hemodynamic support. If bleeding is not controlled, the following procoagulants can be administered: activated prothrombin complex concentrate, prothrombin complex concentrate and recombinant factor VIIa. There is also a higher chance of post procedural hemorrhage compared to enoxaparin (1.55% vs. 1.39% respectively). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Xarelto •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rivaroxaban is a factor Xa inhibitor used to treat deep vein thrombosis (DVT) and pulmonary embolism (PE). May also be used as thrombosis prophylaxis in specific situations.

Concomitant use of rivaroxaban with drugs affecting hemostasis, including other anticoagulants, leads to an additive effect on anti-factor Xa activity of ribaroxavan and increases the risk of bleeding. The severity of the interaction is major.

Question: Does Abciximab and Rivaroxaban interact? Information: •Drug A: Abciximab •Drug B: Rivaroxaban •Severity: MAJOR •Description: Abciximab may increase the anticoagulant activities of Rivaroxaban. •Extended Description: Concomitant use of rivaroxaban with drugs affecting hemostasis, including other anticoagulants, leads to an additive effect on anti-factor Xa activity of ribaroxavan and increases the risk of bleeding. •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): Rivaroxaban is indicated for the prevention of venous thromboembolic events (VTE) in patients who have undergone total hips replacements and total knee replacement surgery; prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE); to reduce risk of recurrent DVT and/or PE. Rivaroxaban is also indicated, in combination with aspirin, for reducing the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Its use is also not recommended in those with severe renal impairment (<30mL/min). Rivaroxaban is also indicated for the treatment and prevention of VTE in pediatric patients (from birth to 18 years of age) and for thromboprophylaxis in pediatric patients ≥2 years old with congenital heart disease following the Fontan procedure. •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): Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban. •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): Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, rivaroxaban is rapidly absorbed and reaches peak plasma concentration in 2-4 hours. Bioavailability of the 10 mg dose is >80%. However, the 15-20 mg dose have a lower bioavailability if taken in the fasted state and consequently should be taken with food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady state Vd is 50 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding is about 92% to 95% •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 two-thirds of the dose is metabolized. It is metabolized by CYP3A4, CYP3A5, CYP2J2 and CYP-independant mechanisms •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately two-thirds of rivaroxaban is excreted into urine (via active tubular secretion in which approximately 36% as unchanged drug and 30% as inactive metabolism). The remaining third of the administered dose is excreted via feces in which 7% is in the form of unchanged drug and 21% as inactive 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): The terminal half life is 5-9 hours in adults and 11-13 hours in the elderly. •Clearance (Drug A): No clearance available •Clearance (Drug B): Systemic clearance is approximately 10 L/h, so rivaroxaban is considered a drug with low clearance. Renal clearance is ~3-4 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Excessive bleeding. Overdosages should be treated using activated charcoal and supportive measures such as mechanical compression and hemodynamic support. If bleeding is not controlled, the following procoagulants can be administered: activated prothrombin complex concentrate, prothrombin complex concentrate and recombinant factor VIIa. There is also a higher chance of post procedural hemorrhage compared to enoxaparin (1.55% vs. 1.39% respectively). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Xarelto •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rivaroxaban is a factor Xa inhibitor used to treat deep vein thrombosis (DVT) and pulmonary embolism (PE). May also be used as thrombosis prophylaxis in specific situations. Output: Concomitant use of rivaroxaban with drugs affecting hemostasis, including other anticoagulants, leads to an additive effect on anti-factor Xa activity of ribaroxavan and increases the risk of bleeding. The severity of the interaction is major.

Does Abciximab and Romosozumab interact?

•Drug A: Abciximab •Drug B: Romosozumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Romosozumab. •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 . •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): Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments. •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): Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts. •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): Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway. Romosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts. Sclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL). Romosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption. Both effects from the same therapy have not been seen in other osteoporosis treatments to date. •Absorption (Drug A): No absorption available •Absorption (Drug B): Romosozumab reaches peak concentration within 2 to 7 days with a median time of 5 days. Subcutaneous bioavailability is 50 to 70%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 3.92L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are generally not protein bound. In about 10% to 18.1% of cases patients develop antibodies against romosozumab. 4.7% of the patients developed neutralizing antibodies. The presence of antibodies against romosozumab can reduce the availability of romosozumab by 22%, and 63% in the case of neutralizing antibodies. •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 romosozumab has not been clarified, however it is expected to be degraded into small peptides and amino acids like other protein drugs. •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. •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): 12.8 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.38mL/hr/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no significant differences in pharmacokinetics cross age, sex, race, progression of osteoporosis, past history of alendronic acid prescribing, and all stages of renal impairment. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemia. A patient's weight will affect their level of romosozumab exposure. Romosozumab has not been shown to be associated with carcinogenicity or impairment of fertility, and is not expected to be mutagenic. Romosozumab is not indicated in pregnancy, lactation, or pedatric patients. Romosozumab is associated with skeletal defects in the offspring of rats given romosozumab and is detected in the excreted milk. Romosozumab is currently undergoing post marketing surveillance to ensure the risk of major adverse cardiac events is not being underestimated. There is currently an expected hazard ratio of 1.30 compared to current treatments for osteoporosis, though hip and vertebral fractures may have an equal impact on overall quality of life. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Evenity 210 Mg Dose •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Romosozumab is a monoclonal antibody used to treat osteoporosis in postmenopausal women at high risk of fracture, patients who are intolerant of other treatments, or patients who have failed other treatments.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Romosozumab interact? Information: •Drug A: Abciximab •Drug B: Romosozumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Romosozumab. •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 . •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): Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments. •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): Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts. •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): Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway. Romosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts. Sclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL). Romosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption. Both effects from the same therapy have not been seen in other osteoporosis treatments to date. •Absorption (Drug A): No absorption available •Absorption (Drug B): Romosozumab reaches peak concentration within 2 to 7 days with a median time of 5 days. Subcutaneous bioavailability is 50 to 70%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 3.92L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Monoclonal antibodies are generally not protein bound. In about 10% to 18.1% of cases patients develop antibodies against romosozumab. 4.7% of the patients developed neutralizing antibodies. The presence of antibodies against romosozumab can reduce the availability of romosozumab by 22%, and 63% in the case of neutralizing antibodies. •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 romosozumab has not been clarified, however it is expected to be degraded into small peptides and amino acids like other protein drugs. •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. •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): 12.8 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.38mL/hr/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no significant differences in pharmacokinetics cross age, sex, race, progression of osteoporosis, past history of alendronic acid prescribing, and all stages of renal impairment. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemia. A patient's weight will affect their level of romosozumab exposure. Romosozumab has not been shown to be associated with carcinogenicity or impairment of fertility, and is not expected to be mutagenic. Romosozumab is not indicated in pregnancy, lactation, or pedatric patients. Romosozumab is associated with skeletal defects in the offspring of rats given romosozumab and is detected in the excreted milk. Romosozumab is currently undergoing post marketing surveillance to ensure the risk of major adverse cardiac events is not being underestimated. There is currently an expected hazard ratio of 1.30 compared to current treatments for osteoporosis, though hip and vertebral fractures may have an equal impact on overall quality of life. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Evenity 210 Mg Dose •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Romosozumab is a monoclonal antibody used to treat osteoporosis in postmenopausal women at high risk of fracture, patients who are intolerant of other treatments, or patients who have failed other treatments. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Ropeginterferon alfa-2b interact?

