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Does Abciximab and Cefpodoxime interact?

•Drug A: Abciximab •Drug B: Cefpodoxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefpodoxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefpodoxime is shown to be effective against most Gram positive and Gram negative bacteria, except Pseudomonas aeruginosa, Enterococcus, and Bacteroides fragilis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefpodoxime is active against a wide spectrum of Gram-positive and Gram-negative bacteria. Cefpodoxime is stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and cephalosporins, due to their production of beta-lactamase, may be susceptible to cefpodoxime. Cefpodoxime is inactivated by certain extended spectrum beta-lactamases. The bactericidal activity of cefpodoxime results from its inhibition of cell wall synthesis. The active metabolite of cefpodoxime binds preferentially to penicillin binding protein 3, which inhibits production of peptidoglycan, the primary constituent of bacterial cell walls. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cefpodoxime proxetil is a prodrug that is absorbed from the gastrointestinal tract and de-esterified to its active metabolite, cefpodoxime. Following oral administration of 100 mg of cefpodoxime proxetil to fasting subjects, approximately 50% of the administered cefpodoxime dose was absorbed systemically. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 22 to 33% in serum and from 21 to 29% in plasma. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Over the recommended dosing range (100 to 400 mg), approximately 29 to 33% of the administered cefpodoxime dose was excreted unchanged in the urine in 12 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): 2.09 to 2.84 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): 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): Cefpodoxime is a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including gonorrhea, community acquired pneumonia, and sinusitis.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Cefpodoxime interact? Information: •Drug A: Abciximab •Drug B: Cefpodoxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefpodoxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefpodoxime is shown to be effective against most Gram positive and Gram negative bacteria, except Pseudomonas aeruginosa, Enterococcus, and Bacteroides fragilis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefpodoxime is active against a wide spectrum of Gram-positive and Gram-negative bacteria. Cefpodoxime is stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and cephalosporins, due to their production of beta-lactamase, may be susceptible to cefpodoxime. Cefpodoxime is inactivated by certain extended spectrum beta-lactamases. The bactericidal activity of cefpodoxime results from its inhibition of cell wall synthesis. The active metabolite of cefpodoxime binds preferentially to penicillin binding protein 3, which inhibits production of peptidoglycan, the primary constituent of bacterial cell walls. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cefpodoxime proxetil is a prodrug that is absorbed from the gastrointestinal tract and de-esterified to its active metabolite, cefpodoxime. Following oral administration of 100 mg of cefpodoxime proxetil to fasting subjects, approximately 50% of the administered cefpodoxime dose was absorbed systemically. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 22 to 33% in serum and from 21 to 29% in plasma. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Over the recommended dosing range (100 to 400 mg), approximately 29 to 33% of the administered cefpodoxime dose was excreted unchanged in the urine in 12 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): 2.09 to 2.84 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): 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): Cefpodoxime is a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including gonorrhea, community acquired pneumonia, and sinusitis. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Cefprozil interact?

•Drug A: Abciximab •Drug B: Cefprozil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefprozil. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of the following infections (respiratory, skin, soft tissue, UTI, ENT) caused by; S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefprozil, a semisynthetic, second-generation cephalosporin, is used to treat otitis media, soft-tissue infections, and respiratory tract infections. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefprozil, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefprozil interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral bioavailability is approximately 95%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.23 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 36% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Cefprozil is eliminated primarily by the kidneys •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.3 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 3 mL/min/kg [fasting subjects] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Single 5000 mg/kg oral doses of cefprozil caused no mortality or signs of toxicity in adult, weaning or neonatal rats, or adult mice. A single oral dose of 3000 mg/kg caused diarrhea and loss of appetite in cynomolgus monkeys, but no mortality. •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): Cefprozil Cefprozilo Cefprozilum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cefprozil is a cephalosporin antibiotic used in the treatment of various bacterial infections, such as pharyngitis, tonsillitis, otitis media, and uncomplicated skin infections.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Cefprozil interact? Information: •Drug A: Abciximab •Drug B: Cefprozil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefprozil. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of the following infections (respiratory, skin, soft tissue, UTI, ENT) caused by; S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefprozil, a semisynthetic, second-generation cephalosporin, is used to treat otitis media, soft-tissue infections, and respiratory tract infections. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefprozil, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefprozil interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral bioavailability is approximately 95%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.23 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 36% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Cefprozil is eliminated primarily by the kidneys •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.3 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 3 mL/min/kg [fasting subjects] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Single 5000 mg/kg oral doses of cefprozil caused no mortality or signs of toxicity in adult, weaning or neonatal rats, or adult mice. A single oral dose of 3000 mg/kg caused diarrhea and loss of appetite in cynomolgus monkeys, but no mortality. •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): Cefprozil Cefprozilo Cefprozilum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cefprozil is a cephalosporin antibiotic used in the treatment of various bacterial infections, such as pharyngitis, tonsillitis, otitis media, and uncomplicated skin infections. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Cefradine interact?

•Drug A: Abciximab •Drug B: Cefradine •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefradine. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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): Cefradine is a first generation cephalosporin antibiotic with a spectrum of activity similar to Cefalexin. Cefradine, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Cefradine interferes with an autolysin inhibitor. •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): Over 90 percent of the drug is excreted unchanged in the urine within six 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): 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): Cefradina Cefradine Cefradinum Cephradin Cephradine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cefradine is a first-generation cephalosporin antibiotic used in the treatment of bacterial infections of the respiratory and urinary tracts and of the skin and soft tissues.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Cefradine interact? Information: •Drug A: Abciximab •Drug B: Cefradine •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefradine. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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): Cefradine is a first generation cephalosporin antibiotic with a spectrum of activity similar to Cefalexin. Cefradine, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Cefradine interferes with an autolysin inhibitor. •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): Over 90 percent of the drug is excreted unchanged in the urine within six 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): 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): Cefradina Cefradine Cefradinum Cephradin Cephradine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cefradine is a first-generation cephalosporin antibiotic used in the treatment of bacterial infections of the respiratory and urinary tracts and of the skin and soft tissues. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftaroline fosamil interact?

•Drug A: Abciximab •Drug B: Ceftaroline fosamil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftaroline fosamil. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftaroline fosamil is indicated for the treatment of patients with the following infections caused by susceptible isolates of the designated microorganisms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): The time that unbound plasma concentration of ceftaroline exceeds the minimum inhibitory concentration (MIC) of the infecting organism has been shown to best correlate with efficacy in a neutropenic murine thigh infection model with S. aureus and S. pneumoniae. No significant effect on QTc (corrected QT interval) interval was detected at peak plasma concentration or at any other 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): Ceftaroline fosamil is an antibacterial drug. •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): Median 20.3 L (18.3-21.6 L). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): approximately 20%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ceftaroline fosamil is converted into bioactive ceftaroline in plasma by a phosphatase enzyme. Hydrolysis of the beta-lactam ring of ceftaroline occurs to form the microbiologically inactive, open-ring metabolite ceftaroline M-1. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): primarily eliminated by the kidneys (6% in feces within 48 hours). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.60 hours (600 mg dose). •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50/LC50: Draize test, rabbit, eye: 100 mg/24H Moderate; Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Teflaro, Zinforo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftarolina fosamilo Ceftaroline Ceftaroline fosamil Ceftarolinum fosamilum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftaroline fosamil is an antibacterial agent used to treat various bacterial infections, such as acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftaroline fosamil interact? Information: •Drug A: Abciximab •Drug B: Ceftaroline fosamil •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftaroline fosamil. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftaroline fosamil is indicated for the treatment of patients with the following infections caused by susceptible isolates of the designated microorganisms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): The time that unbound plasma concentration of ceftaroline exceeds the minimum inhibitory concentration (MIC) of the infecting organism has been shown to best correlate with efficacy in a neutropenic murine thigh infection model with S. aureus and S. pneumoniae. No significant effect on QTc (corrected QT interval) interval was detected at peak plasma concentration or at any other 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): Ceftaroline fosamil is an antibacterial drug. •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): Median 20.3 L (18.3-21.6 L). •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): approximately 20%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ceftaroline fosamil is converted into bioactive ceftaroline in plasma by a phosphatase enzyme. Hydrolysis of the beta-lactam ring of ceftaroline occurs to form the microbiologically inactive, open-ring metabolite ceftaroline M-1. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): primarily eliminated by the kidneys (6% in feces within 48 hours). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.60 hours (600 mg dose). •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50/LC50: Draize test, rabbit, eye: 100 mg/24H Moderate; Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Teflaro, Zinforo •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftarolina fosamilo Ceftaroline Ceftaroline fosamil Ceftarolinum fosamilum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftaroline fosamil is an antibacterial agent used to treat various bacterial infections, such as acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftazidime interact?

•Drug A: Abciximab •Drug B: Ceftazidime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftazidime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftazidime is indicated for the treatment of lower respiratory tract infections, skin and skin structure infections, urinary tract infections, bacterial septicemia, bone and joint infections, gynecologic infections, intra-abdominal infections (including peritonitis), and central nervous system infections (including meningitis) caused by susceptible bacteria. Ceftazidime is indicated in combination with avibactam to treat infections caused by susceptible Gram-negative organisms, including complicated intra-abdominal infections (cIAI), in conjunction with metronidazole, and complicated urinary tract infections (cUTI), including pyelonephritis, in patients aged three months and older. This combination is also indicated to treat hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients aged 18 years and older. In all cases, to mitigate the risk of bacterial resistance and preserve clinical efficacy, ceftazidime should only be used for infections that are confirmed or strongly suspected to be caused by susceptible bacterial strains. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3). Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, including Pseudomonas aeruginosa. However, it is less active than first- and second-generation cephalosporins against Staphylococcus aureus and other Gram-positive bacteria and also has low activity against anaerobes. Ceftazidime has confirmed activity against clinically relevant Gram-negative bacteria including Citrobacter spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., _Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, and some Gram-positive bacteria including Staphylococcus spp. and Streptococcus spp. There are also in vitro data for ceftazidime efficacy against a wide variety of other bacteria, such as Acinetobacter baumannii and Neisseria gonorrhoeae, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria. Although β-lactam antibiotics like ceftazidime are generally well tolerated, there remains a risk of serious acute hypersensitivity reactions, which is higher in patients with a known allergy to ceftazidime or any other β-lactam antibiotic. As with all antibiotics, ceftazidime may result in the overgrowth of non-susceptible organisms and potentially serious effects including Clostridium difficile -associated diarrhea (CDAD); CDAD should be considered in patients who develop diarrhea and, in confirmed cases, supportive care initiated immediately. Ceftazidime is primarily renally excreted such that high and prolonged serum concentrations can occur in patients with renal insufficiency, leading to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Treatment may lead to the development or induction of resistance with a risk of treatment failure. Periodic susceptibility testing should be considered, and monotherapy failure may necessitate the addition of another antibiotic such as an aminoglycoside. Cephalosporin use may decrease prothrombin activity, which may be improved by exogenous vitamin K. Inadvertent intra-arterial administration of ceftazidime may result in distal necrosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal. Ceftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria. In vitro experiments in Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae suggest that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2 as well; although binding to other PBPs, such as PBP4, is detectable, the concentrations required are much greater than those achieved clinically. Similarly, ceftazidime showed binding to Staphylococcus aureus PBP 1, 2, and 3 with a much lower affinity for PBP4. Recent data for Mycobacterium abcessus suggest that ceftazidime can inhibit PonA1, PonA2, and PbpA at intermediate concentrations. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ceftazidime administered intravenously in healthy males produced mean C max values of between 42 and 170 μg/mL for doses between 500 mg and 2 g, and are reached immediately following the end of the infusion period. The C max for 1 g of ceftazidime administered intramuscularly is attained approximately one hour following injection and is between 37 and 43 mg/L. Following intramuscular administration of 500 mg and 1 g of ceftazidime, the serum concentration remained above 4 μg/mL for six and eight hours, respectively. Ceftazidime C max and AUC show linear proportionality to the dose over the therapeutic range. In individuals with normal renal function, ceftazidime given intravenously every eight hours for 10 days as either 1 or 2 g doses showed no accumulation. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Ceftazidime has a volume of distribution of 15-20 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ceftazidime plasma protein binding ranges from 5-22.8% (typically less than 10%) and is independent of concentration. Ceftazidime has been shown to bind human serum 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): Ceftazidime is not appreciably metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 80% to 90% of an intramuscular or intravenous dose of ceftazidime is excreted unchanged by the kidneys over a 24-hour period. When administered intravenously, 50% of the dose appears in the urine within two hours, with another 32% of the dose appearing by eight hours post-administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Ceftazidime has an elimination half-life of 1.5-2.8 hours in healthy subjects. As ceftazidime is primarily renally excreted, its half-life is significantly prolonged in patients with renal impairment. In patients with creatinine clearance < 12 mL/min, the half-life is prolonged to between 14 and 30 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean renal clearance of ceftazidime in healthy subjects ranges from 72 to 141 mL/min while the calculated plasma clearance is approximately 115 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ceftazidime overdosage has occurred in patients with renal failure. Reactions included seizure activity, encephalopathy, asterixis, neuromuscular excitability, and coma. Patients who receive an acute overdosage should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis or peritoneal dialysis may aid in the removal of ceftazidime from the body. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Avycaz, Fortaz, Tazicef, Zavicefta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftazidim Ceftazidima Ceftazidime Ceftazidimum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftazidime is an injected broad-spectrum third-generation cephalosporin beta-lactam antibiotic used to treat or prevent a variety of bacterial infections, including pneumonia, gynecological infections, bone and joint infections, and septicemia, among others.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftazidime interact? Information: •Drug A: Abciximab •Drug B: Ceftazidime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftazidime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftazidime is indicated for the treatment of lower respiratory tract infections, skin and skin structure infections, urinary tract infections, bacterial septicemia, bone and joint infections, gynecologic infections, intra-abdominal infections (including peritonitis), and central nervous system infections (including meningitis) caused by susceptible bacteria. Ceftazidime is indicated in combination with avibactam to treat infections caused by susceptible Gram-negative organisms, including complicated intra-abdominal infections (cIAI), in conjunction with metronidazole, and complicated urinary tract infections (cUTI), including pyelonephritis, in patients aged three months and older. This combination is also indicated to treat hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients aged 18 years and older. In all cases, to mitigate the risk of bacterial resistance and preserve clinical efficacy, ceftazidime should only be used for infections that are confirmed or strongly suspected to be caused by susceptible bacterial strains. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3). Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, including Pseudomonas aeruginosa. However, it is less active than first- and second-generation cephalosporins against Staphylococcus aureus and other Gram-positive bacteria and also has low activity against anaerobes. Ceftazidime has confirmed activity against clinically relevant Gram-negative bacteria including Citrobacter spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., _Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, and some Gram-positive bacteria including Staphylococcus spp. and Streptococcus spp. There are also in vitro data for ceftazidime efficacy against a wide variety of other bacteria, such as Acinetobacter baumannii and Neisseria gonorrhoeae, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria. Although β-lactam antibiotics like ceftazidime are generally well tolerated, there remains a risk of serious acute hypersensitivity reactions, which is higher in patients with a known allergy to ceftazidime or any other β-lactam antibiotic. As with all antibiotics, ceftazidime may result in the overgrowth of non-susceptible organisms and potentially serious effects including Clostridium difficile -associated diarrhea (CDAD); CDAD should be considered in patients who develop diarrhea and, in confirmed cases, supportive care initiated immediately. Ceftazidime is primarily renally excreted such that high and prolonged serum concentrations can occur in patients with renal insufficiency, leading to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Treatment may lead to the development or induction of resistance with a risk of treatment failure. Periodic susceptibility testing should be considered, and monotherapy failure may necessitate the addition of another antibiotic such as an aminoglycoside. Cephalosporin use may decrease prothrombin activity, which may be improved by exogenous vitamin K. Inadvertent intra-arterial administration of ceftazidime may result in distal necrosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal. Ceftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria. In vitro experiments in Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae suggest that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2 as well; although binding to other PBPs, such as PBP4, is detectable, the concentrations required are much greater than those achieved clinically. Similarly, ceftazidime showed binding to Staphylococcus aureus PBP 1, 2, and 3 with a much lower affinity for PBP4. Recent data for Mycobacterium abcessus suggest that ceftazidime can inhibit PonA1, PonA2, and PbpA at intermediate concentrations. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ceftazidime administered intravenously in healthy males produced mean C max values of between 42 and 170 μg/mL for doses between 500 mg and 2 g, and are reached immediately following the end of the infusion period. The C max for 1 g of ceftazidime administered intramuscularly is attained approximately one hour following injection and is between 37 and 43 mg/L. Following intramuscular administration of 500 mg and 1 g of ceftazidime, the serum concentration remained above 4 μg/mL for six and eight hours, respectively. Ceftazidime C max and AUC show linear proportionality to the dose over the therapeutic range. In individuals with normal renal function, ceftazidime given intravenously every eight hours for 10 days as either 1 or 2 g doses showed no accumulation. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Ceftazidime has a volume of distribution of 15-20 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ceftazidime plasma protein binding ranges from 5-22.8% (typically less than 10%) and is independent of concentration. Ceftazidime has been shown to bind human serum 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): Ceftazidime is not appreciably metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 80% to 90% of an intramuscular or intravenous dose of ceftazidime is excreted unchanged by the kidneys over a 24-hour period. When administered intravenously, 50% of the dose appears in the urine within two hours, with another 32% of the dose appearing by eight hours post-administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Ceftazidime has an elimination half-life of 1.5-2.8 hours in healthy subjects. As ceftazidime is primarily renally excreted, its half-life is significantly prolonged in patients with renal impairment. In patients with creatinine clearance < 12 mL/min, the half-life is prolonged to between 14 and 30 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean renal clearance of ceftazidime in healthy subjects ranges from 72 to 141 mL/min while the calculated plasma clearance is approximately 115 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ceftazidime overdosage has occurred in patients with renal failure. Reactions included seizure activity, encephalopathy, asterixis, neuromuscular excitability, and coma. Patients who receive an acute overdosage should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis or peritoneal dialysis may aid in the removal of ceftazidime from the body. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Avycaz, Fortaz, Tazicef, Zavicefta •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftazidim Ceftazidima Ceftazidime Ceftazidimum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftazidime is an injected broad-spectrum third-generation cephalosporin beta-lactam antibiotic used to treat or prevent a variety of bacterial infections, including pneumonia, gynecological infections, bone and joint infections, and septicemia, among others. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftibuten interact?

•Drug A: Abciximab •Drug B: Ceftibuten •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftibuten. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsilitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftibuten is an antibiotic with bactericidal actions. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ceftibuten exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall. This binding leads to inhibition of cell-wall synthesis. •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): 0.21 L/kg [adult subjects] 0.5 L/kg [fasting pediatric patients] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ceftibuten is 65% bound to plasma proteins. The protein binding is independent of plasma ceftibuten concentration. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): A study with radiolabeled ceftibuten administered to 6 healthy adult male volunteers demonstrated that cis-ceftibuten is the predominant component in both plasma and urine. About 10% of ceftibuten is converted to the trans-isomer is approximately 1/8 as antimicrobially potent as the cis-isomer. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ceftibuten is excreted in the urine; 95% of the administered radioactivity was recovered either in 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): 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): Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cedax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftibuten Ceftibutene Ceftibuteno Ceftibutenum cis-ceftibuten •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftibuten is a third-generation cephalosporin antibiotic commonly used in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsillitis.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftibuten interact? Information: •Drug A: Abciximab •Drug B: Ceftibuten •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftibuten. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsilitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftibuten is an antibiotic with bactericidal actions. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ceftibuten exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall. This binding leads to inhibition of cell-wall synthesis. •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): 0.21 L/kg [adult subjects] 0.5 L/kg [fasting pediatric patients] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ceftibuten is 65% bound to plasma proteins. The protein binding is independent of plasma ceftibuten concentration. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): A study with radiolabeled ceftibuten administered to 6 healthy adult male volunteers demonstrated that cis-ceftibuten is the predominant component in both plasma and urine. About 10% of ceftibuten is converted to the trans-isomer is approximately 1/8 as antimicrobially potent as the cis-isomer. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ceftibuten is excreted in the urine; 95% of the administered radioactivity was recovered either in 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): 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): Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cedax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftibuten Ceftibutene Ceftibuteno Ceftibutenum cis-ceftibuten •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftibuten is a third-generation cephalosporin antibiotic commonly used in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsillitis. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftizoxime interact?

•Drug A: Abciximab •Drug B: Ceftizoxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftizoxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cetizoxime was previously indicated for the treatment of infections due to susceptible strains of bacteria. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftizoxime is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ceftizoxime is an aminothiazolyl cephalosporin with an extended spectrum of activity against many gram-negative, nosocomially acquired pathogens. It has excellent beta-lactamase stability, with good in vitro activity against Haemophilus influenzae, Neisseria gonorrhoeae and Klebsiella pneumoniae. Ceftizoxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that ceftizoxime interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean apparent volume of distribution ranges between 15 - 28L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 30% protein-bound across the standard concentration range. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ceftizoxime is not metabolized and is excreted virtually unchanged by the kidneys in 24 hours. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excreted virtually unchanged by the kidneys in 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 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): Cefizox •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftizoxima Ceftizoxime Ceftizoximum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftizoxime is a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including lower respiratory tract infection, urinary tract infection, and gonorrhea.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftizoxime interact? Information: •Drug A: Abciximab •Drug B: Ceftizoxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftizoxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cetizoxime was previously indicated for the treatment of infections due to susceptible strains of bacteria. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftizoxime is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ceftizoxime is an aminothiazolyl cephalosporin with an extended spectrum of activity against many gram-negative, nosocomially acquired pathogens. It has excellent beta-lactamase stability, with good in vitro activity against Haemophilus influenzae, Neisseria gonorrhoeae and Klebsiella pneumoniae. Ceftizoxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that ceftizoxime interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean apparent volume of distribution ranges between 15 - 28L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 30% protein-bound across the standard concentration range. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ceftizoxime is not metabolized and is excreted virtually unchanged by the kidneys in 24 hours. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Excreted virtually unchanged by the kidneys in 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 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): Cefizox •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ceftizoxima Ceftizoxime Ceftizoximum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ceftizoxime is a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including lower respiratory tract infection, urinary tract infection, and gonorrhea. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftobiprole medocaril interact?

•Drug A: Abciximab •Drug B: Ceftobiprole medocaril •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftobiprole medocaril. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftobiprole medocaril is an antibacterial indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis. It is additionally indicated in adult patients with acute bacterial skin and skin structure infections (ABSSSI). It is indicated in adult and pediatric patients ≥3 months of age for the treatment of community-acquired bacterial pneumonia (CABP). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Zevtera •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): Ceftobiprole medocaril is a cephalosporin indicated in the treatment of pneumonia.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftobiprole medocaril interact? Information: •Drug A: Abciximab •Drug B: Ceftobiprole medocaril •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftobiprole medocaril. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftobiprole medocaril is an antibacterial indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis. It is additionally indicated in adult patients with acute bacterial skin and skin structure infections (ABSSSI). It is indicated in adult and pediatric patients ≥3 months of age for the treatment of community-acquired bacterial pneumonia (CABP). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Zevtera •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): Ceftobiprole medocaril is a cephalosporin indicated in the treatment of pneumonia. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftobiprole interact?

•Drug A: Abciximab •Drug B: Ceftobiprole •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftobiprole. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftobiprole, administered as a pro-drug ( ceftobiprole medocaril ), is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis.[L50442] It is additionally indicated in adult patients with acute bacterial skin and skin structure infections (ABSSSI).[L50442] It is indicated in adult and pediatric patients ≥3 months of age for the treatment of community-acquired bacterial pneumonia (CABP).[L50442] •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistant Staphylococcus aureus. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cephalosporins, such as ceftobiprole, are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan. •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): Ceftobiprole is a cephalosporin antibiotic used to treat both community and hospital-acquired pneumonia caused by susceptible bacteria.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftobiprole interact? Information: •Drug A: Abciximab •Drug B: Ceftobiprole •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftobiprole. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftobiprole, administered as a pro-drug ( ceftobiprole medocaril ), is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis.[L50442] It is additionally indicated in adult patients with acute bacterial skin and skin structure infections (ABSSSI).[L50442] It is indicated in adult and pediatric patients ≥3 months of age for the treatment of community-acquired bacterial pneumonia (CABP).[L50442] •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistant Staphylococcus aureus. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cephalosporins, such as ceftobiprole, are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan. •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): Ceftobiprole is a cephalosporin antibiotic used to treat both community and hospital-acquired pneumonia caused by susceptible bacteria. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Ceftriaxone interact?

•Drug A: Abciximab •Drug B: Ceftriaxone •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftriaxone. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftriaxone is used for the treatment of the infections (respiratory, skin, soft tissue, UTI, ENT) caused by susceptible organisms. Organisms that are generally susceptible to ceftriaxone include S. pneumoniae, S. pyogenes (group A beta-hemolytic streptococci), coagulase-negative staphylococci, Some Enterobacter spp, H. influenzae, N. gonorrhoeae, P. mirabilis, E. coli, Klebsiella spp, M. catarrhalis, B. burgdorferi, and some oral anaerobes. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has in vitro activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ceftriaxone is only given as an injection, either intramuscularly or intravenously. Ceftriaxone is less than 1% bioavailable if given orally. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of an intravenous or intramuscular dose in healthy patients is 5.78 to 13.5 L. The volume of distribution of an intravenous or intramuscular dose in septic patients is 6.48 to 35.2 L. Ceftriaxone has good enough CSF penetration to be used as an effective treatment of bacterial meningitis. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ceftriaxone is 95% 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): Metabolism of ceftriaxone is negligible. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ceftriaxone is primarily eliminated in the urine (33-67%). The remainder is eliminated through secretion in the bile and removed from the body via 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 ceftriaxone is 5.8-8.7 hours. The half-life of ceftriaxone in the middle ear fluid has been estimated to be 25 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of ceftriaxone in healthy adults receiving a 0.15-3g dose is 0.58 to 1.45 L/hour. The renal clearance of ceftriaxone is 0.32 to 0.73 L/hour. In intensive care unit patients, ceftriaxone's total drug clearance was 0.96L/h (0.55-1.28 L/h), and unbound drug clearance was 1.91 L/h (1.46-6.20 L/h). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ceftriaxone overdose may increase the risk of urolithiasis and subsequent post-renal acute renal failure (PARF). Other symptoms of overdose unavailable in the literature. However, they are likely similar to the adverse effects of the medication. If overdose of ceftriaxone occurs, treat with symptomatic and supportive treatment, as ceftriaxone levels will not be reduced by dialysis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rocephin •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): Ceftriaxone is a broad-spectrum cephalosporin antibiotic used for the treatment of bacterial infections in various locations, such as in the respiratory tract, skin, soft tissue, and urinary tract.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Ceftriaxone interact? Information: •Drug A: Abciximab •Drug B: Ceftriaxone •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftriaxone. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ceftriaxone is used for the treatment of the infections (respiratory, skin, soft tissue, UTI, ENT) caused by susceptible organisms. Organisms that are generally susceptible to ceftriaxone include S. pneumoniae, S. pyogenes (group A beta-hemolytic streptococci), coagulase-negative staphylococci, Some Enterobacter spp, H. influenzae, N. gonorrhoeae, P. mirabilis, E. coli, Klebsiella spp, M. catarrhalis, B. burgdorferi, and some oral anaerobes. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has in vitro activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ceftriaxone is only given as an injection, either intramuscularly or intravenously. Ceftriaxone is less than 1% bioavailable if given orally. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of an intravenous or intramuscular dose in healthy patients is 5.78 to 13.5 L. The volume of distribution of an intravenous or intramuscular dose in septic patients is 6.48 to 35.2 L. Ceftriaxone has good enough CSF penetration to be used as an effective treatment of bacterial meningitis. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ceftriaxone is 95% 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): Metabolism of ceftriaxone is negligible. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ceftriaxone is primarily eliminated in the urine (33-67%). The remainder is eliminated through secretion in the bile and removed from the body via 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 ceftriaxone is 5.8-8.7 hours. The half-life of ceftriaxone in the middle ear fluid has been estimated to be 25 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of ceftriaxone in healthy adults receiving a 0.15-3g dose is 0.58 to 1.45 L/hour. The renal clearance of ceftriaxone is 0.32 to 0.73 L/hour. In intensive care unit patients, ceftriaxone's total drug clearance was 0.96L/h (0.55-1.28 L/h), and unbound drug clearance was 1.91 L/h (1.46-6.20 L/h). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ceftriaxone overdose may increase the risk of urolithiasis and subsequent post-renal acute renal failure (PARF). Other symptoms of overdose unavailable in the literature. However, they are likely similar to the adverse effects of the medication. If overdose of ceftriaxone occurs, treat with symptomatic and supportive treatment, as ceftriaxone levels will not be reduced by dialysis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rocephin •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): Ceftriaxone is a broad-spectrum cephalosporin antibiotic used for the treatment of bacterial infections in various locations, such as in the respiratory tract, skin, soft tissue, and urinary tract. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Cefuroxime interact?

•Drug A: Abciximab •Drug B: Cefuroxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefuroxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 many different types of bacterial infections such as bronchitis, sinusitis, tonsillitis, ear infections, skin infections, gonorrhea, and urinary tract infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefuroxime is a β-lactam type antibiotic. More specifically, it is a second-generation cephalosporin. Cephalosporins work the same way as penicillins: they interfere with the peptidoglycan synthesis of the bacterial wall by inhibiting the final transpeptidation needed for the cross-links. This effect is bactericidal. Cefuroxime is effective against the following organisms: Aerobic Gram-positive Microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes. Aerobic Gram-negative Microorganisms: Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including beta-lactamase-producing strains), Neisseria gonorrhoeae (including beta-lactamase-producing strains). Spirochetes: Borrelia burgdorferi. Cefuroxime axetil is the prodrug •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefuroxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefuroxime interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorbed from the gastrointestinal tract. Absorption is greater when taken after food (absolute bioavailability increases from 37% to 52%). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 50% to serum 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): The axetil moiety is metabolized to acetaldehyde and acetic 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): Approximately 80 minutes following intramuscular or intravenous injection. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Allergic reactions might be expected, including rash, nasal congestion, cough, dry throat, eye irritation, or anaphylactic shock. Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ceftin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Cefuroxim Cefuroxima Cefuroxime Cefuroximo Cefuroximum Cephuroxime •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cefuroxime is a cephalosporin indicated for the treatment of a variety of infections including acute bacterial otitis media, several upper respiratory tract infections, skin infections, urinary tract infections, gonorrhea, early Lyme disease, and impetigo.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Cefuroxime interact? Information: •Drug A: Abciximab •Drug B: Cefuroxime •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefuroxime. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 many different types of bacterial infections such as bronchitis, sinusitis, tonsillitis, ear infections, skin infections, gonorrhea, and urinary tract infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cefuroxime is a β-lactam type antibiotic. More specifically, it is a second-generation cephalosporin. Cephalosporins work the same way as penicillins: they interfere with the peptidoglycan synthesis of the bacterial wall by inhibiting the final transpeptidation needed for the cross-links. This effect is bactericidal. Cefuroxime is effective against the following organisms: Aerobic Gram-positive Microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes. Aerobic Gram-negative Microorganisms: Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including beta-lactamase-producing strains), Neisseria gonorrhoeae (including beta-lactamase-producing strains). Spirochetes: Borrelia burgdorferi. Cefuroxime axetil is the prodrug •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cefuroxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefuroxime interferes with an autolysin inhibitor. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorbed from the gastrointestinal tract. Absorption is greater when taken after food (absolute bioavailability increases from 37% to 52%). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 50% to serum 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): The axetil moiety is metabolized to acetaldehyde and acetic 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): Approximately 80 minutes following intramuscular or intravenous injection. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Allergic reactions might be expected, including rash, nasal congestion, cough, dry throat, eye irritation, or anaphylactic shock. Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ceftin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Cefuroxim Cefuroxima Cefuroxime Cefuroximo Cefuroximum Cephuroxime •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cefuroxime is a cephalosporin indicated for the treatment of a variety of infections including acute bacterial otitis media, several upper respiratory tract infections, skin infections, urinary tract infections, gonorrhea, early Lyme disease, and impetigo. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Celecoxib interact?

•Drug A: Abciximab •Drug B: Celecoxib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Celecoxib 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): Celecoxib is indicated for symptomatic treatment of adult osteoarthritis (OA) and adult rheumatoid arthritis (RA). Celecoxib is not a substitute for aspirin for cardiovascular event prophylaxis. It may be also be used to treat acute pain from various sources, juvenile rheumatoid arthritis in children over 2, ankylosing spondylitis, and primary dysmenorrhea. Celecoxib, in combination with tramadol, is indicated for the management of acute pain in adults severe enough to require an opioid analgesic and in whom alternative treatments are inadequate. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Celecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding. A note on the risk of cardiovascular events Significant concerns regarding the safety of COX-2 selective NSAIDs emerged in the early 2000s. Rofecoxib, another member of the COX-2 inhibitor drug class, also known as Vioxx, was withdrawn from the market due to prothrombotic cardiovascular risks. Following an FDA Advisory Committee meeting in 2005, in which data from large clinical outcome trials were evaluated, the FDA concluded that the risk for cardiovascular thrombotic events for both COX-2 selective NSAIDs and nonselective NSAIDs was evident. It was determined that the benefits of celecoxib treatment, however, outweighed the risks. Postmarketing cardiovascular outcomes trial (PRECISION) revealed that the lowest possible dose of celecoxib was similar in cardiovascular safety to moderate strength doses of both naproxen and ibuprofen. Patients who had previous cardiovascular events including acute MI, coronary revascularization, or coronary stent insertion were not evaluated in the trial. It is not advisable to administer NSAIDS to these groups of 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): Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. COX-2 is expressed heavily in inflamed tissues where it is induced by inflammatory mediators. The inhibition of this enzyme reduces the synthesis of metabolites that include prostaglandin E2 (PGE2), prostacyclin (PGI2), thromboxane (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 (PGF2). Resultant inhibition of these mediators leads to the alleviation of pain and inflammation. By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. Celecoxib poses less of an ulceration risk than other NSAIDS, owing to its decreased effect on gastric mucosal prostaglandin synthesis when compared to placebo. Celecoxib exerts anticancer effects by binding to the cadherin-11 (CDH11)protein, which is thought to be involved in the progression of tumors, and inhibiting the 3-phosphoinositide-dependent kinase-1 (PDK-1) signaling mechanism. In addition, celecoxib has been found to inhibit carbonic anhydrase enzymes 2 and 3, further enhancing its anticancer effects. As mentioned in the pharmacodynamics section of this drug entry, celecoxib may cause an increased risk of thrombotic events. The risk of thrombosis resulting from COX-2 inhibition is caused by the vasoconstricting actions of thromboxane A2, leading to enhanced platelet aggregation, which is uncontrolled when the actions of prostacyclin, a platelet aggregation inhibitor, are suppressed through the inhibition of COX-2. •Absorption (Drug A): No absorption available •Absorption (Drug B): Celecoxib is absorbed rapidly in the gastrointestinal tract. When a single oral dose of 200 mg was given to healthy research subjects, the peak plasma levels of celecoxib occurred within 3 hours. The Cmax is 705 ng/mL. When multiple doses are given, steady-state concentrations are reached on or before day 5. When taken with a high-fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. The AUC of celecoxib has been shown to be significantly lower in patients with chronic renal impairment. A meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher AUC (area under the curve) of celecoxib in black patients compared to Caucasians for unknown reasons. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of celecoxib at steady state (Vss/F) is about 429 L, which suggests wide distribution into various tissues. Celecoxib is not preferentially bound to red blood cells. Another resource reports a volume of distribution of 455 ± 166L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding of celecoxib is 97%, and it is primarily 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): A large part of celecoxib metabolism is mediated by cytochrome P450 2C9 in the liver with some contribution from CYP3A4 and CYP2C8 and possible contributions from CYP2D6. It is metabolized by biotransformation to carboxylic acid and glucuronide metabolites. Three metabolites, a primary alcohol, a carboxylic acid, and a glucuronide conjugate, have been found in human plasma after celecoxib administration. These are considered inactive metabolites in regards to COX enzyme inhibition. Patients who are known or suspected to have decreased cytochrome P450 2C9 activity or function, based on their previous history, should be administered celecoxib with caution as they may have abnormally high serum concentrations resulting from decreased metabolism celecoxib. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Celecoxib is primarily eliminated by hepatic metabolism with small amounts (<3%) of the unchanged drug found in both the urine and feces. About 57% of an oral dose of celecoxib is excreted in the feces and 27% is found to be excreted into the urine in the form of metabolites. The main metabolite in urine and feces is identified as the carboxylic acid metabolite (73%). The amount of glucuronide in the urine is reported to be low. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 effective half-life of celecoxib is approximately 11 hours when a single 200 mg dose is given to healthy subjects. The terminal half-life of celecoxib varies because of its low solubility, which prolongs absorption. •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance (CL/F), single oral 200 mg dose, healthy subjects = 27.7 L/hr. Clearance may be decreased by about 47% in patients with chronic renal insufficiency, according to a pharmacokinetic study. Studies have not been performed in patients with severe renal impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral TDLo in humans 5.71 mg/kg. It is not advisable to administer celecoxib in patients with renal impairment or advanced hepatic impairment, as this may lead to increased serum concentrations, causing toxicity. Symptoms of overdose may include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting. Because serious gastrointestinal tract ulceration and bleeding can occur without preceding symptoms, patients should be monitored for signs/symptoms of gastrointestinal bleeding. Symptomatic and supportive measures should be taken in a celecoxib overdose. The induction of emesis or administration of active charcoal should take place if the patient is seen within 4 hours of celecoxib ingestion. Diuresis, urinary alkalinization, hemodialysis, or hemoperfusion may not be useful in a celecoxib overdose due to its high level of protein binding. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Celebrex, Elyxyb, Seglentis •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Celecoxib Célécoxib Celecoxibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Celecoxib is an NSAID used to treat osteoarthritis, rheumatoid arthritis, acute pain, menstrual symptoms, and to reduce polyps is familial adenomatous polyposis.

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 Celecoxib interact? Information: •Drug A: Abciximab •Drug B: Celecoxib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Celecoxib 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): Celecoxib is indicated for symptomatic treatment of adult osteoarthritis (OA) and adult rheumatoid arthritis (RA). Celecoxib is not a substitute for aspirin for cardiovascular event prophylaxis. It may be also be used to treat acute pain from various sources, juvenile rheumatoid arthritis in children over 2, ankylosing spondylitis, and primary dysmenorrhea. Celecoxib, in combination with tramadol, is indicated for the management of acute pain in adults severe enough to require an opioid analgesic and in whom alternative treatments are inadequate. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Celecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding. A note on the risk of cardiovascular events Significant concerns regarding the safety of COX-2 selective NSAIDs emerged in the early 2000s. Rofecoxib, another member of the COX-2 inhibitor drug class, also known as Vioxx, was withdrawn from the market due to prothrombotic cardiovascular risks. Following an FDA Advisory Committee meeting in 2005, in which data from large clinical outcome trials were evaluated, the FDA concluded that the risk for cardiovascular thrombotic events for both COX-2 selective NSAIDs and nonselective NSAIDs was evident. It was determined that the benefits of celecoxib treatment, however, outweighed the risks. Postmarketing cardiovascular outcomes trial (PRECISION) revealed that the lowest possible dose of celecoxib was similar in cardiovascular safety to moderate strength doses of both naproxen and ibuprofen. Patients who had previous cardiovascular events including acute MI, coronary revascularization, or coronary stent insertion were not evaluated in the trial. It is not advisable to administer NSAIDS to these groups of 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): Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. COX-2 is expressed heavily in inflamed tissues where it is induced by inflammatory mediators. The inhibition of this enzyme reduces the synthesis of metabolites that include prostaglandin E2 (PGE2), prostacyclin (PGI2), thromboxane (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 (PGF2). Resultant inhibition of these mediators leads to the alleviation of pain and inflammation. By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. Celecoxib poses less of an ulceration risk than other NSAIDS, owing to its decreased effect on gastric mucosal prostaglandin synthesis when compared to placebo. Celecoxib exerts anticancer effects by binding to the cadherin-11 (CDH11)protein, which is thought to be involved in the progression of tumors, and inhibiting the 3-phosphoinositide-dependent kinase-1 (PDK-1) signaling mechanism. In addition, celecoxib has been found to inhibit carbonic anhydrase enzymes 2 and 3, further enhancing its anticancer effects. As mentioned in the pharmacodynamics section of this drug entry, celecoxib may cause an increased risk of thrombotic events. The risk of thrombosis resulting from COX-2 inhibition is caused by the vasoconstricting actions of thromboxane A2, leading to enhanced platelet aggregation, which is uncontrolled when the actions of prostacyclin, a platelet aggregation inhibitor, are suppressed through the inhibition of COX-2. •Absorption (Drug A): No absorption available •Absorption (Drug B): Celecoxib is absorbed rapidly in the gastrointestinal tract. When a single oral dose of 200 mg was given to healthy research subjects, the peak plasma levels of celecoxib occurred within 3 hours. The Cmax is 705 ng/mL. When multiple doses are given, steady-state concentrations are reached on or before day 5. When taken with a high-fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. The AUC of celecoxib has been shown to be significantly lower in patients with chronic renal impairment. A meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher AUC (area under the curve) of celecoxib in black patients compared to Caucasians for unknown reasons. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of celecoxib at steady state (Vss/F) is about 429 L, which suggests wide distribution into various tissues. Celecoxib is not preferentially bound to red blood cells. Another resource reports a volume of distribution of 455 ± 166L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding of celecoxib is 97%, and it is primarily 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): A large part of celecoxib metabolism is mediated by cytochrome P450 2C9 in the liver with some contribution from CYP3A4 and CYP2C8 and possible contributions from CYP2D6. It is metabolized by biotransformation to carboxylic acid and glucuronide metabolites. Three metabolites, a primary alcohol, a carboxylic acid, and a glucuronide conjugate, have been found in human plasma after celecoxib administration. These are considered inactive metabolites in regards to COX enzyme inhibition. Patients who are known or suspected to have decreased cytochrome P450 2C9 activity or function, based on their previous history, should be administered celecoxib with caution as they may have abnormally high serum concentrations resulting from decreased metabolism celecoxib. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Celecoxib is primarily eliminated by hepatic metabolism with small amounts (<3%) of the unchanged drug found in both the urine and feces. About 57% of an oral dose of celecoxib is excreted in the feces and 27% is found to be excreted into the urine in the form of metabolites. The main metabolite in urine and feces is identified as the carboxylic acid metabolite (73%). The amount of glucuronide in the urine is reported to be low. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 effective half-life of celecoxib is approximately 11 hours when a single 200 mg dose is given to healthy subjects. The terminal half-life of celecoxib varies because of its low solubility, which prolongs absorption. •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance (CL/F), single oral 200 mg dose, healthy subjects = 27.7 L/hr. Clearance may be decreased by about 47% in patients with chronic renal insufficiency, according to a pharmacokinetic study. Studies have not been performed in patients with severe renal impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral TDLo in humans 5.71 mg/kg. It is not advisable to administer celecoxib in patients with renal impairment or advanced hepatic impairment, as this may lead to increased serum concentrations, causing toxicity. Symptoms of overdose may include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting. Because serious gastrointestinal tract ulceration and bleeding can occur without preceding symptoms, patients should be monitored for signs/symptoms of gastrointestinal bleeding. Symptomatic and supportive measures should be taken in a celecoxib overdose. The induction of emesis or administration of active charcoal should take place if the patient is seen within 4 hours of celecoxib ingestion. Diuresis, urinary alkalinization, hemodialysis, or hemoperfusion may not be useful in a celecoxib overdose due to its high level of protein binding. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Celebrex, Elyxyb, Seglentis •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Celecoxib Célécoxib Celecoxibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Celecoxib is an NSAID used to treat osteoarthritis, rheumatoid arthritis, acute pain, menstrual symptoms, and to reduce polyps is familial adenomatous polyposis. 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 Cemiplimab interact?