•Drug A: Abciximab •Drug B: Ropeginterferon alfa-2b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ropeginterferon alfa-2b. •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. •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): Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera. •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): Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential. •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): Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis. PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, JAK2 V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in JAK2 may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) in vitro. Interferon alfa-2b has been used for decades in PV despite the lack of formal approval. Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling. The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells. Interestingly, in vitro studies have revealed that ropeginterferon alfa-2b is specific to some extent for JAK2 -mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials. Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state C min was 1.4-12 ng/mL, C max was 4.4-31 ng/mL, and AUC was 1011-7809 ng*h/mL. The estimated geometric mean (%CV) of the absorption rate constant if 0.12 day (27%) and the estimated steady-state C max occurs between 2-5 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera 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): Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ropeginterferon alfa-2b is expected to be eliminated predominantly by hepatic metabolism. •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): Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 μg has a half-life of approximately seven days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 μg has a clearance of 1.7-2.5 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Besremi •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ropeginterferon alfa-2b is a mono-pegylated type I interferon used to treat polycythemia vera.

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. The severity of the interaction is minor.

Question: Does Abciximab and Ropeginterferon alfa-2b interact? Information: •Drug A: Abciximab •Drug B: Ropeginterferon alfa-2b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ropeginterferon alfa-2b. •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. •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): Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera. •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): Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential. •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): Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis. PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, JAK2 V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in JAK2 may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) in vitro. Interferon alfa-2b has been used for decades in PV despite the lack of formal approval. Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling. The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells. Interestingly, in vitro studies have revealed that ropeginterferon alfa-2b is specific to some extent for JAK2 -mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials. Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state C min was 1.4-12 ng/mL, C max was 4.4-31 ng/mL, and AUC was 1011-7809 ng*h/mL. The estimated geometric mean (%CV) of the absorption rate constant if 0.12 day (27%) and the estimated steady-state C max occurs between 2-5 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera 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): Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ropeginterferon alfa-2b is expected to be eliminated predominantly by hepatic metabolism. •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): Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 μg has a half-life of approximately seven days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 μg has a clearance of 1.7-2.5 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Besremi •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ropeginterferon alfa-2b is a mono-pegylated type I interferon used to treat polycythemia vera. Output: 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. The severity of the interaction is minor.

Does Abciximab and Rozanolixizumab interact?

•Drug A: Abciximab •Drug B: Rozanolixizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Rozanolixizumab. •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 . •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): Rozanolixizumab-noli is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. •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 pharmacological effect of rozanolixizumab-noli was assessed by measuring the decrease in serum IgG levels and AChR and MuSK autoantibody levels. In patients testing positive for AChR and MuSK autoantibodies who were treated with RYSTIGGO, there was a reduction in total IgG levels relative to baseline. Decreases in AChR autoantibody and MuSK autoantibody levels followed a similar pattern. •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): Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rozanolixizumab-noli exhibited nonlinear pharmacokinetics. Rozanolixizumab-noli exposure increased in a greater than dose-proportional manner over a dose range from 1 mg/kg to 20 mg/kg (two times the maximum recommended dose) following subcutaneous administration. Following subcutaneous administration of rozanolixizumab-noli, peak plasma levels were achieved after approximately 2 days in healthy subjects. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of rozanolixizumab-noli is 6.6 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): Rozanolixizumab-noli is expected to be degraded by proteolytic enzymes into small peptides 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): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance for the rozanolixizumab-noli is 0.89 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are limited data on rozanolixizumab-noli use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Following the administration of rozanolixizumab-noli to pregnant monkeys at doses greater than those used clinically, increases in embryonic death, reduced body weight, and impaired immune function were observed in the absence of maternal toxicity. Subcutaneous administration of rozanolixizumab-noli (0 or 150 mg/kg) every 3 days for 26 weeks to sexually mature cynomolgus monkeys resulted in no adverse effects on sperm parameters (count, motility, or morphology) or estrus cyclicity. The dose tested in monkeys is 30 times the maximum recommended human dose of approximately 10 mg/kg, on a mg/kg/week basis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rystiggo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rozanolixizumab is a humanized monoclonal antibody targeting the human neonatal Fc receptor (FcRn) used to treat generalized myasthenia gravis.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Rozanolixizumab interact? Information: •Drug A: Abciximab •Drug B: Rozanolixizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Rozanolixizumab. •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 . •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): Rozanolixizumab-noli is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. •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 pharmacological effect of rozanolixizumab-noli was assessed by measuring the decrease in serum IgG levels and AChR and MuSK autoantibody levels. In patients testing positive for AChR and MuSK autoantibodies who were treated with RYSTIGGO, there was a reduction in total IgG levels relative to baseline. Decreases in AChR autoantibody and MuSK autoantibody levels followed a similar pattern. •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): Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rozanolixizumab-noli exhibited nonlinear pharmacokinetics. Rozanolixizumab-noli exposure increased in a greater than dose-proportional manner over a dose range from 1 mg/kg to 20 mg/kg (two times the maximum recommended dose) following subcutaneous administration. Following subcutaneous administration of rozanolixizumab-noli, peak plasma levels were achieved after approximately 2 days in healthy subjects. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of rozanolixizumab-noli is 6.6 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): Rozanolixizumab-noli is expected to be degraded by proteolytic enzymes into small peptides 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): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance for the rozanolixizumab-noli is 0.89 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are limited data on rozanolixizumab-noli use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Following the administration of rozanolixizumab-noli to pregnant monkeys at doses greater than those used clinically, increases in embryonic death, reduced body weight, and impaired immune function were observed in the absence of maternal toxicity. Subcutaneous administration of rozanolixizumab-noli (0 or 150 mg/kg) every 3 days for 26 weeks to sexually mature cynomolgus monkeys resulted in no adverse effects on sperm parameters (count, motility, or morphology) or estrus cyclicity. The dose tested in monkeys is 30 times the maximum recommended human dose of approximately 10 mg/kg, on a mg/kg/week basis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rystiggo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rozanolixizumab is a humanized monoclonal antibody targeting the human neonatal Fc receptor (FcRn) used to treat generalized myasthenia gravis. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Rurioctocog alfa pegol interact?

•Drug A: Abciximab •Drug B: Rurioctocog alfa pegol •Severity: MAJOR •Description: The therapeutic efficacy of Rurioctocog alfa pegol 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. •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): Rurioctocog alfa pegol is indicated for the treatment and prophylaxis of bleeding in patients 12 years and above with hemophilia A (congenital factor VIII 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): Rurioctocog alfa pegol is a recombinant coagulation factor that promotes blood clotting. In clinical trials, personalized administration of rurioctocog alfa pegol based on each patient's clinical profile led to increased plasma levels of factor VIII and reduced bleeding episodes at six and 12 months of treatment. Rurioctocog alfa pegol has a long duration of action compared to octocog alfa: it has an extended half-life of 1.4 to 1.5-fold compared to octocog alfa in adolescents and adults. •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 VIII plays an essential role in the intrinsic pathway of the blood coagulation cascade: as a cofactor for activated factor IX (FIXa), factor VIII significantly facilitates the conversion of FIXa-mediated transformation of inactive factor X (FX) to its active form (FXa). FXa then promotes the conversion of prothrombin into thrombin, a key serine protease of the coagulation cascade. Proper blood clotting cannot be achieved with the deficient levels of factor VIII, leading to increased excessive bleeding spontaneously or as a result of accidental or surgical trauma. Hemophilia A is an X-chromosomal linked hereditary disorder of blood coagulation due to defects in the F8C gene that encodes coagulation factor VIII, leading to decreased production of functional factor VIII. Rurioctocog alfa pegol is a pegylated recombinant human factor VIII that aims to restore the plasma levels and hemostatic activity of functional factor VIII. It can be used for both prophylactic or on-demand treatment of bleeding episodes associated with hemophilia A. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration of rurioctocog alfa pegol, the mean ± SD C max was 117 ± 28 IU/dL in adolescents and 145 ± 29 IU/dL in adults. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous administration, the mean ± SD volume of distribution at steady-state was 0.54 ± 0.22 dL/kg in adolescents and 0.40 ± 0.09 dL/kg in adults. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Once rurioctocog alfa pegol enters the circulation, it binds to von Willebrand factor, just like how an endogenous factor VIII would. There is limited information on the binding profile of rurioctocog alfa pegol to plasma proteins other than von Willebrand factor. •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 rurioctocog alfa pegol; however, it is expected to undergo catabolism just like endogenous coagulation factor VIII. Metabolism pathways and CYP involvement are not known to exist regarding coagulation factors. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is limited information regarding the route of elimination of rurioctocog alfa pegol. •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 rurioctocog alfa pegol, the mean ± SD terminal half-life was 13.80 ± 4.01 hours in adolescents and 15.01 ± 3.89 hours in adults. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following intravenous administration of rurioctocog alfa pegol, the mean ± SD clearance was 2.58 ± 0.84 mL/(kg·h) in adolescents and 2.16 ± 0.75 mL/(kg·h) in adults. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information on the LD 50 of rurioctocog alfa pegol. No symptoms of overdose with recombinant coagulation factor VIII have been reported. •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): Rurioctocog alfa pegol •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rurioctocog alfa pegol is a pegylated recombinant human coagulation factor VIII used to treat and prevent bleeding episodes in patients 12 years and above with hemophilia A.

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. The severity of the interaction is major.

Question: Does Abciximab and Rurioctocog alfa pegol interact? Information: •Drug A: Abciximab •Drug B: Rurioctocog alfa pegol •Severity: MAJOR •Description: The therapeutic efficacy of Rurioctocog alfa pegol 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. •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): Rurioctocog alfa pegol is indicated for the treatment and prophylaxis of bleeding in patients 12 years and above with hemophilia A (congenital factor VIII 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): Rurioctocog alfa pegol is a recombinant coagulation factor that promotes blood clotting. In clinical trials, personalized administration of rurioctocog alfa pegol based on each patient's clinical profile led to increased plasma levels of factor VIII and reduced bleeding episodes at six and 12 months of treatment. Rurioctocog alfa pegol has a long duration of action compared to octocog alfa: it has an extended half-life of 1.4 to 1.5-fold compared to octocog alfa in adolescents and adults. •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 VIII plays an essential role in the intrinsic pathway of the blood coagulation cascade: as a cofactor for activated factor IX (FIXa), factor VIII significantly facilitates the conversion of FIXa-mediated transformation of inactive factor X (FX) to its active form (FXa). FXa then promotes the conversion of prothrombin into thrombin, a key serine protease of the coagulation cascade. Proper blood clotting cannot be achieved with the deficient levels of factor VIII, leading to increased excessive bleeding spontaneously or as a result of accidental or surgical trauma. Hemophilia A is an X-chromosomal linked hereditary disorder of blood coagulation due to defects in the F8C gene that encodes coagulation factor VIII, leading to decreased production of functional factor VIII. Rurioctocog alfa pegol is a pegylated recombinant human factor VIII that aims to restore the plasma levels and hemostatic activity of functional factor VIII. It can be used for both prophylactic or on-demand treatment of bleeding episodes associated with hemophilia A. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following intravenous administration of rurioctocog alfa pegol, the mean ± SD C max was 117 ± 28 IU/dL in adolescents and 145 ± 29 IU/dL in adults. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous administration, the mean ± SD volume of distribution at steady-state was 0.54 ± 0.22 dL/kg in adolescents and 0.40 ± 0.09 dL/kg in adults. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Once rurioctocog alfa pegol enters the circulation, it binds to von Willebrand factor, just like how an endogenous factor VIII would. There is limited information on the binding profile of rurioctocog alfa pegol to plasma proteins other than von Willebrand factor. •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 rurioctocog alfa pegol; however, it is expected to undergo catabolism just like endogenous coagulation factor VIII. Metabolism pathways and CYP involvement are not known to exist regarding coagulation factors. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is limited information regarding the route of elimination of rurioctocog alfa pegol. •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 rurioctocog alfa pegol, the mean ± SD terminal half-life was 13.80 ± 4.01 hours in adolescents and 15.01 ± 3.89 hours in adults. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following intravenous administration of rurioctocog alfa pegol, the mean ± SD clearance was 2.58 ± 0.84 mL/(kg·h) in adolescents and 2.16 ± 0.75 mL/(kg·h) in adults. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information on the LD 50 of rurioctocog alfa pegol. No symptoms of overdose with recombinant coagulation factor VIII have been reported. •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): Rurioctocog alfa pegol •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Rurioctocog alfa pegol is a pegylated recombinant human coagulation factor VIII used to treat and prevent bleeding episodes in patients 12 years and above with hemophilia A. Output: 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. The severity of the interaction is major.

Does Abciximab and Ruxolitinib interact?