•Drug A: Abciximab •Drug B: Cemiplimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Cemiplimab. •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): Cemiplimab is indicated to treat: Locally advanced or metastatic cutaneous squamous cell carcinoma (mCSCC) in patients who are not candidates for curative surgery or curative radiation. Locally advanced basal cell carcinoma (laBCC) in previously treated patients with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. Metastatic basal cell carcinoma (mBCC) in patients who were previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. This indication is approved under accelerated approval based on tumour response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit. Locally advanced non-small cell lung cancer (NSCLC) in combination with platinum‐based chemotherapy for the first‐line treatment of adults with no EGFR, ALK or ROS1 aberrations, who are not candidates for surgical resection or definitive chemoradiation. It is also indicated to treat metastatic NSCLC in combination with platinum‐based chemotherapy as first-line treatment in adults. Locally advanced or metastatic NSCLC as monotherapy for the first-line treatment of adults whose tumours have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Patients with locally advanced NSCLC must not be candidates for surgical resection or definitive chemoradiation. Recurrent or metastatic cervical cancer in adults with disease progression on or after platinum-based chemotherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cemiplimab inhibits tumour growth via an immune-mediated mechanism. Cemiplimab works to promote T cell-mediated immune response against tumours by blocking programmed death-1 (PD-1), a negative regulator of T cells. Cemiplimab targets PD-1 with high affinity and potency. In syngeneic mouse tumour models, blocking PD-1 activity by cemiplimab resulted in decreased tumour growth. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): T cells mediate antitumour activity following activation by antigen receptor signalling and CD28 costimulatory signalling. T cell proliferation and activation are regulated by a number of T cell immune regulatory checkpoints, including programmed death-1 (PD-1). PD-1 is an inhibitory co-receptor that is predominantly expressed on the surface of T cells to block T cell activation. Its ligands, PD-L1 and PD-L2, bind to PD-1 to activate downstream signalling cascades that ultimately result in the inhibition of T cell function such as T cell proliferation, cytokine production, and cytotoxicity. PD-1 receptor signalling pathway serves to maintain tolerance and regulate any ineffective or harmful immune responses; however, PD-1 signalling can also attenuate immune responses in cases where such protection is needed, such as autoimmune disorders and malignancy. PD-L1 and PD-L2 are expressed on antigen-presenting cells (APCs) as well as on some types of tumour cells as part of an adaptive immune response by tumours. PD-1 is also upregulated in some cancers, impeding T cell-mediated antitumour activity. Cemiplimab is a human PD-1-blocking antibody that binds to PD-1 and blocks its interaction with its ligands. By disinhibiting PD-1 mediated suppression of T cell activity, cemiplimab works to potentiate T cell cytotoxicity against tumours. •Absorption (Drug A): No absorption available •Absorption (Drug B): In a pharmacokinetic study involving patients with various solid tumours, the pharmacokinetics of cemiplimab was linear and dose-proportional in the dose range of 1 mg/kg to 10 mg/kg cemiplimab administered intravenously every two weeks. When cemiplimab was administered at a dose of 350 mg every three weeks, the median steady-state concentrations (coefficient of variation, CV%) of cemiplimab ranged between 61 mg/L (45%) and 171 mg/L (28%). Steady-state exposure is achieved after four months of treatment. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution (coefficient of variation, CV%) of cemiplimab at steady-state is 5.3 L (26%). •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): As with other monoclonal antibodies, cemiplimab is expected to undergo nonspecific degradation into small peptides and individual amino acids. •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): The elimination half-life (CV%) at steady state is 20.3 days (29%). •Clearance (Drug A): No clearance available •Clearance (Drug B): Cemiplimab clearance (CV%) after the first dose is 0.29 L/day (33%) and decreases over time by 29%, resulting in a steady-state clearance (CL ss ) (CV%) of 0.2 L/day (40%). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information regarding acute toxicity and overdose of cemiplimab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be initiated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Libtayo •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): Cemiplimab is a programmed death receptor-1 blocking antibody used to treat cutaneous squamous cell carcinoma, basal cell carcinoma, and 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 Cemiplimab interact? Information: •Drug A: Abciximab •Drug B: Cemiplimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Cemiplimab. •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): Cemiplimab is indicated to treat: Locally advanced or metastatic cutaneous squamous cell carcinoma (mCSCC) in patients who are not candidates for curative surgery or curative radiation. Locally advanced basal cell carcinoma (laBCC) in previously treated patients with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. Metastatic basal cell carcinoma (mBCC) in patients who were previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. This indication is approved under accelerated approval based on tumour response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit. Locally advanced non-small cell lung cancer (NSCLC) in combination with platinum‐based chemotherapy for the first‐line treatment of adults with no EGFR, ALK or ROS1 aberrations, who are not candidates for surgical resection or definitive chemoradiation. It is also indicated to treat metastatic NSCLC in combination with platinum‐based chemotherapy as first-line treatment in adults. Locally advanced or metastatic NSCLC as monotherapy for the first-line treatment of adults whose tumours have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Patients with locally advanced NSCLC must not be candidates for surgical resection or definitive chemoradiation. Recurrent or metastatic cervical cancer in adults with disease progression on or after platinum-based chemotherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cemiplimab inhibits tumour growth via an immune-mediated mechanism. Cemiplimab works to promote T cell-mediated immune response against tumours by blocking programmed death-1 (PD-1), a negative regulator of T cells. Cemiplimab targets PD-1 with high affinity and potency. In syngeneic mouse tumour models, blocking PD-1 activity by cemiplimab resulted in decreased tumour growth. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): T cells mediate antitumour activity following activation by antigen receptor signalling and CD28 costimulatory signalling. T cell proliferation and activation are regulated by a number of T cell immune regulatory checkpoints, including programmed death-1 (PD-1). PD-1 is an inhibitory co-receptor that is predominantly expressed on the surface of T cells to block T cell activation. Its ligands, PD-L1 and PD-L2, bind to PD-1 to activate downstream signalling cascades that ultimately result in the inhibition of T cell function such as T cell proliferation, cytokine production, and cytotoxicity. PD-1 receptor signalling pathway serves to maintain tolerance and regulate any ineffective or harmful immune responses; however, PD-1 signalling can also attenuate immune responses in cases where such protection is needed, such as autoimmune disorders and malignancy. PD-L1 and PD-L2 are expressed on antigen-presenting cells (APCs) as well as on some types of tumour cells as part of an adaptive immune response by tumours. PD-1 is also upregulated in some cancers, impeding T cell-mediated antitumour activity. Cemiplimab is a human PD-1-blocking antibody that binds to PD-1 and blocks its interaction with its ligands. By disinhibiting PD-1 mediated suppression of T cell activity, cemiplimab works to potentiate T cell cytotoxicity against tumours. •Absorption (Drug A): No absorption available •Absorption (Drug B): In a pharmacokinetic study involving patients with various solid tumours, the pharmacokinetics of cemiplimab was linear and dose-proportional in the dose range of 1 mg/kg to 10 mg/kg cemiplimab administered intravenously every two weeks. When cemiplimab was administered at a dose of 350 mg every three weeks, the median steady-state concentrations (coefficient of variation, CV%) of cemiplimab ranged between 61 mg/L (45%) and 171 mg/L (28%). Steady-state exposure is achieved after four months of treatment. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution (coefficient of variation, CV%) of cemiplimab at steady-state is 5.3 L (26%). •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): As with other monoclonal antibodies, cemiplimab is expected to undergo nonspecific degradation into small peptides and individual amino acids. •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): The elimination half-life (CV%) at steady state is 20.3 days (29%). •Clearance (Drug A): No clearance available •Clearance (Drug B): Cemiplimab clearance (CV%) after the first dose is 0.29 L/day (33%) and decreases over time by 29%, resulting in a steady-state clearance (CL ss ) (CV%) of 0.2 L/day (40%). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information regarding acute toxicity and overdose of cemiplimab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be initiated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Libtayo •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): Cemiplimab is a programmed death receptor-1 blocking antibody used to treat cutaneous squamous cell carcinoma, basal cell carcinoma, and 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 Cephalexin interact?

•Drug A: Abciximab •Drug B: Cephalexin •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cephalexin. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cephalexin is indicated for the treatment of certain infections caused by susceptible bacteria. These infections include respiratory tract infections, otitis media, skin and skin structure infections, bone infections, and genitourinary tract infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cephalexin (also called Cefalexin) is a first generation cephalosporin antibiotic. It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations. It is effective against most gram-positive bacteria through its inihibition of the cross linking reaction between N-acetyl muramicacid and N-acetylglucosamine in the cell wall, leading to cell lysis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cephalexin is a first generation cephalosporin antibiotic. Cephalosporins contain a beta lactam and dihydrothiazide. Unlike penicillins, cephalosprins are more resistant to the action of beta lactamase. Cephalexin inhibits bacterial cell wall synthesis, leading breakdown and eventualy cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed from the upper gastrointestinal tract with nearly 100% oral bioavailability. Cephalexin is not absorbed in the stomach but is absorbed in the upper intestine. Patients taking 250mg of cephalexin reach a maximum plasma concentration of 7.7mcg/mL and patients taking 500mg reach 12.3mcg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 5.2-5.8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Cephalexin is 10-15% bound to serum proteins including serum 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): Cephalexin is not metabolized in the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cephalexin is over 90% excreted in the urine after 6 hours by glomerular filtration and tubular secretion with a mean urinary recovery of 99.3%. Cephalexin is 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): The half life of cephalexin is 49.5 minutes in a fasted state and 76.5 minutes with food though these times were not significantly different in the study. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance from one subject was 376mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting. An overdose is generally managed through supportive treatment as diuresis, dialysis, hemodialysis, and charcoal hemoperfusion are not well studied in this case. The oral median lethal dose of cephalexin in rats is >5000 mg/kg. The oral LD50 in a monkey is >1g/kg and the lowest dose causing a toxic effect in humans is 14mg/kg. Cephalexin has not been shown to be harmful in pregnancy and is not associated with teratogeniticy. Cephalexin is present in breast milk, though infants may be exposed to <1% of the dose given to the mother. The effects of breast milk exposure to cephalexin have not been established and so caution must be exercised and the risk and benefit of cephalexin use in breastfeeding must be weighed. Cephalexin has not been studied for carcinogenicity or mutagenicity. Cephalexin has no affect on fertility in rats. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Keflex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Cefalexin Cefalexina Céfalexine Cefalexinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cephalexin is a first generation cephalosporin used to treat certain susceptible bacterial infections.

Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Question: Does Abciximab and Cephalexin interact? Information: •Drug A: Abciximab •Drug B: Cephalexin •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Cephalexin. •Extended Description: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Cephalexin is indicated for the treatment of certain infections caused by susceptible bacteria. These infections include respiratory tract infections, otitis media, skin and skin structure infections, bone infections, and genitourinary tract infections. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cephalexin (also called Cefalexin) is a first generation cephalosporin antibiotic. It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations. It is effective against most gram-positive bacteria through its inihibition of the cross linking reaction between N-acetyl muramicacid and N-acetylglucosamine in the cell wall, leading to cell lysis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cephalexin is a first generation cephalosporin antibiotic. Cephalosporins contain a beta lactam and dihydrothiazide. Unlike penicillins, cephalosprins are more resistant to the action of beta lactamase. Cephalexin inhibits bacterial cell wall synthesis, leading breakdown and eventualy cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed from the upper gastrointestinal tract with nearly 100% oral bioavailability. Cephalexin is not absorbed in the stomach but is absorbed in the upper intestine. Patients taking 250mg of cephalexin reach a maximum plasma concentration of 7.7mcg/mL and patients taking 500mg reach 12.3mcg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 5.2-5.8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Cephalexin is 10-15% bound to serum proteins including serum 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): Cephalexin is not metabolized in the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cephalexin is over 90% excreted in the urine after 6 hours by glomerular filtration and tubular secretion with a mean urinary recovery of 99.3%. Cephalexin is 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): The half life of cephalexin is 49.5 minutes in a fasted state and 76.5 minutes with food though these times were not significantly different in the study. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance from one subject was 376mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting. An overdose is generally managed through supportive treatment as diuresis, dialysis, hemodialysis, and charcoal hemoperfusion are not well studied in this case. The oral median lethal dose of cephalexin in rats is >5000 mg/kg. The oral LD50 in a monkey is >1g/kg and the lowest dose causing a toxic effect in humans is 14mg/kg. Cephalexin has not been shown to be harmful in pregnancy and is not associated with teratogeniticy. Cephalexin is present in breast milk, though infants may be exposed to <1% of the dose given to the mother. The effects of breast milk exposure to cephalexin have not been established and so caution must be exercised and the risk and benefit of cephalexin use in breastfeeding must be weighed. Cephalexin has not been studied for carcinogenicity or mutagenicity. Cephalexin has no affect on fertility in rats. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Keflex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Cefalexin Cefalexina Céfalexine Cefalexinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cephalexin is a first generation cephalosporin used to treat certain susceptible bacterial infections. Output: Certain cephalosporins contain a N-methylthiotetrazole ring which is known to inhibit the production of vitamin K-dependent clotting factor and thus, its use can result in a prolonged prothrombin time. Coadministration of cephalosporins with anticoagulant therapies can produce a significant decrease in the therapeutic effect of the anticoagulant, producing dangerous effects. The severity of the interaction is minor.

Does Abciximab and Certolizumab pegol interact?

•Drug A: Abciximab •Drug B: Certolizumab pegol •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Certolizumab pegol. •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): Certolizumab pegol has been approved for several different conditions listed below: Symptomatic management of Chron's disease patients and for the maintenance of clinical response in patients with moderate to severe disease with inadequate response to conventional therapy. Treatment of adult patients with moderate to severely active rheumatoid arthritis. Treatment of adult patients with active psoriatic arthritis. Treatment of adult patients with active ankylosing spondylitis. Treatment of adult patients with moderate-to-severe plaque psoriasis that are candidates for systemic therapy or phototherapy. Treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation. In Canada, certolizumab pegol is additionally approved in combination with methotrexate for the symptomatic treatment, including major clinical response, and for the reduction of joint damage in adult patients with moderately to severely active rheumatoid arthritis and psoriatic arthritis. Inflammation is a biological response against a potential threat. This response can be normal but in certain conditions, the immune system can attack the body's normal cells or tissues which causes an abnormal inflammation. TNF-alpha has been identified as a key regulator of the inflammatory response. The signaling cascades of this inflammatory mediator can produce a wide range of reactions including cell death, survival, differentiation, proliferation and migration. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 part of the mechanism of action and nature of the drug, certolizumab does not induce apoptosis in cultured lymphocytes and monocytes. However, as a piece of the inhibition of inflammation, certolizumab pegol inhibits lipopolysaccharide-induced production of IL-1 beta and it induces nonapoptotic cell death via signaling transmembrane TNF-alpha. In vitro studies with certolizumab pegol in human tissue did not show any unexpected binding at 3 mcg/ml nor at 10 mcg/ml. Due to the drug class, certolizumab pegol is not expected to present adverse effects on the major vital systems. In phase III clinical trials in psoriatic arthritis patients, certolizumab pegol was reported to generate improvements in skin disease, joint involvement, dactylitis, enthesitis and general life quality. The clinical effect of certolizumab was paired to a comparable safety profile to other TNF-alpha inhibitors. The clinical effectiveness of certolizumab pegol was mainly studied in six randomized controlled trials that compared its effect versus placebo. In a comparative study, the efficacy for certolizumab pegol registered ranged from 30-65% while in placebo ranged from 4-25%. However, in other additional trials, certolizumab was proven to present a similar clinical efficacy to other disease-modifying antirheumatic drugs in patients with inadequate response to TNF 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): Certolizumab targets the activation of TNF-alpha with high affinity (KD 90 pM and IC90 0.004 mcg/ml) which inhibits the downstream inflammatory process. It acts by binding and neutralizing the soluble and membrane portions of TNF-alpha without inducing complement or antibody-dependent cytotoxicity due to the lack of the Fc region. The inhibition of TNF-alpha is achieved in a dose-dependent manner and it does not present activity against lymphotoxin alpha (TNF-beta). One additional feature od certolizumab pegol is that, due to the presence of the PEGylation, it is more significantly distributed into inflamed tissues when compared to other TNF-alpha inhibitors such as infliximab and adalimumab. •Absorption (Drug A): No absorption available •Absorption (Drug B): After subcutaneous administration, the peak plasma concentration is reached between 54 and 171 hours with a bioavailability of 80%. Certolizumab presents a linear pharmacokinetic profile with a peak plasma concentration of 43-49 mcg/ml. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Certolizumab pegol volume of distribution is reported to be in the range of 4-8 L. It is known to have a very good distribution in the joints when compared to other TNF-alpha inhibitors. •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): The presence of PEG group in certolizumab pegol delays the metabolism and elimination of this drug. However, once under metabolism, the PEG group gets cleaved from the parent compound and the antibody section is thought to be internalized cells and rescued from metabolism by recycling. Later, it is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. On the other hand, the PEG section is processed normally by the action of the alcohol dehydrogenase to the formation of carboxylic acid. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): As certolizumab is a monoclonal antibody, the elimination route is not widely studied. However, it is known that the elimination of the PEG moiety is dependent on the renal function which links it directly with a high portion of renal elimination. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The circulatory half-life of certolizumab is of 14 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance rate of certolizumab pegol ranged between 9-14 ml/h when administered intravenously. However, when administered subcutaneously, the clearance rate is estimated to range between 14-21 ml/h depending on the patient condition. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral ld50 observed in mice is determined to be of 300 mg/kg. To this date, there have not been reports of overdosage, however, in case of accidental overexposure close monitoring is recommended. Certolizumab pegol does not present mutagenic potential nor presents effects in fertility and reproductive performance. On the other hand, carcinogenicity studies have not been performed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cimzia •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): Certolizumab pegol is a tumor necrosis factor (TNF) blocker used to treat a variety of autoimmune and autoinflammatory conditions like Crohn's disease, rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis, and plaque psoriasis.

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 Certolizumab pegol interact? Information: •Drug A: Abciximab •Drug B: Certolizumab pegol •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Certolizumab pegol. •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): Certolizumab pegol has been approved for several different conditions listed below: Symptomatic management of Chron's disease patients and for the maintenance of clinical response in patients with moderate to severe disease with inadequate response to conventional therapy. Treatment of adult patients with moderate to severely active rheumatoid arthritis. Treatment of adult patients with active psoriatic arthritis. Treatment of adult patients with active ankylosing spondylitis. Treatment of adult patients with moderate-to-severe plaque psoriasis that are candidates for systemic therapy or phototherapy. Treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation. In Canada, certolizumab pegol is additionally approved in combination with methotrexate for the symptomatic treatment, including major clinical response, and for the reduction of joint damage in adult patients with moderately to severely active rheumatoid arthritis and psoriatic arthritis. Inflammation is a biological response against a potential threat. This response can be normal but in certain conditions, the immune system can attack the body's normal cells or tissues which causes an abnormal inflammation. TNF-alpha has been identified as a key regulator of the inflammatory response. The signaling cascades of this inflammatory mediator can produce a wide range of reactions including cell death, survival, differentiation, proliferation and migration. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 part of the mechanism of action and nature of the drug, certolizumab does not induce apoptosis in cultured lymphocytes and monocytes. However, as a piece of the inhibition of inflammation, certolizumab pegol inhibits lipopolysaccharide-induced production of IL-1 beta and it induces nonapoptotic cell death via signaling transmembrane TNF-alpha. In vitro studies with certolizumab pegol in human tissue did not show any unexpected binding at 3 mcg/ml nor at 10 mcg/ml. Due to the drug class, certolizumab pegol is not expected to present adverse effects on the major vital systems. In phase III clinical trials in psoriatic arthritis patients, certolizumab pegol was reported to generate improvements in skin disease, joint involvement, dactylitis, enthesitis and general life quality. The clinical effect of certolizumab was paired to a comparable safety profile to other TNF-alpha inhibitors. The clinical effectiveness of certolizumab pegol was mainly studied in six randomized controlled trials that compared its effect versus placebo. In a comparative study, the efficacy for certolizumab pegol registered ranged from 30-65% while in placebo ranged from 4-25%. However, in other additional trials, certolizumab was proven to present a similar clinical efficacy to other disease-modifying antirheumatic drugs in patients with inadequate response to TNF 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): Certolizumab targets the activation of TNF-alpha with high affinity (KD 90 pM and IC90 0.004 mcg/ml) which inhibits the downstream inflammatory process. It acts by binding and neutralizing the soluble and membrane portions of TNF-alpha without inducing complement or antibody-dependent cytotoxicity due to the lack of the Fc region. The inhibition of TNF-alpha is achieved in a dose-dependent manner and it does not present activity against lymphotoxin alpha (TNF-beta). One additional feature od certolizumab pegol is that, due to the presence of the PEGylation, it is more significantly distributed into inflamed tissues when compared to other TNF-alpha inhibitors such as infliximab and adalimumab. •Absorption (Drug A): No absorption available •Absorption (Drug B): After subcutaneous administration, the peak plasma concentration is reached between 54 and 171 hours with a bioavailability of 80%. Certolizumab presents a linear pharmacokinetic profile with a peak plasma concentration of 43-49 mcg/ml. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Certolizumab pegol volume of distribution is reported to be in the range of 4-8 L. It is known to have a very good distribution in the joints when compared to other TNF-alpha inhibitors. •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): The presence of PEG group in certolizumab pegol delays the metabolism and elimination of this drug. However, once under metabolism, the PEG group gets cleaved from the parent compound and the antibody section is thought to be internalized cells and rescued from metabolism by recycling. Later, it is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. On the other hand, the PEG section is processed normally by the action of the alcohol dehydrogenase to the formation of carboxylic acid. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): As certolizumab is a monoclonal antibody, the elimination route is not widely studied. However, it is known that the elimination of the PEG moiety is dependent on the renal function which links it directly with a high portion of renal elimination. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The circulatory half-life of certolizumab is of 14 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance rate of certolizumab pegol ranged between 9-14 ml/h when administered intravenously. However, when administered subcutaneously, the clearance rate is estimated to range between 14-21 ml/h depending on the patient condition. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral ld50 observed in mice is determined to be of 300 mg/kg. To this date, there have not been reports of overdosage, however, in case of accidental overexposure close monitoring is recommended. Certolizumab pegol does not present mutagenic potential nor presents effects in fertility and reproductive performance. On the other hand, carcinogenicity studies have not been performed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cimzia •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): Certolizumab pegol is a tumor necrosis factor (TNF) blocker used to treat a variety of autoimmune and autoinflammatory conditions like Crohn's disease, rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis, and plaque psoriasis. 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 Cetuximab interact?

•Drug A: Abciximab •Drug B: Cetuximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Cetuximab 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): Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy. Cetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes leucovorin, fluorouracil, and irinotecan; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan. Additionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with encorafenib but only after prior therapy. Cetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cetuximab is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells with high specificity and higher affinity than epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are natural ligands of EGFR. Cetuximab works by inhibiting the growth and survival of EGFR-positive tumours. In vitro, it promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. On the contrary, cetuximab does not exert its anti-tumour effects on human tumour xenografts lacking EGFR expression. Cetuximab potentiates the cytotoxic effects of chemotherapeutics and radiation therapy when used in combination. In human tumour xenograft models in mice, cetuximab and irinotecan synergistically inhibited the growth of orthotopic anaplastic thyroid carcinoma xenografts in vitro and in vivo. Cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan and achieved 93% in vivo inhibition of tumour growth when combined with irinotecan, compared to 77% and 79% inhibition when cetuximab and irinotecan were used alone, 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 epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a type I receptor tyrosine kinase expressed on both normal and malignant cells. It has been investigated as a therapeutic target for anticancer treatment, as it is often upregulated in cancer types, including head and neck, colon, and rectal cancers. When activated by its ligand, EGFR undergoes a conformational change and dimerization to form homodimers or heterodimers with another member of the ErbB family of receptors. Dimerization of EGFR activates the intracellular tyrosine kinase region of EGFR and promotes autophosphorylation, initiating a series of downstream signalling cascades, including cell differentiation, proliferation, migration, angiogenesis, and apoptosis. This EGFR signalling pathway is often dysregulated in cancer cells, leading to aberrant cell growth and enhanced cell survival. Cetuximab is a monoclonal antibody that binds specifically to the EGFR on both normal and tumour cells to competitively inhibit the binding of epidermal growth factor (EGF) and other ligands that are produced by normal and tumour tissue epithelial cells. Upon binding to domain III of EGFR - which is the binding site for its growth factor ligands - cetuximab prevents the receptor from adopting an extended conformation and thereby inhibits EGFR activation, as well as phosphorylation and activation of receptor-associated kinases (MAPK, PI3K/Akt, Jak/Stat). Inhibition of the EGFR signalling pathway ultimately leads to inhibition of cell cycle progression, cell survival pathways, and tumour cell motility and invasion. Cetuximab also induces cell apoptosis and decreases matrix metalloproteinase and vascular endothelial growth factor (VEGF) production. In vitro, cetuximab was shown to inhibit tumour angiogenesis. Binding of cetuximab to EGFR also results in internalization of the antibody-receptor complex, leading to an overall downregulation of EGFR expression. K-ras is a small G-protein downstream of EGFR that plays an important role in promoting the EGFR signalling cascade: in some malignant cells, K-ras can acquire activating mutations in exon 2 and thus be continuously active regardless of EGFR regulation. Since mutant Ras proteins can isolate the pathway from the effect of EGFR, K-Ras mutations can render EGFR inhibitors like cetuximab ineffective in exerting anti-tumour effects. Cetuximab is thus only limited in its use for K-Ras wild-type, EGFR-expressing cancers. •Absorption (Drug A): No absorption available •Absorption (Drug B): After administration of a 400 mg/m initial dose followed by a 250 mg/m weekly dose, the steady-state levels of cetuximab was reached by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 µg/mL to 235 µg/mL and 41 µg/mL to 85 µg/mL, respectively. T max is about 3 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of the distribution is about 2-3 L/m and is independent of dose. •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): Like other monoclonal antibodies, cetuximab 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): There is limited 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): After administration of a 400 mg/m initial dose followed by a 250 mg/m weekly dose, the mean half-life for cetuximab was approximately 112 hours, with a range of 63 to 230 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the estimated clearance rate was 0.103 L/h. At doses ranging from 200 to 400 mg/m, complete saturation of systemic clearance was observed. In a population pharmacokinetic study, female patients had a 25% lower intrinsic cetuximab clearance than male patients, although there was no evidence of the need for dose modification based on sex. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The intravenous LD 50 is > 300 mg/kg in mice and > 200 mg/kg in rats. There is limited information on the overdose from cetuximab. In clinical trials, cetuximab was associated with serious and fatal infusion reactions, cardiopulmonary arrest or sudden death, and serious dermatologic toxicities. Pulmonary toxicities, such as interstitial lung disease, interstitial pneumonitis with non-cardiogenic pulmonary edema, and exacerbation of pre-existing fibrotic lung disease have been reported. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Erbitux •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): Cetuximab is an endothelial growth factor receptor binding fragment used to treat colorectal cancer as well as squamous cell carcinoma of the head and neck.

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 Cetuximab interact? Information: •Drug A: Abciximab •Drug B: Cetuximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Cetuximab 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): Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy. Cetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes leucovorin, fluorouracil, and irinotecan; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan. Additionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with encorafenib but only after prior therapy. Cetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cetuximab is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells with high specificity and higher affinity than epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are natural ligands of EGFR. Cetuximab works by inhibiting the growth and survival of EGFR-positive tumours. In vitro, it promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. On the contrary, cetuximab does not exert its anti-tumour effects on human tumour xenografts lacking EGFR expression. Cetuximab potentiates the cytotoxic effects of chemotherapeutics and radiation therapy when used in combination. In human tumour xenograft models in mice, cetuximab and irinotecan synergistically inhibited the growth of orthotopic anaplastic thyroid carcinoma xenografts in vitro and in vivo. Cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan and achieved 93% in vivo inhibition of tumour growth when combined with irinotecan, compared to 77% and 79% inhibition when cetuximab and irinotecan were used alone, 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 epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a type I receptor tyrosine kinase expressed on both normal and malignant cells. It has been investigated as a therapeutic target for anticancer treatment, as it is often upregulated in cancer types, including head and neck, colon, and rectal cancers. When activated by its ligand, EGFR undergoes a conformational change and dimerization to form homodimers or heterodimers with another member of the ErbB family of receptors. Dimerization of EGFR activates the intracellular tyrosine kinase region of EGFR and promotes autophosphorylation, initiating a series of downstream signalling cascades, including cell differentiation, proliferation, migration, angiogenesis, and apoptosis. This EGFR signalling pathway is often dysregulated in cancer cells, leading to aberrant cell growth and enhanced cell survival. Cetuximab is a monoclonal antibody that binds specifically to the EGFR on both normal and tumour cells to competitively inhibit the binding of epidermal growth factor (EGF) and other ligands that are produced by normal and tumour tissue epithelial cells. Upon binding to domain III of EGFR - which is the binding site for its growth factor ligands - cetuximab prevents the receptor from adopting an extended conformation and thereby inhibits EGFR activation, as well as phosphorylation and activation of receptor-associated kinases (MAPK, PI3K/Akt, Jak/Stat). Inhibition of the EGFR signalling pathway ultimately leads to inhibition of cell cycle progression, cell survival pathways, and tumour cell motility and invasion. Cetuximab also induces cell apoptosis and decreases matrix metalloproteinase and vascular endothelial growth factor (VEGF) production. In vitro, cetuximab was shown to inhibit tumour angiogenesis. Binding of cetuximab to EGFR also results in internalization of the antibody-receptor complex, leading to an overall downregulation of EGFR expression. K-ras is a small G-protein downstream of EGFR that plays an important role in promoting the EGFR signalling cascade: in some malignant cells, K-ras can acquire activating mutations in exon 2 and thus be continuously active regardless of EGFR regulation. Since mutant Ras proteins can isolate the pathway from the effect of EGFR, K-Ras mutations can render EGFR inhibitors like cetuximab ineffective in exerting anti-tumour effects. Cetuximab is thus only limited in its use for K-Ras wild-type, EGFR-expressing cancers. •Absorption (Drug A): No absorption available •Absorption (Drug B): After administration of a 400 mg/m initial dose followed by a 250 mg/m weekly dose, the steady-state levels of cetuximab was reached by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 µg/mL to 235 µg/mL and 41 µg/mL to 85 µg/mL, respectively. T max is about 3 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of the distribution is about 2-3 L/m and is independent of dose. •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): Like other monoclonal antibodies, cetuximab 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): There is limited 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): After administration of a 400 mg/m initial dose followed by a 250 mg/m weekly dose, the mean half-life for cetuximab was approximately 112 hours, with a range of 63 to 230 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the estimated clearance rate was 0.103 L/h. At doses ranging from 200 to 400 mg/m, complete saturation of systemic clearance was observed. In a population pharmacokinetic study, female patients had a 25% lower intrinsic cetuximab clearance than male patients, although there was no evidence of the need for dose modification based on sex. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The intravenous LD 50 is > 300 mg/kg in mice and > 200 mg/kg in rats. There is limited information on the overdose from cetuximab. In clinical trials, cetuximab was associated with serious and fatal infusion reactions, cardiopulmonary arrest or sudden death, and serious dermatologic toxicities. Pulmonary toxicities, such as interstitial lung disease, interstitial pneumonitis with non-cardiogenic pulmonary edema, and exacerbation of pre-existing fibrotic lung disease have been reported. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Erbitux •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): Cetuximab is an endothelial growth factor receptor binding fragment used to treat colorectal cancer as well as squamous cell carcinoma of the head and neck. 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 Chenodeoxycholic acid interact?

•Drug A: Abciximab •Drug B: Chenodeoxycholic acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Chenodeoxycholic 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): Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic acid is ineffective with stones of a high calcium or bile acid content. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids. •Absorption (Drug A): No absorption available •Absorption (Drug B): Chenodiol is well absorbed from the small intestine. •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): Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. At steady-state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacterial action to lithocholic acid. About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. During chenodiol therapy there is only a minor increase in biliary lithocholate, while fecal bile acids are increased three- to fourfold. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 80% of its bacterial metabolite lithocholate 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): 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): Hepatotoxic. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Chenodal •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Acide chenodeoxycholique Acido chenodeoxicholico Acidum chenodeoxycholicum Anthropodeoxycholic acid Anthropodesoxycholic acid CDCA Chenic acid Chenocholic acid Chenodeoxycholate Chenodeoxycholic acid Chenodesoxycholic acid Chenodiol Gallodesoxycholic 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): Chenodeoxycholic acid is a bile acid used for the treatment of primary biliary cirrhosis.

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 Chenodeoxycholic acid interact? Information: •Drug A: Abciximab •Drug B: Chenodeoxycholic acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Chenodeoxycholic 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): Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic acid is ineffective with stones of a high calcium or bile acid content. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids. •Absorption (Drug A): No absorption available •Absorption (Drug B): Chenodiol is well absorbed from the small intestine. •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): Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. At steady-state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacterial action to lithocholic acid. About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. During chenodiol therapy there is only a minor increase in biliary lithocholate, while fecal bile acids are increased three- to fourfold. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 80% of its bacterial metabolite lithocholate 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): 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): Hepatotoxic. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Chenodal •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Acide chenodeoxycholique Acido chenodeoxicholico Acidum chenodeoxycholicum Anthropodeoxycholic acid Anthropodesoxycholic acid CDCA Chenic acid Chenocholic acid Chenodeoxycholate Chenodeoxycholic acid Chenodesoxycholic acid Chenodiol Gallodesoxycholic 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): Chenodeoxycholic acid is a bile acid used for the treatment of primary biliary cirrhosis. 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 Chlorambucil interact?

•Drug A: Abciximab •Drug B: Chlorambucil •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Chlorambucil. •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 chronic lymphatic (lymphocytic) leukemia, childhood minimal-change nephrotic syndrome, and malignant lymphomas including lymphosarcoma, giant follicular lymphoma, Hodgkin's disease, non-Hodgkin's lymphomas, and Waldenström’s Macroglobulinemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Chlorambucil is an antineoplastic in the class of alkylating agents that 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 99% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary 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): 1.5 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): Leukeran •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ambochlorin Chlorambucil Chloraminophen Clorambucilo •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Chlorambucil is a chemotherapy agent used in the management of chronic lymphocytic leukemia and malignant lymphomas.

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 Chlorambucil interact? Information: •Drug A: Abciximab •Drug B: Chlorambucil •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Chlorambucil. •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 chronic lymphatic (lymphocytic) leukemia, childhood minimal-change nephrotic syndrome, and malignant lymphomas including lymphosarcoma, giant follicular lymphoma, Hodgkin's disease, non-Hodgkin's lymphomas, and Waldenström’s Macroglobulinemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Chlorambucil is an antineoplastic in the class of alkylating agents that 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 99% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary 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): 1.5 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): Leukeran •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ambochlorin Chlorambucil Chloraminophen Clorambucilo •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Chlorambucil is a chemotherapy agent used in the management of chronic lymphocytic leukemia and malignant lymphomas. 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 Chloramphenicol interact?

•Drug A: Abciximab •Drug B: Chloramphenicol •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Chloramphenicol. •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 treatment of cholera, as it destroys the vibrios and decreases the diarrhea. It is effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to treat bacterial conjunctivitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Chloramphenicol is a broad-spectrum antibiotic that was derived from the bacterium Streptomyces venezuelae and is now produced synthetically. Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). Chloramphenicol is bacteriostatic but may be bactericidal in high concentrations or when used against highly susceptible organisms. Chloramphenicol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Chloramphenicol is lipid-soluble, allowing it to diffuse through the bacterial cell membrane. It then reversibly binds to the L16 protein of the 50S subunit of bacterial ribosomes, where transfer of amino acids to growing peptide chains is prevented (perhaps by suppression of peptidyl transferase activity), thus inhibiting peptide bond formation and subsequent protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly and completely absorbed from gastrointestinal tract following oral administration (bioavailability 80%). Well absorbed following intramuscular administration (bioavailability 70%). Intraocular and some systemic absorption also occurs after topical application to the eye. •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): Plasma protein binding is 50-60% in adults and 32% is premature 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): Hepatic, with 90% conjugated to inactive glucuronide. •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): Half-life in adults with normal hepatic and renal function is 1.5 - 3.5 hours. In patients with impaired renal function half-life is 3 - 4 hours. In patients with severely impaired hepatic function half-life is 4.6 - 11.6 hours. Half-life in children 1 month to 16 years old is 3 - 6.5 hours, while half-life in infants 1 to 2 days old is 24 hours or longer and is highly variable, especially in low birth-weight infants. •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 = 1500 mg/kg; Oral, rat: LD 50 = 2500 mg/kg. Toxic reactions including fatalities have occurred in the premature and newborn; the signs and symptoms associated with these reactions have been referred to as the gray syndrome. Symptoms include (in order of appearance) abdominal distension with or without emesis, progressive pallid cyanosis, vasomotor collapse frequently accompanied by irregular respiration, and death within a few hours of onset of these symptoms. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Chloromycetin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chloramphénicol Chloramphenicol Chloramphenicolum Chlornitromycin Cloramfenicol Cloranfenicol Laevomycetinum Levomicetina Levomycetin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Chloramphenicol is a broad spectrum antibiotic that is effective against a variety of susceptible and serious bacterial infections but is not frequently used because of its high risk of bone marrow toxicity.

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 Chloramphenicol interact? Information: •Drug A: Abciximab •Drug B: Chloramphenicol •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Chloramphenicol. •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 treatment of cholera, as it destroys the vibrios and decreases the diarrhea. It is effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to treat bacterial conjunctivitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Chloramphenicol is a broad-spectrum antibiotic that was derived from the bacterium Streptomyces venezuelae and is now produced synthetically. Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). Chloramphenicol is bacteriostatic but may be bactericidal in high concentrations or when used against highly susceptible organisms. Chloramphenicol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Chloramphenicol is lipid-soluble, allowing it to diffuse through the bacterial cell membrane. It then reversibly binds to the L16 protein of the 50S subunit of bacterial ribosomes, where transfer of amino acids to growing peptide chains is prevented (perhaps by suppression of peptidyl transferase activity), thus inhibiting peptide bond formation and subsequent protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly and completely absorbed from gastrointestinal tract following oral administration (bioavailability 80%). Well absorbed following intramuscular administration (bioavailability 70%). Intraocular and some systemic absorption also occurs after topical application to the eye. •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): Plasma protein binding is 50-60% in adults and 32% is premature 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): Hepatic, with 90% conjugated to inactive glucuronide. •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): Half-life in adults with normal hepatic and renal function is 1.5 - 3.5 hours. In patients with impaired renal function half-life is 3 - 4 hours. In patients with severely impaired hepatic function half-life is 4.6 - 11.6 hours. Half-life in children 1 month to 16 years old is 3 - 6.5 hours, while half-life in infants 1 to 2 days old is 24 hours or longer and is highly variable, especially in low birth-weight infants. •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 = 1500 mg/kg; Oral, rat: LD 50 = 2500 mg/kg. Toxic reactions including fatalities have occurred in the premature and newborn; the signs and symptoms associated with these reactions have been referred to as the gray syndrome. Symptoms include (in order of appearance) abdominal distension with or without emesis, progressive pallid cyanosis, vasomotor collapse frequently accompanied by irregular respiration, and death within a few hours of onset of these symptoms. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Chloromycetin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chloramphénicol Chloramphenicol Chloramphenicolum Chlornitromycin Cloramfenicol Cloranfenicol Laevomycetinum Levomicetina Levomycetin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Chloramphenicol is a broad spectrum antibiotic that is effective against a variety of susceptible and serious bacterial infections but is not frequently used because of its high risk of bone marrow toxicity. 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 Chlorothiazide interact?

•Drug A: Abciximab •Drug B: Chlorothiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Chlorothiazide. •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): Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na /Cl reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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, chlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide 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 chlorothiazide is less well understood although it 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): 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): Approximately 40% 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): Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 45-120 minutes •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: > 10 g/kg. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Diuril •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chlorothiazid Chlorothiazide Chlorothiazidum Chlorthiazide Clorotiazida •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Chlorothiazide is a thiazide diuretic used to treat hypertension and edema in congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.

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 Chlorothiazide interact? Information: •Drug A: Abciximab •Drug B: Chlorothiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Chlorothiazide. •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): Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na /Cl reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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, chlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide 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 chlorothiazide is less well understood although it 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): 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): Approximately 40% 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): Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 45-120 minutes •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: > 10 g/kg. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Diuril •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chlorothiazid Chlorothiazide Chlorothiazidum Chlorthiazide Clorotiazida •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Chlorothiazide is a thiazide diuretic used to treat hypertension and edema in congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. 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 Cholic Acid interact?

•Drug A: Abciximab •Drug B: Cholic Acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Cholic 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): Oral cholic acid is indicated for: treatment of bile acid synthesis disorders due to single enzyme defects; and as adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Cholbam, Orphacol •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): Cholic Acid is a bile acid used for the treatment of bile acid synthesis disorders due to single enzyme defects and as an adjunctive treatment of peroxisomal disorders with disrupted liver function.

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 Cholic Acid interact? Information: •Drug A: Abciximab •Drug B: Cholic Acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Cholic 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): Oral cholic acid is indicated for: treatment of bile acid synthesis disorders due to single enzyme defects; and as adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Cholbam, Orphacol •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): Cholic Acid is a bile acid used for the treatment of bile acid synthesis disorders due to single enzyme defects and as an adjunctive treatment of peroxisomal disorders with disrupted liver function. 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 Choline magnesium trisalicylate interact?

•Drug A: Abciximab •Drug B: Choline magnesium trisalicylate •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): Choline magnesium trisalicylate is used to reduce pain and inflammation caused by conditions such as arthritis. This medication is also used to treat fever 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): Trisalicylate-choline is a non-steroidal anti-inflammatory drug (NSAID) that contains a combination of choline salicylate and magnesium salicylate. Does not affect platelet aggregation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Inhibits prostaglandin synthesis; acts on the hypothalamus heat-regulating center to reduce fever; blocks the generation of pain impulses •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): renal •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Salicylate intoxication, known as salicylism, may occur with large doses or extended therapy. Common symptoms of salicylism include headache, dizziness, tinnitus, hearing impairment, confusion, drowsiness, sweating, vomiting, diarrhea, and hyperventilation. A more severe degree of salicylate intoxication can lead to CNS disturbances, alteration in electrolyte balance, respiratory and metabolic acidosis, hyperthermia, and dehydration. •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): No summary available

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 Choline magnesium trisalicylate interact? Information: •Drug A: Abciximab •Drug B: Choline magnesium trisalicylate •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): Choline magnesium trisalicylate is used to reduce pain and inflammation caused by conditions such as arthritis. This medication is also used to treat fever 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): Trisalicylate-choline is a non-steroidal anti-inflammatory drug (NSAID) that contains a combination of choline salicylate and magnesium salicylate. Does not affect platelet aggregation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Inhibits prostaglandin synthesis; acts on the hypothalamus heat-regulating center to reduce fever; blocks the generation of pain impulses •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): renal •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Salicylate intoxication, known as salicylism, may occur with large doses or extended therapy. Common symptoms of salicylism include headache, dizziness, tinnitus, hearing impairment, confusion, drowsiness, sweating, vomiting, diarrhea, and hyperventilation. A more severe degree of salicylate intoxication can lead to CNS disturbances, alteration in electrolyte balance, respiratory and metabolic acidosis, hyperthermia, and dehydration. •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): No summary available 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 Choline salicylate interact?

•Drug A: Abciximab •Drug B: Choline salicylate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Choline 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): The oral gel is indicated for the relief of pain and discomfort of common mouth ulcers, cold sores, denture sore spots, infant teething and mouth ulcers, and sore spots due to orthodontic devices in children. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 is an anti-inflammatory and antipyretic medication,. If is often used in oral gel form for the relief of pain, discomfort, and inflammation caused by common mouth ulcers, cold sores, denture and sore spots, as well as mouth ulcers, and sore spots because of orthodontic devices. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Choline salicylate relieves pain by inhibition of prostaglandin synthesis and reduces fever by acting on the hypothalamus heat-regulating center. It also inhibits the generation of impulses through the inhibition of cyclooxygenase enzyme (COX),. Cyclooxygenase is involved in the production of prostaglandins, in response to injury and after various other stimuli. The prostaglandins promote pain, swelling, and inflammation. The choline salicylate decreases inflammation and pain by reducing the production of these prostaglandins in the area of the mouth it is applied to. •Absorption (Drug A): No absorption available •Absorption (Drug B): Onset: 1-2 hr after ingestion In the oral form, choline salicylate is absorbed across the buccal mucosa. There is a need for caution not to exceed the stated dose and monitor for any signs of suggested salicylism, especially when this drug is used for infants. In one study, it was found that this drug was more rapidly absorbed than ASA (absorption t1/2 = 0.1 vs 0.36 h). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.15 L/kg (salicylate), and widely distributed throughout extracellular water and most tissues •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Salicylic acid is highly (80-90%) 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): The metabolism of salicylic acid is by glycine and phenolic or acyl glucuronate conjugation with small amounts of the drug undergoing hydroxylation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Both metabolites of choline salicylate, and a small amount of intact salicylic acid are excreted, primarily 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 plasma half-life of salicylic acid is 2-4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50, oral in mouse: 2690mg/kg. Ld50, subcutaneous in mouse: 1gm/kg. Interferes with thyroid function test. Gastrointestinal (GI) disorders, fatigue, hypersensitivity reactions, skin eruptions, hemolytic anemia, weakness, dyspnoea; local irritation (rectally); Reye's syndrome. Potentially Fatal: Paroxysmal bronchospasm; hepatotoxicity; renal impairment/failure; thrombocytopenia, iron-deficiency anemia, occult bleeding, leukopenia; mild chronic salicylate intoxication. Salicylate poisoning is normally associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths due to salicylate poisoning occur in patients whose serum concentrations of salicylate are over 700 mg/L (5.1 mmol/L). Single doses of less than 100 mg/kg are very unlikely to lead to serious poisoning. Patients should be provided with supportive therapy or treatment for salicylate poisoning as necessary. This may include treatment like activated charcoal, urinary alkalinization and, in severe cases, hemodialysis. •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): No summary available

.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 Choline salicylate interact? Information: •Drug A: Abciximab •Drug B: Choline salicylate •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Choline 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): The oral gel is indicated for the relief of pain and discomfort of common mouth ulcers, cold sores, denture sore spots, infant teething and mouth ulcers, and sore spots due to orthodontic devices in children. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 is an anti-inflammatory and antipyretic medication,. If is often used in oral gel form for the relief of pain, discomfort, and inflammation caused by common mouth ulcers, cold sores, denture and sore spots, as well as mouth ulcers, and sore spots because of orthodontic devices. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Choline salicylate relieves pain by inhibition of prostaglandin synthesis and reduces fever by acting on the hypothalamus heat-regulating center. It also inhibits the generation of impulses through the inhibition of cyclooxygenase enzyme (COX),. Cyclooxygenase is involved in the production of prostaglandins, in response to injury and after various other stimuli. The prostaglandins promote pain, swelling, and inflammation. The choline salicylate decreases inflammation and pain by reducing the production of these prostaglandins in the area of the mouth it is applied to. •Absorption (Drug A): No absorption available •Absorption (Drug B): Onset: 1-2 hr after ingestion In the oral form, choline salicylate is absorbed across the buccal mucosa. There is a need for caution not to exceed the stated dose and monitor for any signs of suggested salicylism, especially when this drug is used for infants. In one study, it was found that this drug was more rapidly absorbed than ASA (absorption t1/2 = 0.1 vs 0.36 h). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.15 L/kg (salicylate), and widely distributed throughout extracellular water and most tissues •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Salicylic acid is highly (80-90%) 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): The metabolism of salicylic acid is by glycine and phenolic or acyl glucuronate conjugation with small amounts of the drug undergoing hydroxylation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Both metabolites of choline salicylate, and a small amount of intact salicylic acid are excreted, primarily 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 plasma half-life of salicylic acid is 2-4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50, oral in mouse: 2690mg/kg. Ld50, subcutaneous in mouse: 1gm/kg. Interferes with thyroid function test. Gastrointestinal (GI) disorders, fatigue, hypersensitivity reactions, skin eruptions, hemolytic anemia, weakness, dyspnoea; local irritation (rectally); Reye's syndrome. Potentially Fatal: Paroxysmal bronchospasm; hepatotoxicity; renal impairment/failure; thrombocytopenia, iron-deficiency anemia, occult bleeding, leukopenia; mild chronic salicylate intoxication. Salicylate poisoning is normally associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths due to salicylate poisoning occur in patients whose serum concentrations of salicylate are over 700 mg/L (5.1 mmol/L). Single doses of less than 100 mg/kg are very unlikely to lead to serious poisoning. Patients should be provided with supportive therapy or treatment for salicylate poisoning as necessary. This may include treatment like activated charcoal, urinary alkalinization and, in severe cases, hemodialysis. •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): No summary available 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 Cilostazol interact?

•Drug A: Abciximab •Drug B: Cilostazol •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Cilostazol is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 alleviation of symptoms of intermittent claudication (pain in the legs that occurs with walking and disappears with rest). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cilostazol reduces the symptoms of intermittent claudication, as indicated by an increased walking distance. Intermittent claudication is pain in the legs that occurs with walking and disappears with rest. The pain occurs due to reduced blood flow to the legs. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cilostazol is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in C max and a 25% increase in AUC. Absolute bioavailability is not known. •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): 95-98% •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. Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Two metabolites are active, with one metabolite appearing to account for at least 50% of the pharmacologic (PDE III inhibition) activity after administration of cilostazol. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Cilostazol is eliminated predominately by metabolism and subsequent urinary excretion of metabolites. The primary route of elimination was via the urine (74%), with the remainder excreted in feces (20%). No measurable amount of unchanged cilostazol was excreted in the urine, and less than 2% of the dose was excreted as 3,4-dehydro-cilostazol. About 30% of the dose was excreted in urine as 4'-trans-hydroxy-cilostazol. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 11-13 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Information on acute overdosage with cilostazol in humans is limited. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: severe headache, diarrhea, hypotension, tachycardia, and possibly cardiac arrhythmias. The oral LD 50 of cilostazol is >5.0 g/kg in mice and rats and >2.0 g/kg in dogs. •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): Cilostazol Cilostazole Cilostazolum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cilostazol is an antiplatelet agent and vasodilator used for the symptomatic relief of intermittent claudication.

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 Cilostazol interact? Information: •Drug A: Abciximab •Drug B: Cilostazol •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Cilostazol is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 alleviation of symptoms of intermittent claudication (pain in the legs that occurs with walking and disappears with rest). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cilostazol reduces the symptoms of intermittent claudication, as indicated by an increased walking distance. Intermittent claudication is pain in the legs that occurs with walking and disappears with rest. The pain occurs due to reduced blood flow to the legs. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cilostazol is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in C max and a 25% increase in AUC. Absolute bioavailability is not known. •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): 95-98% •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. Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Two metabolites are active, with one metabolite appearing to account for at least 50% of the pharmacologic (PDE III inhibition) activity after administration of cilostazol. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Cilostazol is eliminated predominately by metabolism and subsequent urinary excretion of metabolites. The primary route of elimination was via the urine (74%), with the remainder excreted in feces (20%). No measurable amount of unchanged cilostazol was excreted in the urine, and less than 2% of the dose was excreted as 3,4-dehydro-cilostazol. About 30% of the dose was excreted in urine as 4'-trans-hydroxy-cilostazol. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 11-13 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Information on acute overdosage with cilostazol in humans is limited. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: severe headache, diarrhea, hypotension, tachycardia, and possibly cardiac arrhythmias. The oral LD 50 of cilostazol is >5.0 g/kg in mice and rats and >2.0 g/kg in dogs. •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): Cilostazol Cilostazole Cilostazolum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cilostazol is an antiplatelet agent and vasodilator used for the symptomatic relief of intermittent claudication. 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 Cisplatin interact?

•Drug A: Abciximab •Drug B: Cisplatin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cisplatin. •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 metastatic testicular tumors, metastatic ovarian tumors and advanced bladder 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): Cisplatin 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following cisplatin doses of 20 to 120 mg/m^2, the concentrations of platinum are highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen; and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Volume of distribution at steady state = 11-12 L/m^2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Cisplatin does not undergo instantaneous and reversible binding to plasma protein that is characteristic of normal drug-protein binding. However, the platinum itself is capable of binding to plasma proteins, including albumin, transferrin, and gamma globulin. Three hours after a bolus injection and two hours after the end of a three-hour infusion, 90% of the plasma platinum is protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Cisplatin decays monoexponentially with a half life of 20 to 30 minutes following administrations of 50 or 100 mg/m^2. Cisplatin has a plasma half-life of 30 minutes. The complexes between albumin and the platinum from cisplatin do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more. •Clearance (Drug A): No clearance available •Clearance (Drug B): 15-16 L/h/m^2 [total body clearance, 7-hour infusion of 100 mg/m^2] 62 mL/min/m^2 [renal clearance, 2-hour infusion of 100 mg/m^2] 50 mL/min/m^2 [renal clearance, 6- to 7-hour infusion of 100 mg/m^2] The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Platinol •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (SP-4-2)-DIAMMINEDICHLOROPLATINUM CDDP Cis-DDP CIS-DIAMMINEDICHLOROPLATINUM CIS-DIAMMINEDICHLOROPLATINUM II Cisplatin cisplatino INT-230-6 COMPONENT CISPLATIN INT230-6 COMPONENT CISPLATIN PLATINUM, DIAMMINEDICHLORO-, (SP-4-2)- •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cisplatin is a platinum based chemotherapy agent used to treat various sarcomas, carcinomas, lymphomas, and germ cell tumors.

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 Cisplatin interact? Information: •Drug A: Abciximab •Drug B: Cisplatin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cisplatin. •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 metastatic testicular tumors, metastatic ovarian tumors and advanced bladder 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): Cisplatin 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following cisplatin doses of 20 to 120 mg/m^2, the concentrations of platinum are highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen; and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Volume of distribution at steady state = 11-12 L/m^2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Cisplatin does not undergo instantaneous and reversible binding to plasma protein that is characteristic of normal drug-protein binding. However, the platinum itself is capable of binding to plasma proteins, including albumin, transferrin, and gamma globulin. Three hours after a bolus injection and two hours after the end of a three-hour infusion, 90% of the plasma platinum is protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Cisplatin decays monoexponentially with a half life of 20 to 30 minutes following administrations of 50 or 100 mg/m^2. Cisplatin has a plasma half-life of 30 minutes. The complexes between albumin and the platinum from cisplatin do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more. •Clearance (Drug A): No clearance available •Clearance (Drug B): 15-16 L/h/m^2 [total body clearance, 7-hour infusion of 100 mg/m^2] 62 mL/min/m^2 [renal clearance, 2-hour infusion of 100 mg/m^2] 50 mL/min/m^2 [renal clearance, 6- to 7-hour infusion of 100 mg/m^2] The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Platinol •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (SP-4-2)-DIAMMINEDICHLOROPLATINUM CDDP Cis-DDP CIS-DIAMMINEDICHLOROPLATINUM CIS-DIAMMINEDICHLOROPLATINUM II Cisplatin cisplatino INT-230-6 COMPONENT CISPLATIN INT230-6 COMPONENT CISPLATIN PLATINUM, DIAMMINEDICHLORO-, (SP-4-2)- •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cisplatin is a platinum based chemotherapy agent used to treat various sarcomas, carcinomas, lymphomas, and germ cell tumors. 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 Citalopram interact?

•Drug A: Abciximab •Drug B: Citalopram •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Citalopram. •Extended Description: Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since citalopram is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. Therefore, the concomitant use of citalopram with an antiplatelet agent can aggravate 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): Citalopram is approved by the FDA for treating adults with major depressive disorder. It has also been used off-label to treat various diseases, including but not limited to sexual dysfunction, ethanol abuse, psychiatric conditions such as obsessive-compulsive disorder (OCD), social anxiety disorder, panic disorder, and diabetic neuropathy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It has been found to relieve or manage symptoms of depression, anxiety, eating disorders and obsessive-compulsive disorder among other mood disorders. The antidepressant, anti-anxiety, and other actions of citalopram are linked to its inhibition of CNS central uptake of serotonin. Serotonergic abnormalities have been reported in patients with mood disorders. Behavioral and neuropsychological effects of serotonin include the regulation of mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, as examples. The onset of action for depression is approximately 1 to 4 weeks. The complete response may take 8-12 weeks after initiation of citalopram. In vitro studies demonstrate that citalopram is a strong and selective inhibitor of neuronal serotonin reuptake and has weak effects on norepinephrine and dopamine central reuptake. The chronic administration of citalopram has been shown to downregulate central norepinephrine receptors, similar to other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 citalopram is unclear but is presumed to be related to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT), potentially through the inhibition of the serotonin transporter (solute carrier family 6 member 4, SLC6A4 ). Citalopram binds with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. Particularly, citalopram has no or very low affinity for 5-HT 1A, 5-HT 2A, dopamine D 1 and D 2, α 1 -, α 2 -, and β-adrenergic, histamine H 1, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): The single- and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dose range of 10 to 40 mg/day. Biotransformation of citalopram is mainly hepatic, with a mean terminal half-life of about 35 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of citalopram in plasma, based on the half-life, is expected to be 2.5 times the plasma concentrations observed after a single dose. Following a single oral dose (40 mg tablet) of citalopram, peak blood levels occur at about 4 hours. The absolute bioavailability of citalopram was about 80% relative to an intravenous dose, and absorption is not affected by food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of citalopram is about 12 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The binding of citalopram (CT), demethylcitalopram (DCT) and didemethylcitalopram (DDCT) to human plasma proteins is about 80%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Citalopram is metabolized mainly in the liver via N -demethylation to its main metabolite, demethylcitalopram by CYP2C19 and CYP3A4. Other metabolites include didemethylcitalopram via CYP2D6 metabolism, citalopram N -oxide and propionic acid derivative via monoamine oxidase enzymes A and B and aldehyde oxidase. Citalopram metabolites exert little pharmacologic activity in comparison to the parent drug and are not likely to contribute to the clinical effect of citalopram. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 12 to 23% of an oral dose of citalopram is found unchanged in the urine, while 10% is found in feces. Following intravenous administrations of citalopram, the fraction of the drug recovered in the urine as citalopram and DCT was about 10% and 5%, 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 mean terminal half-life of citalopram is about 35 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The systemic clearance of citalopram was 330 mL/min, with approximately 20% of that due to renal clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage. Available data from published epidemiologic studies and postmarketing reports with citalopram use in pregnancy have not established an increased risk of major birth defects or miscarriage. Published studies demonstrated that citalopram levels in both cord blood and amniotic fluid are similar to those observed in maternal serum. There are risks of persistent pulmonary hypertension of the newborn (PPHN) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including citalopram, during pregnancy. There also are risks associated with untreated depression in pregnancy. Citalopram was administered orally to pregnant rats during the period of organogenesis at doses of 32, 56, and 112 mg/kg/day, which are approximately 8, 14, and 27 times the Maximum Recommended Human Dose (MRHD) of 40 mg, based on mg/m2 body surface area. Citalopram caused maternal toxicity of CNS clinical signs and decreased weight gain at 112 mg/kg/day, which is 27 times the MRHD. At this maternally toxic dose, citalopram decreased embryo/fetal growth and survival and increased fetal abnormalities (including cardiovascular and skeletal defects). The no observed adverse effect level (NOAEL) for maternal and embryofetal toxicity is 56 mg/kg/day, which is approximately 14 times the MRHD. Citalopram was administered orally to pregnant rabbits during the period of organogenesis at doses up to 16 mg/kg/day, which is approximately 8 times the MRHD of 40 mg, based on mg/m2 body surface area. No maternal or embryofetal toxicity was observed. The NOAEL for maternal and embryofetal toxicity is 16 mg/kg/day, which is approximately 8 times the MRHD. Citalopram was administered orally to pregnant rats during late gestation and lactation periods at doses of 4.8, 12.8, and 32 mg/kg/day, which are approximately 1, 3, and 8 times the MRHD of 40 mg, based on mg/m2 body surface area. Citalopram increased offspring mortality during the first 4 days of birth and decreased offspring growth at 32 mg/kg/day, which is approximately 8 times the MRHD. The NOAEL for developmental toxicity is 12.8 mg/kg/day, which is approximately 3 times the MRHD. In a separate study, similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, which is approximately 6 times the MRHD. A NOAEL was not determined in that study. SSRIs, including citalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction. The following have been reported with citalopram tablet overdosage: • Seizures, which may be delayed, and altered mental status including coma. • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, and torsade de pointes. Hypertension is most commonly seen, but hypotension can rarely be seen alone or with co‐ingestants including alcohol. • Serotonin syndrome (patients with a multiple drug overdosage with other pro-serotonergic drugs may have a higher risk). Prolonged cardiac monitoring is recommended in citalopram overdosage ingestions due to the arrhythmia risk. Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a citalopram overdose. Consider contacting a Poison Center (1‐800‐221‐2222) or a medical toxicologist for additional overdosage management recommendations. Citalopram increased the incidence of small intestine carcinoma in rats treated for 24 months at doses of 8 and 24 mg/kg/day in the diet, which are approximately 2 and 6 times the Maximum Recommended Human Dose (MRHD) of 40 mg, respectively, based on mg/m2 body surface area. A no-effect level (NOEL) for this finding was not established. Citalopram did not increase the incidence of tumors in mice treated for 18 months at doses up to 240 mg/kg/day in the diet, which is approximately 30 times the MRDH of 40 mg based on mg/m2 body surface area. Citalopram was mutagenic in the in vitro bacterial reverse mutation assay (Ames test) in 2 of 5 bacterial strains (Salmonella TA98 and TA1537) in the absence of metabolic activation. It was clastogenic in the in vitro Chinese hamster lung cell assay for chromosomal aberrations in the presence and absence of metabolic activation. Citalopram was not mutagenic in the in vitro mammalian forward gene mutation assay (HPRT) in mouse lymphoma cells or in in vitro/in vivo unscheduled DNA synthesis (UDS) assay in rat liver. It was not clastogenic in the in vitro chromosomal aberration assay in human lymphocytes or in two in vivo mouse micronucleus assays. Citalopram was administered orally to female and male rats at doses of 32, 48, and 72 mg/kg/day prior to and throughout mating and continuing to gestation. These doses are approximately 8, 12, and 17 times the MRHD of 40 mg based on mg/m2 body surface area. Mating and fertility were decreased at doses ≥ 32 mg/kg/day, which is approximately 8 times the MRHD. Gestation duration was increased to 48 mg/kg/day, which is approximately 12 times the MRHD. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Celexa, Ctp •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): Citalopram is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression.

Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since citalopram is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. Therefore, the concomitant use of citalopram with an antiplatelet agent can aggravate the risk of bleeding. The severity of the interaction is moderate.

Question: Does Abciximab and Citalopram interact? Information: •Drug A: Abciximab •Drug B: Citalopram •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Citalopram. •Extended Description: Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since citalopram is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. Therefore, the concomitant use of citalopram with an antiplatelet agent can aggravate 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): Citalopram is approved by the FDA for treating adults with major depressive disorder. It has also been used off-label to treat various diseases, including but not limited to sexual dysfunction, ethanol abuse, psychiatric conditions such as obsessive-compulsive disorder (OCD), social anxiety disorder, panic disorder, and diabetic neuropathy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It has been found to relieve or manage symptoms of depression, anxiety, eating disorders and obsessive-compulsive disorder among other mood disorders. The antidepressant, anti-anxiety, and other actions of citalopram are linked to its inhibition of CNS central uptake of serotonin. Serotonergic abnormalities have been reported in patients with mood disorders. Behavioral and neuropsychological effects of serotonin include the regulation of mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, as examples. The onset of action for depression is approximately 1 to 4 weeks. The complete response may take 8-12 weeks after initiation of citalopram. In vitro studies demonstrate that citalopram is a strong and selective inhibitor of neuronal serotonin reuptake and has weak effects on norepinephrine and dopamine central reuptake. The chronic administration of citalopram has been shown to downregulate central norepinephrine receptors, similar to other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 citalopram is unclear but is presumed to be related to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT), potentially through the inhibition of the serotonin transporter (solute carrier family 6 member 4, SLC6A4 ). Citalopram binds with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. Particularly, citalopram has no or very low affinity for 5-HT 1A, 5-HT 2A, dopamine D 1 and D 2, α 1 -, α 2 -, and β-adrenergic, histamine H 1, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): The single- and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dose range of 10 to 40 mg/day. Biotransformation of citalopram is mainly hepatic, with a mean terminal half-life of about 35 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of citalopram in plasma, based on the half-life, is expected to be 2.5 times the plasma concentrations observed after a single dose. Following a single oral dose (40 mg tablet) of citalopram, peak blood levels occur at about 4 hours. The absolute bioavailability of citalopram was about 80% relative to an intravenous dose, and absorption is not affected by food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of citalopram is about 12 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The binding of citalopram (CT), demethylcitalopram (DCT) and didemethylcitalopram (DDCT) to human plasma proteins is about 80%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Citalopram is metabolized mainly in the liver via N -demethylation to its main metabolite, demethylcitalopram by CYP2C19 and CYP3A4. Other metabolites include didemethylcitalopram via CYP2D6 metabolism, citalopram N -oxide and propionic acid derivative via monoamine oxidase enzymes A and B and aldehyde oxidase. Citalopram metabolites exert little pharmacologic activity in comparison to the parent drug and are not likely to contribute to the clinical effect of citalopram. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 12 to 23% of an oral dose of citalopram is found unchanged in the urine, while 10% is found in feces. Following intravenous administrations of citalopram, the fraction of the drug recovered in the urine as citalopram and DCT was about 10% and 5%, 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 mean terminal half-life of citalopram is about 35 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The systemic clearance of citalopram was 330 mL/min, with approximately 20% of that due to renal clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage. Available data from published epidemiologic studies and postmarketing reports with citalopram use in pregnancy have not established an increased risk of major birth defects or miscarriage. Published studies demonstrated that citalopram levels in both cord blood and amniotic fluid are similar to those observed in maternal serum. There are risks of persistent pulmonary hypertension of the newborn (PPHN) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including citalopram, during pregnancy. There also are risks associated with untreated depression in pregnancy. Citalopram was administered orally to pregnant rats during the period of organogenesis at doses of 32, 56, and 112 mg/kg/day, which are approximately 8, 14, and 27 times the Maximum Recommended Human Dose (MRHD) of 40 mg, based on mg/m2 body surface area. Citalopram caused maternal toxicity of CNS clinical signs and decreased weight gain at 112 mg/kg/day, which is 27 times the MRHD. At this maternally toxic dose, citalopram decreased embryo/fetal growth and survival and increased fetal abnormalities (including cardiovascular and skeletal defects). The no observed adverse effect level (NOAEL) for maternal and embryofetal toxicity is 56 mg/kg/day, which is approximately 14 times the MRHD. Citalopram was administered orally to pregnant rabbits during the period of organogenesis at doses up to 16 mg/kg/day, which is approximately 8 times the MRHD of 40 mg, based on mg/m2 body surface area. No maternal or embryofetal toxicity was observed. The NOAEL for maternal and embryofetal toxicity is 16 mg/kg/day, which is approximately 8 times the MRHD. Citalopram was administered orally to pregnant rats during late gestation and lactation periods at doses of 4.8, 12.8, and 32 mg/kg/day, which are approximately 1, 3, and 8 times the MRHD of 40 mg, based on mg/m2 body surface area. Citalopram increased offspring mortality during the first 4 days of birth and decreased offspring growth at 32 mg/kg/day, which is approximately 8 times the MRHD. The NOAEL for developmental toxicity is 12.8 mg/kg/day, which is approximately 3 times the MRHD. In a separate study, similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, which is approximately 6 times the MRHD. A NOAEL was not determined in that study. SSRIs, including citalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction. The following have been reported with citalopram tablet overdosage: • Seizures, which may be delayed, and altered mental status including coma. • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, and torsade de pointes. Hypertension is most commonly seen, but hypotension can rarely be seen alone or with co‐ingestants including alcohol. • Serotonin syndrome (patients with a multiple drug overdosage with other pro-serotonergic drugs may have a higher risk). Prolonged cardiac monitoring is recommended in citalopram overdosage ingestions due to the arrhythmia risk. Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a citalopram overdose. Consider contacting a Poison Center (1‐800‐221‐2222) or a medical toxicologist for additional overdosage management recommendations. Citalopram increased the incidence of small intestine carcinoma in rats treated for 24 months at doses of 8 and 24 mg/kg/day in the diet, which are approximately 2 and 6 times the Maximum Recommended Human Dose (MRHD) of 40 mg, respectively, based on mg/m2 body surface area. A no-effect level (NOEL) for this finding was not established. Citalopram did not increase the incidence of tumors in mice treated for 18 months at doses up to 240 mg/kg/day in the diet, which is approximately 30 times the MRDH of 40 mg based on mg/m2 body surface area. Citalopram was mutagenic in the in vitro bacterial reverse mutation assay (Ames test) in 2 of 5 bacterial strains (Salmonella TA98 and TA1537) in the absence of metabolic activation. It was clastogenic in the in vitro Chinese hamster lung cell assay for chromosomal aberrations in the presence and absence of metabolic activation. Citalopram was not mutagenic in the in vitro mammalian forward gene mutation assay (HPRT) in mouse lymphoma cells or in in vitro/in vivo unscheduled DNA synthesis (UDS) assay in rat liver. It was not clastogenic in the in vitro chromosomal aberration assay in human lymphocytes or in two in vivo mouse micronucleus assays. Citalopram was administered orally to female and male rats at doses of 32, 48, and 72 mg/kg/day prior to and throughout mating and continuing to gestation. These doses are approximately 8, 12, and 17 times the MRHD of 40 mg based on mg/m2 body surface area. Mating and fertility were decreased at doses ≥ 32 mg/kg/day, which is approximately 8 times the MRHD. Gestation duration was increased to 48 mg/kg/day, which is approximately 12 times the MRHD. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Celexa, Ctp •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): Citalopram is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression. Output: Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since citalopram is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. Therefore, the concomitant use of citalopram with an antiplatelet agent can aggravate the risk of bleeding. The severity of the interaction is moderate.

Does Abciximab and Cladribine interact?

•Drug A: Abciximab •Drug B: Cladribine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cladribine. •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 active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Cladribine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2′-deoxyadenosine 5′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established. Cladribine also has therapeutic effects in patients with multiple sclerosis; although the mechanism of action for this therapeutic effect is not fully elucidated, it is thought to involve cytotoxic effects on B and T lymphocytes by impairing DNA synthesis which in turn results in depletion of lymphocytes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral bioavailability is 34 to 48%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 4.5 ± 2.8 L/kg [patients with hematologic malignancies] 9 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 20% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate •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): 5.4 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 978 +/- 422 mL/h/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Litak, Mavenclad •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 2-CdA 2-chloro-deoxyadenosine 2-Chlorodeoxyadenosine 2ClAdo Cladribina Cladribine Cladribinum CldAdo •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cladribine is a purine antimetabolite used for the management of relapsing forms of Multiple Sclerosis (MS), used in patients who have not responded to or who were unable to tolerate alternative MS drugs.

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 Cladribine interact? Information: •Drug A: Abciximab •Drug B: Cladribine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cladribine. •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 active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Cladribine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2′-deoxyadenosine 5′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established. Cladribine also has therapeutic effects in patients with multiple sclerosis; although the mechanism of action for this therapeutic effect is not fully elucidated, it is thought to involve cytotoxic effects on B and T lymphocytes by impairing DNA synthesis which in turn results in depletion of lymphocytes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral bioavailability is 34 to 48%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 4.5 ± 2.8 L/kg [patients with hematologic malignancies] 9 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 20% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate •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): 5.4 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 978 +/- 422 mL/h/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Litak, Mavenclad •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 2-CdA 2-chloro-deoxyadenosine 2-Chlorodeoxyadenosine 2ClAdo Cladribina Cladribine Cladribinum CldAdo •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cladribine is a purine antimetabolite used for the management of relapsing forms of Multiple Sclerosis (MS), used in patients who have not responded to or who were unable to tolerate alternative MS drugs. 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 Clofarabine interact?

•Drug A: Abciximab •Drug B: Clofarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Clofarabine. •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 pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer 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): Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell 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): 172 L/m2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 47% bound to plasma proteins, predominantly 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): Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine 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): The terminal half-life is estimated to be 5.2 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 28.8 L/h/m2 [Pediatric patients (2 - 19 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) receiving 52 mg/m2 dose] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m basis) has been 70 mg/m /day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included grade 4 hyperbilirubinemia, grade 2 and 3 vomiting, and grade 3 maculopapular rash. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Clolar, Evoltra •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): CAFdA Clofarabin Clofarabina Clofarabine Clofarabinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Clofarabine is a purine nucleoside used to treat relapsed or refractory acute lymphoblastic leukemia in patients 1 to 21 years old.

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 Clofarabine interact? Information: •Drug A: Abciximab •Drug B: Clofarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Clofarabine. •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 pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer 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): Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell 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): 172 L/m2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 47% bound to plasma proteins, predominantly 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): Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine 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): The terminal half-life is estimated to be 5.2 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 28.8 L/h/m2 [Pediatric patients (2 - 19 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) receiving 52 mg/m2 dose] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m basis) has been 70 mg/m /day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included grade 4 hyperbilirubinemia, grade 2 and 3 vomiting, and grade 3 maculopapular rash. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Clolar, Evoltra •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): CAFdA Clofarabin Clofarabina Clofarabine Clofarabinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Clofarabine is a purine nucleoside used to treat relapsed or refractory acute lymphoblastic leukemia in patients 1 to 21 years old. 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 Clopidogrel interact?

•Drug A: Abciximab •Drug B: Clopidogrel •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Clopidogrel is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Clopidogrel is indicated to reduce the risk of myocardial infarction for patients with non-ST elevated acute coronary syndrome (ACS), patients with ST-elevated myocardial infarction, and in recent MI, stroke, or established peripheral arterial 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): Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke. It has a long duration of action as it is taken once daily and a large therapeutic window as it is given in doses of 75-300mg daily. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Clopidogrel is activated via a 2 steps reaction to an active thiol-containing metabolite. This active form is a platelet inhibitor that irreversibly binds to P2Y 12 ADP receptors on platelets. This binding prevents ADP binding to P2Y 12 receptors, activation of the glycoprotein GPIIb/IIIa complex, and platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): A 75mg oral dose of clopidogrel is 50% absorbed from the intestine. Clopidogrel can be taken with or without food. A meal decreases the AUC of the active metabolite by 57%. The active metabolite of clopidogrel reaches a maximum concentration after 30-60 minutes. Clopidogrel reached a C max of 2.04±2.0ng/mL in 1.40±1.07h. The AUC for a 300mg oral dose of clopidogrel was 45.1±16.2ng*h/mL for poor metabolizers, 65.6±19.1ng*h/mL for intermediate metabolizers, and 104.3±57.3ng*h/mL for extensive metabolizers. The C max was 31.3±13ng/mL for poor metabolizers, 43.9±14ng/mL for intermediate metabolizers, and 60.8±34.3ng/mL for extensive metabolizers. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of clopidogrel is 39,240±33,520L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Both the active and inactive metabolites of clopidogrel are 98% protein bound in plasma. Studies in cows show clopidogrel 71-85.5% bound to serum 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): 85-90% of an oral dose undergoes first pass metabolism by carboxylesterase 1 in the liver to an inactive carboxylic acid metabolite. about 2% of clopidogrel is oxidized to 2-oxoclopidogrel. This conversion is 35.8% by CYP1A2, 19.4% by CYP2B6, and 44.9% by CYP2C19 though other studies suggest CYP3A4, CYP3A5, and CYP2C9 also contribute. 2-oxoclopidogrel is further metabolized to the active metabolite. This conversion is 32.9% by CYP2B6, 6.79% by CYP2C9, 20.6% by CYP2C19, and 39.8% by CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): An oral dose of radiolabelled clopidogrel is excreted 50% in the urine and 46% in the feces over 5 days. The remainder of clopidogrel is irreversibly bound to platelets for their lifetime, or approximately 8-11 days. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): That half life of clopidogrel is approximately 6 hours following a 75mg oral dose while the half life of the active metabolite is approximately 30 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of a 75mg oral dose was 18,960±15,890L/h and for a 300mg oral dose was 16,980±10,410L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): A single dose of clopidogrel at 1500-2000mg/kg was lethal to mice and rats while 3000mg/kg was lethal to baboons. Symptoms of overdose include vomiting, breathing difficulty, gastrointestinal hemorrhage, and prostration. Clopidogrel is irreversibly bound to platelets for their lifetime, which is approximately 11 days. Overdoses of clopidogrel can be treated with platelet transfusions to restore clotting ability. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Duoplavin, Plavix, Zyllt •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Clopidogrel Clopidogrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Clopidogrel is an antiplatelet agent used to prevent blood clots in peripheral vascular disease, coronary artery disease, and cerebrovascular disease.

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 Clopidogrel interact? Information: •Drug A: Abciximab •Drug B: Clopidogrel •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Clopidogrel is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Clopidogrel is indicated to reduce the risk of myocardial infarction for patients with non-ST elevated acute coronary syndrome (ACS), patients with ST-elevated myocardial infarction, and in recent MI, stroke, or established peripheral arterial 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): Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke. It has a long duration of action as it is taken once daily and a large therapeutic window as it is given in doses of 75-300mg daily. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Clopidogrel is activated via a 2 steps reaction to an active thiol-containing metabolite. This active form is a platelet inhibitor that irreversibly binds to P2Y 12 ADP receptors on platelets. This binding prevents ADP binding to P2Y 12 receptors, activation of the glycoprotein GPIIb/IIIa complex, and platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): A 75mg oral dose of clopidogrel is 50% absorbed from the intestine. Clopidogrel can be taken with or without food. A meal decreases the AUC of the active metabolite by 57%. The active metabolite of clopidogrel reaches a maximum concentration after 30-60 minutes. Clopidogrel reached a C max of 2.04±2.0ng/mL in 1.40±1.07h. The AUC for a 300mg oral dose of clopidogrel was 45.1±16.2ng*h/mL for poor metabolizers, 65.6±19.1ng*h/mL for intermediate metabolizers, and 104.3±57.3ng*h/mL for extensive metabolizers. The C max was 31.3±13ng/mL for poor metabolizers, 43.9±14ng/mL for intermediate metabolizers, and 60.8±34.3ng/mL for extensive metabolizers. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of clopidogrel is 39,240±33,520L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Both the active and inactive metabolites of clopidogrel are 98% protein bound in plasma. Studies in cows show clopidogrel 71-85.5% bound to serum 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): 85-90% of an oral dose undergoes first pass metabolism by carboxylesterase 1 in the liver to an inactive carboxylic acid metabolite. about 2% of clopidogrel is oxidized to 2-oxoclopidogrel. This conversion is 35.8% by CYP1A2, 19.4% by CYP2B6, and 44.9% by CYP2C19 though other studies suggest CYP3A4, CYP3A5, and CYP2C9 also contribute. 2-oxoclopidogrel is further metabolized to the active metabolite. This conversion is 32.9% by CYP2B6, 6.79% by CYP2C9, 20.6% by CYP2C19, and 39.8% by CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): An oral dose of radiolabelled clopidogrel is excreted 50% in the urine and 46% in the feces over 5 days. The remainder of clopidogrel is irreversibly bound to platelets for their lifetime, or approximately 8-11 days. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): That half life of clopidogrel is approximately 6 hours following a 75mg oral dose while the half life of the active metabolite is approximately 30 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of a 75mg oral dose was 18,960±15,890L/h and for a 300mg oral dose was 16,980±10,410L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): A single dose of clopidogrel at 1500-2000mg/kg was lethal to mice and rats while 3000mg/kg was lethal to baboons. Symptoms of overdose include vomiting, breathing difficulty, gastrointestinal hemorrhage, and prostration. Clopidogrel is irreversibly bound to platelets for their lifetime, which is approximately 11 days. Overdoses of clopidogrel can be treated with platelet transfusions to restore clotting ability. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Duoplavin, Plavix, Zyllt •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Clopidogrel Clopidogrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Clopidogrel is an antiplatelet agent used to prevent blood clots in peripheral vascular disease, coronary artery disease, and cerebrovascular disease. 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 Coagulation Factor IX (Recombinant) interact?

•Drug A: Abciximab •Drug B: Coagulation Factor IX (Recombinant) •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation Factor IX (Recombinant) can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 hemophilia (Christmas 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): Binds vitamin K and factor VIIIa. Cleaves the Arg-Ile bond in factor X to form active factor Xa. Plays a key role in blood coagulation and clotting. Injections of factor IX are used to treat hemophilia B, which is sometimes called Christmas disease. AlphaNine is injected to increase plasma levels of Factor IX and can temporarily correct this coagulation defect. The activated partial thromboplastin time (aPTT) is prolonged in people with hemophilia B. Treatment with factor IX concentrate may normalize the aPTT by temporarily replacing the factor IX. The administration of BeneFIX increases plasma levels of factor IX, and can temporarily correct the coagulation defect in these 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): Coagulation Factor IX is an important protein in the process of hemostasis and normal blood clotting as it plays a key role within the coagulation cascade. It is located within the blood plasma as a zymogen, an antecedent to enzymatic function, in its inactivated state. Factor IX is dependent on the presence of Vitamin K, and is activated to a serine protease by the function of Coagulation Factor XIa. Factor XIa cleaves the peptide bond associated with protein activation in Factor IX, leaving Factor IX with two exposed chains, a light chain and a heavy chain. These two chains are held together by several disulfide bonds that reinforce the structure of Factor IX's activated form. After being activated, Factor IX forms a complex with calcium ions, membrane phospholipids and Coagulation Factor VIII to activate Coagulation Factor X. The activation of Factor X then performs a similarly integral step in the blood coagulation cascade. The ultimate result of phenotypically normal coagulation factors is the creation of platelets for normal blood clotting. •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): 18.8 ± 5.4 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 8.62 ± 1.7 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Benefix, Idelvion, Ixinity, Rixubis •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): Coagulation Factor IX (Recombinant) is a form of recombinant human coagulation Factor IX used to treat hemophilia B.

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 Coagulation Factor IX (Recombinant) interact? Information: •Drug A: Abciximab •Drug B: Coagulation Factor IX (Recombinant) •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation Factor IX (Recombinant) can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 hemophilia (Christmas 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): Binds vitamin K and factor VIIIa. Cleaves the Arg-Ile bond in factor X to form active factor Xa. Plays a key role in blood coagulation and clotting. Injections of factor IX are used to treat hemophilia B, which is sometimes called Christmas disease. AlphaNine is injected to increase plasma levels of Factor IX and can temporarily correct this coagulation defect. The activated partial thromboplastin time (aPTT) is prolonged in people with hemophilia B. Treatment with factor IX concentrate may normalize the aPTT by temporarily replacing the factor IX. The administration of BeneFIX increases plasma levels of factor IX, and can temporarily correct the coagulation defect in these 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): Coagulation Factor IX is an important protein in the process of hemostasis and normal blood clotting as it plays a key role within the coagulation cascade. It is located within the blood plasma as a zymogen, an antecedent to enzymatic function, in its inactivated state. Factor IX is dependent on the presence of Vitamin K, and is activated to a serine protease by the function of Coagulation Factor XIa. Factor XIa cleaves the peptide bond associated with protein activation in Factor IX, leaving Factor IX with two exposed chains, a light chain and a heavy chain. These two chains are held together by several disulfide bonds that reinforce the structure of Factor IX's activated form. After being activated, Factor IX forms a complex with calcium ions, membrane phospholipids and Coagulation Factor VIII to activate Coagulation Factor X. The activation of Factor X then performs a similarly integral step in the blood coagulation cascade. The ultimate result of phenotypically normal coagulation factors is the creation of platelets for normal blood clotting. •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): 18.8 ± 5.4 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 8.62 ± 1.7 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Benefix, Idelvion, Ixinity, Rixubis •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): Coagulation Factor IX (Recombinant) is a form of recombinant human coagulation Factor IX used to treat hemophilia B. 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 Coagulation Factor IX Human interact?

•Drug A: Abciximab •Drug B: Coagulation Factor IX Human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation Factor IX Human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Factor IX is used to treat Christmas disease. Factor IX deficiency is treated by injection factor IX produced from human plasma. Tranexamic acid may be of value in patients undergoing surgery who have inherited factor IX deficiency in order to reduce the perioperative risk of 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): Binds vitamin K and factor VIIIa. Cleaves the Arg-Ile bond in factor X to form active factor Xa. Plays a key role in blood coagulation and clotting. Injections of factor IX are used to treat hemophilia B, which is sometimes called Christmas disease. AlphaNine is injected to increase plasma levels of Factor IX and can temporarily correct this coagulation defect. The activated partial thromboplastin time (aPTT) is prolonged in people with hemophilia B. Treatment with factor IX concentrate may normalize the aPTT by temporarily replacing the factor IX. The administration of BeneFIX increases plasma levels of factor IX, and can temporarily correct the coagulation defect in these 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): Coagulation Factor IX is an important protein in the process of hemostasis and normal blood clotting as it plays a key role within the coagulation cascade. It is located within the blood plasma as a zymogen, an antecedent to enzymatic function, in its inactivated state. Factor IX is dependent on the presence of Vitamin K, and is activated to a serine protease by the function of Coagulation Factor XIa. Factor XIa cleaves the peptide bond associated with protein activation in Factor IX, leaving Factor IX with two exposed chains, a light chain and a heavy chain. These two chains are held together by several disulfide bonds that reinforce the structure of Factor IX's activated form. After being activated, Factor IX forms a complex with calcium ions, membrane phospholipids and Coagulation Factor VIII to activate Coagulation Factor X. The activation of Factor X then performs a similarly integral step in the blood coagulation cascade. The ultimate result of phenotypically normal coagulation factors is the creation of platelets for normal blood clotting. •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): 18.8 ± 5.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 8.62 ± 1.7. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alphanine Sd, Balfaxar, Beriplex, Immunine Vh, 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): Coagulation Factor IX Human is a coagulation factor used to treat hemophilia B or factor IX hemophilia.

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 Coagulation Factor IX Human interact? Information: •Drug A: Abciximab •Drug B: Coagulation Factor IX Human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation Factor IX Human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Factor IX is used to treat Christmas disease. Factor IX deficiency is treated by injection factor IX produced from human plasma. Tranexamic acid may be of value in patients undergoing surgery who have inherited factor IX deficiency in order to reduce the perioperative risk of 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): Binds vitamin K and factor VIIIa. Cleaves the Arg-Ile bond in factor X to form active factor Xa. Plays a key role in blood coagulation and clotting. Injections of factor IX are used to treat hemophilia B, which is sometimes called Christmas disease. AlphaNine is injected to increase plasma levels of Factor IX and can temporarily correct this coagulation defect. The activated partial thromboplastin time (aPTT) is prolonged in people with hemophilia B. Treatment with factor IX concentrate may normalize the aPTT by temporarily replacing the factor IX. The administration of BeneFIX increases plasma levels of factor IX, and can temporarily correct the coagulation defect in these 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): Coagulation Factor IX is an important protein in the process of hemostasis and normal blood clotting as it plays a key role within the coagulation cascade. It is located within the blood plasma as a zymogen, an antecedent to enzymatic function, in its inactivated state. Factor IX is dependent on the presence of Vitamin K, and is activated to a serine protease by the function of Coagulation Factor XIa. Factor XIa cleaves the peptide bond associated with protein activation in Factor IX, leaving Factor IX with two exposed chains, a light chain and a heavy chain. These two chains are held together by several disulfide bonds that reinforce the structure of Factor IX's activated form. After being activated, Factor IX forms a complex with calcium ions, membrane phospholipids and Coagulation Factor VIII to activate Coagulation Factor X. The activation of Factor X then performs a similarly integral step in the blood coagulation cascade. The ultimate result of phenotypically normal coagulation factors is the creation of platelets for normal blood clotting. •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): 18.8 ± 5.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 8.62 ± 1.7. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alphanine Sd, Balfaxar, Beriplex, Immunine Vh, 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): Coagulation Factor IX Human is a coagulation factor used to treat hemophilia B or factor IX hemophilia. 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 Coagulation factor VII human interact?

•Drug A: Abciximab •Drug B: Coagulation factor VII human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation factor VII human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption since given IV. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 45 ml/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binds to coagulation factor X and IX and tissue 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): Degraded by catabolism •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Catabolism •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 5 h •Clearance (Drug A): No clearance available •Clearance (Drug B): 7.4 ml/kgh •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No evidence of toxicity. Adverse effect of excessive clotting in certain individuals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Balfaxar, Beriplex, 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): Coagulation factor VII human is a coagulation factor used to treat bleeding disorders such as hemophilia and Glanzmann's thrombasthenia.

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 Coagulation factor VII human interact? Information: •Drug A: Abciximab •Drug B: Coagulation factor VII human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation factor VII human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption since given IV. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 45 ml/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Binds to coagulation factor X and IX and tissue 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): Degraded by catabolism •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Catabolism •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 5 h •Clearance (Drug A): No clearance available •Clearance (Drug B): 7.4 ml/kgh •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No evidence of toxicity. Adverse effect of excessive clotting in certain individuals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Balfaxar, Beriplex, 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): Coagulation factor VII human is a coagulation factor used to treat bleeding disorders such as hemophilia and Glanzmann's thrombasthenia. 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 Coagulation factor VIIa Recombinant Human interact?

•Drug A: Abciximab •Drug B: Coagulation factor VIIa Recombinant Human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation factor VIIa Recombinant Human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 hemorrhagic complications in hemophilia A and B. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 in the treatment of bleeding episodes in hemophilia A or B. NovoSeven is recombinant Factor VIIa and, when complexed with tissue factor can activate coagulation Factor X to Factor Xa, as well as coagulation Factor IX to Factor IXa. Factor Xa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local clotting. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): NovoSeven activates the coagulation or clotting cascade by cleaving Factor IX and Factor X, which activates them and then leads to activation of thrombin and fibrin. •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): 121 ± 30 mL/kg [adults] 153 ± 29 mL/kg [children] 280 to 290 mL/kg [congenital Factor VII deficiency] •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): 33 - 37 mL/h x kg [healthy] 1375 +/- 396 mL/hr [severe hemophilia A male children] 57.3 +/- 9.5 mL/hr/kg [severe hemophilia A male children] 2767 +/- 385 mL/hr [severe hemophilia A men] 37.6 +/- 13.1 mL/hr/kg [severe hemophilia A men] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Niastase RT, Novoseven, Sevenfact •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): Coagulation factor VIIa Recombinant Human is a form of recombinant human coagulation Factor VII used to treat hemophilia A and B.

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 Coagulation factor VIIa Recombinant Human interact? Information: •Drug A: Abciximab •Drug B: Coagulation factor VIIa Recombinant Human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation factor VIIa Recombinant Human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 hemorrhagic complications in hemophilia A and B. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 in the treatment of bleeding episodes in hemophilia A or B. NovoSeven is recombinant Factor VIIa and, when complexed with tissue factor can activate coagulation Factor X to Factor Xa, as well as coagulation Factor IX to Factor IXa. Factor Xa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local clotting. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): NovoSeven activates the coagulation or clotting cascade by cleaving Factor IX and Factor X, which activates them and then leads to activation of thrombin and fibrin. •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): 121 ± 30 mL/kg [adults] 153 ± 29 mL/kg [children] 280 to 290 mL/kg [congenital Factor VII deficiency] •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): 33 - 37 mL/h x kg [healthy] 1375 +/- 396 mL/hr [severe hemophilia A male children] 57.3 +/- 9.5 mL/hr/kg [severe hemophilia A male children] 2767 +/- 385 mL/hr [severe hemophilia A men] 37.6 +/- 13.1 mL/hr/kg [severe hemophilia A men] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Niastase RT, Novoseven, Sevenfact •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): Coagulation factor VIIa Recombinant Human is a form of recombinant human coagulation Factor VII used to treat hemophilia A and B. 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 Coagulation factor X human interact?

•Drug A: Abciximab •Drug B: Coagulation factor X human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation factor X human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): The human coagulation factor X is indicated in adults and children with hereditary Factor X deficiency for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding in patients with mild and moderate hereditary Factor X deficiency. It is also indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with acute major 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): Clinical human coagulation Factor X solution increases plasma levels of Factor X and can temporarily correct the coagulation defect in these patients, as reflected by decrease in the activated Partial Thromboplastin Time (aPTT) and prothrombin time (PT). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 X is an inactive zymogen that is synthesized in the liver, which can be activated by Factor IXa (via the intrinsic pathway) or by Factor VIIa (via the extrinsic pathway). It is composed of a light chain which contains the Gla (glutamic acid) domain and two epidermal growth factor domains, and a heavy chain that contains the catalytic serine protease domain. The conversion of inactive Factor X into the active form Factor Xa requires the cleavage of a 52-residue peptide from the heavy chain and the release of 52-residue activation peptide that contains the His236, Asp228 and Ser379 catalytic site. This activation step can occur through the extrinsic or intrinsic pathway and is considered to be the first step in the common pathway to fibrin formation. Factor Xa plays a critical initiation step of the coagulation pathway by cleaving and activating prothrombin to thrombin in complex with FVa, Ca2+ and phospholipids. This complex is also known as the prothrombinase complex. Thrombin then acts upon soluble fibrinogen and Factor XIII to generate a cross-linked fibrin clot. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single intravenous dose of 25 IU/kg, the mean peak plasma concentration (CV%) was 0.504 (17.2) IU/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following a single intravenous dose of 25 IU/kg, the mean volume of distribution at steady state (CV%) was 56.3 (24.0) 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): Following a single intravenous dose of 25 IU/kg, the mean plasma half-life (CV%) was 30.3 (22.8) hr. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a single intravenous dose of 25 IU/kg, the mean total body clearance was 1.35 (21.7) mL/kg/hr. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Balfaxar, Beriplex, Coagadex, 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): Coagulation factor X human is a coagulation factor used to treat Factor X deficiency 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 Coagulation factor X human interact? Information: •Drug A: Abciximab •Drug B: Coagulation factor X human •Severity: MAJOR •Description: The therapeutic efficacy of Coagulation factor X human can be decreased when used in combination with Abciximab. •Extended Description: Blood coagulation factors promote the blood coagulation pathways to ultimately form the insoluble fibrin clot. In contrast, fibrinolytic agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin to break down the insoluble clot [A38173]. Desired procoagulant effects of blood coagulation factors may be reduced with the combination use of fibrinolytic agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): The human coagulation factor X is indicated in adults and children with hereditary Factor X deficiency for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding in patients with mild and moderate hereditary Factor X deficiency. It is also indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with acute major 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): Clinical human coagulation Factor X solution increases plasma levels of Factor X and can temporarily correct the coagulation defect in these patients, as reflected by decrease in the activated Partial Thromboplastin Time (aPTT) and prothrombin time (PT). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 X is an inactive zymogen that is synthesized in the liver, which can be activated by Factor IXa (via the intrinsic pathway) or by Factor VIIa (via the extrinsic pathway). It is composed of a light chain which contains the Gla (glutamic acid) domain and two epidermal growth factor domains, and a heavy chain that contains the catalytic serine protease domain. The conversion of inactive Factor X into the active form Factor Xa requires the cleavage of a 52-residue peptide from the heavy chain and the release of 52-residue activation peptide that contains the His236, Asp228 and Ser379 catalytic site. This activation step can occur through the extrinsic or intrinsic pathway and is considered to be the first step in the common pathway to fibrin formation. Factor Xa plays a critical initiation step of the coagulation pathway by cleaving and activating prothrombin to thrombin in complex with FVa, Ca2+ and phospholipids. This complex is also known as the prothrombinase complex. Thrombin then acts upon soluble fibrinogen and Factor XIII to generate a cross-linked fibrin clot. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single intravenous dose of 25 IU/kg, the mean peak plasma concentration (CV%) was 0.504 (17.2) IU/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following a single intravenous dose of 25 IU/kg, the mean volume of distribution at steady state (CV%) was 56.3 (24.0) 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): Following a single intravenous dose of 25 IU/kg, the mean plasma half-life (CV%) was 30.3 (22.8) hr. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a single intravenous dose of 25 IU/kg, the mean total body clearance was 1.35 (21.7) mL/kg/hr. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Balfaxar, Beriplex, Coagadex, 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): Coagulation factor X human is a coagulation factor used to treat Factor X deficiency 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 Collagenase clostridium histolyticum interact?

•Drug A: Abciximab •Drug B: Collagenase clostridium histolyticum •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Collagenase clostridium histolyticum. •Extended Description: Anticoagulant agents may increase the risk of hemorrhage in patients treated with collagenase clostridium histolyticum. Penile ecchymoses and bleeding/hematoma at the injection site are commonly observed adverse effects of collagenase clostridium histolyticum that may be worsened with the administration of antiplatelet drugs, which can promote bleeding. Recent studies, however, contradict this finding and did not demonstrate at increased incidence of bleeding episodes. Further research is warranted. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Collagenase clostridium histolyticum is indicated for the treatment of adults with Dupuytren's contracture with a palpable cord. Additionally, it is used to treat men with Peyronie's disease diagnosed with a penile curvature deformity of at least a 30-degree angle at the beginning of therapy in addition to palpable plaques. Collagenase ointment is used for the tissue debridement of chronic dermal ulcers and severely burned tissues. The combination collagenase product, also known as Qwo, is used for the treatment of moderate to severe cellulite in the buttocks of adult women. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Collagenase digests collagen, treating conditions such as Peyronie's disease, cellulite, chronic ulcers, burns, and contractures. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Peyronie's disease is a fibrous lesion of the tunica albuginea in the penile tissues. Cellulite is a multifactorial condition resulting in the accumulation of fibrotic dermal septae and the expansion of subcutaneous fat. Dupuytren's contracture is a fibroproliferative disease that results in the fibrous deposition of collagen in the hands, limiting mobility and functionality of the hands. The collagen deposition in the abovementioned conditions is the target of collagenase enzyme therapy. These enzymes are proteinases acting to hydrolyze collagen's triple-helical conformation, resulting in the lysis of collagen deposits and relief from the necrotic tissue and plaques associated with several conditions. On a molecular level, collagenases cleave polypeptide chains that make up the collagen triple helix structure at various loci, leading to solubilization from the collagen fibril. •Absorption (Drug A): No absorption available •Absorption (Drug B): There is currently limited readily available regarding the absorption of collagenase through the skin. In a pharmacokinetic study, the serum concentrations of clostridium type I collagenase (AUX-I) and clostridium type II collagenase (AUX-II) were measured. Both were detected under the lower limit of quantitation of 5 ng/mL and 25 ng/mL, respectively, in volunteers administered one dose of the collagenase histolyticum combination product, Qwo, at a dose of up to 3.36 mg in a maximum of 4 body areas. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): There is no currently available information regarding the presence of collagenase in body fluids or uptake by particular organs and passage through the blood-brain barrier. Systemic pharmacokinetic studies evaluation volume of distribution have not been performed, however, collagenase histolyticum is likely to have local degradative effects in the region of the application without effects on the vasculature and elastic tissue. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no readily available information regarding the protein binding of collagenase. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No formal systemic metabolism studies have been performed with collagenase histolyticum. •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): Clearance information for collagenase is not readily available. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No clinical reaction has been attributed to an overdose of collagenase in clinical trials. If required, the collagenase enzymes can be inactivated with a povidone-iodine wash. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Qwo, Santyl, Xiaflex •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): Collagenase clostridium histolyticum is a collagenase enzyme used to promote debridement of necrotic tissue in burns and skin ulcers as well as to treat Dupuytren's contracture and Peyronie's disease.