•Drug A: Abciximab •Drug B: Ruxolitinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ruxolitinib. •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. •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): Ruxolitinib is indicated for the treatment of the following conditions: intermediate or high-risk myelofibrosis (MF), including prima1y MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults. It is also used to treat disease-related splenomegaly or symptoms in adult patients with these conditions. polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea. steroid-refracto1y acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older. chronic GVHD in patients aged 12 years and older who have failed one or two lines of systemic therapy. Topical ruxolitinib is indicated for: the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. the treatment of non-segmental vitiligo in adult and pediatric patients 12 years of age and older. •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): Ruxolitinib is an antineoplastic agent that inhibits cell proliferation, induces apoptosis of malignant cells, and reduces pro-inflammatory cytokine plasma levels by inhibiting JAK-induced phosphorylation of signal transducer and activator of transcription (STAT). Inhibition of STAT3 phosphorylation, which is used as a marker of JAK activity, by ruxolitinib is achieved at two hours after dosing which returned to near baseline by 10 hours in patients with myelofibrosis and polycythemia vera. In clinical trials, ruxolitinib reduced splenomegaly and improved symptoms of myelofibrosis. In a mouse model of myeloproliferative neoplasms, administration of ruxolitinib was associated with prolonged survival. Ruxolitinib inhibits both mutant and wild-type JAK2; however, JAK2V617F mutation, which is often seen in approximately 50% of patients with myelofibrosis, was shown to reduce ruxolitinib sensitivity, which may also be associated with possible resistance to JAK inhibitor 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): The Janus kinase (JAK) family of protein tyrosine kinases comprises JAK1, JAK2, JAK3, and non-receptor tyrosine kinase 2 (TYK2). JAKs play a pivotal role in intracellular signalling pathways of various cytokines and growth factors essential to hematopoiesis, such as interleukin, erythropoietin, and thrombopoietin. JAKs have diverse functions: JAK1 and JAK3 promote lymphocyte differentiation, survival, and function, while JAK2 promotes signal transduction of erythropoietin and thrombopoietin. JAKs are in close proximity to the cytokine and growth factor receptor’s cytoplasmic region. Upon binding of cytokines and growth factors, JAKs are activated, undergoing cross-phosphorylation and tyrosine phosphorylation. This process also reveals selective binding sites for STATs, which are DNA-binding proteins that also bind to the cytoplasmic region of cytokine or growth factor receptors. Activated JAKs and STATs translocate to the nucleus as transcription factors to regulate gene expression of pro-inflammatory cytokines such as IL-6, IL-10, and nuclear factor κB (NF-κB). They also activate downstream pathways that promote erythroid, myeloid, and megakaryocytic development. The molecular pathogenesis of myeloproliferative neoplasms is not fully understood; however, JAK2 is constitutively activated and the JAK-STAT signalling pathway becomes deregulated and aberrant. Ruxolitinib is a selective and potent inhibitor of JAK2 and JAK1, with some affinity against JAK3 and TYK2. Anticancer effects of ruxolitinib are attributed to its inhibition of JAKs and JAK-mediated phosphorylation of STAT3. By downregulating the JAK-STAT pathway, ruxolitinib inhibits myeloproliferation and suppresses the plasma levels of pro-inflammatory cytokines such as IL-6 and TNF-α. Activated JAKs are also implicated in graft-versus-host-disease (GVHD), which is a severe immune complication of allogeneic hematopoietic cell transplantation GVHD is associated with significant morbidity and mortality, especially for patients who do not respond well to corticosteroid therapy. Activated JAKS stimulate T-effector cell responses, leading to increased proliferation of effector T cells and heightened production of pro-inflammatory cytokines. By blocking JAK1 and JAk2, ruxolitinib inhibits donor T-cell expansion and suppresses pro-inflammatory responses. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, ruxolitinib undergoes rapid absorption and the peak concentrations are reached within one hour after administration. Over a single-dose range of 5 mg to 200 mg, the mean maximal plasma concentration (C max ) increases proportionally. C max ranged from 205 nM to 7100 nM and AUC ranged from 862 nM x hr to 30700 nM x hr. T max ranges from one to two hours following oral administration. Oral bioavailability is at least 95%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution (%coefficient of variation) at steady-state is 72 L (29%) in patients with myelofibrosis and 75 L (23%) in patients with polycythemia vera. It is not known whether ruxolitinib crosses the blood-brain barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ruxolitinib is approximately 97% bound to plasma proteins, mostly 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): More than 99% of orally-administered ruxolitinib undergoes metabolism mediated by CYP3A4 and, to a lesser extent, CYP2C9. The major circulating metabolites in human plasma were M18 formed by 2-hydroxylation, and M16 and M27 (stereoisomers) formed by 3-hydroxylation. Other identified metabolites include M9 and M49, which are formed by hydroxylation and ketone formation. Not all metabolite structures are fully characterized and it is speculated that many metabolites exist in stereoisomers. Metabolites of ruxolitinib retain inhibitory activity against JAK1 and JAk2 to a lesser degree than the parent drug. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following oral administration of a single radiolabeled dose of ruxolitinib, the drug was mainly eliminated through metabolism. About 74% of the total dose was excreted in urine and 22% was excreted in feces, mostly in the form of hydroxyl and oxo metabolites of ruxolitinib. The unchanged parent drug accounted for less than 1% of the excreted total radioactivity. •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 ruxolitinib is approximately 3 hours and the mean half-life of its metabolites is approximately 5.8 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ruxolitinib clearance (% coefficient of variation) is 17.7 L/h in women and 22.1 L/h in men with myelofibrosis. Drug clearance was 12.7 L/h (42%) in patients with polycythemia vera and 11.9 L/h (43%) in patients with acute graft-versus-host disease. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 was 250 mg/kg. Single doses of ruxolitinib up to 200 mg were tolerated well. Higher doses than recommended repeat doses are associated with myelosuppression, including leukopenia, anemia, and thrombocytopenia. There is no known antidote for overdoses with ruxolitinib: it is recommended that patients are given appropriate supportive treatment. Hemodialysis is not expected to enhance the elimination of ruxolitinib. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jakafi, Jakavi, Opzelura •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ruxolitinib is a kinase inhibitor used to treat various types of myelofibrosis, polycythemia vera in patients who have not responded to or cannot tolerate hydroxyurea, and to treat graft-versus-host disease in cases that are refractory to steroid treatment.

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. The severity of the interaction is minor.