Anticoagulant agents may increase the risk of hemorrhage in patients treated with collagenase clostridium histolyticum. Penile ecchymoses and bleeding/hematoma at the injection site are commonly observed adverse effects of collagenase clostridium histolyticum that may be worsened with the administration of antiplatelet drugs, which can promote bleeding. Recent studies, however, contradict this finding and did not demonstrate at increased incidence of bleeding episodes. Further research is warranted. The severity of the interaction is moderate.

Question: Does Abciximab and Collagenase clostridium histolyticum interact? Information: •Drug A: Abciximab •Drug B: Collagenase clostridium histolyticum •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Collagenase clostridium histolyticum. •Extended Description: Anticoagulant agents may increase the risk of hemorrhage in patients treated with collagenase clostridium histolyticum. Penile ecchymoses and bleeding/hematoma at the injection site are commonly observed adverse effects of collagenase clostridium histolyticum that may be worsened with the administration of antiplatelet drugs, which can promote bleeding. Recent studies, however, contradict this finding and did not demonstrate at increased incidence of bleeding episodes. Further research is warranted. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Collagenase clostridium histolyticum is indicated for the treatment of adults with Dupuytren's contracture with a palpable cord. Additionally, it is used to treat men with Peyronie's disease diagnosed with a penile curvature deformity of at least a 30-degree angle at the beginning of therapy in addition to palpable plaques. Collagenase ointment is used for the tissue debridement of chronic dermal ulcers and severely burned tissues. The combination collagenase product, also known as Qwo, is used for the treatment of moderate to severe cellulite in the buttocks of adult women. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Collagenase digests collagen, treating conditions such as Peyronie's disease, cellulite, chronic ulcers, burns, and contractures. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Peyronie's disease is a fibrous lesion of the tunica albuginea in the penile tissues. Cellulite is a multifactorial condition resulting in the accumulation of fibrotic dermal septae and the expansion of subcutaneous fat. Dupuytren's contracture is a fibroproliferative disease that results in the fibrous deposition of collagen in the hands, limiting mobility and functionality of the hands. The collagen deposition in the abovementioned conditions is the target of collagenase enzyme therapy. These enzymes are proteinases acting to hydrolyze collagen's triple-helical conformation, resulting in the lysis of collagen deposits and relief from the necrotic tissue and plaques associated with several conditions. On a molecular level, collagenases cleave polypeptide chains that make up the collagen triple helix structure at various loci, leading to solubilization from the collagen fibril. •Absorption (Drug A): No absorption available •Absorption (Drug B): There is currently limited readily available regarding the absorption of collagenase through the skin. In a pharmacokinetic study, the serum concentrations of clostridium type I collagenase (AUX-I) and clostridium type II collagenase (AUX-II) were measured. Both were detected under the lower limit of quantitation of 5 ng/mL and 25 ng/mL, respectively, in volunteers administered one dose of the collagenase histolyticum combination product, Qwo, at a dose of up to 3.36 mg in a maximum of 4 body areas. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): There is no currently available information regarding the presence of collagenase in body fluids or uptake by particular organs and passage through the blood-brain barrier. Systemic pharmacokinetic studies evaluation volume of distribution have not been performed, however, collagenase histolyticum is likely to have local degradative effects in the region of the application without effects on the vasculature and elastic tissue. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no readily available information regarding the protein binding of collagenase. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No formal systemic metabolism studies have been performed with collagenase histolyticum. •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): Clearance information for collagenase is not readily available. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No clinical reaction has been attributed to an overdose of collagenase in clinical trials. If required, the collagenase enzymes can be inactivated with a povidone-iodine wash. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Qwo, Santyl, Xiaflex •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): Collagenase clostridium histolyticum is a collagenase enzyme used to promote debridement of necrotic tissue in burns and skin ulcers as well as to treat Dupuytren's contracture and Peyronie's disease. Output: Anticoagulant agents may increase the risk of hemorrhage in patients treated with collagenase clostridium histolyticum. Penile ecchymoses and bleeding/hematoma at the injection site are commonly observed adverse effects of collagenase clostridium histolyticum that may be worsened with the administration of antiplatelet drugs, which can promote bleeding. Recent studies, however, contradict this finding and did not demonstrate at increased incidence of bleeding episodes. Further research is warranted. The severity of the interaction is moderate.

Does Abciximab and Conjugated estrogens interact?

•Drug A: Abciximab •Drug B: Conjugated estrogens •Severity: MODERATE •Description: Conjugated estrogens may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): The conjugated estrogens are indicated for several different conditions including: Treatment of moderate to severe vasomotor symptoms due to menopause. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. Palliative treatment of breast cancer in appropriately selected patients with metastatic disease. Palliative treatment of androgen-dependent carcinoma of the prostate. Preventive therapy of postmenopausal osteoporosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 binding of estrogens to the estrogen receptor produces the activation of nuclear receptors in order to bind to estrogen response elements in certain target genes. This mechanistic cascade results in histone acetylation, alteration of chromatin conformation and the initiation of transcription of certain specific drugs. In preclinical studies, the conjugated estrogens are known to have a similar estrogenic potency than estrone and the equilin components of the conjugated estrogens have similar potency in the liver when compared to bioidentical estradiol. It has also been tested and confirmed that conjugated estrogens present a selective estrogen receptor modulator profile which allows it to have a large beneficial effect on the bone and cardiovascular system. Clinically, the administration of conjugated estrogens is known to promote vasomotor stability, maintain genitourinary function, and normal growth and development of female sex hormones. It has also been shown to prevent accelerated bone loss by inhibiting bone resorption and restoring the balance of bone resorption. In the hormonal area, it is shown to inhibit luteinizing hormone and decrease the serum concentration of testosterone. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 conjugated estrogens, equally to the normal physiological estrogen, work by agonistically binding to the estrogen receptors alpha and beta. The estrogen receptors vary in quantity and proportion according to the tissues and hence, the activity of this conjugated estrogens is very variable. The activity made by the conjugated estrogens is driven by the increase in the synthesis of DNA, RNA and various proteins in responsive tissues which in order will reduce the release of gonadotropin-releasing hormone, follicle-stimulating hormone and leuteinizing hormone. The specific mechanism of action cannot be described only in terms of total estrogenic action as the pharmacokinetic profile, the tissue specificity and the tissue metabolism is different for each component of the product. •Absorption (Drug A): No absorption available •Absorption (Drug B): The conjugated estrogens are well absorbed in the gastrointestinal tract and the maximum plasma concentration of the conjugated estrogens is reached after 7 hours depending on the estrone component. The maximal plasma concentration of conjugated estrogens after multiple doses of 0.45 mg is reported to be of 2.6 ng/ml with an AUC in the steady state of 35 ng.h/ml. Unconjugated estrogens are known to be cleared from the circulation at a faster rate than their ester forms. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The physiological distribution of estrogens in the body is very similar to what is seen in endogenous estrogens and hence, it is widely distributed. The conjugated estrogens are mainly found in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Conjugated estrogens are bound to plasma proteins and this bound state can represent around 50-80% of the administered dose. It circulates in the blood mainly bound to sex-hormone binding globulin and 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): The conjugated estrogens are metabolized by a number of different pathways. One of the metabolic pathways of the conjugated estrogens is driven by the action of the cytochrome isoenzyme CYP3A4. On the other hand, the conjugated estrogens can also be processed by a dynamic equilibrium of metabolic interconversion and sulfate conjugation. Some of the principal metabolic reactions of the conjugated estrogens are driven by the conversion of 17beta-estradiol to estrone and the further change to estriol. A portion of the administered conjugated estrogens will remain in the blood as sulfate conjugates which serve as a circulating reservoir for the generation of new estrogens. In the endometrium, equilin is metabolized to 2-hydroxy and 4-hydroxy equilin as well as 2-hydroxy and 4-hydroxy estradiol. This hydroxylation process is very large in various of the components of the conjugated estrogens and hence, the major metabolites in urine are known to be 17-ketosteroid-16-alpha-hydroxy estrone, 16-alpha-hydroxy-17-beta-dihydro equilin and 16-alpha-hydroxy-17-beta-dihydroequilenin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The conjugated estrogens are eliminated mainly in the urine. In this renal elimination, it is possible to find 17 beta-estradiol, estrone, estriol, as well as the glucuronide and sulfate conjugates of the estrogens. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 the conjugated estrogens is reported to be of 17 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The reported normal clearance rate for estrogens is of approximately 615 L/m2. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The reported oral LD50 in the rat is of more than 5000 mg/kg. Serious overdosage symptoms have not been reported. There have been only reports of nausea, vomiting, and withdrawal in bleeding in females. Long-term continuous administration of estrogens is correlated to increased risk on the incidence of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Congest, Duavee, Duavive, Premarin, Premphase 28 Day, Prempro 0.625/2.5 28 Day •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): Conjugated estrogens is a mixture of estrogens used in estrogen replacement therapy for menopause and hypoestrogenism, used in the treatment of various malignancies, and used in the treatment of postmenopausal osteoporosis.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Conjugated estrogens interact? Information: •Drug A: Abciximab •Drug B: Conjugated estrogens •Severity: MODERATE •Description: Conjugated estrogens may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): The conjugated estrogens are indicated for several different conditions including: Treatment of moderate to severe vasomotor symptoms due to menopause. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. Palliative treatment of breast cancer in appropriately selected patients with metastatic disease. Palliative treatment of androgen-dependent carcinoma of the prostate. Preventive therapy of postmenopausal osteoporosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 binding of estrogens to the estrogen receptor produces the activation of nuclear receptors in order to bind to estrogen response elements in certain target genes. This mechanistic cascade results in histone acetylation, alteration of chromatin conformation and the initiation of transcription of certain specific drugs. In preclinical studies, the conjugated estrogens are known to have a similar estrogenic potency than estrone and the equilin components of the conjugated estrogens have similar potency in the liver when compared to bioidentical estradiol. It has also been tested and confirmed that conjugated estrogens present a selective estrogen receptor modulator profile which allows it to have a large beneficial effect on the bone and cardiovascular system. Clinically, the administration of conjugated estrogens is known to promote vasomotor stability, maintain genitourinary function, and normal growth and development of female sex hormones. It has also been shown to prevent accelerated bone loss by inhibiting bone resorption and restoring the balance of bone resorption. In the hormonal area, it is shown to inhibit luteinizing hormone and decrease the serum concentration of testosterone. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 conjugated estrogens, equally to the normal physiological estrogen, work by agonistically binding to the estrogen receptors alpha and beta. The estrogen receptors vary in quantity and proportion according to the tissues and hence, the activity of this conjugated estrogens is very variable. The activity made by the conjugated estrogens is driven by the increase in the synthesis of DNA, RNA and various proteins in responsive tissues which in order will reduce the release of gonadotropin-releasing hormone, follicle-stimulating hormone and leuteinizing hormone. The specific mechanism of action cannot be described only in terms of total estrogenic action as the pharmacokinetic profile, the tissue specificity and the tissue metabolism is different for each component of the product. •Absorption (Drug A): No absorption available •Absorption (Drug B): The conjugated estrogens are well absorbed in the gastrointestinal tract and the maximum plasma concentration of the conjugated estrogens is reached after 7 hours depending on the estrone component. The maximal plasma concentration of conjugated estrogens after multiple doses of 0.45 mg is reported to be of 2.6 ng/ml with an AUC in the steady state of 35 ng.h/ml. Unconjugated estrogens are known to be cleared from the circulation at a faster rate than their ester forms. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The physiological distribution of estrogens in the body is very similar to what is seen in endogenous estrogens and hence, it is widely distributed. The conjugated estrogens are mainly found in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Conjugated estrogens are bound to plasma proteins and this bound state can represent around 50-80% of the administered dose. It circulates in the blood mainly bound to sex-hormone binding globulin and 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): The conjugated estrogens are metabolized by a number of different pathways. One of the metabolic pathways of the conjugated estrogens is driven by the action of the cytochrome isoenzyme CYP3A4. On the other hand, the conjugated estrogens can also be processed by a dynamic equilibrium of metabolic interconversion and sulfate conjugation. Some of the principal metabolic reactions of the conjugated estrogens are driven by the conversion of 17beta-estradiol to estrone and the further change to estriol. A portion of the administered conjugated estrogens will remain in the blood as sulfate conjugates which serve as a circulating reservoir for the generation of new estrogens. In the endometrium, equilin is metabolized to 2-hydroxy and 4-hydroxy equilin as well as 2-hydroxy and 4-hydroxy estradiol. This hydroxylation process is very large in various of the components of the conjugated estrogens and hence, the major metabolites in urine are known to be 17-ketosteroid-16-alpha-hydroxy estrone, 16-alpha-hydroxy-17-beta-dihydro equilin and 16-alpha-hydroxy-17-beta-dihydroequilenin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The conjugated estrogens are eliminated mainly in the urine. In this renal elimination, it is possible to find 17 beta-estradiol, estrone, estriol, as well as the glucuronide and sulfate conjugates of the estrogens. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 the conjugated estrogens is reported to be of 17 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The reported normal clearance rate for estrogens is of approximately 615 L/m2. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The reported oral LD50 in the rat is of more than 5000 mg/kg. Serious overdosage symptoms have not been reported. There have been only reports of nausea, vomiting, and withdrawal in bleeding in females. Long-term continuous administration of estrogens is correlated to increased risk on the incidence of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Congest, Duavee, Duavive, Premarin, Premphase 28 Day, Prempro 0.625/2.5 28 Day •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): Conjugated estrogens is a mixture of estrogens used in estrogen replacement therapy for menopause and hypoestrogenism, used in the treatment of various malignancies, and used in the treatment of postmenopausal osteoporosis. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Does Abciximab and Cyclophosphamide interact?

•Drug A: Abciximab •Drug B: Cyclophosphamide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cyclophosphamide. •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): Cyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric 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): Cyclophosphamide 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration, peak concentrations occur at one hour. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 30-50 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 20% of cyclophosphamide is protein bound with no dose dependent changes. Some metabolites are protein bound to an extent greater than 60%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cyclophosphamide is eliminated primarily in the form of metabolites. 10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 3-12 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance = 63 ± 7.6 L/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Procytox •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (±)-2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORINE 2-OXIDE MONOHYDRATE (RS)-Cyclophosphamide Ciclofosfamida Ciclofosfamide Cyclophosphamid Cyclophosphamide Cyclophosphamidum Cytophosphane •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cyclophosphamide is a nitrogen mustard used to treat lymphomas, myelomas, leukemia, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma.

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 Cyclophosphamide interact? Information: •Drug A: Abciximab •Drug B: Cyclophosphamide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cyclophosphamide. •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): Cyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric 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): Cyclophosphamide 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration, peak concentrations occur at one hour. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 30-50 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 20% of cyclophosphamide is protein bound with no dose dependent changes. Some metabolites are protein bound to an extent greater than 60%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Cyclophosphamide is eliminated primarily in the form of metabolites. 10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 3-12 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance = 63 ± 7.6 L/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Procytox •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (±)-2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORINE 2-OXIDE MONOHYDRATE (RS)-Cyclophosphamide Ciclofosfamida Ciclofosfamide Cyclophosphamid Cyclophosphamide Cyclophosphamidum Cytophosphane •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cyclophosphamide is a nitrogen mustard used to treat lymphomas, myelomas, leukemia, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma. 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 Cyproterone acetate interact?

•Drug A: Abciximab •Drug B: Cyproterone acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Cyproterone 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): For the palliative treatment of patients with advanced prostatic 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): Cyproterone is an antiandrogen. It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 direct antiandrogenic effect of cyproterone is blockage of the binding of dihydrotestosterone to the specific receptors in the prostatic carcinoma cell. In addition, cyproterone exerts a negative feed-back on the hypothalamo-pituitary axis, by inhibiting the secretion of luteinizing hormone resulting in diminished production of testicular testosterone. •Absorption (Drug A): No absorption available •Absorption (Drug B): Completely 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): 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. Cyproterone acetate is metabolized by the CYP3A4 enzyme, forming the active metabolite 15beta-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): It is excreted approximately 60% in the bile and 33% 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): Elimination Following oral or intramuscular administration, the plasma half-life is 38 and 96 hours, respectively. •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): Androcur, Cléo -35, Cyestra-35, Diane •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): Cyproterone acetate is a steroid used in combination with ethinyl estradiol to treat women with severe acne and symptoms of androgenization. Also used alone at much higher doses for palliative treatment of patients with prostate cancer

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 Cyproterone acetate interact? Information: •Drug A: Abciximab •Drug B: Cyproterone acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Cyproterone 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): For the palliative treatment of patients with advanced prostatic 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): Cyproterone is an antiandrogen. It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 direct antiandrogenic effect of cyproterone is blockage of the binding of dihydrotestosterone to the specific receptors in the prostatic carcinoma cell. In addition, cyproterone exerts a negative feed-back on the hypothalamo-pituitary axis, by inhibiting the secretion of luteinizing hormone resulting in diminished production of testicular testosterone. •Absorption (Drug A): No absorption available •Absorption (Drug B): Completely 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): 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. Cyproterone acetate is metabolized by the CYP3A4 enzyme, forming the active metabolite 15beta-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): It is excreted approximately 60% in the bile and 33% 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): Elimination Following oral or intramuscular administration, the plasma half-life is 38 and 96 hours, respectively. •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): Androcur, Cléo -35, Cyestra-35, Diane •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): Cyproterone acetate is a steroid used in combination with ethinyl estradiol to treat women with severe acne and symptoms of androgenization. Also used alone at much higher doses for palliative treatment of patients with prostate cancer 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 Cytarabine interact?

•Drug A: Abciximab •Drug B: Cytarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cytarabine. •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 acute non-lymphocytic leukemia, acute lymphocytic leukemia and blast phase of chronic myelocytic leukemia. Cytarabine is indicated in combination with daunorubicin for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year 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): Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal 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. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cytarabine acts through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-phase. Although the mechanism of action is not completely understood, it appears that cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of cytarabine into both DNA and RNA has also been reported. •Absorption (Drug A): No absorption available •Absorption (Drug B): Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract. •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): 13% •Metabolism (Drug A): 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): The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, followed by urinary excretion of ara-U. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Cytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cytosar, Vyxeos •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Citarabina Cytarabine Cytarabinum Cytosine arabinoside •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cytarabine is a pyrimidine nucleoside analogue used to treat acute non-lymphocytic leukemia, lymphocytic leukemia, and the blast phase of chronic myelocytic 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 Cytarabine interact? Information: •Drug A: Abciximab •Drug B: Cytarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Cytarabine. •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 acute non-lymphocytic leukemia, acute lymphocytic leukemia and blast phase of chronic myelocytic leukemia. Cytarabine is indicated in combination with daunorubicin for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year 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): Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal 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. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cytarabine acts through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-phase. Although the mechanism of action is not completely understood, it appears that cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of cytarabine into both DNA and RNA has also been reported. •Absorption (Drug A): No absorption available •Absorption (Drug B): Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract. •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): 13% •Metabolism (Drug A): 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): The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, followed by urinary excretion of ara-U. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Cytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cytosar, Vyxeos •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Citarabina Cytarabine Cytarabinum Cytosine arabinoside •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Cytarabine is a pyrimidine nucleoside analogue used to treat acute non-lymphocytic leukemia, lymphocytic leukemia, and the blast phase of chronic myelocytic 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 Dabigatran etexilate interact?

•Drug A: Abciximab •Drug B: Dabigatran etexilate •Severity: MAJOR •Description: Dabigatran etexilate may increase the anticoagulant activities of Abciximab. •Extended Description: Dabigatran etexilate is an anticoagulant agent that may create a synergistic effect when co-administered with other anticoagulant drugs. This may significantly increase the anticoagulant actions of the drugs and the risk of nonfatal bleeding or serious, potentially fatal bleeding associated with that drug class. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Dabigatran etexilate is available in both oral pellet and capsule form. Dabigatran etexilate pellets are indicated for the treatment of venous thromboembolic events (VTE) in pediatric patients between three months and 12 years of age who have been treated with a parenteral anticoagulant for at least 5 days. They are also indicated in the same age group to reduce the risk of recurrence of VTE in patients who have been previously treated. In capsule form, dabigatran etexilate is indicated in adults to reduce the risk of stroke and systemic embolism associated with non-valvular atrial fibrillation and for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days. It is also indicated in adults to reduce the risk of recurrence of DVT and PE in patients who have been previously treated and for the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery. Lastly, it is indicated in pediatric patients between eight and 18 years of age for the treatment of venous thromboembolic events (VTE) in patients who have been treated with a parenteral anticoagulant for at least 5 days and to reduce the risk of recurrence of VTE in patients who have been previously treated. Dabigatran etexilate is also approved by the EMA to prevent VTE in adult patients. For pediatric patients, Dabigatran etexilate is used to treat TVE and prevent recurrent TVE for patients from birth to less than 18 years of age. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dabigatran etexilate is a double prodrug that is hydrolyzed to the active dabigatran by intestinal and hepatic carboxylesterases. Dabigatran is a reversible competitive thrombin inhibitor that directly inhibits the conversion by thrombin of fibrinogen to fibrin, impairing the clotting process and acting as an anticoagulant. Dabigatran use prolongs coagulation markers such as the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT), and dilute thrombin time (dTT), but not the international normalized ratio (INR), which cannot be used in this context as it can in warfarin monitoring. As with all anticoagulant therapies, dabigatran carries a risk of bleeding, which may increase with concomitant use of antiplatelet agents, fibrinolytic therapy, heparins, or chronic NSAID use, and should be monitored for. Premature discontinuation of dabigatran, in the absence of an alternative anticoagulant, also carries an increased risk of thromboembolic events. Due to the risk of an epidural or spinal hematoma, dabigatran should generally not be used in the context of neuraxial anesthesia or spinal puncture; if such use is unavoidable, careful monitoring should be employed. Dabigatran should not be used in patients with prosthetic heart valves due to an increased occurrence of major bleeding and thromboembolic events. Dabigatran is a substrate of the P-gp transporter and should generally not be administered together with P-gp inhibitors or inducers, especially in patients with impaired renal function. Lastly, dabigatran or any other direct-acting oral anticoagulant should not be administered in patients with triple-positive antiphospholipid syndrome (APS) due to an increased risk of recurrent thrombotic events. In case of the need for emergency reversal, idarucizumab is available for use in adult patients; the safety and efficacy of idarucizumab has not been established in pediatric patients yet, for whom reversal may be achieved through hemodialysis, prothrombin complex concentrates, or recombinant FVIIa. However, none of these have been sufficiently evaluated in clinical trials. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hemostasis is a complex process that balances coagulation to prevent excessive thrombus formation or excessive bleeding. Central to the coagulation process is the serine protease thrombin (FIIa), which is synthesized as inactive prothrombin (FII) and subsequently activated by FXa/FVa, leading to a positive feedback loop and the production of large quantities of thrombin; once enough thrombin is formed, it cleaves soluble fibrinogen to form insoluble fibrin fibres that, together with aggregated platelets, form a clot. Although beneficial in wound healing, aberrant thrombus formation can lead to serious health consequences. Dabigatran is a univalent reversible direct thrombin inhibitor (DTI) that competitively inhibits thrombin with a K i of 4.5 ± 0.2 nmol/L. Furthermore, the reversible nature of the inhibition is believed to allow for some normal physiological thrombin function, which may help alleviate some adverse effects associated with anticoagulation therapy. In addition, dabigatran has several glucuronidated metabolites, all of which have been shown to possess in vitro activity similar to the parent compound. In addition to a direct effect on thrombin activity, dabigatran has also been shown to inhibit platelet aggregation, another step in the coagulation pathway. However, the mechanism remains unclear as dabigatran inhibits platelet aggregation stimulated by thrombin and von Willebrand factor (vWF), but not by other pathways such as ADP- or thromboxane A2-induced aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral dabigatran has a bioavailability of 3-7%, although the relative bioavailability of dabigatran pellets is 37% higher than that for capsules and the bioavailability increases to 75% when the capsule shell is removed; dabigatran capsules should not be tampered with in any way prior to administration. The C max is achieved by one hour following oral dosing, which is extended to two hours if accompanied by a high-fat meal. Dabigatran can be taken with or without food. Dabigatran pharmacokinetics are approximately linear over a range of 10-400 mg in healthy adults and adult patients and it has an accumulation factor of two in adult and pediatric patients. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Dabigatran has a volume of distribution of 50-70L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Dabigatran is ~35% bound to plasma proteins, including human serum 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): Dabigatran is administered as the orally available prodrug dabigatran etexilate that is subsequently metabolized to the active form. In vitro studies and observations regarding the oral bioavailability and levels of plasma prodrug suggest extensive first-pass metabolism by carboxylesterases, first by intestinal CES2 to form BIBR0951 (also known as M2) and then subsequently by hepatic CES1 to form dabigatran. Dabigatran etexilate can also first undergo CES1-mediated hydrolysis to BIBR1087 (M1) followed by CES2-mediated hydrolysis to dabigatran, though it is hypothesized that the former pathway accounts for most of the active form in plasma. Dabigatran can undergo 1- O -acyl glucuronidation by UGT1A9, UGT2B7, and UGT2B15 followed by acyl migration to form the corresponding 2- O -, 3- O -, and 4- O -acyl glucuronides; all of these acyl glucuronides exhibit activity similar to dabigatran but account for a small fraction of recovered metabolites. In addition to these better characterized metabolic pathways, detailed LC/MS characterization suggests a wide variety of possible metabolites following oral or intravenous administration, most of which are present in only trace amounts in plasma, urine, or feces. These include a variety of oxidation, hydrolysis, and conjugation products, including through the addition of mannitol. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dabigatran is primarily eliminated in the urine. Following oral administration of radiolabeled dabigatran, 7% of the radioactivity is recovered in urine and 86% is recovered in feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Dabigatran has a half-life of 12-17 hours in adult patients and 12-14 hours in pediatric patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following intravenous administration, renal clearance constitutes ~80% of total dabigatran clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No human studies involving pregnancy, labor and delivery, nursing, or pediatrics. Geriatric patients are at higher risk of adverse effects than younger patients but the risk to benefit ratio is generally still favourable for older patients. Patients with a creatinine clearance of 15-30mL/min should have their doses of dabigatran etexilate reduced, and no data is available for patients with a creatinine clearance below 15mL/min. In animal studies, dabigatran increases the rates of dead offspring and causes uterine and vaginal bleeding close to birth. Dabigatran may or may not be excreted in breast milk so the risk and benefit of stopping the drug or stopping breast feeding must be considered. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pradaxa •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): Dabigatran etexilate is an anticoagulant used for the prevention of venous thromboembolic events or stroke in patients with recent elective hip or knee replacement surgery and atrial fibrillation.

Dabigatran etexilate is an anticoagulant agent that may create a synergistic effect when co-administered with other anticoagulant drugs. This may significantly increase the anticoagulant actions of the drugs and the risk of nonfatal bleeding or serious, potentially fatal bleeding associated with that drug class. The severity of the interaction is major.

Question: Does Abciximab and Dabigatran etexilate interact? Information: •Drug A: Abciximab •Drug B: Dabigatran etexilate •Severity: MAJOR •Description: Dabigatran etexilate may increase the anticoagulant activities of Abciximab. •Extended Description: Dabigatran etexilate is an anticoagulant agent that may create a synergistic effect when co-administered with other anticoagulant drugs. This may significantly increase the anticoagulant actions of the drugs and the risk of nonfatal bleeding or serious, potentially fatal bleeding associated with that drug class. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Dabigatran etexilate is available in both oral pellet and capsule form. Dabigatran etexilate pellets are indicated for the treatment of venous thromboembolic events (VTE) in pediatric patients between three months and 12 years of age who have been treated with a parenteral anticoagulant for at least 5 days. They are also indicated in the same age group to reduce the risk of recurrence of VTE in patients who have been previously treated. In capsule form, dabigatran etexilate is indicated in adults to reduce the risk of stroke and systemic embolism associated with non-valvular atrial fibrillation and for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days. It is also indicated in adults to reduce the risk of recurrence of DVT and PE in patients who have been previously treated and for the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery. Lastly, it is indicated in pediatric patients between eight and 18 years of age for the treatment of venous thromboembolic events (VTE) in patients who have been treated with a parenteral anticoagulant for at least 5 days and to reduce the risk of recurrence of VTE in patients who have been previously treated. Dabigatran etexilate is also approved by the EMA to prevent VTE in adult patients. For pediatric patients, Dabigatran etexilate is used to treat TVE and prevent recurrent TVE for patients from birth to less than 18 years of age. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dabigatran etexilate is a double prodrug that is hydrolyzed to the active dabigatran by intestinal and hepatic carboxylesterases. Dabigatran is a reversible competitive thrombin inhibitor that directly inhibits the conversion by thrombin of fibrinogen to fibrin, impairing the clotting process and acting as an anticoagulant. Dabigatran use prolongs coagulation markers such as the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT), and dilute thrombin time (dTT), but not the international normalized ratio (INR), which cannot be used in this context as it can in warfarin monitoring. As with all anticoagulant therapies, dabigatran carries a risk of bleeding, which may increase with concomitant use of antiplatelet agents, fibrinolytic therapy, heparins, or chronic NSAID use, and should be monitored for. Premature discontinuation of dabigatran, in the absence of an alternative anticoagulant, also carries an increased risk of thromboembolic events. Due to the risk of an epidural or spinal hematoma, dabigatran should generally not be used in the context of neuraxial anesthesia or spinal puncture; if such use is unavoidable, careful monitoring should be employed. Dabigatran should not be used in patients with prosthetic heart valves due to an increased occurrence of major bleeding and thromboembolic events. Dabigatran is a substrate of the P-gp transporter and should generally not be administered together with P-gp inhibitors or inducers, especially in patients with impaired renal function. Lastly, dabigatran or any other direct-acting oral anticoagulant should not be administered in patients with triple-positive antiphospholipid syndrome (APS) due to an increased risk of recurrent thrombotic events. In case of the need for emergency reversal, idarucizumab is available for use in adult patients; the safety and efficacy of idarucizumab has not been established in pediatric patients yet, for whom reversal may be achieved through hemodialysis, prothrombin complex concentrates, or recombinant FVIIa. However, none of these have been sufficiently evaluated in clinical trials. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hemostasis is a complex process that balances coagulation to prevent excessive thrombus formation or excessive bleeding. Central to the coagulation process is the serine protease thrombin (FIIa), which is synthesized as inactive prothrombin (FII) and subsequently activated by FXa/FVa, leading to a positive feedback loop and the production of large quantities of thrombin; once enough thrombin is formed, it cleaves soluble fibrinogen to form insoluble fibrin fibres that, together with aggregated platelets, form a clot. Although beneficial in wound healing, aberrant thrombus formation can lead to serious health consequences. Dabigatran is a univalent reversible direct thrombin inhibitor (DTI) that competitively inhibits thrombin with a K i of 4.5 ± 0.2 nmol/L. Furthermore, the reversible nature of the inhibition is believed to allow for some normal physiological thrombin function, which may help alleviate some adverse effects associated with anticoagulation therapy. In addition, dabigatran has several glucuronidated metabolites, all of which have been shown to possess in vitro activity similar to the parent compound. In addition to a direct effect on thrombin activity, dabigatran has also been shown to inhibit platelet aggregation, another step in the coagulation pathway. However, the mechanism remains unclear as dabigatran inhibits platelet aggregation stimulated by thrombin and von Willebrand factor (vWF), but not by other pathways such as ADP- or thromboxane A2-induced aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Oral dabigatran has a bioavailability of 3-7%, although the relative bioavailability of dabigatran pellets is 37% higher than that for capsules and the bioavailability increases to 75% when the capsule shell is removed; dabigatran capsules should not be tampered with in any way prior to administration. The C max is achieved by one hour following oral dosing, which is extended to two hours if accompanied by a high-fat meal. Dabigatran can be taken with or without food. Dabigatran pharmacokinetics are approximately linear over a range of 10-400 mg in healthy adults and adult patients and it has an accumulation factor of two in adult and pediatric patients. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Dabigatran has a volume of distribution of 50-70L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Dabigatran is ~35% bound to plasma proteins, including human serum 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): Dabigatran is administered as the orally available prodrug dabigatran etexilate that is subsequently metabolized to the active form. In vitro studies and observations regarding the oral bioavailability and levels of plasma prodrug suggest extensive first-pass metabolism by carboxylesterases, first by intestinal CES2 to form BIBR0951 (also known as M2) and then subsequently by hepatic CES1 to form dabigatran. Dabigatran etexilate can also first undergo CES1-mediated hydrolysis to BIBR1087 (M1) followed by CES2-mediated hydrolysis to dabigatran, though it is hypothesized that the former pathway accounts for most of the active form in plasma. Dabigatran can undergo 1- O -acyl glucuronidation by UGT1A9, UGT2B7, and UGT2B15 followed by acyl migration to form the corresponding 2- O -, 3- O -, and 4- O -acyl glucuronides; all of these acyl glucuronides exhibit activity similar to dabigatran but account for a small fraction of recovered metabolites. In addition to these better characterized metabolic pathways, detailed LC/MS characterization suggests a wide variety of possible metabolites following oral or intravenous administration, most of which are present in only trace amounts in plasma, urine, or feces. These include a variety of oxidation, hydrolysis, and conjugation products, including through the addition of mannitol. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dabigatran is primarily eliminated in the urine. Following oral administration of radiolabeled dabigatran, 7% of the radioactivity is recovered in urine and 86% is recovered in feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Dabigatran has a half-life of 12-17 hours in adult patients and 12-14 hours in pediatric patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following intravenous administration, renal clearance constitutes ~80% of total dabigatran clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No human studies involving pregnancy, labor and delivery, nursing, or pediatrics. Geriatric patients are at higher risk of adverse effects than younger patients but the risk to benefit ratio is generally still favourable for older patients. Patients with a creatinine clearance of 15-30mL/min should have their doses of dabigatran etexilate reduced, and no data is available for patients with a creatinine clearance below 15mL/min. In animal studies, dabigatran increases the rates of dead offspring and causes uterine and vaginal bleeding close to birth. Dabigatran may or may not be excreted in breast milk so the risk and benefit of stopping the drug or stopping breast feeding must be considered. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pradaxa •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): Dabigatran etexilate is an anticoagulant used for the prevention of venous thromboembolic events or stroke in patients with recent elective hip or knee replacement surgery and atrial fibrillation. Output: Dabigatran etexilate is an anticoagulant agent that may create a synergistic effect when co-administered with other anticoagulant drugs. This may significantly increase the anticoagulant actions of the drugs and the risk of nonfatal bleeding or serious, potentially fatal bleeding associated with that drug class. The severity of the interaction is major.

Does Abciximab and Dacarbazine interact?

•Drug A: Abciximab •Drug B: Dacarbazine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dacarbazine. •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 metastatic malignant melanoma. In addition, dacarbazine is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other antineoplastic agents. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 is not known, but appears to exert cytotoxic effects via its action as an alkylating agent. Other theories include DNA synthesis inhibition by its action as a purine analog, and interaction with SH groups. Dacarbazine is not cell cycle-phase specific. •Absorption (Drug A): No absorption available •Absorption (Drug B): Erratic, slow and incomplete. •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): Less than 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 •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =350mg/kg (orally in mice) •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): Biocarbazine Dacarbazin Dacarbazina Dacarbazine Dacarbazinum DTIC ICDMT •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dacarbazine is an antineoplastic agent used to treat malignant melanoma and Hodgkin's disease.

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 Dacarbazine interact? Information: •Drug A: Abciximab •Drug B: Dacarbazine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dacarbazine. •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 metastatic malignant melanoma. In addition, dacarbazine is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other antineoplastic agents. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 is not known, but appears to exert cytotoxic effects via its action as an alkylating agent. Other theories include DNA synthesis inhibition by its action as a purine analog, and interaction with SH groups. Dacarbazine is not cell cycle-phase specific. •Absorption (Drug A): No absorption available •Absorption (Drug B): Erratic, slow and incomplete. •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): Less than 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 •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =350mg/kg (orally in mice) •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): Biocarbazine Dacarbazin Dacarbazina Dacarbazine Dacarbazinum DTIC ICDMT •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dacarbazine is an antineoplastic agent used to treat malignant melanoma and Hodgkin's disease. 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 Dactinomycin interact?

•Drug A: Abciximab •Drug B: Dactinomycin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dactinomycin. •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 Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer as part of a combination chemotherapy and/or multi-modality treatment regimen •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): poorly absorbed from gastrointestinal tract •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): 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 •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): 36 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): hepatoxicity •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cosmegen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 3H-PHENOXAZINE-1,9-DICARBOXAMIDE, 2-AMINO-N,N'-BIS(HEXADECAHYDRO-6,13-DIISOPROPYL-2,5,9-TRIMETHYL-1,4,7,11,14-PENTAOXO-1H-PYRROLO(2,1-I)(1,4,7,10,13)OXATETRAAZACYCLOHEXADECIN-10-YL)-4,6-DIMETHYL-3-OXO- ActD Actinomycin C1 Actinomycin D ACTINOMYCIN I1 Actinomycin IV ACTINOMYCIN X1 ACTINOMYCIN-D ANA-conjugated dactinomycin nanoemulsion Dactinomicina Dactinomycin Dactinomycine Dactinomycinum DILACTONE ACTINOMYCIN D ACID Meractinomycin N,N'-((2-AMINO-4,6-DIMETHYL-3-OXO-3H-PHENOXAZINE-1,9-DIYL)-BIS(CARBONYLIMINO(2-HYDROXYPROPYLIDENE)CARBONYLIMINOISOBUTYLIDENECARBONYL-1,2-PYRROLIDINEDIYLCARBONYL(METHYLIMINO)METHYLENECARBONYL))BIS(N-METHYL-L-VALINE) DILACTONE ONCOSTATIN K •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dactinomycin is an actinomycin used to treat a wide variety of 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 Dactinomycin interact? Information: •Drug A: Abciximab •Drug B: Dactinomycin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dactinomycin. •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 Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer as part of a combination chemotherapy and/or multi-modality treatment regimen •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): poorly absorbed from gastrointestinal tract •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): 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 •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): 36 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): hepatoxicity •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cosmegen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 3H-PHENOXAZINE-1,9-DICARBOXAMIDE, 2-AMINO-N,N'-BIS(HEXADECAHYDRO-6,13-DIISOPROPYL-2,5,9-TRIMETHYL-1,4,7,11,14-PENTAOXO-1H-PYRROLO(2,1-I)(1,4,7,10,13)OXATETRAAZACYCLOHEXADECIN-10-YL)-4,6-DIMETHYL-3-OXO- ActD Actinomycin C1 Actinomycin D ACTINOMYCIN I1 Actinomycin IV ACTINOMYCIN X1 ACTINOMYCIN-D ANA-conjugated dactinomycin nanoemulsion Dactinomicina Dactinomycin Dactinomycine Dactinomycinum DILACTONE ACTINOMYCIN D ACID Meractinomycin N,N'-((2-AMINO-4,6-DIMETHYL-3-OXO-3H-PHENOXAZINE-1,9-DIYL)-BIS(CARBONYLIMINO(2-HYDROXYPROPYLIDENE)CARBONYLIMINOISOBUTYLIDENECARBONYL-1,2-PYRROLIDINEDIYLCARBONYL(METHYLIMINO)METHYLENECARBONYL))BIS(N-METHYL-L-VALINE) DILACTONE ONCOSTATIN K •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dactinomycin is an actinomycin used to treat a wide variety of 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 Dalteparin interact?

•Drug A: Abciximab •Drug B: Dalteparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dalteparin. •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): Dalteparin is used as a prophylaxis for deep-vein thrombosis and pulmonary embolisms in patients undergoing general surgery (e.g., abdominal, gynecologic, urologic), and in patients with acute medical conditions (e.g. cancer, bed rest, heart failure, severe lung disease). It is also used in patients who have severely restricted mobility, which poses a risk for thromboembolic complications. Dalteparin is also used concomitantly with aspirin and/or other therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors) to reduce the risk of acute cardiac ischemic events. The patients who undergo this treatment combination have unstable angina or non-ST-segment elevation/non-Q-wave myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes). It is also used in the prevention of clotting during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dalteparin has an antithrombin binding site that is essential for high affinity binding to the plasma protein antithrombin (ATIII). Anti-Xa activity of plasma is used as both as an estimate of clotting activity, and as a basis to determine dosage. Its use should be avoided in patients with a creatinine clearance less than 20mL/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): Dalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time [(i.e. activated partial thomboplastin time (APTT)] is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage. •Absorption (Drug A): No absorption available •Absorption (Drug B): Almost completely absorbed after subcutaneous (sc) doses, with a bioavialability of about 87%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 3 litres •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Less than unfractionated heparin, which is more than 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): Liver and the reticulo-endothelial system are the sites of biotransformation. They are partially metabolized by desulphatation and depolymerization. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After 4 hours, about 20% is seen in urine. Most of the remainder is found in the liver, gastrointestinal tract and kidney. The kidneys are the major site of dalteparin excretion (approximately 70% based on animal 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): Terminal Half life: Intravenous - 2 hours. Subcutaneous - 3-5hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Excreted via kidneys. The plasma clearance rate is 33 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdosage: hemorrhagic complications. Adverse Drug Reaction: (common) osteopenia with extended use; mild, reversible non-immunological thrombocytopenia; transient elevation of liver transaminases; alopecia. (uncommon): severe immunologically-mediated heparin-induced thrombocytopenia; anaphylactic reactions; skin rash, skin necrosis; retroperitoneal hemorrhage; angioedema •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fragmin •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): Dalteparin is a low molecular weight heparin used for the prophylaxis of thrombotic events in certain patients and prevent acute cardiac ischemic events in patients with 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 Dalteparin interact? Information: •Drug A: Abciximab •Drug B: Dalteparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dalteparin. •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): Dalteparin is used as a prophylaxis for deep-vein thrombosis and pulmonary embolisms in patients undergoing general surgery (e.g., abdominal, gynecologic, urologic), and in patients with acute medical conditions (e.g. cancer, bed rest, heart failure, severe lung disease). It is also used in patients who have severely restricted mobility, which poses a risk for thromboembolic complications. Dalteparin is also used concomitantly with aspirin and/or other therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors) to reduce the risk of acute cardiac ischemic events. The patients who undergo this treatment combination have unstable angina or non-ST-segment elevation/non-Q-wave myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes). It is also used in the prevention of clotting during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dalteparin has an antithrombin binding site that is essential for high affinity binding to the plasma protein antithrombin (ATIII). Anti-Xa activity of plasma is used as both as an estimate of clotting activity, and as a basis to determine dosage. Its use should be avoided in patients with a creatinine clearance less than 20mL/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): Dalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time [(i.e. activated partial thomboplastin time (APTT)] is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage. •Absorption (Drug A): No absorption available •Absorption (Drug B): Almost completely absorbed after subcutaneous (sc) doses, with a bioavialability of about 87%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 3 litres •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Less than unfractionated heparin, which is more than 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): Liver and the reticulo-endothelial system are the sites of biotransformation. They are partially metabolized by desulphatation and depolymerization. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After 4 hours, about 20% is seen in urine. Most of the remainder is found in the liver, gastrointestinal tract and kidney. The kidneys are the major site of dalteparin excretion (approximately 70% based on animal 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): Terminal Half life: Intravenous - 2 hours. Subcutaneous - 3-5hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Excreted via kidneys. The plasma clearance rate is 33 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdosage: hemorrhagic complications. Adverse Drug Reaction: (common) osteopenia with extended use; mild, reversible non-immunological thrombocytopenia; transient elevation of liver transaminases; alopecia. (uncommon): severe immunologically-mediated heparin-induced thrombocytopenia; anaphylactic reactions; skin rash, skin necrosis; retroperitoneal hemorrhage; angioedema •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fragmin •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): Dalteparin is a low molecular weight heparin used for the prophylaxis of thrombotic events in certain patients and prevent acute cardiac ischemic events in patients with 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 Damoctocog alfa pegol interact?

•Drug A: Abciximab •Drug B: Damoctocog alfa pegol •Severity: MAJOR •Description: The therapeutic efficacy of Damoctocog 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): Indicated for use in previously treated adults and adolescents (12 years of age and above) with hemophilia A (congenital Factor VIII deficiency) for: On-demand treatment and control of bleeding episodes, perioperative management of bleeding, 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): This agent is engineered to prolong blood FVIII activity while maintaining coagulation activity using PEGylation, where a PEG (Polyethylene glycol) molecule is continually attached to the factor VIII protein at a specific site,. This prevents and controls bleeding episodes associated with hemophilia A. The aPTT is prolonged in people diagnosed with hemophilia A. The determination of aPTT is a conventional in vitro assay for assessing the biological activity of Factor VIII. Treatment with damoctogog alfa pegol normalizes the aPTT similar to that achieved with plasma-derived Factor VIII. The administration of this agent increases plasma levels of Factor VIII and can temporarily correct the coagulation defect that exists in hemophilia A 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): This drug is a site-specifically PEGylated recombinant antihemophilic factor, which temporarily replaces the missing coagulation Factor VIII. The site-specific PEGylation in the A3 domain reduces binding to the physiological Factor VIII clearance receptors resulting in a longer half-life and increased AUC (area under the curve). The active protein, prior to conjugation is a recombinant B-domain deleted human coagulation Factor VIII (BDD-rFVIII) produced by recombinant DNA technology in Baby Hamster Kidney (BHK) cells. Damoctagol alfa pegol is manufactured by site-specific conjugation of the BDD-rFVIII variant K1804C at the cysteine amino acid position 1804 (within the A3 domain) with a single maleimide-derivatized, 60 kilodalton (kDa) branched PEG (two 30 kDa PEG) moiety. The A3 domain was identified and selected for conjugation to provide both a continual coagulation activity and high PEGylation efficiency. •Absorption (Drug A): No absorption available •Absorption (Drug B): After a single dose, AUC (area under the curve) was 1640 ± 550 with a dose of 25 IU/kg. •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): 18.6 ± 4.6h after a single dose •Clearance (Drug A): No clearance available •Clearance (Drug B): 142 ± 33 mL/h on with a dose of 25 IU/kg and 121 ± 53 mL/h with a dose of 60 IU/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most commonly reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥ 12 years of age (≥ 5%) were headache, cough, nausea, and fever. Hypersensitivity reactions, which includes severe allergic reactions, have occurred. Monitor patients for hypersensitivity symptoms. Should hypersensitivity symptoms occur, stop treatment with this agent and administer appropriate supportive treatment. Hypersensitivity reactions may also be related to antibodies targeted against polyethylene glycol (PEG). Development of Factor VIII neutralizing antibodies can also occur. If expected plasma Factor VIII activity levels are not reached, or if bleeding is not controlled as expected with the administered dose, perform an assay that quantifies Factor VIII inhibitor concentration. Immune response to PEG, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed mainly in subjects less than 6 years of age. Evaluate patients experiencing symptoms of hypersensitivity reactions in the absence of detectable Factor VIII inhibitors for possible bleeding or impaired recovery. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jivi •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): Damoctocog alfa pegol is a recombinant Factor VIII used to treat hemophilia A to control bleeding, perioperative bleeding, and also for prophylaxis of 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 Damoctocog alfa pegol interact? Information: •Drug A: Abciximab •Drug B: Damoctocog alfa pegol •Severity: MAJOR •Description: The therapeutic efficacy of Damoctocog 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): Indicated for use in previously treated adults and adolescents (12 years of age and above) with hemophilia A (congenital Factor VIII deficiency) for: On-demand treatment and control of bleeding episodes, perioperative management of bleeding, 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): This agent is engineered to prolong blood FVIII activity while maintaining coagulation activity using PEGylation, where a PEG (Polyethylene glycol) molecule is continually attached to the factor VIII protein at a specific site,. This prevents and controls bleeding episodes associated with hemophilia A. The aPTT is prolonged in people diagnosed with hemophilia A. The determination of aPTT is a conventional in vitro assay for assessing the biological activity of Factor VIII. Treatment with damoctogog alfa pegol normalizes the aPTT similar to that achieved with plasma-derived Factor VIII. The administration of this agent increases plasma levels of Factor VIII and can temporarily correct the coagulation defect that exists in hemophilia A 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): This drug is a site-specifically PEGylated recombinant antihemophilic factor, which temporarily replaces the missing coagulation Factor VIII. The site-specific PEGylation in the A3 domain reduces binding to the physiological Factor VIII clearance receptors resulting in a longer half-life and increased AUC (area under the curve). The active protein, prior to conjugation is a recombinant B-domain deleted human coagulation Factor VIII (BDD-rFVIII) produced by recombinant DNA technology in Baby Hamster Kidney (BHK) cells. Damoctagol alfa pegol is manufactured by site-specific conjugation of the BDD-rFVIII variant K1804C at the cysteine amino acid position 1804 (within the A3 domain) with a single maleimide-derivatized, 60 kilodalton (kDa) branched PEG (two 30 kDa PEG) moiety. The A3 domain was identified and selected for conjugation to provide both a continual coagulation activity and high PEGylation efficiency. •Absorption (Drug A): No absorption available •Absorption (Drug B): After a single dose, AUC (area under the curve) was 1640 ± 550 with a dose of 25 IU/kg. •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): 18.6 ± 4.6h after a single dose •Clearance (Drug A): No clearance available •Clearance (Drug B): 142 ± 33 mL/h on with a dose of 25 IU/kg and 121 ± 53 mL/h with a dose of 60 IU/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most commonly reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥ 12 years of age (≥ 5%) were headache, cough, nausea, and fever. Hypersensitivity reactions, which includes severe allergic reactions, have occurred. Monitor patients for hypersensitivity symptoms. Should hypersensitivity symptoms occur, stop treatment with this agent and administer appropriate supportive treatment. Hypersensitivity reactions may also be related to antibodies targeted against polyethylene glycol (PEG). Development of Factor VIII neutralizing antibodies can also occur. If expected plasma Factor VIII activity levels are not reached, or if bleeding is not controlled as expected with the administered dose, perform an assay that quantifies Factor VIII inhibitor concentration. Immune response to PEG, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed mainly in subjects less than 6 years of age. Evaluate patients experiencing symptoms of hypersensitivity reactions in the absence of detectable Factor VIII inhibitors for possible bleeding or impaired recovery. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jivi •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): Damoctocog alfa pegol is a recombinant Factor VIII used to treat hemophilia A to control bleeding, perioperative bleeding, and also for prophylaxis of 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 Danaparoid interact?

•Drug A: Abciximab •Drug B: Danaparoid •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Danaparoid. •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 for the prophylaxis of post-operative deep venous thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients undergoing elective hip replacement 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): Danaparoid contains a mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate in amounts of approximately 84%, 12% and 4%, respectively. Danaparoid is as an antithrombotic agent that prevents the formation of fibrin in the coagulation pathway. It has a high antifactor Xa to antifactor IIa (thrombin) activity that primarily works via antithrombin III-mediated inhibition of factor Xa. The ratio of antifactor Xa to antifactor II activity is ≥ 20:1. Danaparoid has a minor effect on platelet function and aggregation. In a worldwide compassionate-use programme involving a total of 667 patients with heparin-induced thrombocytopenia (HIT), treatment with danaparoid resulted in 93% of successful outcomes in resolving HIT. In healthy volunteers, danaparoid caused significantly less prolongation o f the activated partial thromboplastin time (APTT) and was associated with a significantly lower thrombin time than unfractionated heparin (UFH) and low molecular weight heparins (LMWHs). Danaparoid displays lower lipolytic activity than UFH in vitro and in healthy individuals, leading to lower plasma levels of free fatty acids. Danaparoid has been associated with the cross-reactivity with pathogenic heparin-induced platelet-factor 4 (PF4) antibodies, which occurs in about 10 % or more by in vitro testing. The clinical relevance of this effect is not fully understood. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 the coagulation cascade leading to clot formation, factor X and factor II requires activation to promote subsequent conversion of fibrinogen to fibrin. The mechanism of action of danaparoid resulting in anticoagulant and antithrombic effects involves a complex interaction between 2 components, factor IIa and in particular, factor Xa. Via binding to antithrombin and inducing a conformational change, danaparoid enhances and catalyzes the the binding of factor Xa to antithrombin, which induces antithrombin-mediated inactivation of factor Xa. This leads to inhibition of thrombin generation and subsequently, thrombus formation. Danaparoid also weakly enhances antithrombin III and heparin cofactor II inactivation of factor IIa. There is evidence that danaparoid also suppresses the activation of factor IX which, in conjunction with simultaneous inhibition of factor X, may lead to antithrombic effects. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly antifactor Xa and antifactor IIa activities. The bioavailability of danaparoid is 100% following subcutaneous administration. Following administration of single subcutaneous doses of 750, 1500, 2250, and 3250 anti-Xa units of danaparoid, the peak plasma anti-Xa activities were 102.4, 206.1, 283.9, and 403.4 mU/mL, respectively. The time to reach maximum anti-Xa activity is approximately 2-5 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. The volumes of distribution of anti-Xa and anti-IIa activities are 9.1 L and 7.3-9.0 L, respectively. •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): There is no evidence of hepatic metabolism and danaparoid is unlikely to undergo cellular metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Renal excretion is the main route of elimination, accounting for approximately 40-50% of the total clearance of antifactor Xa activity following intravenous administration of danaparoid. Therefore in patients with severe renal impairment, the elimination half-life of anti-Xa activity may be prolonged. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. The elimination half-life ranges from 19.2 to 24.5 hours during anti-Xa activity and ranges from 1.8 to 4.3 hours during anti-IIa activity. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. Total plasma clearance is about 0.36 L/h during anti-Xa activity, which may be accelerated with higher body surface area. Total plasma clearance during anti-IIa activity ranges from 2.3 to 3 L. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Subcutaneous administration of a single dose at 3800 anti-Xa units/kg, which is 20.5 times the recommended dose for humans based on body surface area, was found to be lethal to female rats. Lethal effects were seen in male rats when administering a single subcutaneous dose at 15200 anti-Xa units/kg, which is approximately 82 times the recommended human dose based on body surface area. In rats, the symptoms of acute toxicity following intravenous administration included respiratory depression, prostration and twitching. Accidental overdosage of danaparoid may lead to severe bleeding complications. While protamine sulfate may partially neutralize the anti-Xa actions of danaparoid, there is no evidence that it is capable of reducing severe non-surgical bleeding during treatment of danaparoid. In case of serious bleeding, danaparoid should be discontinued and blood transfusions should be administered if necessary. Withdrawal of danaparoid is expected to restore the coagulation balance without rebound phenomenon. There is no evidence of danaparoid to have a potential to induce carcinogenesis, mutagenesis and impairment of fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Orgaran •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): Danaparoid is a heparinoid with anticoagulant and antithrombotic activities used for the treatment of acute episode of Heparin-Induced Thrombocytopenia (HIT), and for prophylaxis in patients with a history of HIT.

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 Danaparoid interact? Information: •Drug A: Abciximab •Drug B: Danaparoid •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Danaparoid. •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 for the prophylaxis of post-operative deep venous thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients undergoing elective hip replacement 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): Danaparoid contains a mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate in amounts of approximately 84%, 12% and 4%, respectively. Danaparoid is as an antithrombotic agent that prevents the formation of fibrin in the coagulation pathway. It has a high antifactor Xa to antifactor IIa (thrombin) activity that primarily works via antithrombin III-mediated inhibition of factor Xa. The ratio of antifactor Xa to antifactor II activity is ≥ 20:1. Danaparoid has a minor effect on platelet function and aggregation. In a worldwide compassionate-use programme involving a total of 667 patients with heparin-induced thrombocytopenia (HIT), treatment with danaparoid resulted in 93% of successful outcomes in resolving HIT. In healthy volunteers, danaparoid caused significantly less prolongation o f the activated partial thromboplastin time (APTT) and was associated with a significantly lower thrombin time than unfractionated heparin (UFH) and low molecular weight heparins (LMWHs). Danaparoid displays lower lipolytic activity than UFH in vitro and in healthy individuals, leading to lower plasma levels of free fatty acids. Danaparoid has been associated with the cross-reactivity with pathogenic heparin-induced platelet-factor 4 (PF4) antibodies, which occurs in about 10 % or more by in vitro testing. The clinical relevance of this effect is not fully understood. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 the coagulation cascade leading to clot formation, factor X and factor II requires activation to promote subsequent conversion of fibrinogen to fibrin. The mechanism of action of danaparoid resulting in anticoagulant and antithrombic effects involves a complex interaction between 2 components, factor IIa and in particular, factor Xa. Via binding to antithrombin and inducing a conformational change, danaparoid enhances and catalyzes the the binding of factor Xa to antithrombin, which induces antithrombin-mediated inactivation of factor Xa. This leads to inhibition of thrombin generation and subsequently, thrombus formation. Danaparoid also weakly enhances antithrombin III and heparin cofactor II inactivation of factor IIa. There is evidence that danaparoid also suppresses the activation of factor IX which, in conjunction with simultaneous inhibition of factor X, may lead to antithrombic effects. •Absorption (Drug A): No absorption available •Absorption (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly antifactor Xa and antifactor IIa activities. The bioavailability of danaparoid is 100% following subcutaneous administration. Following administration of single subcutaneous doses of 750, 1500, 2250, and 3250 anti-Xa units of danaparoid, the peak plasma anti-Xa activities were 102.4, 206.1, 283.9, and 403.4 mU/mL, respectively. The time to reach maximum anti-Xa activity is approximately 2-5 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. The volumes of distribution of anti-Xa and anti-IIa activities are 9.1 L and 7.3-9.0 L, respectively. •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): There is no evidence of hepatic metabolism and danaparoid is unlikely to undergo cellular metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Renal excretion is the main route of elimination, accounting for approximately 40-50% of the total clearance of antifactor Xa activity following intravenous administration of danaparoid. Therefore in patients with severe renal impairment, the elimination half-life of anti-Xa activity may be prolonged. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. The elimination half-life ranges from 19.2 to 24.5 hours during anti-Xa activity and ranges from 1.8 to 4.3 hours during anti-IIa activity. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. Total plasma clearance is about 0.36 L/h during anti-Xa activity, which may be accelerated with higher body surface area. Total plasma clearance during anti-IIa activity ranges from 2.3 to 3 L. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Subcutaneous administration of a single dose at 3800 anti-Xa units/kg, which is 20.5 times the recommended dose for humans based on body surface area, was found to be lethal to female rats. Lethal effects were seen in male rats when administering a single subcutaneous dose at 15200 anti-Xa units/kg, which is approximately 82 times the recommended human dose based on body surface area. In rats, the symptoms of acute toxicity following intravenous administration included respiratory depression, prostration and twitching. Accidental overdosage of danaparoid may lead to severe bleeding complications. While protamine sulfate may partially neutralize the anti-Xa actions of danaparoid, there is no evidence that it is capable of reducing severe non-surgical bleeding during treatment of danaparoid. In case of serious bleeding, danaparoid should be discontinued and blood transfusions should be administered if necessary. Withdrawal of danaparoid is expected to restore the coagulation balance without rebound phenomenon. There is no evidence of danaparoid to have a potential to induce carcinogenesis, mutagenesis and impairment of fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Orgaran •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): Danaparoid is a heparinoid with anticoagulant and antithrombotic activities used for the treatment of acute episode of Heparin-Induced Thrombocytopenia (HIT), and for prophylaxis in patients with a history of HIT. 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 Daratumumab interact?

•Drug A: Abciximab •Drug B: Daratumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Daratumumab. •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): Daratumumab is indicated as an intravenous injection alone or in combination with other medications for the treatment of multiple myeloma. It is available as a combination product with hyaluronidase for the treatment of adults with multiple myeloma as monotherapy or combination therapy and light chain amyloidosis in combination with other 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): Daratumumab is a monoclonal antibody that targets and induces apoptosis in cells that highly express CD38, including multiple myeloma cells. It has a long duration of action as it is given every 1-4 weeks. Patients should be counselled regarding the risk of hypersensitivity, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interferences with cross-matching and red blood cell antibody screening. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): CD38 is a glycoprotein present on the surface of hematopoietic cells and is responsible for a number of cell signalling functions. Daratumumab is an immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that targets CD38. Cancers like multiple myeloma overexpress CD38, allowing daratumumab to have higher affinity for these cells. This binding allows daratumumab to induce apoptosis, antibody dependent cellular phagocytosis, and antibody and complement-dependent cytotoxicity. Antibody dependent cellular phagocytosis is mediated by the FC region of the antibody inducing phagocytes such as macrophages, antibody dependent cellular cytotoxicity is mediated by the FC region of the antibody inducing effector cells such as natural killer cells, and complement dependent cytotoxicity is mediated by the FC region of the antibody binding to and inducing complement protein activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Subcutaneous daratumumab reaches a C max of 592µg/mL compared to intravenous daratumumab, which reaches a C max of 688µg/mL. The AUC of subcutaneous daratumumab is 4017µg/mL*day compared to intravenous daratumumab, which has an AUC of 4019µg/mL*day. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Daratumumab intravenous monotherapy has a volume of distribution of 4.7 ± 1.3L and the combination therapy has a volume of distribution of 4.4 ± 1.5L. Subcutaneous daratumumab has a volume of distribution of the central compartment of 5.2L and a volume of distribution of the peripheral compartment of 3.8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Data regarding protein binding of daratumumab in serum is not readily available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Monoclonal antibodies are expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies are metabolized to amino acids used for synthesis of new proteins or are eliminated by 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): Intravenous daratumumab has a terminal half life of 18 ± 9 days. Subcutaneous daratumumab has a half life of 20 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Intravenous daratumumab has a clearance of 171.4 ± 95.3mL/day. Subcutaneous daratumumab has a clearance of 119mL/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses of daratumumab are not readily available. Patients should be treated with symptomatic and supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Darzalex, Darzalex Faspro •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): Daratumumab is a CD38-directed cytolytic antibody used alone or as an adjunct drug in the treatment of multiple myeloma and light chain amyloidosis.

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 Daratumumab interact? Information: •Drug A: Abciximab •Drug B: Daratumumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Daratumumab. •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): Daratumumab is indicated as an intravenous injection alone or in combination with other medications for the treatment of multiple myeloma. It is available as a combination product with hyaluronidase for the treatment of adults with multiple myeloma as monotherapy or combination therapy and light chain amyloidosis in combination with other 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): Daratumumab is a monoclonal antibody that targets and induces apoptosis in cells that highly express CD38, including multiple myeloma cells. It has a long duration of action as it is given every 1-4 weeks. Patients should be counselled regarding the risk of hypersensitivity, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interferences with cross-matching and red blood cell antibody screening. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): CD38 is a glycoprotein present on the surface of hematopoietic cells and is responsible for a number of cell signalling functions. Daratumumab is an immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that targets CD38. Cancers like multiple myeloma overexpress CD38, allowing daratumumab to have higher affinity for these cells. This binding allows daratumumab to induce apoptosis, antibody dependent cellular phagocytosis, and antibody and complement-dependent cytotoxicity. Antibody dependent cellular phagocytosis is mediated by the FC region of the antibody inducing phagocytes such as macrophages, antibody dependent cellular cytotoxicity is mediated by the FC region of the antibody inducing effector cells such as natural killer cells, and complement dependent cytotoxicity is mediated by the FC region of the antibody binding to and inducing complement protein activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Subcutaneous daratumumab reaches a C max of 592µg/mL compared to intravenous daratumumab, which reaches a C max of 688µg/mL. The AUC of subcutaneous daratumumab is 4017µg/mL*day compared to intravenous daratumumab, which has an AUC of 4019µg/mL*day. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Daratumumab intravenous monotherapy has a volume of distribution of 4.7 ± 1.3L and the combination therapy has a volume of distribution of 4.4 ± 1.5L. Subcutaneous daratumumab has a volume of distribution of the central compartment of 5.2L and a volume of distribution of the peripheral compartment of 3.8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Data regarding protein binding of daratumumab in serum is not readily available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Monoclonal antibodies are expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies are metabolized to amino acids used for synthesis of new proteins or are eliminated by 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): Intravenous daratumumab has a terminal half life of 18 ± 9 days. Subcutaneous daratumumab has a half life of 20 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Intravenous daratumumab has a clearance of 171.4 ± 95.3mL/day. Subcutaneous daratumumab has a clearance of 119mL/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding overdoses of daratumumab are not readily available. Patients should be treated with symptomatic and supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Darzalex, Darzalex Faspro •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): Daratumumab is a CD38-directed cytolytic antibody used alone or as an adjunct drug in the treatment of multiple myeloma and light chain amyloidosis. 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 Dasatinib interact?

•Drug A: Abciximab •Drug B: Dasatinib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Dasatinib is combined with Abciximab. •Extended Description: Bleeding events arising from drug-induced thrombocytopenia, including CNS and gastrointestinal hemorrhages, have occurred with dasatinib therapy. Co-administering dasatinib with other agents with potential to cause bleeding, such as anticoagulants, may significantly increase the risk for both non-fatal and fatal bleeding and haemorrhages. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Dasatinib is indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, as well as adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib, and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Dasatinib is also indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase or newly diagnosed Ph+ ALL in combination with chemotherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dasatinib is an orally available small-molecule multikinase inhibitor. During clinical trials, less than 1% of patients treated with dasatinib had QTc prolongation as an adverse reaction, and 1% experienced a QTcF higher than 500 ms. The use of dasatinib is also associated with myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, pulmonary arterial hypertension, severe dermatologic reactions, tumor lysis syndrome and hepatotoxicity. It may also cause embryo-fetal toxicity and lead to adverse reactions associated with bone growth and development 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): Dasatinib is a tyrosine kinase inhibitor with several targets. At nanomolar concentrations, it inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. In patients with chronic myeloid leukemia (CML), the tyrosine kinase activity of BCR-ABL is deregulated, leading to the growth, proliferation and survival of cancerous hematopoietic cells. Dasatinib binds to the active and inactive conformation of the ABL kinase domain with a higher affinity than imatinib. In chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL, dasatinib inhibits cell growth. Also, dasatinib has in vitro activity against leukemic cell lines that are either sensitive or resistant to imatinib. It has been suggested that dasatinib is able to overcome imatinib resistance caused by BCR-ABL kinase domain mutations because it does not require interaction with some of the residues involved in those mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dasatinib has a dose-proportional pharmacokinetic profile and a linear elimination between 15 mg/day (0.15 times the lowest approved recommended dose) and 240 mg/day (1.7 times the highest approved recommended dose). At 100 mg once a day, dasatinib has a C max and AUC of 82.2 ng/mL and 397 ng/mL*hr, respectively. In healthy adult subjects given dasatinib as dispersed tablets in juice, the adjusted geometric mean ratio compared to intact tablets was 0.97 for C max, and 0.84 for AUC. The T max of dasatinib is between 0.5 and 6 hours following oral administration. Following a single dose of 100 mg, a high-fat meal increases the AUC of dasatinib by 14%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Dasatinib has an apparent volume of distribution of 2505 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, the binding of dasatinib to human plasma proteins is approximately 96%. •Metabolism (Drug A): 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 humans, dasatinib is mainly metabolized by CYP3A4, although flavin-containing monooxygenase 3 (FMO3) and uridine diphosphate-glucuronosyltransferase (UGT) enzymes are also involved in the formation of dasatinib metabolites. Five pharmacologically active dasatinib metabolites have been identified: M4, M5, M6, M20 and M24. M4, M20, and M24 are mainly generated by CYP3A4, M5 is generated by FMO3, and M6 is generated by a cytosolic oxidoreductase. M4 is equipotent to dasatinib and represents approximately 5% of the AUC. However, it is unlikely to play a major role in the observed pharmacology of dasatinib. M5 and M6 are more than 10 times less active than dasatinib and are considered minor circulating metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dasatinib is mainly eliminated via feces. Within 10 days, 4% of dasatinib is recovered in urine, while 85% is recovered in feces. Approximately 0.1% and 19% of the administered dasatinib dose was recovered unchanged in urine and feces, respectively, and the rest was recovered as metabolites. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life of dasatinib is 3-5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of dasatinib does not vary over time. Dasatinib has an apparent oral clearance of 363.8 L/hr. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdose cases with dasatinib occurred in isolated cases during clinical studies. Patients that received 280 mg of dasatinib per day for 1 week developed severe myelosuppression and bleeding. Since dasatinib is associated with severe myelosuppression, patients that ingest more than the recommended dosage should be monitored closely for myelosuppression and receive appropriate supportive treatment. Acute overdose in animals was associated with cardiotoxicity. In rodents, ventricular necrosis and valvular/ventricular/atrial hemorrhage were detected at single doses higher than or equal to 100 mg/kg (600 mg/m ). In monkeys receiving single doses higher than or equal to 10 mg/kg (120 mg/m ), there was a tendency for increased systolic and diastolic blood pressure. In rats, the oral LD 50 of dasatinib is 50-100 mg/kg, and in monkeys, it is 25-45 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Sprycel •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Anh. dasatinib BMS dasatinib Dasatinib Dasatinib (anh.) Dasatinibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dasatinib is a tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia.

Bleeding events arising from drug-induced thrombocytopenia, including CNS and gastrointestinal hemorrhages, have occurred with dasatinib therapy. Co-administering dasatinib with other agents with potential to cause bleeding, such as anticoagulants, may significantly increase the risk for both non-fatal and fatal bleeding and haemorrhages. The severity of the interaction is moderate.

Question: Does Abciximab and Dasatinib interact? Information: •Drug A: Abciximab •Drug B: Dasatinib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Dasatinib is combined with Abciximab. •Extended Description: Bleeding events arising from drug-induced thrombocytopenia, including CNS and gastrointestinal hemorrhages, have occurred with dasatinib therapy. Co-administering dasatinib with other agents with potential to cause bleeding, such as anticoagulants, may significantly increase the risk for both non-fatal and fatal bleeding and haemorrhages. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Dasatinib is indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, as well as adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib, and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Dasatinib is also indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase or newly diagnosed Ph+ ALL in combination with chemotherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dasatinib is an orally available small-molecule multikinase inhibitor. During clinical trials, less than 1% of patients treated with dasatinib had QTc prolongation as an adverse reaction, and 1% experienced a QTcF higher than 500 ms. The use of dasatinib is also associated with myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, pulmonary arterial hypertension, severe dermatologic reactions, tumor lysis syndrome and hepatotoxicity. It may also cause embryo-fetal toxicity and lead to adverse reactions associated with bone growth and development 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): Dasatinib is a tyrosine kinase inhibitor with several targets. At nanomolar concentrations, it inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. In patients with chronic myeloid leukemia (CML), the tyrosine kinase activity of BCR-ABL is deregulated, leading to the growth, proliferation and survival of cancerous hematopoietic cells. Dasatinib binds to the active and inactive conformation of the ABL kinase domain with a higher affinity than imatinib. In chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL, dasatinib inhibits cell growth. Also, dasatinib has in vitro activity against leukemic cell lines that are either sensitive or resistant to imatinib. It has been suggested that dasatinib is able to overcome imatinib resistance caused by BCR-ABL kinase domain mutations because it does not require interaction with some of the residues involved in those mutations. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dasatinib has a dose-proportional pharmacokinetic profile and a linear elimination between 15 mg/day (0.15 times the lowest approved recommended dose) and 240 mg/day (1.7 times the highest approved recommended dose). At 100 mg once a day, dasatinib has a C max and AUC of 82.2 ng/mL and 397 ng/mL*hr, respectively. In healthy adult subjects given dasatinib as dispersed tablets in juice, the adjusted geometric mean ratio compared to intact tablets was 0.97 for C max, and 0.84 for AUC. The T max of dasatinib is between 0.5 and 6 hours following oral administration. Following a single dose of 100 mg, a high-fat meal increases the AUC of dasatinib by 14%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Dasatinib has an apparent volume of distribution of 2505 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, the binding of dasatinib to human plasma proteins is approximately 96%. •Metabolism (Drug A): 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 humans, dasatinib is mainly metabolized by CYP3A4, although flavin-containing monooxygenase 3 (FMO3) and uridine diphosphate-glucuronosyltransferase (UGT) enzymes are also involved in the formation of dasatinib metabolites. Five pharmacologically active dasatinib metabolites have been identified: M4, M5, M6, M20 and M24. M4, M20, and M24 are mainly generated by CYP3A4, M5 is generated by FMO3, and M6 is generated by a cytosolic oxidoreductase. M4 is equipotent to dasatinib and represents approximately 5% of the AUC. However, it is unlikely to play a major role in the observed pharmacology of dasatinib. M5 and M6 are more than 10 times less active than dasatinib and are considered minor circulating metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dasatinib is mainly eliminated via feces. Within 10 days, 4% of dasatinib is recovered in urine, while 85% is recovered in feces. Approximately 0.1% and 19% of the administered dasatinib dose was recovered unchanged in urine and feces, respectively, and the rest was recovered as metabolites. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life of dasatinib is 3-5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of dasatinib does not vary over time. Dasatinib has an apparent oral clearance of 363.8 L/hr. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdose cases with dasatinib occurred in isolated cases during clinical studies. Patients that received 280 mg of dasatinib per day for 1 week developed severe myelosuppression and bleeding. Since dasatinib is associated with severe myelosuppression, patients that ingest more than the recommended dosage should be monitored closely for myelosuppression and receive appropriate supportive treatment. Acute overdose in animals was associated with cardiotoxicity. In rodents, ventricular necrosis and valvular/ventricular/atrial hemorrhage were detected at single doses higher than or equal to 100 mg/kg (600 mg/m ). In monkeys receiving single doses higher than or equal to 10 mg/kg (120 mg/m ), there was a tendency for increased systolic and diastolic blood pressure. In rats, the oral LD 50 of dasatinib is 50-100 mg/kg, and in monkeys, it is 25-45 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Sprycel •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Anh. dasatinib BMS dasatinib Dasatinib Dasatinib (anh.) Dasatinibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dasatinib is a tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia. Output: Bleeding events arising from drug-induced thrombocytopenia, including CNS and gastrointestinal hemorrhages, have occurred with dasatinib therapy. Co-administering dasatinib with other agents with potential to cause bleeding, such as anticoagulants, may significantly increase the risk for both non-fatal and fatal bleeding and haemorrhages. The severity of the interaction is moderate.

Does Abciximab and Daunorubicin interact?

•Drug A: Abciximab •Drug B: Daunorubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Daunorubicin. •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 remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. Daunorubicin is indicated in combination with cytarabine for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year 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): Daunorubicin is an anthracycline antibiotic and antineoplastic agent. It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over 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): Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Daunorubicin was found to have a tmax of 2 h and a cmax of 24.8 μg/mL after a 90 min infusion of the liposomal formulation at a dose of 44 mg/m. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Daunorubicin has a steady-state volume of distribution of 1.91 L/m reported with the liposomal formulation. The average volume of distribution reported for the liposomal formulation 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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Daunorubicin is eliminated hepatically. 40% of daunorubicin is excreted in the bile while 25% is excreted in an active form (daunorubicin or daunorubicinol) in the urine. In the liposomal formulation, only 9% of active molecules are excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Daunorubicin has been determined to have a terminal half-life of 18.5 h (+/- 4.9). Daunorubicinol, the primary active metabolite has been determined to have a terminal half-life of 26.7 h (+/- 12.8). The mean half-life of elimination of liposomal daunorubicin has been reported to be 22.1 h in pharmacokinetic studies and 31.5 h in official FDA labeling. •Clearance (Drug A): No clearance available •Clearance (Drug B): Daunorubicin has a clearance of 68.4 mL/h/m determined using the liposomal formulation. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cerubidine, Vyxeos •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Acetyladriamycin Daunomycin Daunorubicin Daunorubicin liposomal Daunorubicina Daunorubicine Daunorubicinum Leukaemomycin C Rubidomycin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Daunorubicin is an anthracycline aminoglycoside used to induce remission of nonlymphocytic leukemia and acute lymphocytic 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 Daunorubicin interact? Information: •Drug A: Abciximab •Drug B: Daunorubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Daunorubicin. •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 remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. Daunorubicin is indicated in combination with cytarabine for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year 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): Daunorubicin is an anthracycline antibiotic and antineoplastic agent. It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over 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): Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Daunorubicin was found to have a tmax of 2 h and a cmax of 24.8 μg/mL after a 90 min infusion of the liposomal formulation at a dose of 44 mg/m. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Daunorubicin has a steady-state volume of distribution of 1.91 L/m reported with the liposomal formulation. The average volume of distribution reported for the liposomal formulation 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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Daunorubicin is eliminated hepatically. 40% of daunorubicin is excreted in the bile while 25% is excreted in an active form (daunorubicin or daunorubicinol) in the urine. In the liposomal formulation, only 9% of active molecules are excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Daunorubicin has been determined to have a terminal half-life of 18.5 h (+/- 4.9). Daunorubicinol, the primary active metabolite has been determined to have a terminal half-life of 26.7 h (+/- 12.8). The mean half-life of elimination of liposomal daunorubicin has been reported to be 22.1 h in pharmacokinetic studies and 31.5 h in official FDA labeling. •Clearance (Drug A): No clearance available •Clearance (Drug B): Daunorubicin has a clearance of 68.4 mL/h/m determined using the liposomal formulation. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cerubidine, Vyxeos •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Acetyladriamycin Daunomycin Daunorubicin Daunorubicin liposomal Daunorubicina Daunorubicine Daunorubicinum Leukaemomycin C Rubidomycin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Daunorubicin is an anthracycline aminoglycoside used to induce remission of nonlymphocytic leukemia and acute lymphocytic 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 Decitabine interact?

•Drug A: Abciximab •Drug B: Decitabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Decitabine. •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): Decitabine is indicated for the treatment of patients with myelodysplastic syndromes (MDS) including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), as well as for MDS scored as belonging to the intermediate-1, intermediate-2, or high-risk group in the International Prognostic Scoring System. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Decitabine is a prodrug analogue of the natural nucleotide 2’-deoxycytidine, which, upon being phosphorylated intracellularly, is incorporated into DNA and exerts numerous effects on gene expression. The use of decitabine is associated with neutropenia and thrombocytopenia. In addition, decitabine can cause fetal harm in pregnant women; effective contraception and avoidance of pregnancy are recommended during treatment with decitabine. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms that manifest in peripheral cytopenias and may eventually progress to secondary acute myeloid leukemia (sAML). Included in the over 45 genes commonly mutated in MDS patients are those involved in DNA methylation and histone modification, and it is well-established that alteration of the epigenetic landscape is a feature of myeloid leukemias. Decitabine is considered a prodrug, as it requires transport into cells and subsequent phosphorylation by distinct kinases to generate the active molecule 5-aza-2'-deoxycytidine-triphosphate, which is incorporated by DNA polymerase during DNA replication. Once incorporated into DNA, decitabine is recognized as a substrate by DNA methyltransferase enzymes (DNMTs), specifically DNMT1, but due to the presence of an N5 rather than C5 atom, traps the DNMT through the irreversible formation of a covalent bond. At low concentrations, this mode of action depletes DNMTs and results in global DNA hypomethylation while at high concentrations, it additionally results in double-strand breaks and cell death. The general hypothesis regarding decitabine's therapeutic efficacy is that the global hypomethylation it induces results in the expression of previously silent tumour suppressor genes. However, there are other putative mechanisms also related to this change in DNA methylation, including indirect alteration of transcription through effects on transcription factors, indirectly altering histone modifications and chromatin structure, and activating pathways involved in DNA damage response. The overall effect of decitabine is a decrease in neoplastic cell proliferation and an increase in the expression of tumour suppressor genes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Decitabine administered intravenously at 15 mg/m for three hours every eight hours over three days resulted in a C max of 73.8 ng/mL (66% coefficient of variation, CV), an AUC 0-∞ of 163 ng*h/mL (62% CV), and a cumulative AUC of 1332 ng*h/mL (95% CI of 1010-1730). Similarly, decitabine at 20 mg/m for one hour once daily over five days resulted in a C max of 147 ng/mL (49% CV), an AUC 0-∞ of 115 ng*h/mL (43% CV), and a cumulative AUC of 570 ng*h/mL (95% CI of 470-700). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Decitabine as an apparent volume of distribution of 4.59 ± 1.42 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Decitabine exhibits negligible (< 1%) plasma protein binding. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Decitabine is phosphorylated inside cells by the sequential action of deoxycytidine kinase, nucleotide monophosphate kinase, and nucleotide diphosphate kinase, prior to being incorporated into newly synthesized DNA by DNA polymerase. Decitabine not incorporated into cellular DNA undergoes deamination by cytidine deaminase followed by additional degradation prior to excretion. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Less than 1% of administered decitabine is excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Decitabine has a half-life of 0.62 hours (49% CV) when administered intravenously at 15 mg/m for three hours every eight hours over three days, and a half-life of 0.54 hours (43% CV) at 20 mg/m for one hour once daily over five days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Decitabine has a clearance of 125 L/hr/m (53% CV) when administered intravenously at 15 mg/m for three hours every eight hours over three days, and a clearance of 210 L/hr/m (47% CV) at 20 mg/m for one hour once daily over five days. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Decitabine has demonstrated mutagenic potential in L5178Y mouse lymphoma cells and an Escherichia coil lac-I transgene within the colonic DNA of mice. Decitabine treatment increased chromosomal rearrangements in fruit fly larvae. In mouse models, decitabine exposure in utero (approximately 7% of the recommended daily dose) resulted in decreased weight and decreased male fertility. Adult male mice administered with between 0.3 and 1% of the recommended daily dose of decitabine three times a week for seven weeks had smaller testes with abnormal histology, decreased sperm count, and decreased fertility. There is no known antidote for decitabine overdose. Patients experiencing an overdose are at an increased risk of severe adverse effects such as myelosuppression, including prolonged and severe neutropenia and thrombocytopenia. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dacogen, Inqovi 5 Tablet Pack •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-azadeoxycytidine Decitabina Decitabine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Decitabine is a chemotherapeutic pyrimidine nucleoside analogue used for the treatment of myelodysplastic syndromes (MDS) by inducing DNA hypomethylation and corresponding alterations in gene expression.

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 Decitabine interact? Information: •Drug A: Abciximab •Drug B: Decitabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Decitabine. •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): Decitabine is indicated for the treatment of patients with myelodysplastic syndromes (MDS) including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), as well as for MDS scored as belonging to the intermediate-1, intermediate-2, or high-risk group in the International Prognostic Scoring System. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Decitabine is a prodrug analogue of the natural nucleotide 2’-deoxycytidine, which, upon being phosphorylated intracellularly, is incorporated into DNA and exerts numerous effects on gene expression. The use of decitabine is associated with neutropenia and thrombocytopenia. In addition, decitabine can cause fetal harm in pregnant women; effective contraception and avoidance of pregnancy are recommended during treatment with decitabine. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms that manifest in peripheral cytopenias and may eventually progress to secondary acute myeloid leukemia (sAML). Included in the over 45 genes commonly mutated in MDS patients are those involved in DNA methylation and histone modification, and it is well-established that alteration of the epigenetic landscape is a feature of myeloid leukemias. Decitabine is considered a prodrug, as it requires transport into cells and subsequent phosphorylation by distinct kinases to generate the active molecule 5-aza-2'-deoxycytidine-triphosphate, which is incorporated by DNA polymerase during DNA replication. Once incorporated into DNA, decitabine is recognized as a substrate by DNA methyltransferase enzymes (DNMTs), specifically DNMT1, but due to the presence of an N5 rather than C5 atom, traps the DNMT through the irreversible formation of a covalent bond. At low concentrations, this mode of action depletes DNMTs and results in global DNA hypomethylation while at high concentrations, it additionally results in double-strand breaks and cell death. The general hypothesis regarding decitabine's therapeutic efficacy is that the global hypomethylation it induces results in the expression of previously silent tumour suppressor genes. However, there are other putative mechanisms also related to this change in DNA methylation, including indirect alteration of transcription through effects on transcription factors, indirectly altering histone modifications and chromatin structure, and activating pathways involved in DNA damage response. The overall effect of decitabine is a decrease in neoplastic cell proliferation and an increase in the expression of tumour suppressor genes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Decitabine administered intravenously at 15 mg/m for three hours every eight hours over three days resulted in a C max of 73.8 ng/mL (66% coefficient of variation, CV), an AUC 0-∞ of 163 ng*h/mL (62% CV), and a cumulative AUC of 1332 ng*h/mL (95% CI of 1010-1730). Similarly, decitabine at 20 mg/m for one hour once daily over five days resulted in a C max of 147 ng/mL (49% CV), an AUC 0-∞ of 115 ng*h/mL (43% CV), and a cumulative AUC of 570 ng*h/mL (95% CI of 470-700). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Decitabine as an apparent volume of distribution of 4.59 ± 1.42 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Decitabine exhibits negligible (< 1%) plasma protein binding. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Decitabine is phosphorylated inside cells by the sequential action of deoxycytidine kinase, nucleotide monophosphate kinase, and nucleotide diphosphate kinase, prior to being incorporated into newly synthesized DNA by DNA polymerase. Decitabine not incorporated into cellular DNA undergoes deamination by cytidine deaminase followed by additional degradation prior to excretion. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Less than 1% of administered decitabine is excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Decitabine has a half-life of 0.62 hours (49% CV) when administered intravenously at 15 mg/m for three hours every eight hours over three days, and a half-life of 0.54 hours (43% CV) at 20 mg/m for one hour once daily over five days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Decitabine has a clearance of 125 L/hr/m (53% CV) when administered intravenously at 15 mg/m for three hours every eight hours over three days, and a clearance of 210 L/hr/m (47% CV) at 20 mg/m for one hour once daily over five days. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Decitabine has demonstrated mutagenic potential in L5178Y mouse lymphoma cells and an Escherichia coil lac-I transgene within the colonic DNA of mice. Decitabine treatment increased chromosomal rearrangements in fruit fly larvae. In mouse models, decitabine exposure in utero (approximately 7% of the recommended daily dose) resulted in decreased weight and decreased male fertility. Adult male mice administered with between 0.3 and 1% of the recommended daily dose of decitabine three times a week for seven weeks had smaller testes with abnormal histology, decreased sperm count, and decreased fertility. There is no known antidote for decitabine overdose. Patients experiencing an overdose are at an increased risk of severe adverse effects such as myelosuppression, including prolonged and severe neutropenia and thrombocytopenia. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dacogen, Inqovi 5 Tablet Pack •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-azadeoxycytidine Decitabina Decitabine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Decitabine is a chemotherapeutic pyrimidine nucleoside analogue used for the treatment of myelodysplastic syndromes (MDS) by inducing DNA hypomethylation and corresponding alterations in gene expression. 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 Deferasirox interact?

•Drug A: Abciximab •Drug B: Deferasirox •Severity: MODERATE •Description: The risk or severity of gastrointestinal bleeding can be increased when Abciximab is combined with Deferasirox. •Extended Description: Incidences of fatal gastrointestinal hemorrhage have been reported in patients undergoing deferasirox therapy. This risk for this adverse reaction is especially high in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Co-administration of deferasirox with other agents known to affect hemostasis or cause bleeding and hemorrhage, such as anticoagulants, may lead to increased risk for non-fatal and fatal gastrointestinal ulceration 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): For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 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): Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Two molecules of deferasirox are capable of binding to 1 atom of iron. Deferasirox works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming a stable complex which is eliminated via the kidneys. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 14.37 ± 2.69 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Deferasirox is highly (~99%) protein bound almost exclusively to serum 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. CYP450-catalyzed (oxidative) metabolism of deferasirox appears to be minor in humans (about 8%). Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% 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): The mean elimination half-life ranged from 8 to 16 hours following oral administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Exjade, Jadenu •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): Deferasirox is an iron chelator used to treat chronic iron overload caused by blood transfusions. Also used in patients with non-transfusion-dependent thalassemia syndromes, and in patients with elevated liver iron concentration and serum ferritin.

Incidences of fatal gastrointestinal hemorrhage have been reported in patients undergoing deferasirox therapy. This risk for this adverse reaction is especially high in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Co-administration of deferasirox with other agents known to affect hemostasis or cause bleeding and hemorrhage, such as anticoagulants, may lead to increased risk for non-fatal and fatal gastrointestinal ulceration and hemorrhage. The severity of the interaction is moderate.

Question: Does Abciximab and Deferasirox interact? Information: •Drug A: Abciximab •Drug B: Deferasirox •Severity: MODERATE •Description: The risk or severity of gastrointestinal bleeding can be increased when Abciximab is combined with Deferasirox. •Extended Description: Incidences of fatal gastrointestinal hemorrhage have been reported in patients undergoing deferasirox therapy. This risk for this adverse reaction is especially high in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Co-administration of deferasirox with other agents known to affect hemostasis or cause bleeding and hemorrhage, such as anticoagulants, may lead to increased risk for non-fatal and fatal gastrointestinal ulceration 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): For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 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): Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Two molecules of deferasirox are capable of binding to 1 atom of iron. Deferasirox works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming a stable complex which is eliminated via the kidneys. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 14.37 ± 2.69 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Deferasirox is highly (~99%) protein bound almost exclusively to serum 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. CYP450-catalyzed (oxidative) metabolism of deferasirox appears to be minor in humans (about 8%). Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% 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): The mean elimination half-life ranged from 8 to 16 hours following oral administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Exjade, Jadenu •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): Deferasirox is an iron chelator used to treat chronic iron overload caused by blood transfusions. Also used in patients with non-transfusion-dependent thalassemia syndromes, and in patients with elevated liver iron concentration and serum ferritin. Output: Incidences of fatal gastrointestinal hemorrhage have been reported in patients undergoing deferasirox therapy. This risk for this adverse reaction is especially high in elderly patients who had advanced hematologic malignancies and/or low platelet counts. Co-administration of deferasirox with other agents known to affect hemostasis or cause bleeding and hemorrhage, such as anticoagulants, may lead to increased risk for non-fatal and fatal gastrointestinal ulceration and hemorrhage. The severity of the interaction is moderate.

Does Abciximab and Defibrotide interact?

•Drug A: Abciximab •Drug B: Defibrotide •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Defibrotide. •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. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in 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

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 Defibrotide interact? Information: •Drug A: Abciximab •Drug B: Defibrotide •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Defibrotide. •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. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in 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: 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 Denosumab interact?

•Drug A: Abciximab •Drug B: Denosumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Denosumab. •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): Denosumab under the brand name Prolia is indicated as a treatment for osteoporosis in menopausal women or men and glucocorticoid-induced osteoporosis in men and women at high risk of fracture. It is also used to increase bone mass in men at high risk for fractures receiving androgen deprivation therapy for nonmetastatic prostate cancer or women at high risk for fractures receiving adjuvant aromatase inhibitor therapy for breast cancer. Denosumab under the brand name Xgeva is indicated to prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors and to treat giant cell tumors of bone in adults and skeletally mature adolescents and hypercalcemia of malignancy refractory to bisphosphonate 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): In clinical studies, treatment with 60 mg of denosumab resulted in a reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days, with maximal reductions occurring by 1 month. CTX levels were below the limit of assay quantitation (0.049 ng/mL) in 39% to 68% of patients 1 to 3 months after dosing of denosumab. At the end of each dosing interval, CTX reductions were partially attenuated from a maximal reduction of ≥ 87% to ≥ 45% (range: 45% to 80%), as serum denosumab levels diminished, reflecting the reversibility of the effects of denosumab on bone remodelling. These effects were sustained with continued treatment. Upon reinitiation, the degree of inhibition of CTX by denosumab was similar to that observed in patients initiating denosumab treatment. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e., osteocalcin and procollagen type 1 N-terminal peptide [P1NP]) were observed starting 1 month after the first dose of denosumab. After discontinuation of denosumab therapy, markers of bone resorption increased to levels 40% to 60% above pretreatment values but returned to baseline levels within 12 months. In patients with breast cancer and bone metastases, the median reduction in urinary N-terminal telopeptide corrected for creatinine (uNTx/Cr) was 82% within 1 week following initiation of denosumab 120 mg administered subcutaneously. In Studies 20050136, 20050244, and 20050103, the median reduction in uNTx/Cr from baseline to Month 3 was approximately 80% in 2075 denosumab-treated patients. In a phase 3 study of patients with newly diagnosed multiple myeloma who received subcutaneous doses of denosumab 120 mg every 4 weeks (Q4W), median reductions in uNTx/Cr of approximately 75% were observed by week 5. Reductions in bone turnover markers were maintained, with median reductions of 74% to 79% for uNTx/Cr from weeks 9 to 49 of continued 120 mg Q4W dosing. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. •Absorption (Drug A): No absorption available •Absorption (Drug B): In a study conducted in healthy male and female volunteers (n = 73, age range: 18 to 64 years) following a single subcutaneously administered denosumab dose of 60 mg after fasting (at least for 12 hours), the mean maximum denosumab concentration (C max ) was 6.75 mcg/mL (standard deviation [SD] = 1.89 mcg/mL). The median time to maximum denosumab concentration (T max ) was 10 days (range: 3 to 21 days). The mean area-under-the-concentration-time curve up to 16 weeks (AUC0-16 weeks) of denosumab was 316 mcg⋅day/mL (SD = 101 mcg⋅day/mL. No accumulation or change in denosumab pharmacokinetics with time was observed upon multiple dosing of 60 mg subcutaneously administered once every 6 months. Serum and seminal fluid concentrations of denosumab were measured in 12 healthy male volunteers (age range: 43-65 years). After a single 60 mg subcutaneous administration of denosumab, the mean (± SD) C max values in the serum and seminal fluid samples were 6170 (± 2070) and 100 (± 81.9) ng/mL, respectively, resulting in a maximum seminal fluid concentration of approximately 2% of serum levels. The median (range) T max values in the serum and seminal fluid samples were 8.0 (7.9 to 21) and 21 (8.0 to 49) days, respectively. Among the subjects, the highest denosumab concentration in the seminal fluid was 301 ng/mL at 22 days post-dose. On the first day of measurement (10 days post-dose), nine of eleven subjects had quantifiable concentrations in semen. On the last day of measurement (106 days post-dose), five subjects still had quantifiable concentrations of denosumab in seminal fluid, with a mean (± SD) seminal fluid concentration of 21.1 (± 36.5) ng/mL across all subjects (n = 12). In patients with newly diagnosed multiple myeloma who received 120 mg every 4 weeks, denosumab concentrations appear to reach a steady state by month 6. In patients with giant cell tumor of bone, after administration of subcutaneous doses of 120 mg once every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy, mean (± standard deviation) serum trough concentrations on Day 8, 15, and one month after the first dose were 19.0 (± 24.1), 31.6 (± 27.3), 36.4 (± 20.6) mcg/mL, respectively. Steady-state was achieved in 3 months after initiation of treatment with a mean serum trough concentration of 23.4 (± 12.1) mcg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central volume of distribution and volume of distribution at steady-state were calculated to be 2.49 L/66 kg and 3.5-7 L respectively. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No information is available on the protein binding of denosumab. •Metabolism (Drug A): 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 on the metabolism of denosumab. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): As an antibody, denosumab is likely cleared by the reticuloendothelial system with minimal renal filtration and 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): After C max, serum denosumab concentrations declined over a period of 4 to 5 months with a mean half-life of 25.4 days (SD = 8.5 days; n = 46). •Clearance (Drug A): No clearance available •Clearance (Drug B): No information is available on the clearance of denosumab. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Denosumab is contraindicated for use in pregnant women because it may cause harm to a fetus. There are insufficient data with denosumab use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth. In clinical trials, hypercalcemia has been reported in pediatric patients with osteogenesis imperfect treated with denosumab products, including Prolia. Some cases required hospitalization and were complicated by acute renal injury. Based on results from animal studies, denosumab may negatively affect long-bone growth and dentition in pediatric patients below the age of 4 years. The carcinogenic and genotoxic potential of denosumab has not been evaluated in long-term animal studies. Denosumab had no effect on female fertility or male reproductive organs in monkeys at doses that were 13- to 50-fold higher than the recommended human dose of 60 mg subcutaneously administered once every 6 months, based on body weight (mg/kg). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Prolia, Xgeva •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): Denosumab is a RANK ligand (RANKL) inhibitor used for the management of osteoporosis in patients at high risk for bone fractures.