Question: Does Abciximab and Ruxolitinib interact? Information: •Drug A: Abciximab •Drug B: Ruxolitinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ruxolitinib. •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. •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): Ruxolitinib is indicated for the treatment of the following conditions: intermediate or high-risk myelofibrosis (MF), including prima1y MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults. It is also used to treat disease-related splenomegaly or symptoms in adult patients with these conditions. polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea. steroid-refracto1y acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older. chronic GVHD in patients aged 12 years and older who have failed one or two lines of systemic therapy. Topical ruxolitinib is indicated for: the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. the treatment of non-segmental vitiligo in adult and pediatric patients 12 years of age and older. •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): Ruxolitinib is an antineoplastic agent that inhibits cell proliferation, induces apoptosis of malignant cells, and reduces pro-inflammatory cytokine plasma levels by inhibiting JAK-induced phosphorylation of signal transducer and activator of transcription (STAT). Inhibition of STAT3 phosphorylation, which is used as a marker of JAK activity, by ruxolitinib is achieved at two hours after dosing which returned to near baseline by 10 hours in patients with myelofibrosis and polycythemia vera. In clinical trials, ruxolitinib reduced splenomegaly and improved symptoms of myelofibrosis. In a mouse model of myeloproliferative neoplasms, administration of ruxolitinib was associated with prolonged survival. Ruxolitinib inhibits both mutant and wild-type JAK2; however, JAK2V617F mutation, which is often seen in approximately 50% of patients with myelofibrosis, was shown to reduce ruxolitinib sensitivity, which may also be associated with possible resistance to JAK inhibitor 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): The Janus kinase (JAK) family of protein tyrosine kinases comprises JAK1, JAK2, JAK3, and non-receptor tyrosine kinase 2 (TYK2). JAKs play a pivotal role in intracellular signalling pathways of various cytokines and growth factors essential to hematopoiesis, such as interleukin, erythropoietin, and thrombopoietin. JAKs have diverse functions: JAK1 and JAK3 promote lymphocyte differentiation, survival, and function, while JAK2 promotes signal transduction of erythropoietin and thrombopoietin. JAKs are in close proximity to the cytokine and growth factor receptor’s cytoplasmic region. Upon binding of cytokines and growth factors, JAKs are activated, undergoing cross-phosphorylation and tyrosine phosphorylation. This process also reveals selective binding sites for STATs, which are DNA-binding proteins that also bind to the cytoplasmic region of cytokine or growth factor receptors. Activated JAKs and STATs translocate to the nucleus as transcription factors to regulate gene expression of pro-inflammatory cytokines such as IL-6, IL-10, and nuclear factor κB (NF-κB). They also activate downstream pathways that promote erythroid, myeloid, and megakaryocytic development. The molecular pathogenesis of myeloproliferative neoplasms is not fully understood; however, JAK2 is constitutively activated and the JAK-STAT signalling pathway becomes deregulated and aberrant. Ruxolitinib is a selective and potent inhibitor of JAK2 and JAK1, with some affinity against JAK3 and TYK2. Anticancer effects of ruxolitinib are attributed to its inhibition of JAKs and JAK-mediated phosphorylation of STAT3. By downregulating the JAK-STAT pathway, ruxolitinib inhibits myeloproliferation and suppresses the plasma levels of pro-inflammatory cytokines such as IL-6 and TNF-α. Activated JAKs are also implicated in graft-versus-host-disease (GVHD), which is a severe immune complication of allogeneic hematopoietic cell transplantation GVHD is associated with significant morbidity and mortality, especially for patients who do not respond well to corticosteroid therapy. Activated JAKS stimulate T-effector cell responses, leading to increased proliferation of effector T cells and heightened production of pro-inflammatory cytokines. By blocking JAK1 and JAk2, ruxolitinib inhibits donor T-cell expansion and suppresses pro-inflammatory responses. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, ruxolitinib undergoes rapid absorption and the peak concentrations are reached within one hour after administration. Over a single-dose range of 5 mg to 200 mg, the mean maximal plasma concentration (C max ) increases proportionally. C max ranged from 205 nM to 7100 nM and AUC ranged from 862 nM x hr to 30700 nM x hr. T max ranges from one to two hours following oral administration. Oral bioavailability is at least 95%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution (%coefficient of variation) at steady-state is 72 L (29%) in patients with myelofibrosis and 75 L (23%) in patients with polycythemia vera. It is not known whether ruxolitinib crosses the blood-brain barrier. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ruxolitinib is approximately 97% bound to plasma proteins, mostly 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): More than 99% of orally-administered ruxolitinib undergoes metabolism mediated by CYP3A4 and, to a lesser extent, CYP2C9. The major circulating metabolites in human plasma were M18 formed by 2-hydroxylation, and M16 and M27 (stereoisomers) formed by 3-hydroxylation. Other identified metabolites include M9 and M49, which are formed by hydroxylation and ketone formation. Not all metabolite structures are fully characterized and it is speculated that many metabolites exist in stereoisomers. Metabolites of ruxolitinib retain inhibitory activity against JAK1 and JAk2 to a lesser degree than the parent drug. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following oral administration of a single radiolabeled dose of ruxolitinib, the drug was mainly eliminated through metabolism. About 74% of the total dose was excreted in urine and 22% was excreted in feces, mostly in the form of hydroxyl and oxo metabolites of ruxolitinib. The unchanged parent drug accounted for less than 1% of the excreted total radioactivity. •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 ruxolitinib is approximately 3 hours and the mean half-life of its metabolites is approximately 5.8 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ruxolitinib clearance (% coefficient of variation) is 17.7 L/h in women and 22.1 L/h in men with myelofibrosis. Drug clearance was 12.7 L/h (42%) in patients with polycythemia vera and 11.9 L/h (43%) in patients with acute graft-versus-host disease. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 was 250 mg/kg. Single doses of ruxolitinib up to 200 mg were tolerated well. Higher doses than recommended repeat doses are associated with myelosuppression, including leukopenia, anemia, and thrombocytopenia. There is no known antidote for overdoses with ruxolitinib: it is recommended that patients are given appropriate supportive treatment. Hemodialysis is not expected to enhance the elimination of ruxolitinib. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jakafi, Jakavi, Opzelura •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ruxolitinib is a kinase inhibitor used to treat various types of myelofibrosis, polycythemia vera in patients who have not responded to or cannot tolerate hydroxyurea, and to treat graft-versus-host disease in cases that are refractory to steroid treatment. Output: 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. The severity of the interaction is minor.

Does Abciximab and Sacituzumab govitecan interact?