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 Denosumab interact? Information: •Drug A: Abciximab •Drug B: Denosumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Denosumab. •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): Denosumab under the brand name Prolia is indicated as a treatment for osteoporosis in menopausal women or men and glucocorticoid-induced osteoporosis in men and women at high risk of fracture. It is also used to increase bone mass in men at high risk for fractures receiving androgen deprivation therapy for nonmetastatic prostate cancer or women at high risk for fractures receiving adjuvant aromatase inhibitor therapy for breast cancer. Denosumab under the brand name Xgeva is indicated to prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors and to treat giant cell tumors of bone in adults and skeletally mature adolescents and hypercalcemia of malignancy refractory to bisphosphonate 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): In clinical studies, treatment with 60 mg of denosumab resulted in a reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days, with maximal reductions occurring by 1 month. CTX levels were below the limit of assay quantitation (0.049 ng/mL) in 39% to 68% of patients 1 to 3 months after dosing of denosumab. At the end of each dosing interval, CTX reductions were partially attenuated from a maximal reduction of ≥ 87% to ≥ 45% (range: 45% to 80%), as serum denosumab levels diminished, reflecting the reversibility of the effects of denosumab on bone remodelling. These effects were sustained with continued treatment. Upon reinitiation, the degree of inhibition of CTX by denosumab was similar to that observed in patients initiating denosumab treatment. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e., osteocalcin and procollagen type 1 N-terminal peptide [P1NP]) were observed starting 1 month after the first dose of denosumab. After discontinuation of denosumab therapy, markers of bone resorption increased to levels 40% to 60% above pretreatment values but returned to baseline levels within 12 months. In patients with breast cancer and bone metastases, the median reduction in urinary N-terminal telopeptide corrected for creatinine (uNTx/Cr) was 82% within 1 week following initiation of denosumab 120 mg administered subcutaneously. In Studies 20050136, 20050244, and 20050103, the median reduction in uNTx/Cr from baseline to Month 3 was approximately 80% in 2075 denosumab-treated patients. In a phase 3 study of patients with newly diagnosed multiple myeloma who received subcutaneous doses of denosumab 120 mg every 4 weeks (Q4W), median reductions in uNTx/Cr of approximately 75% were observed by week 5. Reductions in bone turnover markers were maintained, with median reductions of 74% to 79% for uNTx/Cr from weeks 9 to 49 of continued 120 mg Q4W dosing. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. •Absorption (Drug A): No absorption available •Absorption (Drug B): In a study conducted in healthy male and female volunteers (n = 73, age range: 18 to 64 years) following a single subcutaneously administered denosumab dose of 60 mg after fasting (at least for 12 hours), the mean maximum denosumab concentration (C max ) was 6.75 mcg/mL (standard deviation [SD] = 1.89 mcg/mL). The median time to maximum denosumab concentration (T max ) was 10 days (range: 3 to 21 days). The mean area-under-the-concentration-time curve up to 16 weeks (AUC0-16 weeks) of denosumab was 316 mcg⋅day/mL (SD = 101 mcg⋅day/mL. No accumulation or change in denosumab pharmacokinetics with time was observed upon multiple dosing of 60 mg subcutaneously administered once every 6 months. Serum and seminal fluid concentrations of denosumab were measured in 12 healthy male volunteers (age range: 43-65 years). After a single 60 mg subcutaneous administration of denosumab, the mean (± SD) C max values in the serum and seminal fluid samples were 6170 (± 2070) and 100 (± 81.9) ng/mL, respectively, resulting in a maximum seminal fluid concentration of approximately 2% of serum levels. The median (range) T max values in the serum and seminal fluid samples were 8.0 (7.9 to 21) and 21 (8.0 to 49) days, respectively. Among the subjects, the highest denosumab concentration in the seminal fluid was 301 ng/mL at 22 days post-dose. On the first day of measurement (10 days post-dose), nine of eleven subjects had quantifiable concentrations in semen. On the last day of measurement (106 days post-dose), five subjects still had quantifiable concentrations of denosumab in seminal fluid, with a mean (± SD) seminal fluid concentration of 21.1 (± 36.5) ng/mL across all subjects (n = 12). In patients with newly diagnosed multiple myeloma who received 120 mg every 4 weeks, denosumab concentrations appear to reach a steady state by month 6. In patients with giant cell tumor of bone, after administration of subcutaneous doses of 120 mg once every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy, mean (± standard deviation) serum trough concentrations on Day 8, 15, and one month after the first dose were 19.0 (± 24.1), 31.6 (± 27.3), 36.4 (± 20.6) mcg/mL, respectively. Steady-state was achieved in 3 months after initiation of treatment with a mean serum trough concentration of 23.4 (± 12.1) mcg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central volume of distribution and volume of distribution at steady-state were calculated to be 2.49 L/66 kg and 3.5-7 L respectively. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No information is available on the protein binding of denosumab. •Metabolism (Drug A): 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 on the metabolism of denosumab. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): As an antibody, denosumab is likely cleared by the reticuloendothelial system with minimal renal filtration and 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): After C max, serum denosumab concentrations declined over a period of 4 to 5 months with a mean half-life of 25.4 days (SD = 8.5 days; n = 46). •Clearance (Drug A): No clearance available •Clearance (Drug B): No information is available on the clearance of denosumab. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Denosumab is contraindicated for use in pregnant women because it may cause harm to a fetus. There are insufficient data with denosumab use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth. In clinical trials, hypercalcemia has been reported in pediatric patients with osteogenesis imperfect treated with denosumab products, including Prolia. Some cases required hospitalization and were complicated by acute renal injury. Based on results from animal studies, denosumab may negatively affect long-bone growth and dentition in pediatric patients below the age of 4 years. The carcinogenic and genotoxic potential of denosumab has not been evaluated in long-term animal studies. Denosumab had no effect on female fertility or male reproductive organs in monkeys at doses that were 13- to 50-fold higher than the recommended human dose of 60 mg subcutaneously administered once every 6 months, based on body weight (mg/kg). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Prolia, Xgeva •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): Denosumab is a RANK ligand (RANKL) inhibitor used for the management of osteoporosis in patients at high risk for bone fractures. 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 Deoxycholic acid interact?

•Drug A: Abciximab •Drug B: Deoxycholic acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Deoxycholic 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): For improvement in appearance of moderate to severe fullness associated with submental fat 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): 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): As a bile acid, deoxycholic acid emulsifies fat in the gut. Synthetically derived deoxycholic acid, when injected, stimulates a targeted breakdown of adipose cells by disrupting the cell membrane and causing adipocytolysis. This results in an inflammatory reaction and clearing of the adipose tissue remnants by macrophages. Deoxycholic acid's actions are reduced by albumin and tissue-associated proteins, therefore its effect is limited to protein-poor subcutaneous fat tissue. Protein-rich tissues like muscle and skin are unaffected by deoxycholic acid, contributing to its safety profile. •Absorption (Drug A): No absorption available •Absorption (Drug B): Deoxycholic acid is rapidly absorbed after subcutaneous administration. After maximum recommended single treatment dose, 100mg, the post-treatment plasma levels returned to endogenous levels within 24 hours. With the proposed treatment guideline, no accumulation is expected. •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): Deoxycholic acid is not metabolized to any significant extent under normal conditions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The exogenous deoxycholic acid joins the endogenous bile acid pool in the enterohepatic circulation and is excreted unchanged in feces along with endogenous deoxycholic acid. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Belkyra, Kybella •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Deoxycholate Deoxycholic acid Desoxycholic acid Desoxycholsäure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Deoxycholic acid is a cytolytic agent injected subcutaneously to improve the appearance submental fat.

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 Deoxycholic acid interact? Information: •Drug A: Abciximab •Drug B: Deoxycholic acid •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Deoxycholic 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): For improvement in appearance of moderate to severe fullness associated with submental fat 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): 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): As a bile acid, deoxycholic acid emulsifies fat in the gut. Synthetically derived deoxycholic acid, when injected, stimulates a targeted breakdown of adipose cells by disrupting the cell membrane and causing adipocytolysis. This results in an inflammatory reaction and clearing of the adipose tissue remnants by macrophages. Deoxycholic acid's actions are reduced by albumin and tissue-associated proteins, therefore its effect is limited to protein-poor subcutaneous fat tissue. Protein-rich tissues like muscle and skin are unaffected by deoxycholic acid, contributing to its safety profile. •Absorption (Drug A): No absorption available •Absorption (Drug B): Deoxycholic acid is rapidly absorbed after subcutaneous administration. After maximum recommended single treatment dose, 100mg, the post-treatment plasma levels returned to endogenous levels within 24 hours. With the proposed treatment guideline, no accumulation is expected. •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): Deoxycholic acid is not metabolized to any significant extent under normal conditions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The exogenous deoxycholic acid joins the endogenous bile acid pool in the enterohepatic circulation and is excreted unchanged in feces along with endogenous deoxycholic acid. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Belkyra, Kybella •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Deoxycholate Deoxycholic acid Desoxycholic acid Desoxycholsäure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Deoxycholic acid is a cytolytic agent injected subcutaneously to improve the appearance submental fat. 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 Desogestrel interact?

•Drug A: Abciximab •Drug B: Desogestrel •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Desogestrel 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): Oral desogestrel is used in combination with ethinylestradiol as a contraceptive agent for the prevention of pregnancy. Desogestrel is part of the combined oral contraceptives that contain a mix of estrogen and progestin which inhibit ovulation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 effects of desogestrel are divided on reproductive including modification of luteinizing hormone and follicle stimulating hormone, declines on the onset of menstruation, and increases the viscosity of the vaginal fluid; and on metabolic that includes increase insulin secretion and resistance, increased lipase activity, and increased fat deposition. The effect of desogestrel on the lipids has been studied extensively and the results are contradictory. Desogestrel main therapeutic effect due to its mechanism of action is known to be related to the inhibition of the ovulation in 97% of the cycles. This effect was proven in clinical trials in non-breastfeeding women from which the Pearl failure rate was reported to be of 0.17 per 100 women-years. This result indicated that desogestrel is more efficient when compared to other progestogen-only pills. All the therapeutic effect is produced by a transformation of the endometrium followed by an inhibition of the ovulation due to the suppression of other hormones. Desogestrel has been widely confirmed to be related to an increase in the risk of venous thromboembolism due to the driven increased in blood coagulation factors, leading to a pronounced prothrombotic state. However, the effects of desogestrel are known to not impact significantly the level of total cholesterol remaining in the range of change of 10% which allows it to be a molecule that presents a favorable lipid profile. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Desogestrel enters the cell passively and acts by binding selectively to the progesterone receptor and generating low androgenic activity. Its binding produces an effect like a transcription factor and thus, it produces modifications in the mRNA synthesis. The active metabolite of desogestrel, etonogestrel, presents a combination of high progestational activity with minimal intrinsic androgenicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration, desogestrel is rapidly absorbed and it reaches a peak concentration of 2 ng/ml after 1.5 hours. The bioavailability of desogestrel is reported to be in the range of 60-80% and the reported AUC is of 3000 ng.h/ml. Almost all the administered dose is modified to the active metabolite, etonogestrel. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of desogestrel is of 1.5 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The main metabolite of desogestrel is mainly found bound to albumin and sex-hormone binding globulin. Around 96-98% of the administered dose of desogestrel is found bound to plasma proteins from which 40-70% is found bound to sex-hormone binding globulin. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Desogestrel is rapidly metabolized in the intestinal mucosa and by first-pass hepatic metabolism to form the major metabolite of desogestrel is etonogestrel which is the biologically active metabolite. This modification is described by the hydroxylation in C3 of the desogestrel molecule. Later, etonogestrel is metabolized following the normal pathways of steroid metabolism. On the other hand, due to the 11-methylene side chain, desogestrel cannot be metabolized to other progestins. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of desogestrel is found to be mainly renal corresponding to about 6 times the dose eliminated in the bile. The elimination of desogestrel is only done as the metabolites and not as the unchanged drug and about 85% of the administered dose can be excreted as metabolites after 6-8 days. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 desogestrel is determined to be of 30 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The metabolic clearance rate of desogestrel is reported to be of about 2 ml/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Administration of large quantities of desogestrel has been shown to produce strong hormonal effects but to lack chronic toxicity. The reported LD50 in rats after oral administration of desogestrel is higher than 2000 mg/kg. Overdose hasn't reported serious effects but only symptoms of nausea and withdrawal of bleeding. Most reports haven't linked the administration of desogestrel with the increased risk of breast cancer. The increased risk has been reported to be related to the duration of use. However, several reports indicate a desogestrel-driven increased risk in cervical intra-epithelial neoplasia but the results are still not conclusive. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Apri 28 Day, Azurette 28 Day, Bekyree 28 Day, Caziant 28 Day, Cesia 28 Day, Cyred 28 Day, Emoquette, Enskyce 28 Day, Freya, Isibloom 28 Day, Juleber 28 Day, Kalliga, Kariva 28 Day, Linessa, Marvelon, Mircette 28 Day, Pimtrea Pack, Reclipsen, Simliya, Velivet 28 Day, Viorele 28 Day, Volnea 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Desogestrel Désogestrel Desogestrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Desogestrel is a synthetic progestin used in contraception, often in combination with ethinyl estradiol.

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 Desogestrel interact? Information: •Drug A: Abciximab •Drug B: Desogestrel •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Desogestrel 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): Oral desogestrel is used in combination with ethinylestradiol as a contraceptive agent for the prevention of pregnancy. Desogestrel is part of the combined oral contraceptives that contain a mix of estrogen and progestin which inhibit ovulation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 effects of desogestrel are divided on reproductive including modification of luteinizing hormone and follicle stimulating hormone, declines on the onset of menstruation, and increases the viscosity of the vaginal fluid; and on metabolic that includes increase insulin secretion and resistance, increased lipase activity, and increased fat deposition. The effect of desogestrel on the lipids has been studied extensively and the results are contradictory. Desogestrel main therapeutic effect due to its mechanism of action is known to be related to the inhibition of the ovulation in 97% of the cycles. This effect was proven in clinical trials in non-breastfeeding women from which the Pearl failure rate was reported to be of 0.17 per 100 women-years. This result indicated that desogestrel is more efficient when compared to other progestogen-only pills. All the therapeutic effect is produced by a transformation of the endometrium followed by an inhibition of the ovulation due to the suppression of other hormones. Desogestrel has been widely confirmed to be related to an increase in the risk of venous thromboembolism due to the driven increased in blood coagulation factors, leading to a pronounced prothrombotic state. However, the effects of desogestrel are known to not impact significantly the level of total cholesterol remaining in the range of change of 10% which allows it to be a molecule that presents a favorable lipid profile. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Desogestrel enters the cell passively and acts by binding selectively to the progesterone receptor and generating low androgenic activity. Its binding produces an effect like a transcription factor and thus, it produces modifications in the mRNA synthesis. The active metabolite of desogestrel, etonogestrel, presents a combination of high progestational activity with minimal intrinsic androgenicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration, desogestrel is rapidly absorbed and it reaches a peak concentration of 2 ng/ml after 1.5 hours. The bioavailability of desogestrel is reported to be in the range of 60-80% and the reported AUC is of 3000 ng.h/ml. Almost all the administered dose is modified to the active metabolite, etonogestrel. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of desogestrel is of 1.5 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The main metabolite of desogestrel is mainly found bound to albumin and sex-hormone binding globulin. Around 96-98% of the administered dose of desogestrel is found bound to plasma proteins from which 40-70% is found bound to sex-hormone binding globulin. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Desogestrel is rapidly metabolized in the intestinal mucosa and by first-pass hepatic metabolism to form the major metabolite of desogestrel is etonogestrel which is the biologically active metabolite. This modification is described by the hydroxylation in C3 of the desogestrel molecule. Later, etonogestrel is metabolized following the normal pathways of steroid metabolism. On the other hand, due to the 11-methylene side chain, desogestrel cannot be metabolized to other progestins. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of desogestrel is found to be mainly renal corresponding to about 6 times the dose eliminated in the bile. The elimination of desogestrel is only done as the metabolites and not as the unchanged drug and about 85% of the administered dose can be excreted as metabolites after 6-8 days. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 desogestrel is determined to be of 30 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The metabolic clearance rate of desogestrel is reported to be of about 2 ml/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Administration of large quantities of desogestrel has been shown to produce strong hormonal effects but to lack chronic toxicity. The reported LD50 in rats after oral administration of desogestrel is higher than 2000 mg/kg. Overdose hasn't reported serious effects but only symptoms of nausea and withdrawal of bleeding. Most reports haven't linked the administration of desogestrel with the increased risk of breast cancer. The increased risk has been reported to be related to the duration of use. However, several reports indicate a desogestrel-driven increased risk in cervical intra-epithelial neoplasia but the results are still not conclusive. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Apri 28 Day, Azurette 28 Day, Bekyree 28 Day, Caziant 28 Day, Cesia 28 Day, Cyred 28 Day, Emoquette, Enskyce 28 Day, Freya, Isibloom 28 Day, Juleber 28 Day, Kalliga, Kariva 28 Day, Linessa, Marvelon, Mircette 28 Day, Pimtrea Pack, Reclipsen, Simliya, Velivet 28 Day, Viorele 28 Day, Volnea 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Desogestrel Désogestrel Desogestrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Desogestrel is a synthetic progestin used in contraception, often in combination with ethinyl estradiol. 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 Desvenlafaxine interact?

•Drug A: Abciximab •Drug B: Desvenlafaxine •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Desvenlafaxine is combined with Abciximab. •Extended Description: Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since desvenlafaxine is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. This results in frequently observed abnormalities in hemostasis associated with antidepressants used. Combining desvenlafaxine with another antiplatelet agent can therefore 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): Desvenlafaxine is indicated for the treatment of major depressive disorder in adults. It has also been used off-label to treat hot flashes in menopausal women. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H 1 -histaminergic, or α 1 -adrenergic receptors in vitro, or inhibitory activity against monoamine oxidase. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity against the cardiac potassium channel, hERG, in vitro. Electrocardiograms were obtained from 1,492 desvenlafaxine treated patients with major depressive disorder and 984 placebo-treated patients in clinical studies lasting up to 8 weeks. No clinically relevant differences were observed between desvenlafaxine treated and placebo-treated patients for QT, QTc, PR, and QRS intervals. In a thorough QTc study with prospectively determined criteria, desvenlafaxine did not cause QT prolongation. No difference was observed between placebo and desvenlafaxine treatments for the QRS interval. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The exact mechanism of the antidepressant action of desvenlafaxine is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Particularly, desvenlafaxine has been found to inhibit the serotonin, norepinephrine, and dopamine transporters with varying degrees of affinity. Desvenlafaxine inhibits serotonin transporters with 10 times the affinity of norepinephrine transporters, and dopamine transporters with the lowest affinity. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute oral bioavailability of desvenlafaxine after oral administration is about 80%. The time to reach maximal concentration (T max ) is estimated to be 7.5 hours after oral administration. The AUC in a 24 h dosing interval at steady state with a 100 mg dose was also calculated to be 6747 ng*h/mL, and the C max 376 ng/mL. Ingestion of a high-fat meal (800 to 1000 calories) increased desvenlafaxine C max about 16% and had no effect on AUC. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution of desvenlafaxine is 3.4 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The plasma protein binding of desvenlafaxine is 30% and is independent of drug concentration. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Desvenlafaxine is primarily metabolized by conjugation (mediated by UGT isoforms) and, to a minor extent, through oxidative metabolism. O-glucuronide conjugation is likely be catalyzed by UGT1A1, UGT1A3, UGT2B4, UGT2B15, and UGT2B17. CYP3A4 and potentially CYP2C19 mediates the oxidative metabolism (N-demethylation) of desvenlafaxine to N,O-didesmethyl venlafaxine. The CYP2D6 metabolic pathway is not involved. The pharmacokinetics of desvenlafaxine was similar in subjects with CYP2D6 poor and extensive metabolizer phenotype. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Desvenlafaxine is mainly excreted in the urine. Approximately 45% of desvenlafaxine is excreted unchanged in urine at 72 hours after oral administration. Approximately 19% of the administered dose is excreted as the glucuronide metabolite and <5% as the oxidative metabolite (N,O-didesmethyl venlafaxine) in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean terminal half-life is 11.1 hours and may be prolonged in patients with renal and/or moderate to severe hepatic impairment. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following the administration of 100 mg of desvenlafaxine in healthy subjects from 18 to 45 years of age, the renal clearance was calculated to be 222 ± 82 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Published epidemiological studies of pregnant women exposed to the parent compound venlafaxine have not reported a clear association with major birth defects or miscarriage. Methodological limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders, and confirmatory studies; therefore, these studies cannot establish or exclude any drug-associated risk during pregnancy. Retrospective cohort studies based on claims data have shown an association between venlafaxine use and preeclampsia, compared to depressed women who did not take an antidepressant during pregnancy. One study that assessed venlafaxine exposure in the second trimester or first half of the third trimester and preeclampsia showed an increased risk compared to unexposed depressed women (adjusted (adj) RR 1.57, 95% CI 1.29 to 1.91). Preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg/day and a duration of treatment >30 days. Another study that assessed venlafaxine exposure in gestational weeks 10 to 20 and preeclampsia showed an increased risk at doses equal to or greater than 150 mg/day. Available data are limited by possible outcome misclassification and possible confounding due to depression severity and other confounders. Retrospective cohort studies based on claims data have suggested an association between venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. One study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred through delivery, compared to unexposed depressed women (adj RR 2.24, 95% CI 1.69 to 2.97). There was no increased risk in women who were exposed to venlafaxine earlier in pregnancy. Limitations of this study include possible confounding due to depression severity and other confounders. Another study showed an increased risk for postpartum hemorrhage when SNRI exposure occurred for at least 15 days in the last month of pregnancy or through delivery, compared to unexposed women (adj RR 1.64 to 1.76). The results of this study may be confounded by the effects of depression. Neonates exposed to SNRIs or SSRIs, 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 SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. Antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patient. Of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients; however, in the short-term placebo-controlled studies, there was a higher incidence of systolic orthostatic hypotension in patients ≥65 years of age compared to patients <65 years of age treated with desvenlafaxine. For elderly patients, possible reduced renal clearance of desvenlafaxine should be considered when determining dose. SSRIs and SNRIs, including desvenlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. There is limited clinical trial experience with desvenlafaxine succinate overdosage in humans. However, desvenlafaxine is the major active metabolite of venlafaxine. Overdose experience reported with venlafaxine (the parent drug of desvenlafaxine) is presented below; the identical information can be found in the Overdosage section of the venlafaxine package insert. In post-marketing experience, overdose with venlafaxine (the parent drug of desvenlafaxine) has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), sinus and ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported. Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher pre-existing burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristic(s) of venlafaxine-treated patients, is not clear. No specific antidotes for desvenlafaxine are known. In managing over dosage, consider the possibility of multiple drug involvement. In case of overdose, call Poison Control Center at 1-800-222-1222 for latest recommendations. Desvenlafaxine succinate administered by oral gavage to mice and rats for 2 years did not increase the incidence of tumors in either study. Mice received desvenlafaxine succinate at dosages up to 500/300 mg/kg/day (dosage lowered after 45 weeks of dosing). The AUC exposure at 300 mg/kg/day dose is estimated at 10 times the AUC exposure at an adult human dose of 100 mg per day. Rats received desvenlafaxine succinate at dosages up to 300 mg/kg/day (males) or 500 mg/kg/day (females). The AUC exposure at the highest dose is estimated at 11 (males) or 26 (females) times the AUC exposure at an adult human dose of 100 mg per day. Desvenlafaxine was not mutagenic in the in vitro bacterial mutation assay (Ames test) and was not clastogenic in an in vitro chromosome aberration assay in cultured CHO cells, an in vivo mouse micronucleus assay, or an in vivo chromosome aberration assay in rats. Additionally, desvenlafaxine was not genotoxic in the in vitro CHO mammalian cell forward mutation assay and was negative in the in vitro BALB/c-3T3 mouse embryo cell transformation assay. When desvenlafaxine succinate was administered orally to male and female rats, fertility was reduced at the high dose of 300 mg/kg/day, which is 10 (males) and 19 (females) times the AUC exposure at an adult human dose of 100 mg per day. There was no effect on fertility at 100 mg/kg/day, which is 3 (males) or 5 (females) times the AUC exposure at an adult human dose of 100 mg per day. These studies did not address reversibility of the effect on fertility. The relevance of these findings to humans is not known. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pristiq •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Desvenlafaxina Desvenlafaxine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Desvenlafaxine is an antidepressant agent and SNRI used for the treatment of major depressive disorders in adults.

Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since desvenlafaxine is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. This results in frequently observed abnormalities in hemostasis associated with antidepressants used. Combining desvenlafaxine with another antiplatelet agent can therefore increase the risk of bleeding. The severity of the interaction is moderate.

Question: Does Abciximab and Desvenlafaxine interact? Information: •Drug A: Abciximab •Drug B: Desvenlafaxine •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Desvenlafaxine is combined with Abciximab. •Extended Description: Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since desvenlafaxine is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. This results in frequently observed abnormalities in hemostasis associated with antidepressants used. Combining desvenlafaxine with another antiplatelet agent can therefore 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): Desvenlafaxine is indicated for the treatment of major depressive disorder in adults. It has also been used off-label to treat hot flashes in menopausal women. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H 1 -histaminergic, or α 1 -adrenergic receptors in vitro, or inhibitory activity against monoamine oxidase. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity against the cardiac potassium channel, hERG, in vitro. Electrocardiograms were obtained from 1,492 desvenlafaxine treated patients with major depressive disorder and 984 placebo-treated patients in clinical studies lasting up to 8 weeks. No clinically relevant differences were observed between desvenlafaxine treated and placebo-treated patients for QT, QTc, PR, and QRS intervals. In a thorough QTc study with prospectively determined criteria, desvenlafaxine did not cause QT prolongation. No difference was observed between placebo and desvenlafaxine treatments for the QRS interval. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The exact mechanism of the antidepressant action of desvenlafaxine is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Particularly, desvenlafaxine has been found to inhibit the serotonin, norepinephrine, and dopamine transporters with varying degrees of affinity. Desvenlafaxine inhibits serotonin transporters with 10 times the affinity of norepinephrine transporters, and dopamine transporters with the lowest affinity. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute oral bioavailability of desvenlafaxine after oral administration is about 80%. The time to reach maximal concentration (T max ) is estimated to be 7.5 hours after oral administration. The AUC in a 24 h dosing interval at steady state with a 100 mg dose was also calculated to be 6747 ng*h/mL, and the C max 376 ng/mL. Ingestion of a high-fat meal (800 to 1000 calories) increased desvenlafaxine C max about 16% and had no effect on AUC. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state volume of distribution of desvenlafaxine is 3.4 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The plasma protein binding of desvenlafaxine is 30% and is independent of drug concentration. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Desvenlafaxine is primarily metabolized by conjugation (mediated by UGT isoforms) and, to a minor extent, through oxidative metabolism. O-glucuronide conjugation is likely be catalyzed by UGT1A1, UGT1A3, UGT2B4, UGT2B15, and UGT2B17. CYP3A4 and potentially CYP2C19 mediates the oxidative metabolism (N-demethylation) of desvenlafaxine to N,O-didesmethyl venlafaxine. The CYP2D6 metabolic pathway is not involved. The pharmacokinetics of desvenlafaxine was similar in subjects with CYP2D6 poor and extensive metabolizer phenotype. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Desvenlafaxine is mainly excreted in the urine. Approximately 45% of desvenlafaxine is excreted unchanged in urine at 72 hours after oral administration. Approximately 19% of the administered dose is excreted as the glucuronide metabolite and <5% as the oxidative metabolite (N,O-didesmethyl venlafaxine) in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The mean terminal half-life is 11.1 hours and may be prolonged in patients with renal and/or moderate to severe hepatic impairment. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following the administration of 100 mg of desvenlafaxine in healthy subjects from 18 to 45 years of age, the renal clearance was calculated to be 222 ± 82 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Published epidemiological studies of pregnant women exposed to the parent compound venlafaxine have not reported a clear association with major birth defects or miscarriage. Methodological limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders, and confirmatory studies; therefore, these studies cannot establish or exclude any drug-associated risk during pregnancy. Retrospective cohort studies based on claims data have shown an association between venlafaxine use and preeclampsia, compared to depressed women who did not take an antidepressant during pregnancy. One study that assessed venlafaxine exposure in the second trimester or first half of the third trimester and preeclampsia showed an increased risk compared to unexposed depressed women (adjusted (adj) RR 1.57, 95% CI 1.29 to 1.91). Preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg/day and a duration of treatment >30 days. Another study that assessed venlafaxine exposure in gestational weeks 10 to 20 and preeclampsia showed an increased risk at doses equal to or greater than 150 mg/day. Available data are limited by possible outcome misclassification and possible confounding due to depression severity and other confounders. Retrospective cohort studies based on claims data have suggested an association between venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. One study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred through delivery, compared to unexposed depressed women (adj RR 2.24, 95% CI 1.69 to 2.97). There was no increased risk in women who were exposed to venlafaxine earlier in pregnancy. Limitations of this study include possible confounding due to depression severity and other confounders. Another study showed an increased risk for postpartum hemorrhage when SNRI exposure occurred for at least 15 days in the last month of pregnancy or through delivery, compared to unexposed women (adj RR 1.64 to 1.76). The results of this study may be confounded by the effects of depression. Neonates exposed to SNRIs or SSRIs, 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 SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. Antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patient. Of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients; however, in the short-term placebo-controlled studies, there was a higher incidence of systolic orthostatic hypotension in patients ≥65 years of age compared to patients <65 years of age treated with desvenlafaxine. For elderly patients, possible reduced renal clearance of desvenlafaxine should be considered when determining dose. SSRIs and SNRIs, including desvenlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. There is limited clinical trial experience with desvenlafaxine succinate overdosage in humans. However, desvenlafaxine is the major active metabolite of venlafaxine. Overdose experience reported with venlafaxine (the parent drug of desvenlafaxine) is presented below; the identical information can be found in the Overdosage section of the venlafaxine package insert. In post-marketing experience, overdose with venlafaxine (the parent drug of desvenlafaxine) has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), sinus and ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported. Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher pre-existing burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristic(s) of venlafaxine-treated patients, is not clear. No specific antidotes for desvenlafaxine are known. In managing over dosage, consider the possibility of multiple drug involvement. In case of overdose, call Poison Control Center at 1-800-222-1222 for latest recommendations. Desvenlafaxine succinate administered by oral gavage to mice and rats for 2 years did not increase the incidence of tumors in either study. Mice received desvenlafaxine succinate at dosages up to 500/300 mg/kg/day (dosage lowered after 45 weeks of dosing). The AUC exposure at 300 mg/kg/day dose is estimated at 10 times the AUC exposure at an adult human dose of 100 mg per day. Rats received desvenlafaxine succinate at dosages up to 300 mg/kg/day (males) or 500 mg/kg/day (females). The AUC exposure at the highest dose is estimated at 11 (males) or 26 (females) times the AUC exposure at an adult human dose of 100 mg per day. Desvenlafaxine was not mutagenic in the in vitro bacterial mutation assay (Ames test) and was not clastogenic in an in vitro chromosome aberration assay in cultured CHO cells, an in vivo mouse micronucleus assay, or an in vivo chromosome aberration assay in rats. Additionally, desvenlafaxine was not genotoxic in the in vitro CHO mammalian cell forward mutation assay and was negative in the in vitro BALB/c-3T3 mouse embryo cell transformation assay. When desvenlafaxine succinate was administered orally to male and female rats, fertility was reduced at the high dose of 300 mg/kg/day, which is 10 (males) and 19 (females) times the AUC exposure at an adult human dose of 100 mg per day. There was no effect on fertility at 100 mg/kg/day, which is 3 (males) or 5 (females) times the AUC exposure at an adult human dose of 100 mg per day. These studies did not address reversibility of the effect on fertility. The relevance of these findings to humans is not known. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Pristiq •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Desvenlafaxina Desvenlafaxine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Desvenlafaxine is an antidepressant agent and SNRI used for the treatment of major depressive disorders in adults. Output: Serotonin is stored within platelets and is released to aggregate platelets during hemostasis for thrombus formation.1,2 Since desvenlafaxine is a serotonin reuptake inhibitor, it could decrease the intraplatelet level of serotonin, thus reducing the serotonin-induced amplification of platelet aggregation. This results in frequently observed abnormalities in hemostasis associated with antidepressants used. Combining desvenlafaxine with another antiplatelet agent can therefore increase the risk of bleeding. The severity of the interaction is moderate.

Does Abciximab and Dexibuprofen interact?

•Drug A: Abciximab •Drug B: Dexibuprofen •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Dexibuprofen is combined with Abciximab. •Extended Description: Concomitant use of antiplatelet and non-steroidal anti-inflammatory agents (NSAIDs) is associated with increased risk of gastrointestinal 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 more information, refer to ibuprofen. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): For more information, refer to ibuprofen. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Like common NSAIDs, dexibuprofen is an active enantiomer of ibuprofen that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. For more information, refer to ibuprofen. •Absorption (Drug A): No absorption available •Absorption (Drug B): The time it take to reach peak plasma concentration is 2.25-5 hours post-administration of oral tablets containing 300mg of dexibuprofen. For more information, refer to ibuprofen. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): For more information, refer to ibuprofen. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): For more information, refer to ibuprofen. •Metabolism (Drug A): 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 more information, refer to ibuprofen. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mainly renal excretion. For more information, refer to ibuprofen. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Oral tablets containing 300mg of dexibuprofen results in 2.2-4.7 hours. For more information, refer to ibuprofen. •Clearance (Drug A): No clearance available •Clearance (Drug B): For more information, refer to ibuprofen. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD50 value in rats is 636 mg/kg. For more information, refer to ibuprofen. •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): d-ibuproten Dexibuprofen Dexibuprofeno •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dexibuprofen is a pharmacologically active enantiomer of racemic ibuprofen (NSAID) used to treat pain and inflammation.

Concomitant use of antiplatelet and non-steroidal anti-inflammatory agents (NSAIDs) is associated with increased risk of gastrointestinal bleeding. The severity of the interaction is moderate.

Question: Does Abciximab and Dexibuprofen interact? Information: •Drug A: Abciximab •Drug B: Dexibuprofen •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Dexibuprofen is combined with Abciximab. •Extended Description: Concomitant use of antiplatelet and non-steroidal anti-inflammatory agents (NSAIDs) is associated with increased risk of gastrointestinal 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 more information, refer to ibuprofen. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): For more information, refer to ibuprofen. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Like common NSAIDs, dexibuprofen is an active enantiomer of ibuprofen that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. For more information, refer to ibuprofen. •Absorption (Drug A): No absorption available •Absorption (Drug B): The time it take to reach peak plasma concentration is 2.25-5 hours post-administration of oral tablets containing 300mg of dexibuprofen. For more information, refer to ibuprofen. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): For more information, refer to ibuprofen. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): For more information, refer to ibuprofen. •Metabolism (Drug A): 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 more information, refer to ibuprofen. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mainly renal excretion. For more information, refer to ibuprofen. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Oral tablets containing 300mg of dexibuprofen results in 2.2-4.7 hours. For more information, refer to ibuprofen. •Clearance (Drug A): No clearance available •Clearance (Drug B): For more information, refer to ibuprofen. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD50 value in rats is 636 mg/kg. For more information, refer to ibuprofen. •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): d-ibuproten Dexibuprofen Dexibuprofeno •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dexibuprofen is a pharmacologically active enantiomer of racemic ibuprofen (NSAID) used to treat pain and inflammation. Output: Concomitant use of antiplatelet and non-steroidal anti-inflammatory agents (NSAIDs) is associated with increased risk of gastrointestinal bleeding. The severity of the interaction is moderate.

Does Abciximab and Dexketoprofen interact?

•Drug A: Abciximab •Drug B: Dexketoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Dexketoprofen 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 short-term treatment of mild to moderate pain, including dysmenorrhoea, musculoskeletal pain and toothache. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): It is a non-steroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis via inhibition of cyclooxygenase pathway (both COX-1 and COX-2) activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral ingestion, the Dexketoprofen onset of action is within 30 minutes. The plasma half-life of Dexketoprofen is about 4-6 hours. The Cmax is about 30 minutes •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): <0.25 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Highly 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): Dexketoprofen is highly lipophilic, and is metabolized in the liver by glucuronidation. In one study, after oral administration of 25 mg of dexketoprofen to young healthy adults, Tmax was approximately 30 min for a Cmax of 3.7 ± 0.72 mg/l. Dexketoprofen trometamol is metabolized by the hepatic cytochrome P450 enzymes (CYP2C8 and CYP2C9). Dexketoprofen trometamol has a number of metabolites, with hydroxyl derivatives making up the greatest volume. In humans, hydroxylation plays a minor role. Dexketoprofen is primarily conjugated to an acyl-glucuronide •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 70 to 80% of the ingested dose is recovered in the urine during the first 12 hours post-ingestion, mainly as the acyl-conjugated form of the drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.65 h •Clearance (Drug A): No clearance available •Clearance (Drug B): Mainly cleared via glucuronide conjugation and followed by renal excretion, mainly unchanged. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Nausea and/or vomiting, stomach pain, diarrhea, digestive problems (dyspepsia) are the most common symptoms of toxicity. More toxicity symptoms include dizziness, sleepiness, disturbed sleep, nervousness, headache, palpitations, flushing, stomach problems, constipation, dry mouth, flatulence, skin rash, tiredness, pain, feeling feverish and shivering, and malaise. Severe toxicity can lead to thrombocytopenia and anemia with bleeding episodes. Dexketoprofen is associated with a small increased risk of myocardial infarction. •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): Dexketoprofen is an NSAID that is the R(-)-enantiomer of racemic ketoprofen with analgesic and anti-inflammatory properties used for the treatment of 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 Dexketoprofen interact? Information: •Drug A: Abciximab •Drug B: Dexketoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Dexketoprofen 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 short-term treatment of mild to moderate pain, including dysmenorrhoea, musculoskeletal pain and toothache. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): It is a non-steroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis via inhibition of cyclooxygenase pathway (both COX-1 and COX-2) activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral ingestion, the Dexketoprofen onset of action is within 30 minutes. The plasma half-life of Dexketoprofen is about 4-6 hours. The Cmax is about 30 minutes •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): <0.25 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Highly 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): Dexketoprofen is highly lipophilic, and is metabolized in the liver by glucuronidation. In one study, after oral administration of 25 mg of dexketoprofen to young healthy adults, Tmax was approximately 30 min for a Cmax of 3.7 ± 0.72 mg/l. Dexketoprofen trometamol is metabolized by the hepatic cytochrome P450 enzymes (CYP2C8 and CYP2C9). Dexketoprofen trometamol has a number of metabolites, with hydroxyl derivatives making up the greatest volume. In humans, hydroxylation plays a minor role. Dexketoprofen is primarily conjugated to an acyl-glucuronide •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 70 to 80% of the ingested dose is recovered in the urine during the first 12 hours post-ingestion, mainly as the acyl-conjugated form of the drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 1.65 h •Clearance (Drug A): No clearance available •Clearance (Drug B): Mainly cleared via glucuronide conjugation and followed by renal excretion, mainly unchanged. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Nausea and/or vomiting, stomach pain, diarrhea, digestive problems (dyspepsia) are the most common symptoms of toxicity. More toxicity symptoms include dizziness, sleepiness, disturbed sleep, nervousness, headache, palpitations, flushing, stomach problems, constipation, dry mouth, flatulence, skin rash, tiredness, pain, feeling feverish and shivering, and malaise. Severe toxicity can lead to thrombocytopenia and anemia with bleeding episodes. Dexketoprofen is associated with a small increased risk of myocardial infarction. •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): Dexketoprofen is an NSAID that is the R(-)-enantiomer of racemic ketoprofen with analgesic and anti-inflammatory properties used for the treatment of 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 Dexrazoxane interact?

•Drug A: Abciximab •Drug B: Dexrazoxane •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dexrazoxane. •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 reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II. •Absorption (Drug A): No absorption available •Absorption (Drug B): IV administration results in complete bioavailability. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 9 to 22.6 L/m^2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Very low (< 2%) •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Dexrazoxane is hydrolysed by the enzyme dihydropyrimidine amidohydrolase in the liver and kidney to active metabolites that are capable of binding to metal ions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2.5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Dexrazoxane] 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Dexrazoxane] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Intraperitoneal, mouse LD 10 = 500 mg/kg. Intravenous, dog LD 10 = 2 gm/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cardioxane, Savene, Totect, Zinecard •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Dexrazoxan Dexrazoxane Dexrazoxano Dexrazoxanum Dextrorazoxane •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dexrazoxane is a cytoprotective drug used to prevent and improve cardiomyopathy associated with doxorubicin treatment for 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 Dexrazoxane interact? Information: •Drug A: Abciximab •Drug B: Dexrazoxane •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dexrazoxane. •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 reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II. •Absorption (Drug A): No absorption available •Absorption (Drug B): IV administration results in complete bioavailability. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 9 to 22.6 L/m^2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Very low (< 2%) •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Dexrazoxane is hydrolysed by the enzyme dihydropyrimidine amidohydrolase in the liver and kidney to active metabolites that are capable of binding to metal ions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2.5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Dexrazoxane] 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Dexrazoxane] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Intraperitoneal, mouse LD 10 = 500 mg/kg. Intravenous, dog LD 10 = 2 gm/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cardioxane, Savene, Totect, Zinecard •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Dexrazoxan Dexrazoxane Dexrazoxano Dexrazoxanum Dextrorazoxane •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dexrazoxane is a cytoprotective drug used to prevent and improve cardiomyopathy associated with doxorubicin treatment for 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 Dextran interact?

•Drug A: Abciximab •Drug B: Dextran •Severity: MAJOR •Description: Dextran may increase the anticoagulant activities of Abciximab. •Extended Description: During the EPIC trial, in the 11 patients who received intravenous low molecular weight dextran with abciximab, five had major bleeding events and four had minor bleeding events . None of the five placebo patients treated with low molecular weight dextran and no abciximab had a major or minor bleeding event . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Dextran is used as the restoration of blood mass during surgical interventions if there is hypovolemia due to trauma or dehydration. It is as well used after the presence of hemorrhage in cases of blood loss to a level inferior to 15% of the blood mass, if compatibility test cannot be completed or when blood lots need to be tested for pathogen detection. Dextran is also used for the prevention of profound postoperative venous thrombosis. Dextran as well presents ophthalmic applications as solutions or ointments for the temporary relief of xerophthalmia or minor ocular irritations. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 is reported that dextran presents an effect on the hemostatic system in particular by prolonging bleeding time. In the same trials, dextran is reported to reduce emboli, reduce platelet adhesiveness and produce hemodilution. These effects have been showed to be greater proportionally with the increase in the molecular weight of the dextran. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 preclinical studies, the mechanism of action is thought to be related to the blockage of the uptake of tissue plasminogen activator by mannose-binding receptors. This process has a direct effect by enhancing endogenous fibrinolysis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dextran presents a very low oral bioavailability that is reduced as the chain gets longer. Thus, the bioavailability of dextran is inversely proportional to the length of the carbohydrate chain. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The reported volume of distribution of dextran suggested a distribution throughout the blood volume. This volume of distribution is reported to be of around 120 ml. The organ that presented a higher accumulation of dextran was the liver. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Dextran is highly retained in the vascular system by binding to plasma proteins including 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): Long chains of dextran such as dextran 60 are highly metabolized in the liver until formation of lower molecular weight products before being excreted from the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of dextran will depend on the length of the carbohydrate chain, the administration route, and the molecular weight. For dextran 1, it is reported to be mainly secreted unchanged in the urine in a ratio of 80% of the administered dose when administered parentally. It is registered that the weight threshold for unrestricted glomerular filtration is about 15 kDa and if the dextran overpasses 50 kDa it will not be renally eliminated in any significant amount. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 will depend on the length of the carbohydrate chain. The higher the molecular weight of the dextran the longer it will be the elimination half-life. The half-life will go from 1.9 hours from dextran 1 to 42 hours in the case of dextran 60. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Some reports have shown adverse effects when used in therapeutical doses and some teratogenic effects have been demonstrated when used in large doses. The current LD50 reported in rats is 10700 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bion Tears, Colirio Ocusan, Genteal Tears, Genteal Tears Mild, Tears Naturale, Tears Renewed •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): Dextran is a low molecular weight dextran used as an adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma, as well as the prophylaxis of venous thrombosis and pulmonary embolism during high-risk medical procedures.

During the EPIC trial, in the 11 patients who received intravenous low molecular weight dextran with abciximab, five had major bleeding events and four had minor bleeding events . None of the five placebo patients treated with low molecular weight dextran and no abciximab had a major or minor bleeding event . The severity of the interaction is major.

Question: Does Abciximab and Dextran interact? Information: •Drug A: Abciximab •Drug B: Dextran •Severity: MAJOR •Description: Dextran may increase the anticoagulant activities of Abciximab. •Extended Description: During the EPIC trial, in the 11 patients who received intravenous low molecular weight dextran with abciximab, five had major bleeding events and four had minor bleeding events . None of the five placebo patients treated with low molecular weight dextran and no abciximab had a major or minor bleeding event . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Dextran is used as the restoration of blood mass during surgical interventions if there is hypovolemia due to trauma or dehydration. It is as well used after the presence of hemorrhage in cases of blood loss to a level inferior to 15% of the blood mass, if compatibility test cannot be completed or when blood lots need to be tested for pathogen detection. Dextran is also used for the prevention of profound postoperative venous thrombosis. Dextran as well presents ophthalmic applications as solutions or ointments for the temporary relief of xerophthalmia or minor ocular irritations. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 is reported that dextran presents an effect on the hemostatic system in particular by prolonging bleeding time. In the same trials, dextran is reported to reduce emboli, reduce platelet adhesiveness and produce hemodilution. These effects have been showed to be greater proportionally with the increase in the molecular weight of the dextran. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 preclinical studies, the mechanism of action is thought to be related to the blockage of the uptake of tissue plasminogen activator by mannose-binding receptors. This process has a direct effect by enhancing endogenous fibrinolysis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dextran presents a very low oral bioavailability that is reduced as the chain gets longer. Thus, the bioavailability of dextran is inversely proportional to the length of the carbohydrate chain. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The reported volume of distribution of dextran suggested a distribution throughout the blood volume. This volume of distribution is reported to be of around 120 ml. The organ that presented a higher accumulation of dextran was the liver. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Dextran is highly retained in the vascular system by binding to plasma proteins including 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): Long chains of dextran such as dextran 60 are highly metabolized in the liver until formation of lower molecular weight products before being excreted from the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of dextran will depend on the length of the carbohydrate chain, the administration route, and the molecular weight. For dextran 1, it is reported to be mainly secreted unchanged in the urine in a ratio of 80% of the administered dose when administered parentally. It is registered that the weight threshold for unrestricted glomerular filtration is about 15 kDa and if the dextran overpasses 50 kDa it will not be renally eliminated in any significant amount. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 will depend on the length of the carbohydrate chain. The higher the molecular weight of the dextran the longer it will be the elimination half-life. The half-life will go from 1.9 hours from dextran 1 to 42 hours in the case of dextran 60. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Some reports have shown adverse effects when used in therapeutical doses and some teratogenic effects have been demonstrated when used in large doses. The current LD50 reported in rats is 10700 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Bion Tears, Colirio Ocusan, Genteal Tears, Genteal Tears Mild, Tears Naturale, Tears Renewed •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): Dextran is a low molecular weight dextran used as an adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma, as well as the prophylaxis of venous thrombosis and pulmonary embolism during high-risk medical procedures. Output: During the EPIC trial, in the 11 patients who received intravenous low molecular weight dextran with abciximab, five had major bleeding events and four had minor bleeding events . None of the five placebo patients treated with low molecular weight dextran and no abciximab had a major or minor bleeding event . The severity of the interaction is major.

Does Abciximab and Diclofenac interact?

•Drug A: Abciximab •Drug B: Diclofenac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Diclofenac 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): Diclofenac is indicated for use in the treatment of pain and inflammation from varying sources including inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, as well as injury-related inflammation due to surgery and physical trauma. It is often used in combination with misoprostol as a gastro-protective agent in patients with high risk of developing NSAID-induced ulcers. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever. It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G 2 which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac. 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. •Absorption (Drug A): No absorption available •Absorption (Drug B): Diclofenac is completely absorbed from the GI tract but likely undergoes significant first pass metabolism with only 60% of the drug reaching systemic circulation unchanged. Many topical formulations are absorbed percutaneous and produce clinically significant plasma concentrations. Absorption is dose proportional over the range of 25-150 mg. Tmax varies between formulations with the oral solution reaching peak plasma concentrations in 10-40min, the enteric coated tablet in 1.5-2h, and the sustained- and extended-release formulations prolonging Tmax even further. Administration with food has no significant effects on AUC but does delay Tmax to 2.5-12h. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Diclofenac has a total volume of distribution of 5-10 L or 0.1-0.2 L/kg. The volume of the central compartment is 0.04 L/kg. Diclofenac distributes to the synovial fluid reaching peak concentration 2-4h after administration. There is limited crossing of the blood brain barrier and cerebrospinal fluid concentrations only reach 8.22% of plasma concentrations. Doses of 50 mg delivered via intramuscular injection produced no detectable diclofenac concentrations in breast milk, however metabolite concentrations were not investigated. Diclofenac has been shown to cross the placenta in mice and rats but human data is unavailable. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Diclofenac is over 99.7% bound to serum proteins, primarily albumin. It is undergoes limited binding to lipoproteins as well with 1.1% bound to HDL, 0.3% to LDL, and 0.15% to VLDL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Diclofenac undergoes oxidative metabolism to hydroxy metabolites as well as conjugation to glucuronic acid, sulfate, and taurine. The primary metabolite is 4'-hydroxy diclofenac which is generated by CYP2C9. This metabolite is very weakly active with one thirtieth the activity of diclofenac. Other metabolites include 3'-hydroxy diclofenac, 3'-hydroxy-4'methoxy diclofenac, 4',5-dihydroxy diclofenac, an acylglucuronide conjugate, and other conjugate metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Diclofenac is mainly eliminated via metabolism. Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces. No significant enterohepatic recycling occurs. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 diclofenac is approximately 2 h, however the apparent half-life including all metabolites is 25.8-33 h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Diclofenac has a plasma clearance 16 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain, and gastrointestinal bleeding. Hypertension, acute renal failure, respiratory depression and coma occur rarely. In case of overdose, provide supportive care and consider inducing emesis and administering activated charcoal if overdose occurred less than 4 hours prior. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aleve Arthritis Pain, Arthrotec, Cambia, Cataflam, Flector, Licart, Lofena, Pennsaid, Previdolrx Analgesic Pak, Salonpas Pain Relieving Patch, Solaraze, Voltaren, Voltaren Emulgel, Xrylix, Zipsor, Zorvolex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Diclofenac Diclofenac acid Diclofenaco Diclofenacum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Diclofenac is an NSAID used to treat the signs and 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 Diclofenac interact? Information: •Drug A: Abciximab •Drug B: Diclofenac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Diclofenac 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): Diclofenac is indicated for use in the treatment of pain and inflammation from varying sources including inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, as well as injury-related inflammation due to surgery and physical trauma. It is often used in combination with misoprostol as a gastro-protective agent in patients with high risk of developing NSAID-induced ulcers. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever. It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G 2 which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac. 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. •Absorption (Drug A): No absorption available •Absorption (Drug B): Diclofenac is completely absorbed from the GI tract but likely undergoes significant first pass metabolism with only 60% of the drug reaching systemic circulation unchanged. Many topical formulations are absorbed percutaneous and produce clinically significant plasma concentrations. Absorption is dose proportional over the range of 25-150 mg. Tmax varies between formulations with the oral solution reaching peak plasma concentrations in 10-40min, the enteric coated tablet in 1.5-2h, and the sustained- and extended-release formulations prolonging Tmax even further. Administration with food has no significant effects on AUC but does delay Tmax to 2.5-12h. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Diclofenac has a total volume of distribution of 5-10 L or 0.1-0.2 L/kg. The volume of the central compartment is 0.04 L/kg. Diclofenac distributes to the synovial fluid reaching peak concentration 2-4h after administration. There is limited crossing of the blood brain barrier and cerebrospinal fluid concentrations only reach 8.22% of plasma concentrations. Doses of 50 mg delivered via intramuscular injection produced no detectable diclofenac concentrations in breast milk, however metabolite concentrations were not investigated. Diclofenac has been shown to cross the placenta in mice and rats but human data is unavailable. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Diclofenac is over 99.7% bound to serum proteins, primarily albumin. It is undergoes limited binding to lipoproteins as well with 1.1% bound to HDL, 0.3% to LDL, and 0.15% to VLDL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Diclofenac undergoes oxidative metabolism to hydroxy metabolites as well as conjugation to glucuronic acid, sulfate, and taurine. The primary metabolite is 4'-hydroxy diclofenac which is generated by CYP2C9. This metabolite is very weakly active with one thirtieth the activity of diclofenac. Other metabolites include 3'-hydroxy diclofenac, 3'-hydroxy-4'methoxy diclofenac, 4',5-dihydroxy diclofenac, an acylglucuronide conjugate, and other conjugate metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Diclofenac is mainly eliminated via metabolism. Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces. No significant enterohepatic recycling occurs. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 diclofenac is approximately 2 h, however the apparent half-life including all metabolites is 25.8-33 h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Diclofenac has a plasma clearance 16 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain, and gastrointestinal bleeding. Hypertension, acute renal failure, respiratory depression and coma occur rarely. In case of overdose, provide supportive care and consider inducing emesis and administering activated charcoal if overdose occurred less than 4 hours prior. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aleve Arthritis Pain, Arthrotec, Cambia, Cataflam, Flector, Licart, Lofena, Pennsaid, Previdolrx Analgesic Pak, Salonpas Pain Relieving Patch, Solaraze, Voltaren, Voltaren Emulgel, Xrylix, Zipsor, Zorvolex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Diclofenac Diclofenac acid Diclofenaco Diclofenacum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Diclofenac is an NSAID used to treat the signs and 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 Dienogest interact?

•Drug A: Abciximab •Drug B: Dienogest •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Dienogest 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): Indicated for use as the treatment of endometriosis alone and as a contraceptive in combination with ethinylestradiol. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use. It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. 1mg/kg of dienogest also directly inhibits ovulation. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder. Dienogest displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα. It has no glucocorticoid or mineralocorticoid effects. In combined oral contraceptive pills (COCP) with ethinyloestradiol, dienogest conjuction therapy effectively reduces the symptoms of acne and hirsutism, as well as improving excessively heavy or prolonged menstrual bleeding. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dienogest acts as an agonist at the progesterone receptor (PR) with weak affinity that is comparable to that of progesterone but has a very potent progestagenic effect in the endometrium, causing endometrial atrophy after prolonged use. It promotes antiproliferative, immunologic and antiangiogenic effects on endometrial tissue. Dienogest reduces the level of endogenous production of oestradiol and thereby suppressing the trophic effects of oestradiol on both the eutopic and ectopic endometrium. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue. It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dienogest is rapidly absorbed following oral administration, with 91% bioavailability. The peak plasma concentration of 47 ng/mL is reached at about 1.5 hours after single ingestion of 2 mg. The stable concentrations of the drug are reached after two days of initial treatment. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution (Vd/F) of dienogest is 40 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Dienogest is 90% nonospecifically bound to albumin. It displays no binding to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG). •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Dienogest undergoes complete metabolism that is mainly mediated by CYP3A4. The metabolites are pharmacologically inactive and rapidly eliminated from the plasma. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The ratio of renal elimination to fecal elimination of dienogest is 3:1, where dienogest is predominantly excreted in the form of inactive metabolites. Most of orally administered drug is excreted in the urine within the first 24 hours of ingestion. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 of dienogest is around 9-10 hours. The half-life of urinary metabolites excretion is 14 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The metabolic clearance rate from serum (Cl/F) is 64 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD50 in mouse is 4 mg/kg. In a long-term carcinogenicity study involving rats and mice, exposure of 10 times the dose of maximum recommended clinical dose of dienogest resulted in increased incidences of pituitary adenomas, fibroepithelial mammary tumours, stromal polyps of the uterus and malignant lymphoma. These tumors are thought to arise from marked species differences in the optimal oestrogen:progestogen ratio for reproductive function. In rat liver foci assay, dienogest did not induce tumor promotion activity. Dienogest does not display genotoxic potential. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Natazia, Visanne •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Dienogest Dienogestril Dienogestum Endometrion •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dienogest is an oral progestin used for the treatment of endometriosis as monotherapy or contraception in combination with ethinylestradiol.

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 Dienogest interact? Information: •Drug A: Abciximab •Drug B: Dienogest •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Dienogest 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): Indicated for use as the treatment of endometriosis alone and as a contraceptive in combination with ethinylestradiol. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use. It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. 1mg/kg of dienogest also directly inhibits ovulation. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder. Dienogest displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα. It has no glucocorticoid or mineralocorticoid effects. In combined oral contraceptive pills (COCP) with ethinyloestradiol, dienogest conjuction therapy effectively reduces the symptoms of acne and hirsutism, as well as improving excessively heavy or prolonged menstrual bleeding. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dienogest acts as an agonist at the progesterone receptor (PR) with weak affinity that is comparable to that of progesterone but has a very potent progestagenic effect in the endometrium, causing endometrial atrophy after prolonged use. It promotes antiproliferative, immunologic and antiangiogenic effects on endometrial tissue. Dienogest reduces the level of endogenous production of oestradiol and thereby suppressing the trophic effects of oestradiol on both the eutopic and ectopic endometrium. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue. It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dienogest is rapidly absorbed following oral administration, with 91% bioavailability. The peak plasma concentration of 47 ng/mL is reached at about 1.5 hours after single ingestion of 2 mg. The stable concentrations of the drug are reached after two days of initial treatment. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution (Vd/F) of dienogest is 40 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Dienogest is 90% nonospecifically bound to albumin. It displays no binding to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG). •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Dienogest undergoes complete metabolism that is mainly mediated by CYP3A4. The metabolites are pharmacologically inactive and rapidly eliminated from the plasma. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The ratio of renal elimination to fecal elimination of dienogest is 3:1, where dienogest is predominantly excreted in the form of inactive metabolites. Most of orally administered drug is excreted in the urine within the first 24 hours of ingestion. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 of dienogest is around 9-10 hours. The half-life of urinary metabolites excretion is 14 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The metabolic clearance rate from serum (Cl/F) is 64 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD50 in mouse is 4 mg/kg. In a long-term carcinogenicity study involving rats and mice, exposure of 10 times the dose of maximum recommended clinical dose of dienogest resulted in increased incidences of pituitary adenomas, fibroepithelial mammary tumours, stromal polyps of the uterus and malignant lymphoma. These tumors are thought to arise from marked species differences in the optimal oestrogen:progestogen ratio for reproductive function. In rat liver foci assay, dienogest did not induce tumor promotion activity. Dienogest does not display genotoxic potential. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Natazia, Visanne •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Dienogest Dienogestril Dienogestum Endometrion •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dienogest is an oral progestin used for the treatment of endometriosis as monotherapy or contraception in combination with ethinylestradiol. 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 Diflunisal interact?

•Drug A: Abciximab •Drug B: Diflunisal •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Diflunisal 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 symptomatic treatment of mild to moderate pain accompanied by inflammation (e.g. musculoskeletal trauma, post-dental extraction, post-episiotomy), 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): Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%. Peak plasma concentrations are achieved 2 - 3 hours 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): At least 98 to 99% of diflunisal in plasma is bound to 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, primarily via glucuronide conjugation (90% of administered dose). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The drug is excreted in the urine as two soluble glucuronide conjugates accounting for about 90% of the administered dose. Little or no diflunisal 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): 8 to 12 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD 50 in rat, mouse, and rabbit is 392 mg/kg, 439 mg/kg, and 603 mg/kg, respectively. Symptoms of overdose include drowsiness, nausea, vomiting, diarrhea, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, and coma. As a monotherapy, the smallest dosage capable of causing death was reported as 15 grams. Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of diflunisal. Short-term use does not appear to be associated with increased cardiovascular risk (except when used immediately following coronary artery bypass graft (CABG) surgery). Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Severe hepatic reactions, including cholestasis and/or jaundice, have been reported. May cause rash or hypersensitivity syndrome. •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): Diflunisal Diflunisalum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Diflunisal is an NSAID used to treat mild to moderate pain, inflammation, 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 Diflunisal interact? Information: •Drug A: Abciximab •Drug B: Diflunisal •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Diflunisal 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 symptomatic treatment of mild to moderate pain accompanied by inflammation (e.g. musculoskeletal trauma, post-dental extraction, post-episiotomy), 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): Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%. Peak plasma concentrations are achieved 2 - 3 hours 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): At least 98 to 99% of diflunisal in plasma is bound to 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, primarily via glucuronide conjugation (90% of administered dose). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The drug is excreted in the urine as two soluble glucuronide conjugates accounting for about 90% of the administered dose. Little or no diflunisal 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): 8 to 12 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD 50 in rat, mouse, and rabbit is 392 mg/kg, 439 mg/kg, and 603 mg/kg, respectively. Symptoms of overdose include drowsiness, nausea, vomiting, diarrhea, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, and coma. As a monotherapy, the smallest dosage capable of causing death was reported as 15 grams. Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of diflunisal. Short-term use does not appear to be associated with increased cardiovascular risk (except when used immediately following coronary artery bypass graft (CABG) surgery). Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Severe hepatic reactions, including cholestasis and/or jaundice, have been reported. May cause rash or hypersensitivity syndrome. •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): Diflunisal Diflunisalum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Diflunisal is an NSAID used to treat mild to moderate pain, inflammation, 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 Digoxin Immune Fab (Ovine) interact?

•Drug A: Abciximab •Drug B: Digoxin Immune Fab (Ovine) •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Digoxin Immune Fab (Ovine). •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 treatment of digitoxin overdose or digitalis glycoside toxicity. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): DigiFab binds molecules of digoxin, making them unavailable for binding at their site of action on cells in the body. The Fab fragment-digoxin complex accumulates in the blood, from which it is excreted by the kidney. The net effect is to shift the equilibrium away from binding of digoxin to its receptors in the body, thereby reversing its 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): Binds excess digoxin or digitoxin molecules circulating in the blood. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.3 L/kg [DigiFab] 0.4 L/kg [Digibind] •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): Cumulative urinary excretion of digoxin was comparable for both products and exceeded 40% of the administered dose by 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): 15-20 hrs •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): Digifab •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): Digoxin Immune Fab (Ovine) is an antibody binding fragment which binds digoxin molecules which is used as an antidote to digoxin overdose.

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 Digoxin Immune Fab (Ovine) interact? Information: •Drug A: Abciximab •Drug B: Digoxin Immune Fab (Ovine) •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Digoxin Immune Fab (Ovine). •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 treatment of digitoxin overdose or digitalis glycoside toxicity. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): DigiFab binds molecules of digoxin, making them unavailable for binding at their site of action on cells in the body. The Fab fragment-digoxin complex accumulates in the blood, from which it is excreted by the kidney. The net effect is to shift the equilibrium away from binding of digoxin to its receptors in the body, thereby reversing its 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): Binds excess digoxin or digitoxin molecules circulating in the blood. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.3 L/kg [DigiFab] 0.4 L/kg [Digibind] •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): Cumulative urinary excretion of digoxin was comparable for both products and exceeded 40% of the administered dose by 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): 15-20 hrs •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): Digifab •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): Digoxin Immune Fab (Ovine) is an antibody binding fragment which binds digoxin molecules which is used as an antidote to digoxin overdose. 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 Dinutuximab interact?

•Drug A: Abciximab •Drug B: Dinutuximab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dinutuximab. •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): Dinutuximab is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In vitro dinutuximab binds to neuroblastoma tumour cells and mediates the lysis of tumour cells via cell-mediated and complement-mediated cytotoxicity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution at steady state (Vdss) is 5.4 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 10 days •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance is 0.21 L/day and increases with body size •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common (incidence 15 %) grade 3 or 4 treatment-related adverse events in dinutuximab compared with standard therapy recipients were neuropathic pain (52 vs. 6 %), fever without neutropenia (39 vs. 6 %), any in-fection (39 vs. 22 %), hypokalaemia (35 vs. 2 %), hypersensitivity reactions (25 vs. 1 %), hyponatraemia (23 vs. 4 %), elevation of alanine transferase levels (23 vs. 3 %) and hypotension (18 vs. 0 %). Based on its mechanism of action, dinutuximab may cause fetal harm when administered to a pregnant woman however, there are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. Non-clinical studies suggest that dinutuximab-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of cell- and complement-mediated cytotoxicity. In clinical trials, 114 (85%) patients treated in the dinutuximab/RA group experienced pain despite pre­-treatment with analgesics including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the dinutuximab/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the dinutuximab infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Unituxin •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): Dinutuximab is an immunotherapeutic agent used in combination with other immunomodulating agents to treat high-risk neuroblastoma in pediatric patients who achieve at least a partial response to prior first-line multiagent, multimodality 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 Dinutuximab interact? Information: •Drug A: Abciximab •Drug B: Dinutuximab •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dinutuximab. •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): Dinutuximab is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In vitro dinutuximab binds to neuroblastoma tumour cells and mediates the lysis of tumour cells via cell-mediated and complement-mediated cytotoxicity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean volume of distribution at steady state (Vdss) is 5.4 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 10 days •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance is 0.21 L/day and increases with body size •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common (incidence 15 %) grade 3 or 4 treatment-related adverse events in dinutuximab compared with standard therapy recipients were neuropathic pain (52 vs. 6 %), fever without neutropenia (39 vs. 6 %), any in-fection (39 vs. 22 %), hypokalaemia (35 vs. 2 %), hypersensitivity reactions (25 vs. 1 %), hyponatraemia (23 vs. 4 %), elevation of alanine transferase levels (23 vs. 3 %) and hypotension (18 vs. 0 %). Based on its mechanism of action, dinutuximab may cause fetal harm when administered to a pregnant woman however, there are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. Non-clinical studies suggest that dinutuximab-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of cell- and complement-mediated cytotoxicity. In clinical trials, 114 (85%) patients treated in the dinutuximab/RA group experienced pain despite pre­-treatment with analgesics including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the dinutuximab/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the dinutuximab infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Unituxin •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): Dinutuximab is an immunotherapeutic agent used in combination with other immunomodulating agents to treat high-risk neuroblastoma in pediatric patients who achieve at least a partial response to prior first-line multiagent, multimodality 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 Dipyridamole interact?

•Drug A: Abciximab •Drug B: Dipyridamole •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dipyridamole. •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 as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): 70% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1 to 2.5 L/kg •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): hepatic •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dipyridamole is metabolized in the liver to the glucuronic acid conjugate and excreted with the bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 40 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.3-3.5 mL/min/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Hypotension, if it occurs, is likely to be of short duration, but a vasopressor drug may be used if necessary. The oral LD 50 in rats is greater than 6,000 mg/kg while in the dogs, the oral LD 50 is approximately 400 mg/kg. LD 50 =8.4g/kg (orally in rat) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aggrenox, Persantine •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): Dipyridamole is a phosphodiesterase inhibitor used to prevent postoperative thromboembolic events.

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 Dipyridamole interact? Information: •Drug A: Abciximab •Drug B: Dipyridamole •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Dipyridamole. •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 as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation. •Absorption (Drug A): No absorption available •Absorption (Drug B): 70% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1 to 2.5 L/kg •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): hepatic •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Dipyridamole is metabolized in the liver to the glucuronic acid conjugate and excreted with the bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 40 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.3-3.5 mL/min/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Hypotension, if it occurs, is likely to be of short duration, but a vasopressor drug may be used if necessary. The oral LD 50 in rats is greater than 6,000 mg/kg while in the dogs, the oral LD 50 is approximately 400 mg/kg. LD 50 =8.4g/kg (orally in rat) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aggrenox, Persantine •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): Dipyridamole is a phosphodiesterase inhibitor used to prevent postoperative thromboembolic events. 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 Docetaxel interact?

•Drug A: Abciximab •Drug B: Docetaxel •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Docetaxel. •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): Docetaxel is indicated as a single agent for the treatment of locally advanced or metastatic breast cancer after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC. It is also indicated as a single agent for locally advanced or metastatic non-small cell lung cancer (NSCLC) after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC. For the treatment of metastatic castration-resistant prostate cancer, docetaxel is indicated with prednisone. Docetaxel is also indicated with cisplatin and fluorouracil for untreated, advanced gastric adenocarcinoma, including the gastroesophageal junction, and with cisplatin and fluorouracil for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Docetaxel is a taxoid antineoplastic agent. It 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 which is essential for vital interphase and mitotic cellular functions. In addition, docetaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. The use of docetaxel may lead to treatment-related deaths in breast cancer and non-small cell lung cancer patients, hepatic impairment, hematologic effects, enterocolitis and neutropenic colitis, hypersensitivity reactions, fluid retention, second primary malignancies, cutaneous reactions, neurologic reactions, eye disorders, asthenia, embryo-fetal toxicity, and tumor lysis syndrome. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel 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, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of microtubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel 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 docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis-stopping protein called Bcl-2 (B-cell leukemia 2), thus arresting its function. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetic profile of docetaxel is consistent with a three-compartment model. The initial rapid decline represents the distribution to the peripheral compartments, and the late (terminal) phase is partly due to a relatively slow efflux of docetaxel from the peripheral compartment. The area under the curve (AUC) was dose proportional at doses between 70 mg/m and 115 mg/m with infusion times of 1 to 2 hours. In a group of patients with solid tumors given 100 mg/m of docetaxel intravenously, the Cmax and AUC were 2.41 μg/mL and 5.93 μg⋅h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Docetaxel has a steady-state volume of distribution of 113 L. Its pharmacokinetic profile is consistent with a three-compartment pharmacokinetic model. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro studies show that 94% of docetaxel is bound to proteins, mainly alpha-1-acid glycoprotein, albumin, and lipoproteins. When measured in cancer patients, docetaxel is 97% bound to plasma protein. Dexamethasone does not affect the protein binding of docetaxel. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Docetaxel undergoes hepatic metabolism. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme. CYP3A5 also plays a role in the metabolism of this drug. In humans, docetaxel is metabolized by CYP3A4/5 into four metabolites: M1, M2, M3 and M4. Docetaxel undergoes hydroxylation of the synthetic isobutoxy side chain, forming metabolite M2. The oxidation of M2 forms an unstable aldehyde that is immediately cyclised into the stereoisomers M1 and M3. M4 is then formed by the oxidation of M1/M3. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Docetaxel was eliminated in urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. In the first 48 hours, approximately 80% of the radioactivity recovered was excreted in feces. One major and three minor metabolites were excreted at this point, with less than 8% as the unchanged drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): With plasma sampling up to 8 to 22 days after docetaxel infusion, the terminal elimination half-life was 116 hours. Doses between 70 and 115 mg/m with infusion times of 1 to 2 hours produce a triphasic elimination profile. The half-life of the alpha, beta, and gamma phases are 4 minutes, 36 minutes, and 11.1 hours, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): After the administration of 20–115 mg/m of intravenous docetaxel to cancer patients, the total body clearance was 21 L/h/m. In patients aged 1 to 20 years with solid tumors that received 55 mg/m to 235 mg/m of docetaxel in a 1-hour intravenous infusion every 3 weeks, clearance was 17.3 L/h/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no known antidote for an overdose of docetaxel injection. In case of overdose, patients should be closely monitored in specialized units. Some of the anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. After an overdose is discovered, patients should receive granulocyte colony-stimulating factor (G-CSF) as soon as possible. Other appropriate symptomatic measures should be taken as needed. In two reports of overdose, one patient received 150 mg/m, and the other received 200 mg/m as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident. In rats, the oral LD 50 of docetaxel is >2000 mg/kg. The intravenous LD 50 in mice is 138 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Taxotere •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Docetaxel •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Docetaxel is a taxoid antineoplastic agent used in the treatment of various cancers, such as locally advanced or metastatic breast cancer, metastatic prostate cancer, gastric adenocarcinoma, and head and neck 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 Docetaxel interact? Information: •Drug A: Abciximab •Drug B: Docetaxel •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Docetaxel. •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): Docetaxel is indicated as a single agent for the treatment of locally advanced or metastatic breast cancer after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC. It is also indicated as a single agent for locally advanced or metastatic non-small cell lung cancer (NSCLC) after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC. For the treatment of metastatic castration-resistant prostate cancer, docetaxel is indicated with prednisone. Docetaxel is also indicated with cisplatin and fluorouracil for untreated, advanced gastric adenocarcinoma, including the gastroesophageal junction, and with cisplatin and fluorouracil for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Docetaxel is a taxoid antineoplastic agent. It 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 which is essential for vital interphase and mitotic cellular functions. In addition, docetaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. The use of docetaxel may lead to treatment-related deaths in breast cancer and non-small cell lung cancer patients, hepatic impairment, hematologic effects, enterocolitis and neutropenic colitis, hypersensitivity reactions, fluid retention, second primary malignancies, cutaneous reactions, neurologic reactions, eye disorders, asthenia, embryo-fetal toxicity, and tumor lysis syndrome. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel 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, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of microtubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel 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 docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis-stopping protein called Bcl-2 (B-cell leukemia 2), thus arresting its function. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetic profile of docetaxel is consistent with a three-compartment model. The initial rapid decline represents the distribution to the peripheral compartments, and the late (terminal) phase is partly due to a relatively slow efflux of docetaxel from the peripheral compartment. The area under the curve (AUC) was dose proportional at doses between 70 mg/m and 115 mg/m with infusion times of 1 to 2 hours. In a group of patients with solid tumors given 100 mg/m of docetaxel intravenously, the Cmax and AUC were 2.41 μg/mL and 5.93 μg⋅h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Docetaxel has a steady-state volume of distribution of 113 L. Its pharmacokinetic profile is consistent with a three-compartment pharmacokinetic model. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro studies show that 94% of docetaxel is bound to proteins, mainly alpha-1-acid glycoprotein, albumin, and lipoproteins. When measured in cancer patients, docetaxel is 97% bound to plasma protein. Dexamethasone does not affect the protein binding of docetaxel. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Docetaxel undergoes hepatic metabolism. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme. CYP3A5 also plays a role in the metabolism of this drug. In humans, docetaxel is metabolized by CYP3A4/5 into four metabolites: M1, M2, M3 and M4. Docetaxel undergoes hydroxylation of the synthetic isobutoxy side chain, forming metabolite M2. The oxidation of M2 forms an unstable aldehyde that is immediately cyclised into the stereoisomers M1 and M3. M4 is then formed by the oxidation of M1/M3. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Docetaxel was eliminated in urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. In the first 48 hours, approximately 80% of the radioactivity recovered was excreted in feces. One major and three minor metabolites were excreted at this point, with less than 8% as the unchanged drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): With plasma sampling up to 8 to 22 days after docetaxel infusion, the terminal elimination half-life was 116 hours. Doses between 70 and 115 mg/m with infusion times of 1 to 2 hours produce a triphasic elimination profile. The half-life of the alpha, beta, and gamma phases are 4 minutes, 36 minutes, and 11.1 hours, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): After the administration of 20–115 mg/m of intravenous docetaxel to cancer patients, the total body clearance was 21 L/h/m. In patients aged 1 to 20 years with solid tumors that received 55 mg/m to 235 mg/m of docetaxel in a 1-hour intravenous infusion every 3 weeks, clearance was 17.3 L/h/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no known antidote for an overdose of docetaxel injection. In case of overdose, patients should be closely monitored in specialized units. Some of the anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. After an overdose is discovered, patients should receive granulocyte colony-stimulating factor (G-CSF) as soon as possible. Other appropriate symptomatic measures should be taken as needed. In two reports of overdose, one patient received 150 mg/m, and the other received 200 mg/m as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident. In rats, the oral LD 50 of docetaxel is >2000 mg/kg. The intravenous LD 50 in mice is 138 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Taxotere •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Docetaxel •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Docetaxel is a taxoid antineoplastic agent used in the treatment of various cancers, such as locally advanced or metastatic breast cancer, metastatic prostate cancer, gastric adenocarcinoma, and head and neck 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 Dostarlimab interact?

•Drug A: Abciximab •Drug B: Dostarlimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Dostarlimab. •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): Dostarlimab is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed despite ongoing or prior treatment with a platinum-containing chemotherapy regimen. It is used as monotherapy or in combination with carboplatin and paclitaxel. It is also indicated for the treatment of dMMR recurrent or advanced solid tumors in adults, as determined by an FDA-approved test, that have progressed on or following prior treatment and in patients who have no satisfactory alternative treatment options. This indication is approved under accelerated approval, and continued approval for this indication may be contingent upon verification and description of and description 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): Dostarlimab is an immunotherapy that facilitates the body's endogenous anti-tumor immune response in the treatment cancer. It is administered over a span of 30 minutes via intravenous infusion every three to six weeks depending on the cycle. Agents that interfere with the PD-1/PD-L1 pathway, including dostarlimab, remove an important immune system inhibitory response and may therefore induce immune-mediated adverse reactions which can be severe or fatal. These reactions can occur in any organ system and can occur at any time after starting therapy, and while they most often manifest during therapy they may also appear after discontinuing the causative agent. Patients receiving therapy with dostarlimab should be monitored closely for evidence of an underlying immune-mediated reaction and evaluated and treated promptly if an immune-mediated reaction is suspected. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR). The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations. Cancers that have mutations resulting in dMMR can upregulate the expression of programmed death receptor-1 (PD-1) ligands 1 and 2 (PD-L1 and -L2) - PD-1 is found on T-cells and, when activated, inhibits their proliferation and the production of cytokines. The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response. Dostarlimab is a monoclonal antibody targeted against PD-1 - it binds to the receptor and prevents interactions with PD-L1 and PD-L2, thus allowing the anti-tumor immune response to proceed unimpeded. •Absorption (Drug A): No absorption available •Absorption (Drug B): During the first cycle, and administered at 500mg intravenously every 3 weeks, the mean C max and AUC 0-tau of dostarlimab-gxly are 171 mcg/mL and 35,730 mcg.h/mL, respectively. When administered at 1000mg every 6 weeks, the mean C max and AUC 0-tau are 309 mcg/mL and 95,820 mcg.h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): At steady-state, the mean volume of distribution of dostarlimab is 5.3L. •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 dostarlimab has not been characterized, but it is expected to be degraded via catabolic pathways into smaller 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): The mean terminal elimination half-life of dostarlimab is 25.4 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): At steady-state, the mean clearance of dostarlimab is 0.007 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no data regarding overdose with dostarlimab. Symptoms of overdosage are likely to be consistent with the adverse effect profile of dostarlimab and may therefore involve significant immune-mediated reactions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jemperli •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): Dostarlimab is an anti-PD-1 monoclonal antibody used in the treatment of mismatch repair deficient endometrial cancers and solid tumours with no alternative treatment options.

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 Dostarlimab interact? Information: •Drug A: Abciximab •Drug B: Dostarlimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Dostarlimab. •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): Dostarlimab is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed despite ongoing or prior treatment with a platinum-containing chemotherapy regimen. It is used as monotherapy or in combination with carboplatin and paclitaxel. It is also indicated for the treatment of dMMR recurrent or advanced solid tumors in adults, as determined by an FDA-approved test, that have progressed on or following prior treatment and in patients who have no satisfactory alternative treatment options. This indication is approved under accelerated approval, and continued approval for this indication may be contingent upon verification and description of and description 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): Dostarlimab is an immunotherapy that facilitates the body's endogenous anti-tumor immune response in the treatment cancer. It is administered over a span of 30 minutes via intravenous infusion every three to six weeks depending on the cycle. Agents that interfere with the PD-1/PD-L1 pathway, including dostarlimab, remove an important immune system inhibitory response and may therefore induce immune-mediated adverse reactions which can be severe or fatal. These reactions can occur in any organ system and can occur at any time after starting therapy, and while they most often manifest during therapy they may also appear after discontinuing the causative agent. Patients receiving therapy with dostarlimab should be monitored closely for evidence of an underlying immune-mediated reaction and evaluated and treated promptly if an immune-mediated reaction is suspected. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR). The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations. Cancers that have mutations resulting in dMMR can upregulate the expression of programmed death receptor-1 (PD-1) ligands 1 and 2 (PD-L1 and -L2) - PD-1 is found on T-cells and, when activated, inhibits their proliferation and the production of cytokines. The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response. Dostarlimab is a monoclonal antibody targeted against PD-1 - it binds to the receptor and prevents interactions with PD-L1 and PD-L2, thus allowing the anti-tumor immune response to proceed unimpeded. •Absorption (Drug A): No absorption available •Absorption (Drug B): During the first cycle, and administered at 500mg intravenously every 3 weeks, the mean C max and AUC 0-tau of dostarlimab-gxly are 171 mcg/mL and 35,730 mcg.h/mL, respectively. When administered at 1000mg every 6 weeks, the mean C max and AUC 0-tau are 309 mcg/mL and 95,820 mcg.h/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): At steady-state, the mean volume of distribution of dostarlimab is 5.3L. •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 dostarlimab has not been characterized, but it is expected to be degraded via catabolic pathways into smaller 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): The mean terminal elimination half-life of dostarlimab is 25.4 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): At steady-state, the mean clearance of dostarlimab is 0.007 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no data regarding overdose with dostarlimab. Symptoms of overdosage are likely to be consistent with the adverse effect profile of dostarlimab and may therefore involve significant immune-mediated reactions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Jemperli •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): Dostarlimab is an anti-PD-1 monoclonal antibody used in the treatment of mismatch repair deficient endometrial cancers and solid tumours with no alternative treatment options. 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 Doxorubicin interact?

•Drug A: Abciximab •Drug B: Doxorubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin. •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): Doxorubicin is indicated for the treatment of neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin and non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor, metastatic neuroblastoma, metastatic soft tissue and bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer. For the liposomal formulation, doxorubicin is indicated for the treatment of ovarian cancer that has progressed or recurred after platinum-based chemotherapy, AIDS-Related Kaposi's Sarcoma after the failure of prior systemic chemotherapy or intolerance to such therapy, and multiple myeloma in combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Doxorubicin is a cytotoxic, cell-cycle non-specific anthracycline antibiotic. It is generally thought to exert its antitumor effect by destabilizing DNA structures through intercalation, thus introducing DNA strand breakages and damages. Not only does it alter the transcriptomes of the cells, failure in repairing DNA structures can also initiate the apoptotic pathways. Additionally, doxorubicin intercalation can also interfere with vital enzyme activity, such as topoisomerase II, DNA polymerase, and RNA polymerase, leading to cell cycle arrests. Finally, doxorubicin can also generate cytotoxic reactive oxygen species to exert cellular damages. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Generally, doxorubicin is thought to exert its antineoplastic activity through 2 primary mechanisms: intercalation into DNA and disrupt topoisomerase-mediated repairs and free radicals-mediated cellular damages. Doxorubicin can intercalate into DNA through the anthraquinone ring, which stabilizes the complex by forming hydrogen bonds with DNA bases. Intercalation of doxorubicin can introduce torsional stress into the polynucleotide structure, thus destabilizing nucleosome structures and leading to nucleosome eviction and replacement. Additionally, the doxorubicin-DNA complex can interfere with topoisomerase II enzyme activity by preventing relegation of topoisomerase-mediated DNA breaks, thus inhibiting replication and transcription and inducing apoptosis. Moreover, doxorubicin can be metabolized by microsomal NADPH-cytochrome P-450 reductase into a semiquinone radical, which can be reoxidized in the presence of oxygen to form oxygen radicals. Reactive oxygen species have been known to cause cellular damage through various mechanisms, including lipid peroxidation and membrane damage, DNA damage, oxidative stress, and apoptosis. Although free radicals generated from this pathway can be deactivated by catalase and superoxide dismutase, tumor and myocardial cells tend to lack these enzymes, thus explaining doxorubicin's effectiveness against cancer cells and tendency to cause cardiotoxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a 10 mg/m administration of liposomal doxorubicin in patients with AIDS-related Kaposi's Sarcoma, the C max and AUC values were calculated to be 4.12 ± 0.215 μg/mL and 277 ± 32.9 μg/mL•h respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state distribution volume of doxorubicin ranges from 809 L/m to 1214 L/m. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The binding of doxorubicin and its major metabolite, doxorubicinol, to plasma proteins is 75% and is independent of plasma concentration of doxorubicin up to 1.1 µg/mL. Doxorubicin does not cross the blood-brain barrier. Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged. The two-electron reduction is the major metabolic pathway of doxorubicin. In this pathway, doxorubicin is reduced to doxorubicinol, a secondary alcohol, by various enzymes, including Alcohol dehydrogenase [NADP(+)], Carbonyl reductase NADPH 1, Carbonyl reductase NADPH 3, and Aldo-keto reductase family 1 member C3. The one-electron reduction is facilitated by several oxidoreductase, both cytosolic and mitochondrial, to form a doxirubicin-semiquinone radical. These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases. This semiquinone metabolite can be re-oxidized to doxorubicin, although with the concurrent formation of reactive oxygen species (ROS) and hydrogen peroxide. It is the ROS generating through this pathway that contributes most to the doxorubicin-related adverse effects, particularly cardiotoxicity, rather than through doxorubicin semiquinone formation. Deglycosidation is a minor metabolic pathway, since it only accounts for 1 to 2% of doxorubicin metabolism. Under the catalysis of cytoplasmic NADPH quinone dehydrogenase, xanthine oxidase, NADPH-cytochrome P450 reductase, doxorubicin can either be reduced to doxorubicin deoxyaglycone or hydrolyzed to doxorubicin hydroxyaglycone. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 40% of the dose appears in the bile in 5 days, while only 5% to 12% of the drug and its metabolites appear in the urine during the same time period. In urine, <3% of the dose was recovered as doxorubicinol over 7 days. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 doxorubicin ranges from 20 hours to 48 hours. The distribution half-life of doxorubicin is approximately 5 minutes. For the liposomal formulation, the first-phase and second-phase half-lives were calculated to be 4.7 ± 1.1 and 52.3 ± 5.6 hours respectively for a 10 mg/m of doxorubicin in patients with AIDS-Related Kaposi’s Sarcoma. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of doxorubicin ranges from 324 mL/min/m2 to 809 mL/min/m by metabolism and biliary excretion. Sexual differences in doxorubicin were also observed, with men having a higher clearance compared to women (1088 mL/min/m versus 433 mL/min/m ). Following the administration of doses ranging from 10 mg/m2 to 75 mg/m of doxorubicin hydrochloride, the plasma clearance was estimated to be 1540 mL/min/m in children greater than 2 years of age and 813 mL/min/m in infants younger than 2 years of age. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Doxorubicin hydrochloride treatment can increase the risk of secondary malignancies based on postmarketing reports. Doxorubicin hydrochloride was mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay. Doxorubicin hydrochloride decreased fertility in female rats at doses of 0.05 and 0.2 mg/kg/day (approximately 0.005 and 0.02 times the recommended human dose, based on body surface area). In females of reproductive potential, Doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment. A single intravenous dose of 0.1 mg/kg doxorubicin hydrochloride (approximately 0.01 times the recommended human dose based on body surface area) was toxic to male reproductive organs in animal studies, producing testicular atrophy, diffuse degeneration of the seminiferous tubules, and oligospermia/hypospermia in rats. Doxorubicin hydrochloride induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice. Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection/for Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection/for Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2. Advise pregnant women of the potential risk to a fetus. Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride. Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Adriamycin, Doxil, Myocet •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 14-hydroxydaunomycin 14-hydroxydaunorubicine Doxorubicin Doxorubicin nanoparticles Doxorubicina Doxorubicine Doxorubicinum Hydroxydaunorubicin MTC-DOX MTC-DOX for Injection •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Doxorubicin is a medication used to treat various cancers, including AIDS-associated Kaposi's Sarcoma and metastatic 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 Doxorubicin interact? Information: •Drug A: Abciximab •Drug B: Doxorubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin. •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): Doxorubicin is indicated for the treatment of neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin and non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor, metastatic neuroblastoma, metastatic soft tissue and bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer. For the liposomal formulation, doxorubicin is indicated for the treatment of ovarian cancer that has progressed or recurred after platinum-based chemotherapy, AIDS-Related Kaposi's Sarcoma after the failure of prior systemic chemotherapy or intolerance to such therapy, and multiple myeloma in combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Doxorubicin is a cytotoxic, cell-cycle non-specific anthracycline antibiotic. It is generally thought to exert its antitumor effect by destabilizing DNA structures through intercalation, thus introducing DNA strand breakages and damages. Not only does it alter the transcriptomes of the cells, failure in repairing DNA structures can also initiate the apoptotic pathways. Additionally, doxorubicin intercalation can also interfere with vital enzyme activity, such as topoisomerase II, DNA polymerase, and RNA polymerase, leading to cell cycle arrests. Finally, doxorubicin can also generate cytotoxic reactive oxygen species to exert cellular damages. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Generally, doxorubicin is thought to exert its antineoplastic activity through 2 primary mechanisms: intercalation into DNA and disrupt topoisomerase-mediated repairs and free radicals-mediated cellular damages. Doxorubicin can intercalate into DNA through the anthraquinone ring, which stabilizes the complex by forming hydrogen bonds with DNA bases. Intercalation of doxorubicin can introduce torsional stress into the polynucleotide structure, thus destabilizing nucleosome structures and leading to nucleosome eviction and replacement. Additionally, the doxorubicin-DNA complex can interfere with topoisomerase II enzyme activity by preventing relegation of topoisomerase-mediated DNA breaks, thus inhibiting replication and transcription and inducing apoptosis. Moreover, doxorubicin can be metabolized by microsomal NADPH-cytochrome P-450 reductase into a semiquinone radical, which can be reoxidized in the presence of oxygen to form oxygen radicals. Reactive oxygen species have been known to cause cellular damage through various mechanisms, including lipid peroxidation and membrane damage, DNA damage, oxidative stress, and apoptosis. Although free radicals generated from this pathway can be deactivated by catalase and superoxide dismutase, tumor and myocardial cells tend to lack these enzymes, thus explaining doxorubicin's effectiveness against cancer cells and tendency to cause cardiotoxicity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a 10 mg/m administration of liposomal doxorubicin in patients with AIDS-related Kaposi's Sarcoma, the C max and AUC values were calculated to be 4.12 ± 0.215 μg/mL and 277 ± 32.9 μg/mL•h respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady-state distribution volume of doxorubicin ranges from 809 L/m to 1214 L/m. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The binding of doxorubicin and its major metabolite, doxorubicinol, to plasma proteins is 75% and is independent of plasma concentration of doxorubicin up to 1.1 µg/mL. Doxorubicin does not cross the blood-brain barrier. Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged. The two-electron reduction is the major metabolic pathway of doxorubicin. In this pathway, doxorubicin is reduced to doxorubicinol, a secondary alcohol, by various enzymes, including Alcohol dehydrogenase [NADP(+)], Carbonyl reductase NADPH 1, Carbonyl reductase NADPH 3, and Aldo-keto reductase family 1 member C3. The one-electron reduction is facilitated by several oxidoreductase, both cytosolic and mitochondrial, to form a doxirubicin-semiquinone radical. These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases. This semiquinone metabolite can be re-oxidized to doxorubicin, although with the concurrent formation of reactive oxygen species (ROS) and hydrogen peroxide. It is the ROS generating through this pathway that contributes most to the doxorubicin-related adverse effects, particularly cardiotoxicity, rather than through doxorubicin semiquinone formation. Deglycosidation is a minor metabolic pathway, since it only accounts for 1 to 2% of doxorubicin metabolism. Under the catalysis of cytoplasmic NADPH quinone dehydrogenase, xanthine oxidase, NADPH-cytochrome P450 reductase, doxorubicin can either be reduced to doxorubicin deoxyaglycone or hydrolyzed to doxorubicin hydroxyaglycone. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 40% of the dose appears in the bile in 5 days, while only 5% to 12% of the drug and its metabolites appear in the urine during the same time period. In urine, <3% of the dose was recovered as doxorubicinol over 7 days. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 doxorubicin ranges from 20 hours to 48 hours. The distribution half-life of doxorubicin is approximately 5 minutes. For the liposomal formulation, the first-phase and second-phase half-lives were calculated to be 4.7 ± 1.1 and 52.3 ± 5.6 hours respectively for a 10 mg/m of doxorubicin in patients with AIDS-Related Kaposi’s Sarcoma. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of doxorubicin ranges from 324 mL/min/m2 to 809 mL/min/m by metabolism and biliary excretion. Sexual differences in doxorubicin were also observed, with men having a higher clearance compared to women (1088 mL/min/m versus 433 mL/min/m ). Following the administration of doses ranging from 10 mg/m2 to 75 mg/m of doxorubicin hydrochloride, the plasma clearance was estimated to be 1540 mL/min/m in children greater than 2 years of age and 813 mL/min/m in infants younger than 2 years of age. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Doxorubicin hydrochloride treatment can increase the risk of secondary malignancies based on postmarketing reports. Doxorubicin hydrochloride was mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay. Doxorubicin hydrochloride decreased fertility in female rats at doses of 0.05 and 0.2 mg/kg/day (approximately 0.005 and 0.02 times the recommended human dose, based on body surface area). In females of reproductive potential, Doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment. A single intravenous dose of 0.1 mg/kg doxorubicin hydrochloride (approximately 0.01 times the recommended human dose based on body surface area) was toxic to male reproductive organs in animal studies, producing testicular atrophy, diffuse degeneration of the seminiferous tubules, and oligospermia/hypospermia in rats. Doxorubicin hydrochloride induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice. Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection/for Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection/for Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2. Advise pregnant women of the potential risk to a fetus. Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride. Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Adriamycin, Doxil, Myocet •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 14-hydroxydaunomycin 14-hydroxydaunorubicine Doxorubicin Doxorubicin nanoparticles Doxorubicina Doxorubicine Doxorubicinum Hydroxydaunorubicin MTC-DOX MTC-DOX for Injection •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Doxorubicin is a medication used to treat various cancers, including AIDS-associated Kaposi's Sarcoma and metastatic 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 Doxycycline interact?