•Drug A: Abciximab •Drug B: Sacituzumab govitecan •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Sacituzumab govitecan. •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 . •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): Sacituzumab govitecan is indicated for adult patients with unresectable locally-advanced or metastatic triple-negative breast cancer (mTNBC) who have undergone two or more prior therapies for metastatic disease by the FDA, Health Canada, and EMA. It is also indicated for the treatment of unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. These indications are approved in the US, Canada, and Europe. In the US, sacituzumab govitecan is additionally indicated for the treatment of locally advanced or metastatic urothelial cancer in adult patients who have received previous platinum-based therapy and either a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication has been approved under accelerated approval, and continued approval may be contingent on the demonstration of clinical benefit in confirmatory trials. •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): Sacituzumab govitecan is a humanized monoclonal antibody/topoisomerase inhibitor conjugate designed to induce DNA damage-mediated cell death preferentially in TROP-2-expressing cancer cells. Detailed pharmacodynamic studies have not been performed for sacituzumab govitecan, although as a therapeutic protein, there is potential for immunogenicity. In addition, sacituzumab govitecan has the potential to cause severe hypersensitivity, nausea and vomiting, and embryo-fetal toxicity. Patients who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia. •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): Sacituzumab govitecan is an antibody-drug conjugate (ADC) targeting TROP-2-expressing cancer cells to induce DNA-damage-mediated cell death. The conjugate comprises a humanized anti-TROP-2 monoclonal antibody (RS7-3G11, also known as RS7) chemically linked by a hydrolyzable CL2A linker to the cytotoxic drug SN-38. The proposed mechanism of action first involves the binding of the RS7 component to TROP-2, which is highly expressed on the cell surface of multiple cancers. Binding of RS7 to TROP-2 results in rapid internalization of bound antibody, and the likely intracellular release of SN-38 via hydrolysis of the CL2A linker. SN-38 is an active metabolite of the anti-cancer drug irinotecan, which is thought to work primarily through inhibition of DNA topoisomerase I, leading to DNA damage and eventual cell death. In addition, recent work has identified a possible secondary mechanism of action for SN-38 by disrupting the binding of Far Upstream Binding Protein 1 (FUBP1) to the FUSE elements regulating oncogene expression. In addition to SN-38-mediated cell death, there is also some evidence that the RS7 component of the conjugate drug possesses antibody-directed cellular toxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients receiving 10 mg/kg sacituzumab govitecan the C max of the conjugate was 243,000 ± 45,600 ng/mL while the C max of free SN-38 was 127 ± 60 ng/mL. Similarly, the AUC 0-168 for the conjugate/free SN-38 was 5,210,000 ± 1,230,000 and 3,900 ± 1,830 ng*h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Sacituzumab govitecan has a mean volume of distribution of 0.045 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): SN-38, the active moiety, remains mostly bound to the IgG component in serum. In patients administered with 10 mg/kg of sacituzumab govitecan, free SN-38 serum levels were measured as 2.3% and 4.5% at 30 minutes and one day, respectively. •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 sacituzumab govitecan has not been extensively studied. The SN-38 moiety is known to undergo O-glucuronidation by UGT1A1, presumably in the liver, and the SN-38 glucuronide metabolite SN-38G is found in the serum of patients undergoing treatment. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No detailed information exists for sacituzumab govitecan elimination; renal elimination of SN-38 is known to be minimal, and it is expected that the fecal route will be the major contributor. •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): Sacituzumab govitecan has a mean half-life of 16 hours, while free SN-38 has a mean half-life of 18 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Sacituzumab govitecan has a clearance rate of 0.002 L/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding sacituzumab govitecan is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as neutropenia, diarrhea, hypersensitivity, nausea/vomiting, and other systemic effects related to cytotoxic drugs. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trodelvy •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Sacituzumab govitecan is sacituzumab govitecan targets TROP-2-expressing cancer cells through a humanized antibody (RS7) before subsequently becoming internalized and releasing the topoisomerase I inhibitor SN-38 to induce DNA damage-mediated apoptosis.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Sacituzumab govitecan interact? Information: •Drug A: Abciximab •Drug B: Sacituzumab govitecan •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Sacituzumab govitecan. •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 . •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): Sacituzumab govitecan is indicated for adult patients with unresectable locally-advanced or metastatic triple-negative breast cancer (mTNBC) who have undergone two or more prior therapies for metastatic disease by the FDA, Health Canada, and EMA. It is also indicated for the treatment of unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. These indications are approved in the US, Canada, and Europe. In the US, sacituzumab govitecan is additionally indicated for the treatment of locally advanced or metastatic urothelial cancer in adult patients who have received previous platinum-based therapy and either a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication has been approved under accelerated approval, and continued approval may be contingent on the demonstration of clinical benefit in confirmatory trials. •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): Sacituzumab govitecan is a humanized monoclonal antibody/topoisomerase inhibitor conjugate designed to induce DNA damage-mediated cell death preferentially in TROP-2-expressing cancer cells. Detailed pharmacodynamic studies have not been performed for sacituzumab govitecan, although as a therapeutic protein, there is potential for immunogenicity. In addition, sacituzumab govitecan has the potential to cause severe hypersensitivity, nausea and vomiting, and embryo-fetal toxicity. Patients who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia. •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): Sacituzumab govitecan is an antibody-drug conjugate (ADC) targeting TROP-2-expressing cancer cells to induce DNA-damage-mediated cell death. The conjugate comprises a humanized anti-TROP-2 monoclonal antibody (RS7-3G11, also known as RS7) chemically linked by a hydrolyzable CL2A linker to the cytotoxic drug SN-38. The proposed mechanism of action first involves the binding of the RS7 component to TROP-2, which is highly expressed on the cell surface of multiple cancers. Binding of RS7 to TROP-2 results in rapid internalization of bound antibody, and the likely intracellular release of SN-38 via hydrolysis of the CL2A linker. SN-38 is an active metabolite of the anti-cancer drug irinotecan, which is thought to work primarily through inhibition of DNA topoisomerase I, leading to DNA damage and eventual cell death. In addition, recent work has identified a possible secondary mechanism of action for SN-38 by disrupting the binding of Far Upstream Binding Protein 1 (FUBP1) to the FUSE elements regulating oncogene expression. In addition to SN-38-mediated cell death, there is also some evidence that the RS7 component of the conjugate drug possesses antibody-directed cellular toxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients receiving 10 mg/kg sacituzumab govitecan the C max of the conjugate was 243,000 ± 45,600 ng/mL while the C max of free SN-38 was 127 ± 60 ng/mL. Similarly, the AUC 0-168 for the conjugate/free SN-38 was 5,210,000 ± 1,230,000 and 3,900 ± 1,830 ng*h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Sacituzumab govitecan has a mean volume of distribution of 0.045 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): SN-38, the active moiety, remains mostly bound to the IgG component in serum. In patients administered with 10 mg/kg of sacituzumab govitecan, free SN-38 serum levels were measured as 2.3% and 4.5% at 30 minutes and one day, respectively. •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 sacituzumab govitecan has not been extensively studied. The SN-38 moiety is known to undergo O-glucuronidation by UGT1A1, presumably in the liver, and the SN-38 glucuronide metabolite SN-38G is found in the serum of patients undergoing treatment. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No detailed information exists for sacituzumab govitecan elimination; renal elimination of SN-38 is known to be minimal, and it is expected that the fecal route will be the major contributor. •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): Sacituzumab govitecan has a mean half-life of 16 hours, while free SN-38 has a mean half-life of 18 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Sacituzumab govitecan has a clearance rate of 0.002 L/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding sacituzumab govitecan is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as neutropenia, diarrhea, hypersensitivity, nausea/vomiting, and other systemic effects related to cytotoxic drugs. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trodelvy •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Sacituzumab govitecan is sacituzumab govitecan targets TROP-2-expressing cancer cells through a humanized antibody (RS7) before subsequently becoming internalized and releasing the topoisomerase I inhibitor SN-38 to induce DNA damage-mediated apoptosis. Output: 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 . The severity of the interaction is minor.

Does Abciximab and Safinamide interact?

•Drug A: Abciximab •Drug B: Safinamide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Safinamide is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Safinamide is indicated as an add-on treatment to levodopa with or without other medicines for Parkinson’s 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): 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): Safinamide is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapid with peak plasma concentrations ranging from 2 to 4 h, total bioavailability is 95%. Food prolonged the rate and did not affect the extent of absorption of safinamide. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1.8 litres/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 88–90% •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 principal step is mediated by amidases which have not been identified, and produces safinamide acid. It is also metabolized to O-debenzylated safinamide and N-delkylated amine. The N-dealkylated amine is then oxidized to a carboxylic acid and finally glucuronidated. Dealkylation reactions are mediated by cytochrome P450s (CYPs), especially CYP3A4. Safinamide acid binds to organic anion transporter 3 (OAT3), but no clinical relevance of this interaction has been determined. Safinamide also binds to ABCG2 transiently. No other transporter affinities have been found in preliminary studies. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 76% renal, 1.5% faeces •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): 22 h •Clearance (Drug A): No clearance available •Clearance (Drug B): total oral clearance of plasma, which accounts for parent safinamide as well as metabolites, was on average only 17.53 ± 2.71 ml/h × kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): uncontrolled involuntary movement, falls, nausea, and trouble sleeping or falling asleep (insomnia) Patients who have an overdose may experience hypertension (high blood pressure), orthostatic hypotension, hallucinations, psychomotor agitation, nausea, vomiting, and dyskinesia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Xadago •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Safinamide is a MAO-B inhibitor used as an add-on treatment to levodopa/carbidopa for Parkinson's disease during "off" episodes.

It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Safinamide interact? Information: •Drug A: Abciximab •Drug B: Safinamide •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Safinamide is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •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): Safinamide is indicated as an add-on treatment to levodopa with or without other medicines for Parkinson’s 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): 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): Safinamide is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapid with peak plasma concentrations ranging from 2 to 4 h, total bioavailability is 95%. Food prolonged the rate and did not affect the extent of absorption of safinamide. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1.8 litres/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 88–90% •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 principal step is mediated by amidases which have not been identified, and produces safinamide acid. It is also metabolized to O-debenzylated safinamide and N-delkylated amine. The N-dealkylated amine is then oxidized to a carboxylic acid and finally glucuronidated. Dealkylation reactions are mediated by cytochrome P450s (CYPs), especially CYP3A4. Safinamide acid binds to organic anion transporter 3 (OAT3), but no clinical relevance of this interaction has been determined. Safinamide also binds to ABCG2 transiently. No other transporter affinities have been found in preliminary studies. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 76% renal, 1.5% faeces •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): 22 h •Clearance (Drug A): No clearance available •Clearance (Drug B): total oral clearance of plasma, which accounts for parent safinamide as well as metabolites, was on average only 17.53 ± 2.71 ml/h × kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): uncontrolled involuntary movement, falls, nausea, and trouble sleeping or falling asleep (insomnia) Patients who have an overdose may experience hypertension (high blood pressure), orthostatic hypotension, hallucinations, psychomotor agitation, nausea, vomiting, and dyskinesia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Xadago •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Safinamide is a MAO-B inhibitor used as an add-on treatment to levodopa/carbidopa for Parkinson's disease during "off" episodes. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Salicylic acid interact?

•Drug A: Abciximab •Drug B: Salicylic acid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Salicylic acid 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. •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): Key additive in many skin-care products for the treatment of acne, psoriasis, callouses, corns, keratosis pilaris and warts. •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): Salicylic acid treats acne by causing skin cells to slough off more readily, preventing pores from clogging up. This effect on skin cells also makes salicylic acid an active ingredient in several shampoos meant to treat dandruff. Use of straight salicylic solution may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock. Subsalicylate in combination with bismuth form the popular stomach relief aid known commonly as Pepto-Bismol. When combined the two key ingredients help control diarrhea, nausea, heartburn, and even gas. It is also very mildly anti-biotic. •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): Salicylic acid directly irreversibly inhibits COX-1 and COX-2 to decrease conversion of arachidonic acid to precursors of prostaglandins and thromboxanes. Salicylate's use in rheumatic diseases is due to it's analgesic and anti-inflammatory activity. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Salicylic acid allows cells of the epidermis to more readily slough off. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid competitively inhibits oxidation of uridine-5-diphosphoglucose (UDPG) with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of the glucuronyl group of uridine-5-phosphoglucuronic acid (UDPGA) to a phenolic acceptor. Inhibition of mucopoly saccharide synthesis is likely responsible for the slowing of wound healing with salicylates. •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 about 170 mL/kg of body weight. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Salicylic acid is about 90% 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): Salicylic acid is extensively metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 10% is excreted unchanged 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): 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): Oral rat LD50: 891 mg/kg. Inhalation rat LC50: > 900 mg/m3/1hr. Irritation: skin rabbit: 500 mg/24H mild. Eye rabbit: 100 mg severe. Investigated a mutagen and reproductive effector. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Actikerall, Bensal, Bioelements Active Astringent, Cantharone Plus, Clearasil, Diprosalic, Keralyt, Salex, Saliject, Salinocaine, Salvax, Ultrasal, Virasal •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Salicylic acid is an acid used to treat acne, psoriasis, calluses, corns, keratosis pilaris, and warts.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Salicylic acid interact? Information: •Drug A: Abciximab •Drug B: Salicylic acid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Salicylic acid 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. •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): Key additive in many skin-care products for the treatment of acne, psoriasis, callouses, corns, keratosis pilaris and warts. •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): Salicylic acid treats acne by causing skin cells to slough off more readily, preventing pores from clogging up. This effect on skin cells also makes salicylic acid an active ingredient in several shampoos meant to treat dandruff. Use of straight salicylic solution may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock. Subsalicylate in combination with bismuth form the popular stomach relief aid known commonly as Pepto-Bismol. When combined the two key ingredients help control diarrhea, nausea, heartburn, and even gas. It is also very mildly anti-biotic. •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): Salicylic acid directly irreversibly inhibits COX-1 and COX-2 to decrease conversion of arachidonic acid to precursors of prostaglandins and thromboxanes. Salicylate's use in rheumatic diseases is due to it's analgesic and anti-inflammatory activity. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Salicylic acid allows cells of the epidermis to more readily slough off. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid competitively inhibits oxidation of uridine-5-diphosphoglucose (UDPG) with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of the glucuronyl group of uridine-5-phosphoglucuronic acid (UDPGA) to a phenolic acceptor. Inhibition of mucopoly saccharide synthesis is likely responsible for the slowing of wound healing with salicylates. •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 about 170 mL/kg of body weight. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Salicylic acid is about 90% 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): Salicylic acid is extensively metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 10% is excreted unchanged 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): 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): Oral rat LD50: 891 mg/kg. Inhalation rat LC50: > 900 mg/m3/1hr. Irritation: skin rabbit: 500 mg/24H mild. Eye rabbit: 100 mg severe. Investigated a mutagen and reproductive effector. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Actikerall, Bensal, Bioelements Active Astringent, Cantharone Plus, Clearasil, Diprosalic, Keralyt, Salex, Saliject, Salinocaine, Salvax, Ultrasal, Virasal •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Salicylic acid is an acid used to treat acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Salsalate interact?

•Drug A: Abciximab •Drug B: Salsalate •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Salsalate 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. •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 relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders. •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): Salsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo. •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 mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 (COX-1) and COX-2, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salsalate) is a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, salsalate does not inhibit platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Salsalate is insoluble in acid gastric fluids (< 0.1 mg/ml at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged. The amount of salicylic acid available from salsalate is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salsalate/5 g aspirin). Food slows the absorption of all salicylates including salsalate. •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): Salicylate: 90-95% bound at plasma salicylate concentrations <100 mcg/mL; 70-85% bound at concentrations of 100-400 mcg/mL; 25-60% bound at concentrations >400 mcg/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): Salsalate is readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body. •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 parent compound has an elimination half-life of about 1 hour. Salicylic acid (the active metabolite) biotransformation is saturated at anti-inflammatory doses of salsalate. Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Death has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome. •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): Disalicylic acid Disalicylsäure O-Salicylcylsalicylsäure o-Salicylsalicylic acid Salicylic acid bimolecular ester Salicyloxysalicylic acid Salicyloylsalicylic acid Salicylsalicylic acid Salsalate Salsalato Salsalatum Sasapyrin Sasapyrine Sasapyrinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Salsalate is a nonsteroidal anti-inflammatory agent used in the symptomatic relief of rheumatoid arthritis, osteoarthritis and related rheumatic disorders.

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. The severity of the interaction is moderate.

Question: Does Abciximab and Salsalate interact? Information: •Drug A: Abciximab •Drug B: Salsalate •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Salsalate 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. •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 relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders. •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): Salsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo. •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 mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 (COX-1) and COX-2, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salsalate) is a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, salsalate does not inhibit platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Salsalate is insoluble in acid gastric fluids (< 0.1 mg/ml at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged. The amount of salicylic acid available from salsalate is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salsalate/5 g aspirin). Food slows the absorption of all salicylates including salsalate. •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): Salicylate: 90-95% bound at plasma salicylate concentrations <100 mcg/mL; 70-85% bound at concentrations of 100-400 mcg/mL; 25-60% bound at concentrations >400 mcg/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): Salsalate is readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body. •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 parent compound has an elimination half-life of about 1 hour. Salicylic acid (the active metabolite) biotransformation is saturated at anti-inflammatory doses of salsalate. Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Death has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome. •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): Disalicylic acid Disalicylsäure O-Salicylcylsalicylsäure o-Salicylsalicylic acid Salicylic acid bimolecular ester Salicyloxysalicylic acid Salicyloylsalicylic acid Salicylsalicylic acid Salsalate Salsalato Salsalatum Sasapyrin Sasapyrine Sasapyrinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Salsalate is a nonsteroidal anti-inflammatory agent used in the symptomatic relief of rheumatoid arthritis, osteoarthritis and related rheumatic disorders. Output: 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. The severity of the interaction is moderate.

Does Abciximab and Sarilumab interact?

•Drug A: Abciximab •Drug B: Sarilumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Sarilumab. •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 . •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): Sarilumab is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs); and adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. •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): Single-dose subcutaneous administration of sarilumab produced a rapid reduction of CRP levels, leading to normal levels after two weeks of treatment. Peak reduction in the absolute neutrophile count was observed after 3 to 4 days of treatment, followed by a recovery to baseline levels. A decrease in fibrinogen and serum amyloid A and an increase in hemoglobin and serum albumin were also detected. •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): Sarilumab is a human recombinant IgG1 antibody that binds to both forms of interleukin 6 receptors (IL-6R), thus inhibiting IL-6-mediated signaling. IL-6 is a pleiotropic cytokine that activates immune cells (T and B cells) and hepatocytes for the release of acute phase proteins like CRP, serum amyloid A and fibrinogen, which are biomarkers of rheumatoid arthritis (RA) activity. IL-6 is also found in synovial fluid and plays a major role in the pathological inflammation and joint destruction features of RA. Thus, it is used for the treatment of RA due to its ability to inhibit intra-articular and systemic IL-6 signaling. •Absorption (Drug A): No absorption available •Absorption (Drug B): Sarilumab is shown to be well absorbed in patients with rheumatoid arthritis after single subcutaneous administration, with a maximum serum concentration presented after 2 to 4 days. For the 150 mg every two weeks dose regimen, the AUC, C min and C max of sarilumab were 202 ± 120 mg.day/L, 6.35 ± 7.54 mg/L, and 20.0 ± 9.20 mg/L, respectively. For the 200 mg every two weeks dose regimen, the AUC, C min and C max of sarilumab were 395 ± 207 mg.day/L, 16.5 ± 14.1 mg/L, and 35.6 ± 15.2 mg/L, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with rheumatoid arthritis, the apparent volume of distribution at steady state was 7.3 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Sarilumab is a covalent heterotetramer composed of two disulfide-linked heavy chains covalently linked to a kappa light chain. The heavy chain has an IgG1 constant region with a single N-linked glycosylation site in the Fc portion of the molecule. The complementarity-determining regions (CDRs) within variable domains of both light and heavy chains combine to form the binding site for IL-6R. As an IgG1 molecule, sarilumab may mediate Fc-effector function upon binding to IL-6Ra, and it is prompt to bind to FcγRI, FcγRIIa, FCγRIIb, FcγRIIIa and FcγRIIIB. •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 sarilumab has not been characterized. As a monoclonal antibody, it is thought to be degraded into small peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): At high concentrations, sarilumab is thought to be eliminated predominantly through a non-saturated proteolytic pathway, while at lower concentrations, the elimination will be done by saturable target-mediated elimination. As a monoclonal antibody, sarilumab is not eliminated through renal or hepatic pathways. •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 will depend on the administered concentration. At 200 mg every 2 weeks, half-life is up to 10 days in patients with rheumatoid arthritis (RA) at steady state. At 150 mg every 2 weeks, half-life is up to 8 days in patients with RA at steady state. After the last steady state dose of 150 and 200 mg, the time to reach nondetectable concentration is 28 and 43 days, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Sarilumab is not eliminated via renal or hepatic pathways. Patients with rheumatoid arthritis have shown a trend toward higher clearance in the presence of anti-sarilumab antibodies. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Repeat dose exposure has been shown to produce a partially reversible decrease in neutrophil count and a reversible decrease in fibrinogen. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kevzara •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Sarilumab is a monoclonal antibody used to treat moderate to severe rheumatoid arthritis who have responded poorly or are intolerant of other DMARDs.

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 . The severity of the interaction is minor.

Question: Does Abciximab and Sarilumab interact? Information: •Drug A: Abciximab •Drug B: Sarilumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Sarilumab. •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 . •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): Sarilumab is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs); and adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. •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): Single-dose subcutaneous administration of sarilumab produced a rapid reduction of CRP levels, leading to normal levels after two weeks of treatment. Peak reduction in the absolute neutrophile count was observed after 3 to 4 days of treatment, followed by a recovery to baseline levels. A decrease in fibrinogen and serum amyloid A and an increase in hemoglobin and serum albumin were also detected. •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): Sarilumab is a human recombinant IgG1 antibody that binds to both forms of interleukin 6 receptors (IL-6R), thus inhibiting IL-6-mediated signaling. IL-6 is a pleiotropic cytokine that activates immune cells (T and B cells) and hepatocytes for the release of acute phase proteins like CRP, serum amyloid A and fibrinogen, which are biomarkers of rheumatoid arthritis (RA) activity. IL-6 is also found in synovial fluid and plays a major role in the pathological inflammation and joint destruction features of RA. Thus, it is used for the treatment of RA due to its ability to inhibit intra-articular and systemic IL-6 signaling. •Absorption (Drug A): No absorption available •Absorption (Drug B): Sarilumab is shown to be well absorbed in patients with rheumatoid arthritis after single subcutaneous administration, with a maximum serum concentration presented after 2 to 4 days. For the 150 mg every two weeks dose regimen, the AUC, C min and C max of sarilumab were 202 ± 120 mg.day/L, 6.35 ± 7.54 mg/L, and 20.0 ± 9.20 mg/L, respectively. For the 200 mg every two weeks dose regimen, the AUC, C min and C max of sarilumab were 395 ± 207 mg.day/L, 16.5 ± 14.1 mg/L, and 35.6 ± 15.2 mg/L, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with rheumatoid arthritis, the apparent volume of distribution at steady state was 7.3 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Sarilumab is a covalent heterotetramer composed of two disulfide-linked heavy chains covalently linked to a kappa light chain. The heavy chain has an IgG1 constant region with a single N-linked glycosylation site in the Fc portion of the molecule. The complementarity-determining regions (CDRs) within variable domains of both light and heavy chains combine to form the binding site for IL-6R. As an IgG1 molecule, sarilumab may mediate Fc-effector function upon binding to IL-6Ra, and it is prompt to bind to FcγRI, FcγRIIa, FCγRIIb, FcγRIIIa and FcγRIIIB. •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 sarilumab has not been characterized. As a monoclonal antibody, it is thought to be degraded into small peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): At high concentrations, sarilumab is thought to be eliminated predominantly through a non-saturated proteolytic pathway, while at lower concentrations, the elimination will be done by saturable target-mediated elimination. As a monoclonal antibody, sarilumab is not eliminated through renal or hepatic pathways. •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 will depend on the administered concentration. At 200 mg every 2 weeks, half-life is up to 10 days in patients with rheumatoid arthritis (RA) at steady state. At 150 mg every 2 weeks, half-life is up to 8 days in patients with RA at steady state. After the last steady state dose of 150 and 200 mg, the time to reach nondetectable concentration is 28 and 43 days, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Sarilumab is not eliminated via renal or hepatic pathways. Patients with rheumatoid arthritis have shown a trend toward higher clearance in the presence of anti-sarilumab antibodies. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Repeat dose exposure has been shown to produce a partially reversible decrease in neutrophil count and a reversible decrease in fibrinogen. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kevzara •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Sarilumab is a monoclonal antibody used to treat moderate to severe rheumatoid arthritis who have responded poorly or are intolerant of other DMARDs. Output: 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 . The severity of the interaction is minor.