•Drug A: Abciximab •Drug B: Doxycycline •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Doxycycline is combined with Abciximab. •Extended Description: There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline, increasing the risk of bleeding events. This is due to the fact that doxycycline has been shown to inhibit plasma prothrombin activity. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Doxycycline is indicated for the treatment of various infections by gram-positive and gram-negative bacteria, aerobes and anaerobes, as well other types of bacteria, including: Early Lyme disease (as evidenced by erythema migraines) due to Borrelia burgdorferi in adults and pediatric patients 8 years of age and older weighing 45 kg and above Rickettsial infections, such as Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers Sexually transmitted infections Respiratory tract infections caused by Mycoplasma pneumoniae and Haemophilus influenzae Specific bacterial infections after indicative bacteriologic testing. These include infections caused by Escherichia coli, Enterobacter aerogenes, Shigella species, Acinetobacter species, and Klebsiella species Ophthalmic infections, such as inclusion conjunctivitis caused by Chlamydia trachomatis Anthrax, including inhalational anthrax (post-exposure) Alternative treatment for selected infections when penicillin is contraindicated Adjunctive therapy in acute intestinal amebiasis and severe acne Lymphogranuloma venereum caused by Chlamydia trachomatis Psittacosis (ornithosis) caused by Chlamydophila psittaci Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immunofluorescence Uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis Nongonococcal urethritis caused by Ureaplasma urealyticum Relapsing fever due to Borrelia recurrentis Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains It is also used to treat infections caused by the following gram-negative microorganisms: Chancroid caused by Haemophilus ducreyi Plague due to Yersinia pestis Tularemia due to Francisella tularensis Cholera caused by Vibrio cholerae Campylobacter fetus infections caused by Campylobacter fetus Brucellosis due to Brucella species (in conjunction with streptomycin ) Bartonellosis due to Bartonella bacilliformis Granuloma inguinale caused by Klebsiella granulomatis •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Doxycycline and other tetracyclines are mainly bacteriostatic and are thought to exert antimicrobial effects by the inhibition of protein synthesis. They suppress the growth of bacteria or keep them in the stationary phase of growth. Tetracyclines have antimicrobial spectrum of activity against a variety of gram-positive and gram-negative microorganisms. Cross-resistance of these microorganisms to tetracyclines is a common occurrence. As it is a highly lipophilic drug, doxycycline crosses multiple membranes of target molecules. Doxycycline shows favorable intra-cellular penetration, with bacteriostatic activity against a wide range of bacteria. Doxycycline also exhibits antiparasitic properties and anti-inflammatory actions. Its anti-inflammatory effects were investigated in various inflammatory skin conditions, such as bullous dermatoses and rosacea. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 synthesis is essential for survival and functioning of cells, including bacteria. Doxycycline inhibits bacterial protein synthesis by allosterically binding to the 30S prokaryotic ribosomal subunit. The drug blocks the association charged aminoacyl-tRNA (aa-tRNA) with the ribosomal A site, which is the acceptor site on the mRNA-ribosome complex. Doxycycline ultimately impedes the elongation phase of protein synthesis and halts the production of essential proteins for bacterial survival and functioning. Doxycycline mediates anti-inflammatory actions by preventing calcium-dependent microtubular assembly and lymphocytic proliferation, thereby inhibiting leukocyte movement during inflammation. It also inhibits nitric oxide synthase, which is an enzyme that produces nitric oxide, an inflammatory signaling molecule. •Absorption (Drug A): No absorption available •Absorption (Drug B): Doxycycline is virtually completely absorbed after oral administration with a bioavailability of ranging from 73-95%. Following an oral dose of 500 mg, the C max of 15.3 mg/L was reached in four hours. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours, decreasing to 1.45 mcg/mL at 24 hours. While a high-fat meal lowers C max and the rate of absorption, the effect is not clinically significant. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): There is limited information available. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): While there is limited information available, tetracyclines bound to plasma proteins in varying degree. •Metabolism (Drug A): 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 available. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Tetracyclines, including doxycycline, are concentrated in bile by the liver and excreted in the urine and feces at high concentrations and in a biologically active form. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with a creatinine clearance of about 75 mL/min. This percentage may fall as low as 1-5%/72 hours in individuals with a creatinine clearance below 10 mL/min. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): There is limited information available. •Clearance (Drug A): No clearance available •Clearance (Drug B): Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous and oral dosing in 44 pediatric patients two to 18 years of age showed allometrically -scaled clearance (CL) ranging from 3.27 to 3.58 L/h/70 kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD 50 is 2000 mg/kg in rats, 1870 mg/kg in mice, and 500 mg/kg in dog. In case of overdosage, doxycycline should be discontinued and symptomatic and supportive treatment should be initiated. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Acticlate, Adoxa, Apprilon, Atridox, Doryx, Doxy, Doxycin, Lymepak, Mondoxyne, Monodox, Morgidox, Okebo, Oracea, Periostat, Targadox, Vibramycin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Doxiciclina Doxycyclin Doxycycline Doxycyclinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Doxycycline is a tetracycline antibiotic used to treat a wide variety of bacterial infections.

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline, increasing the risk of bleeding events. This is due to the fact that doxycycline has been shown to inhibit plasma prothrombin activity. The severity of the interaction is moderate.

Question: Does Abciximab and Doxycycline interact? Information: •Drug A: Abciximab •Drug B: Doxycycline •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Doxycycline is combined with Abciximab. •Extended Description: There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline, increasing the risk of bleeding events. This is due to the fact that doxycycline has been shown to inhibit plasma prothrombin activity. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Doxycycline is indicated for the treatment of various infections by gram-positive and gram-negative bacteria, aerobes and anaerobes, as well other types of bacteria, including: Early Lyme disease (as evidenced by erythema migraines) due to Borrelia burgdorferi in adults and pediatric patients 8 years of age and older weighing 45 kg and above Rickettsial infections, such as Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers Sexually transmitted infections Respiratory tract infections caused by Mycoplasma pneumoniae and Haemophilus influenzae Specific bacterial infections after indicative bacteriologic testing. These include infections caused by Escherichia coli, Enterobacter aerogenes, Shigella species, Acinetobacter species, and Klebsiella species Ophthalmic infections, such as inclusion conjunctivitis caused by Chlamydia trachomatis Anthrax, including inhalational anthrax (post-exposure) Alternative treatment for selected infections when penicillin is contraindicated Adjunctive therapy in acute intestinal amebiasis and severe acne Lymphogranuloma venereum caused by Chlamydia trachomatis Psittacosis (ornithosis) caused by Chlamydophila psittaci Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immunofluorescence Uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis Nongonococcal urethritis caused by Ureaplasma urealyticum Relapsing fever due to Borrelia recurrentis Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains It is also used to treat infections caused by the following gram-negative microorganisms: Chancroid caused by Haemophilus ducreyi Plague due to Yersinia pestis Tularemia due to Francisella tularensis Cholera caused by Vibrio cholerae Campylobacter fetus infections caused by Campylobacter fetus Brucellosis due to Brucella species (in conjunction with streptomycin ) Bartonellosis due to Bartonella bacilliformis Granuloma inguinale caused by Klebsiella granulomatis •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Doxycycline and other tetracyclines are mainly bacteriostatic and are thought to exert antimicrobial effects by the inhibition of protein synthesis. They suppress the growth of bacteria or keep them in the stationary phase of growth. Tetracyclines have antimicrobial spectrum of activity against a variety of gram-positive and gram-negative microorganisms. Cross-resistance of these microorganisms to tetracyclines is a common occurrence. As it is a highly lipophilic drug, doxycycline crosses multiple membranes of target molecules. Doxycycline shows favorable intra-cellular penetration, with bacteriostatic activity against a wide range of bacteria. Doxycycline also exhibits antiparasitic properties and anti-inflammatory actions. Its anti-inflammatory effects were investigated in various inflammatory skin conditions, such as bullous dermatoses and rosacea. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 synthesis is essential for survival and functioning of cells, including bacteria. Doxycycline inhibits bacterial protein synthesis by allosterically binding to the 30S prokaryotic ribosomal subunit. The drug blocks the association charged aminoacyl-tRNA (aa-tRNA) with the ribosomal A site, which is the acceptor site on the mRNA-ribosome complex. Doxycycline ultimately impedes the elongation phase of protein synthesis and halts the production of essential proteins for bacterial survival and functioning. Doxycycline mediates anti-inflammatory actions by preventing calcium-dependent microtubular assembly and lymphocytic proliferation, thereby inhibiting leukocyte movement during inflammation. It also inhibits nitric oxide synthase, which is an enzyme that produces nitric oxide, an inflammatory signaling molecule. •Absorption (Drug A): No absorption available •Absorption (Drug B): Doxycycline is virtually completely absorbed after oral administration with a bioavailability of ranging from 73-95%. Following an oral dose of 500 mg, the C max of 15.3 mg/L was reached in four hours. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours, decreasing to 1.45 mcg/mL at 24 hours. While a high-fat meal lowers C max and the rate of absorption, the effect is not clinically significant. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): There is limited information available. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): While there is limited information available, tetracyclines bound to plasma proteins in varying degree. •Metabolism (Drug A): 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 available. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Tetracyclines, including doxycycline, are concentrated in bile by the liver and excreted in the urine and feces at high concentrations and in a biologically active form. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with a creatinine clearance of about 75 mL/min. This percentage may fall as low as 1-5%/72 hours in individuals with a creatinine clearance below 10 mL/min. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): There is limited information available. •Clearance (Drug A): No clearance available •Clearance (Drug B): Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous and oral dosing in 44 pediatric patients two to 18 years of age showed allometrically -scaled clearance (CL) ranging from 3.27 to 3.58 L/h/70 kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral LD 50 is 2000 mg/kg in rats, 1870 mg/kg in mice, and 500 mg/kg in dog. In case of overdosage, doxycycline should be discontinued and symptomatic and supportive treatment should be initiated. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Acticlate, Adoxa, Apprilon, Atridox, Doryx, Doxy, Doxycin, Lymepak, Mondoxyne, Monodox, Morgidox, Okebo, Oracea, Periostat, Targadox, Vibramycin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Doxiciclina Doxycyclin Doxycycline Doxycyclinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Doxycycline is a tetracycline antibiotic used to treat a wide variety of bacterial infections. Output: There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline, increasing the risk of bleeding events. This is due to the fact that doxycycline has been shown to inhibit plasma prothrombin activity. The severity of the interaction is moderate.

Does Abciximab and Drospirenone interact?

•Drug A: Abciximab •Drug B: Drospirenone •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Drospirenone 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): Drospirenone, in combination with ethinyl estradiol or estetrol, is indicated as an oral contraceptive for the prevention of pregnancy. In addition to its use for contraceptive effects, this combination is used to treat moderate acne vulgaris and the symptoms of premenstrual dysphoric disorder. The drug has approved indications for combination with estrogens for the treatment of menopause-associated symptoms, such as vasomotor symptoms and vulvovaginal atrophy. Drospirenone combined with estrogen may also may aid in the prevention of osteoporosis in women who have been post-menopausal for at least a year and are not candidates for other therapies. It can sometimes be found in preparations containing estrogen and folic acid for folic acid replenishment during oral contraception. When used for the treatment of acne vulgaris, drospirenone-containing contraceptives should only be used in women ≥14 years of age who have experienced menarche, desire oral contraception, and do not have any contraindications to oral contraceptives. Off-label uses for this drug include the treatment of menstrual irregularities, dysmenorrhea, hirsutism, and endometriosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy. It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile. Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings. A note on venous thromboembolism risk and antimineralcorticoid effects As with other oral contraceptives, the risk of venous thromboembolism and cardiovascular events may be increased when drospirenone is taken. The risk is especially higher in smokers and women aged 35 and older. Women taking this drug should be advised not to smoke. In addition, drospirenone, due to its antimineralcorticoid effects, may increase the risk of hyperkalemia. Patients at high risk for hyperkalemia should not be administered this drug. Consult the official prescribing information for detailed and updated information on the cardiovascular and other risks associated with drospirenone use. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation. Drospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion. Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism. Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of drospirenone is approximately 76% due to first-pass effects. The maximum plasma concentration of drospirenone occurs within 1 to 2 hours after oral administration and is estimated to range between 60 and 87 ng/mL. A European prescribing monograph for the combination product of estradiol and drospirenone indicates that drospirenone is both completely and rapidly absorbed. It reports a Cmax of 21.9 ng/ml, achieved approximately 1-hour post-administration. The absolute bioavailability is reported to range between 76 to 85%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of drospirenone is estimated to be 4 L/kg, according to the FDA label for Yaz. Prescribing information from a combination of estradiol and drospirenone estimates the volume of distribution to range from 3.7- 4.2 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Drospirenone is about 95% to 97% bound to serum plasma protein, likely to albumin. During in vitro studies, drospirenone was found to bind with low affinity to sex hormone-binding globulin (SHBG). Another reference indicates that drospirenone binds to serum albumin but does not bind to sex hormone-binding globulin (SHBG), nor corticoid binding globulin (CBG). Only 3-5% of the total drospirenone concentration is measured as a free steroid. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Drospirenone is heavily metabolized. The two major inactive metabolites identified are the acid form of drospirenone produced by the opening of its lactone ring, known as M11, and the 4,5-dihydro-drospirenone-3-sulfate (M14). Drospirenone also undergoes oxidative metabolism via the hepatic cytochrome enzyme CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Various metabolites of drospirenone are measured in the urine and feces. Drospirenone elimination from the body is almost after 10 days post-administration when negligible amounts of drospirenone are found unchanged in both the urine and feces. Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine. In the feces, approximately 17% to 20% of identifiable metabolites are found to be excreted as glucuronides and sulfates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 drospirenone is estimated to be 30 hours. The half-life of drospirenone metabolite excretion in the urine and feces is approximately 40 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Drospirenone is rapidly cleared, typically within 2-3 days of administration of the last active tablet. The rate of clearance of drospirenone calculated in the serum ranges from 1.2-1.5 ml/min/kg, however, this value can vary by up to 25% according to the patient. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 of drospirenone in rats is >2000 mg/kg. Overdose information An overdose of drospirenone, like other oral contraceptives, may lead to cause nausea or withdrawal bleeding. For drospirenone in particular, as an analog of spironolactone, may affect the levels of serum sodium and potassium. Their concentrations should be monitored in cases of overdose in addition to monitoring from metabolic acidosis and hyperkalemia, which may also result. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Angeliq 0.25/0.5 28 Day, Beyaz 28 Day, Gianvi 28-day, Jasmiel 28 Day, Lo-zumandimine 28 Day, Loryna, Nextstellis 28 Day, Nikki 28 Day, Ocella 28 Day, Safyral 28 Day, Slynd, Syeda 28 Day, Tydemy 28 Day, Vestura, Yasmin, Yasmin 28 Day, Yaz 28 Day, Yaz Plus, Zarah, Zumandimine 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,2-Dihydrospirorenone Dehydrospirorenone Drospirenona Drospirenone Drospirénone Drospirenonum DRSP •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Drospirenone is a progestin used in oral contraceptive pills for the prevention of pregnancy and other conditions.

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 Drospirenone interact? Information: •Drug A: Abciximab •Drug B: Drospirenone •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Drospirenone 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): Drospirenone, in combination with ethinyl estradiol or estetrol, is indicated as an oral contraceptive for the prevention of pregnancy. In addition to its use for contraceptive effects, this combination is used to treat moderate acne vulgaris and the symptoms of premenstrual dysphoric disorder. The drug has approved indications for combination with estrogens for the treatment of menopause-associated symptoms, such as vasomotor symptoms and vulvovaginal atrophy. Drospirenone combined with estrogen may also may aid in the prevention of osteoporosis in women who have been post-menopausal for at least a year and are not candidates for other therapies. It can sometimes be found in preparations containing estrogen and folic acid for folic acid replenishment during oral contraception. When used for the treatment of acne vulgaris, drospirenone-containing contraceptives should only be used in women ≥14 years of age who have experienced menarche, desire oral contraception, and do not have any contraindications to oral contraceptives. Off-label uses for this drug include the treatment of menstrual irregularities, dysmenorrhea, hirsutism, and endometriosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy. It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile. Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings. A note on venous thromboembolism risk and antimineralcorticoid effects As with other oral contraceptives, the risk of venous thromboembolism and cardiovascular events may be increased when drospirenone is taken. The risk is especially higher in smokers and women aged 35 and older. Women taking this drug should be advised not to smoke. In addition, drospirenone, due to its antimineralcorticoid effects, may increase the risk of hyperkalemia. Patients at high risk for hyperkalemia should not be administered this drug. Consult the official prescribing information for detailed and updated information on the cardiovascular and other risks associated with drospirenone use. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation. Drospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion. Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism. Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability of drospirenone is approximately 76% due to first-pass effects. The maximum plasma concentration of drospirenone occurs within 1 to 2 hours after oral administration and is estimated to range between 60 and 87 ng/mL. A European prescribing monograph for the combination product of estradiol and drospirenone indicates that drospirenone is both completely and rapidly absorbed. It reports a Cmax of 21.9 ng/ml, achieved approximately 1-hour post-administration. The absolute bioavailability is reported to range between 76 to 85%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of drospirenone is estimated to be 4 L/kg, according to the FDA label for Yaz. Prescribing information from a combination of estradiol and drospirenone estimates the volume of distribution to range from 3.7- 4.2 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Drospirenone is about 95% to 97% bound to serum plasma protein, likely to albumin. During in vitro studies, drospirenone was found to bind with low affinity to sex hormone-binding globulin (SHBG). Another reference indicates that drospirenone binds to serum albumin but does not bind to sex hormone-binding globulin (SHBG), nor corticoid binding globulin (CBG). Only 3-5% of the total drospirenone concentration is measured as a free steroid. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Drospirenone is heavily metabolized. The two major inactive metabolites identified are the acid form of drospirenone produced by the opening of its lactone ring, known as M11, and the 4,5-dihydro-drospirenone-3-sulfate (M14). Drospirenone also undergoes oxidative metabolism via the hepatic cytochrome enzyme CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Various metabolites of drospirenone are measured in the urine and feces. Drospirenone elimination from the body is almost after 10 days post-administration when negligible amounts of drospirenone are found unchanged in both the urine and feces. Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine. In the feces, approximately 17% to 20% of identifiable metabolites are found to be excreted as glucuronides and sulfates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 drospirenone is estimated to be 30 hours. The half-life of drospirenone metabolite excretion in the urine and feces is approximately 40 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Drospirenone is rapidly cleared, typically within 2-3 days of administration of the last active tablet. The rate of clearance of drospirenone calculated in the serum ranges from 1.2-1.5 ml/min/kg, however, this value can vary by up to 25% according to the patient. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 of drospirenone in rats is >2000 mg/kg. Overdose information An overdose of drospirenone, like other oral contraceptives, may lead to cause nausea or withdrawal bleeding. For drospirenone in particular, as an analog of spironolactone, may affect the levels of serum sodium and potassium. Their concentrations should be monitored in cases of overdose in addition to monitoring from metabolic acidosis and hyperkalemia, which may also result. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Angeliq 0.25/0.5 28 Day, Beyaz 28 Day, Gianvi 28-day, Jasmiel 28 Day, Lo-zumandimine 28 Day, Loryna, Nextstellis 28 Day, Nikki 28 Day, Ocella 28 Day, Safyral 28 Day, Slynd, Syeda 28 Day, Tydemy 28 Day, Vestura, Yasmin, Yasmin 28 Day, Yaz 28 Day, Yaz Plus, Zarah, Zumandimine 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,2-Dihydrospirorenone Dehydrospirorenone Drospirenona Drospirenone Drospirénone Drospirenonum DRSP •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Drospirenone is a progestin used in oral contraceptive pills for the prevention of pregnancy and other conditions. 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 Dulaglutide interact?

•Drug A: Abciximab •Drug B: Dulaglutide •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Dulaglutide. •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): Dulaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years of age with type 2 diabetes mellitus. It is also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dulaglutide reduces fasting glucose concentrations and reduces postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus through the agonism of the GLP-1 receptor. This drug primarily acts as an incretin mimetic hormone or analog of human glucagon-like peptide-1, which normally acts on the GLP-1 receptor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dulaglutide activates the GLP-1 receptor found in pancreatic beta cells, increasing intracellular cyclic AMP (cAMP) in beta cells, leading to insulin release and subsequent reduction of blood glucose concentrations. Additionally, dulaglutide decreases glucagon secretion and slows gastric emptying. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dulaglutide is slowly absorbed after subcutaneous injection. In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing. The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Protein binding information for dulaglutide 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): Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Elimination of dulaglutide is expected to occur through degradation to individual amino acids. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 a pharmacokinetic study of 20 healthy adults, the average half-life of dulaglutide administered at various doses was approximately 3.75 days (89.9 hours). This extended half-life allows for once-weekly dosing. Prescribing information indicates a half-life of approximately 5 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for dulaglutide is not readily available in the literature. Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms. Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trulicity •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): Dulaglutide is a GLP-1 agonist used to manage type 2 diabetes mellitus.

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 Dulaglutide interact? Information: •Drug A: Abciximab •Drug B: Dulaglutide •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Dulaglutide. •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): Dulaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years of age with type 2 diabetes mellitus. It is also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dulaglutide reduces fasting glucose concentrations and reduces postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus through the agonism of the GLP-1 receptor. This drug primarily acts as an incretin mimetic hormone or analog of human glucagon-like peptide-1, which normally acts on the GLP-1 receptor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dulaglutide activates the GLP-1 receptor found in pancreatic beta cells, increasing intracellular cyclic AMP (cAMP) in beta cells, leading to insulin release and subsequent reduction of blood glucose concentrations. Additionally, dulaglutide decreases glucagon secretion and slows gastric emptying. •Absorption (Drug A): No absorption available •Absorption (Drug B): Dulaglutide is slowly absorbed after subcutaneous injection. In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing. The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Protein binding information for dulaglutide 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): Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Elimination of dulaglutide is expected to occur through degradation to individual amino acids. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 a pharmacokinetic study of 20 healthy adults, the average half-life of dulaglutide administered at various doses was approximately 3.75 days (89.9 hours). This extended half-life allows for once-weekly dosing. Prescribing information indicates a half-life of approximately 5 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for dulaglutide is not readily available in the literature. Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms. Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trulicity •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): Dulaglutide is a GLP-1 agonist used to manage type 2 diabetes mellitus. 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 Duloxetine interact?

•Drug A: Abciximab •Drug B: Duloxetine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Duloxetine 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): Indicated for: 1) Management of Major Depressive Disorder. 2) Management of Generalized Anxiety Disorder. 3) Management of diabetic peripheral neuropathy. 4) Management of fibromyalgia. 5) Management of chronic musculoskeletal pain. 6) Management of osteoarthritis of the knee in adults. 7) Management of chronic lower back pain in adults. 8) Management of stress urinary incontinence in adult women. Off-label uses include: 1) Management of chemotherapy-induced peripheral neuropathy. 2) Management of stress urinary incontinence in adult men after prostatectomy until recovery is complete. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter. This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores. It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg. Action at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain. This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys. While duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained. Increased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors. Action on the external urinary sphincter is mediated via duloxetine's CNS effects. Increased serotonin and norepinephrine concentrations in Onuf's nucleus leads to increased activation of 5-HT 2, 5-HT 3, and α 1 adrenergic receptors. 5-HT 2 and α 1 are both G q coupled and their activation increases the activity of the inositol trisphosphate/phospholipase C (IP 3 /PLC) pathway. This pathway leads to release of intracellular calcium stores, increasing intracellular calcium concentrations, and facilitating neuronal excitability. 5-HT 3 functions as a ligand-gated sodium channel which allows sodium to flow into the neuron when activated. Increased flow of sodium into the neuron contributes to depolarization and activation of voltage gated channels involved in action potential generation. The combined action of these three receptors contributes to increased excitability of the pudendal motor nerve in response to glutamate. Also related to duloxetine's action at the spinal cord is its modulation of pain. Increasing the concentration of serotonin and norepinephrine in the dorsal horn of the spinal cord increases descending inhibition of pain through activation of 5-HT 1A, 5-HT 1B, 5-HT 1D, 5-HT 2, 5-HT 3, α 1 -adrenergic, and α 2 -adrenergic receptors. 5-HT 2, 5-HT 3, and α 1 -adrenergic mediate neuronal activation as described above. The activated neuron in this case is the GABAergic inhibitory interneuron which synapses onto the nociceptive projection neuron to inhibit the transmission of painful stimuli to the brain. The 5-HT 1 and α 2 receptors are G i /G o coupled and their activation leads to increased potassium current through inward rectifier channels and decreased adenylyl cyclase/protein kinase A signaling which contributes to neuronal inhibition. These inhibitory receptors are present on the projection neuron itself as well as the dorsal root ganglion which precedes it and serves to directly suppress the transmission of painful stimuli. The mechanisms involved in duloxetine's benefits in depression and anxiety have not been fully elucidated. Dysfunctional serotonin and norepinephrine signaling are thought to be involved and increases in the availability of these neurotransmitters at the synaptic cleft thought to mediate a therapeutic effect. It is postulated that the involvement of serotonin and norepinephrine in area responsible for emotional modulation such as the limbic system contributes to the effects in mood disorders specifically but this has yet to be confirmed. Duloxetine's hypertensive effect is related to its intended pharmacological effect. Increased availability of norepinephrine leads to activation of adrenergic receptors on the vascular endothelium. Since the action of α 1 receptors predominates, vasoconstriction results as the G q coupled receptor mediates calcium release from the sarcoplasmic reticulum to facilitate smooth muscle contraction. •Absorption (Drug A): No absorption available •Absorption (Drug B): Duloxetine is incompletely absorbed with a mean bioavailability of 50% although there is wide variability in the range of 30-80%. The population absorption constant (ka) is 0.168 h.The molecule is susceptible to hydrolysis in acidic environments necessitating the use of an enteric coating to protect it during transit through the stomach. This creates a 2 hour lag time from administration to the start of absorption. The Tmax is 6 hours including the lag time. Administering duloxetine with food 3 hour delay in Tmax along with an 10% decrease in AUC. Similarly, administering the dose at bedtime produces a 4 hour delay and 18% decrease in AUC with a 29% reduction in Cmax. These are attributed to delayed gastric emptying in both cases but are not expected to impact therapy to a clinically significant degree. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Apparent Vd of 1620-1800 L. Duloxetine crosses the blood-brain barrier and collects in the cerebral cortex at a higher concentration than the plasma. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Over 90% bound to plasma proteins, primarily albumin and α1 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): Duloxetine is extensively metabolized primarily by CYP1A2 and CYP2D6 with the former being the greater contributor. It is hydroxylated at the 4, 5, or 6 positions on the naphthalene ring with the 4-hydroxy metabolite proceeding directly to a glucuronide conjugate while the 5 and 6-hydroxy metabolites proceed through a catechol and a 5-hydroxy, 6-methoxy intermediate before undergoing glucuronide or sulfate conjugation. CYP2C9 is known to be a minor contributor to the 5-hydroxy metabolite. Another uncharacterized metabolite is known to be excreted in the feces but comprises <5% of the total excreted drug. Many other metabolites exist but have not been identified due their low contribution to the overall profile of duloxetine and lack of clinical significance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 70% of duloxetine is excreted in the urine mainly as conjugated metabolites. Another 20% is present in the feces as the parent drug, 4-hydroxy metabolite, and an uncharacterized metabolite. Biliary secretion is thought to play a role due to timeline of fecal excretion exceeding the time expected of normal GI transit. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 of 12 h with a range of 8-17. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is a large degree of interindividual variation reported in the clearance of duloxetine with values ranging from 57-114 L/h. Steady state concentrations have still been shown to be dose proportional with a doubling of dose from 30 to 60 mg and from 60 to 120 mg producing 2.3 and 2.6 times the Css respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdose Fatalities have been reported with doses of 1000mg involving both mixed drugs as well as duloxetine alone. Signs and symptoms of overdose include: somnolence, coma, serotonin syndrome, seizure, syncope, hypo- or hypertension, tachycardia, and vomiting. No antidote exists and the drug is unlikely to be cleared by hemodialysis. Supportive care is recommended along with activated charcoal and gastric lavage to reduce absorption. If serotonin syndrome occurs specific treatment such as temperature control or cyproheptadine may be initiated. Carcinogenicity & Mutagenicity Increased incidence of hepatocellular carcinomas and adenomas were reported in female mice fed 140 mg/kg/day duloxetine for 2 years, equivalent to 6 times the maximum recommended human dose (MRHD). No effect was reported with doses of 50mg/kg/day (2 time MRHD) in females or 100 mg/kg/day in males (4 times MRHD). Similar investigation in rats produced no carcinogenicity at doses of 27 mg/kg/day (2 times MRHD)in females and 36 mg/kg/day in males (4 times MRHD). No mutagenicity, clastogenicity, induction of sister chromatid exchange, or genotoxicity has been observed in toxicology investigations. Reproductive Toxicity Neither male or female rats displayed adverse reproductive effects at doses up to 45 mg/kg/day (4 times MRHD). Lactation An estimated 25% of plasma duloxetine appears in breast milk with the estimated daily infant dose being 0.14% of the maternal dose. Breast milk concentrations have been observed to peak 3 hours after administration. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cymbalta, Drizalma, Irenka, Yentreve •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-duloxetine Duloxetina Duloxetine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat generalized anxiety disorder, neuropathic pain, osteoarthritis, and stress incontinence.

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 Duloxetine interact? Information: •Drug A: Abciximab •Drug B: Duloxetine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Duloxetine 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): Indicated for: 1) Management of Major Depressive Disorder. 2) Management of Generalized Anxiety Disorder. 3) Management of diabetic peripheral neuropathy. 4) Management of fibromyalgia. 5) Management of chronic musculoskeletal pain. 6) Management of osteoarthritis of the knee in adults. 7) Management of chronic lower back pain in adults. 8) Management of stress urinary incontinence in adult women. Off-label uses include: 1) Management of chemotherapy-induced peripheral neuropathy. 2) Management of stress urinary incontinence in adult men after prostatectomy until recovery is complete. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter. This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores. It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg. Action at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain. This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys. While duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained. Increased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors. Action on the external urinary sphincter is mediated via duloxetine's CNS effects. Increased serotonin and norepinephrine concentrations in Onuf's nucleus leads to increased activation of 5-HT 2, 5-HT 3, and α 1 adrenergic receptors. 5-HT 2 and α 1 are both G q coupled and their activation increases the activity of the inositol trisphosphate/phospholipase C (IP 3 /PLC) pathway. This pathway leads to release of intracellular calcium stores, increasing intracellular calcium concentrations, and facilitating neuronal excitability. 5-HT 3 functions as a ligand-gated sodium channel which allows sodium to flow into the neuron when activated. Increased flow of sodium into the neuron contributes to depolarization and activation of voltage gated channels involved in action potential generation. The combined action of these three receptors contributes to increased excitability of the pudendal motor nerve in response to glutamate. Also related to duloxetine's action at the spinal cord is its modulation of pain. Increasing the concentration of serotonin and norepinephrine in the dorsal horn of the spinal cord increases descending inhibition of pain through activation of 5-HT 1A, 5-HT 1B, 5-HT 1D, 5-HT 2, 5-HT 3, α 1 -adrenergic, and α 2 -adrenergic receptors. 5-HT 2, 5-HT 3, and α 1 -adrenergic mediate neuronal activation as described above. The activated neuron in this case is the GABAergic inhibitory interneuron which synapses onto the nociceptive projection neuron to inhibit the transmission of painful stimuli to the brain. The 5-HT 1 and α 2 receptors are G i /G o coupled and their activation leads to increased potassium current through inward rectifier channels and decreased adenylyl cyclase/protein kinase A signaling which contributes to neuronal inhibition. These inhibitory receptors are present on the projection neuron itself as well as the dorsal root ganglion which precedes it and serves to directly suppress the transmission of painful stimuli. The mechanisms involved in duloxetine's benefits in depression and anxiety have not been fully elucidated. Dysfunctional serotonin and norepinephrine signaling are thought to be involved and increases in the availability of these neurotransmitters at the synaptic cleft thought to mediate a therapeutic effect. It is postulated that the involvement of serotonin and norepinephrine in area responsible for emotional modulation such as the limbic system contributes to the effects in mood disorders specifically but this has yet to be confirmed. Duloxetine's hypertensive effect is related to its intended pharmacological effect. Increased availability of norepinephrine leads to activation of adrenergic receptors on the vascular endothelium. Since the action of α 1 receptors predominates, vasoconstriction results as the G q coupled receptor mediates calcium release from the sarcoplasmic reticulum to facilitate smooth muscle contraction. •Absorption (Drug A): No absorption available •Absorption (Drug B): Duloxetine is incompletely absorbed with a mean bioavailability of 50% although there is wide variability in the range of 30-80%. The population absorption constant (ka) is 0.168 h.The molecule is susceptible to hydrolysis in acidic environments necessitating the use of an enteric coating to protect it during transit through the stomach. This creates a 2 hour lag time from administration to the start of absorption. The Tmax is 6 hours including the lag time. Administering duloxetine with food 3 hour delay in Tmax along with an 10% decrease in AUC. Similarly, administering the dose at bedtime produces a 4 hour delay and 18% decrease in AUC with a 29% reduction in Cmax. These are attributed to delayed gastric emptying in both cases but are not expected to impact therapy to a clinically significant degree. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Apparent Vd of 1620-1800 L. Duloxetine crosses the blood-brain barrier and collects in the cerebral cortex at a higher concentration than the plasma. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Over 90% bound to plasma proteins, primarily albumin and α1 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): Duloxetine is extensively metabolized primarily by CYP1A2 and CYP2D6 with the former being the greater contributor. It is hydroxylated at the 4, 5, or 6 positions on the naphthalene ring with the 4-hydroxy metabolite proceeding directly to a glucuronide conjugate while the 5 and 6-hydroxy metabolites proceed through a catechol and a 5-hydroxy, 6-methoxy intermediate before undergoing glucuronide or sulfate conjugation. CYP2C9 is known to be a minor contributor to the 5-hydroxy metabolite. Another uncharacterized metabolite is known to be excreted in the feces but comprises <5% of the total excreted drug. Many other metabolites exist but have not been identified due their low contribution to the overall profile of duloxetine and lack of clinical significance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 70% of duloxetine is excreted in the urine mainly as conjugated metabolites. Another 20% is present in the feces as the parent drug, 4-hydroxy metabolite, and an uncharacterized metabolite. Biliary secretion is thought to play a role due to timeline of fecal excretion exceeding the time expected of normal GI transit. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 of 12 h with a range of 8-17. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is a large degree of interindividual variation reported in the clearance of duloxetine with values ranging from 57-114 L/h. Steady state concentrations have still been shown to be dose proportional with a doubling of dose from 30 to 60 mg and from 60 to 120 mg producing 2.3 and 2.6 times the Css respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdose Fatalities have been reported with doses of 1000mg involving both mixed drugs as well as duloxetine alone. Signs and symptoms of overdose include: somnolence, coma, serotonin syndrome, seizure, syncope, hypo- or hypertension, tachycardia, and vomiting. No antidote exists and the drug is unlikely to be cleared by hemodialysis. Supportive care is recommended along with activated charcoal and gastric lavage to reduce absorption. If serotonin syndrome occurs specific treatment such as temperature control or cyproheptadine may be initiated. Carcinogenicity & Mutagenicity Increased incidence of hepatocellular carcinomas and adenomas were reported in female mice fed 140 mg/kg/day duloxetine for 2 years, equivalent to 6 times the maximum recommended human dose (MRHD). No effect was reported with doses of 50mg/kg/day (2 time MRHD) in females or 100 mg/kg/day in males (4 times MRHD). Similar investigation in rats produced no carcinogenicity at doses of 27 mg/kg/day (2 times MRHD)in females and 36 mg/kg/day in males (4 times MRHD). No mutagenicity, clastogenicity, induction of sister chromatid exchange, or genotoxicity has been observed in toxicology investigations. Reproductive Toxicity Neither male or female rats displayed adverse reproductive effects at doses up to 45 mg/kg/day (4 times MRHD). Lactation An estimated 25% of plasma duloxetine appears in breast milk with the estimated daily infant dose being 0.14% of the maternal dose. Breast milk concentrations have been observed to peak 3 hours after administration. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cymbalta, Drizalma, Irenka, Yentreve •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-duloxetine Duloxetina Duloxetine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat generalized anxiety disorder, neuropathic pain, osteoarthritis, and stress incontinence. 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 Dupilumab interact?

•Drug A: Abciximab •Drug B: Dupilumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Dupilumab. •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): In the US, dupilumab is indicated for the treatment of patients aged six months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In Europe and Canada, the drug for this indication is approved for patients aged six years and older. In Europe, patients six to 11 years of age should have severe atopic dermatitis and be candidates for systemic therapy. Dupilumab can be used with or without topical corticosteroids for this condition. Dupilumab is indicated as an add-on maintenance treatment of patients aged six years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. However, the drug is not indicated for relief of acute bronchospasm or status asthmaticus. Dupilumab is indicated as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis. In Canada and Europe, it is used with intranasal corticosteroids. In the US and Europe, dupilumab is also indicated for the treatment of adults and children aged 12 years and older weighing at least 40 kg with eosinophilic esophagitis (EoE), and adults with prurigo nodularis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dupilumab is an recombinant human IgG4 antibody to the IL-4 receptor that works by inhibiting the activation of certain pro-inflammatory cytokines that are implicated in the pathophysiology of several allergic and atopic conditions, including asthma, chronic rhinosinusitis with nasal polyps, and food and environmental allergies. In vivo, dupilumab was shown to reduce the levels of type 2 inflammatory biomarkers associated with atopic dermatitis, such as thymus and activation-regulated chemokine (TARC/CCL17), total serum IgE, allergen-specific IgE, and lactate dehydrogenase (LDH). A decrease in the levels of biomarkers of asthma, such as FeNO, eotaxin-3, IgE, periostin, and eotaxin-3 (CCL26) was also observed. Since dupilumab works to suppress the immune response, it is proposed that it may influence the immune response against some infections, such as helminth infections, by inhibiting IL-4/IL-13 signaling. It is advised that infections are appropriately treated until resolved before initiating dupilumab therapy. While findings of some in vitro and in vivo studies suggest that some cytokine modulators may influence the expression and activity of specific cytochrome P450 (CYP450) enzymes, an open-label drug-drug interaction study demonstrated that dupilumab displays no significant effect on the activity of CYP450 enzymes studied (CYP3A, CYP2C19, CYP2C9, CYP1A2, and CYP2D6). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Type 2 inflammatory processes in various allergic and atopic conditions, such as asthma and atopic diseases, involve the type 2 helper T-cell (Th2) immunity. Upregulation of this Type 2/Th2 pathway is commonly observed in other inflammatory conditions and the activation of Th2 cells is linked to the production of Th2-associated cytokines, such as interleukin (IL) 4, IL-5, IL-9, and IL-13. IL-4 and IL-13 play a central role in inducing inflammatory conditions such as allergic rhinitis, asthma, and atopic dermatitis, by regulating Type 2 inflammation and immune function. These inflammatory cytokines work by modulating gene expression downstream of receptor signalling, regulating Th2 cell differentiation, and activating inflammatory cells such as mast cells and macrophages. There are two types of receptors for IL-4: the type 1 receptor, which is composed of the IL-4 chain (IL-4Rα) and a γ chain (γC), and the type 2 receptor, which is composed of the IL-4Rα chain and the α1 chain of the IL-13 receptor (IL-13Rα1). Essentially, IL‐4Rα is a component shared by the IL‐4 and IL-13 receptor complexes and is ubiquitously expressed on both innate and adaptive immune cells to promote the signaling of IL-4 and IL-13. The type I receptor is primarily expressed on lymphocytes and controls Th2-cell differentiation, whereas the type II receptor is mostly found across resident and myeloid cells. Dupilumab is a fully human monoclonal antibody directed against IL‐4Rα to inhibit the signalling of IL‐4 and IL‐13. Dupilumab inhibits IL-4 signalling via the Type I receptor (IL-4Rα/γc), and both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα). It ultimately downregulates type-2 immunity. •Absorption (Drug A): No absorption available •Absorption (Drug B): The Cmax following administration of a single subcutaneous dose of 600 mg or 400 mg of dupilumab were 70.1 ± 24.1 mcg/mL or 41.8 ± 12.4 mcg/mL, respectively. The Tmax ranged from 3 to 7 days following administration of a single subcutaneous dose ranging from 75 to 600 mg. Following a subcutaneous dose, the absolute bioavailability of dupilumab ranged between 61% and 64% in patients with atopic dermatitis or asthma. In clinical trials, the steady-state concentrations were reached by week 16 following the administration of 600 mg starting dose and 300 mg dose every other week. At these concentrations, the mean trough concentrations ranged from 60.3 ± 35.1 mcg/mL to 79.9 ± 41.4 mcg/mL for 300 mg dose and from 29.2 ± 18.7 to 36.5 ± 22.2 mcg/mL for 200 mg dose administered every other week. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated volume of distribution is 4.8 ± 1.3 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is limited data on the serum protein binding profile of dupilumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Being a monoclonal antibody, dupilumab is not expected to undergo significant hepatic metabolism. While the metabolism of dupilumab has not been characterized, it is speculated that dupilumab undergoes nonspecific degradation into smaller peptides and amino acids, as often observed with endogenous IgG. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Being a monoclonal antibody, dupilumab is not expected to undergo significant renal elimination. It is proposed that dupilumab is eliminated via parallel linear and nonlinear pathways. At higher concentrations, dupilumab is primarily cleared through a non-saturable proteolytic pathway. At lower concentrations, it undergoes a non-linear saturable IL-4R α target-mediated 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): There is limited human data on the half-life of dupilumab. In single-dose pharmacokinetic studies, the mean half-life of dupilumab following intravenous or subcutaneous administration ranged from 4.8 to 7 days in rats and 11.7 to 20.5 days in cynomolgus monkeys. In these studies, the mean half-life was comparable was comparable following intravenous and subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is limited data on the clearance of dupilumab. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited data on the overdose of dupilumab. As there is no specific treatment for dupilumab, close monitoring of the patient with appropriate symptomatic treatment is advised in case of suspected overdosage.[] •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dupixent •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): Dupilumab is a monoclonal antibody used to treat moderate to severe atopic dermatitis, asthma, and nasal polyps accompanied by chronic rhinosinusitis in adolescents and 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 Dupilumab interact? Information: •Drug A: Abciximab •Drug B: Dupilumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Dupilumab. •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): In the US, dupilumab is indicated for the treatment of patients aged six months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In Europe and Canada, the drug for this indication is approved for patients aged six years and older. In Europe, patients six to 11 years of age should have severe atopic dermatitis and be candidates for systemic therapy. Dupilumab can be used with or without topical corticosteroids for this condition. Dupilumab is indicated as an add-on maintenance treatment of patients aged six years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. However, the drug is not indicated for relief of acute bronchospasm or status asthmaticus. Dupilumab is indicated as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis. In Canada and Europe, it is used with intranasal corticosteroids. In the US and Europe, dupilumab is also indicated for the treatment of adults and children aged 12 years and older weighing at least 40 kg with eosinophilic esophagitis (EoE), and adults with prurigo nodularis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dupilumab is an recombinant human IgG4 antibody to the IL-4 receptor that works by inhibiting the activation of certain pro-inflammatory cytokines that are implicated in the pathophysiology of several allergic and atopic conditions, including asthma, chronic rhinosinusitis with nasal polyps, and food and environmental allergies. In vivo, dupilumab was shown to reduce the levels of type 2 inflammatory biomarkers associated with atopic dermatitis, such as thymus and activation-regulated chemokine (TARC/CCL17), total serum IgE, allergen-specific IgE, and lactate dehydrogenase (LDH). A decrease in the levels of biomarkers of asthma, such as FeNO, eotaxin-3, IgE, periostin, and eotaxin-3 (CCL26) was also observed. Since dupilumab works to suppress the immune response, it is proposed that it may influence the immune response against some infections, such as helminth infections, by inhibiting IL-4/IL-13 signaling. It is advised that infections are appropriately treated until resolved before initiating dupilumab therapy. While findings of some in vitro and in vivo studies suggest that some cytokine modulators may influence the expression and activity of specific cytochrome P450 (CYP450) enzymes, an open-label drug-drug interaction study demonstrated that dupilumab displays no significant effect on the activity of CYP450 enzymes studied (CYP3A, CYP2C19, CYP2C9, CYP1A2, and CYP2D6). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Type 2 inflammatory processes in various allergic and atopic conditions, such as asthma and atopic diseases, involve the type 2 helper T-cell (Th2) immunity. Upregulation of this Type 2/Th2 pathway is commonly observed in other inflammatory conditions and the activation of Th2 cells is linked to the production of Th2-associated cytokines, such as interleukin (IL) 4, IL-5, IL-9, and IL-13. IL-4 and IL-13 play a central role in inducing inflammatory conditions such as allergic rhinitis, asthma, and atopic dermatitis, by regulating Type 2 inflammation and immune function. These inflammatory cytokines work by modulating gene expression downstream of receptor signalling, regulating Th2 cell differentiation, and activating inflammatory cells such as mast cells and macrophages. There are two types of receptors for IL-4: the type 1 receptor, which is composed of the IL-4 chain (IL-4Rα) and a γ chain (γC), and the type 2 receptor, which is composed of the IL-4Rα chain and the α1 chain of the IL-13 receptor (IL-13Rα1). Essentially, IL‐4Rα is a component shared by the IL‐4 and IL-13 receptor complexes and is ubiquitously expressed on both innate and adaptive immune cells to promote the signaling of IL-4 and IL-13. The type I receptor is primarily expressed on lymphocytes and controls Th2-cell differentiation, whereas the type II receptor is mostly found across resident and myeloid cells. Dupilumab is a fully human monoclonal antibody directed against IL‐4Rα to inhibit the signalling of IL‐4 and IL‐13. Dupilumab inhibits IL-4 signalling via the Type I receptor (IL-4Rα/γc), and both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα). It ultimately downregulates type-2 immunity. •Absorption (Drug A): No absorption available •Absorption (Drug B): The Cmax following administration of a single subcutaneous dose of 600 mg or 400 mg of dupilumab were 70.1 ± 24.1 mcg/mL or 41.8 ± 12.4 mcg/mL, respectively. The Tmax ranged from 3 to 7 days following administration of a single subcutaneous dose ranging from 75 to 600 mg. Following a subcutaneous dose, the absolute bioavailability of dupilumab ranged between 61% and 64% in patients with atopic dermatitis or asthma. In clinical trials, the steady-state concentrations were reached by week 16 following the administration of 600 mg starting dose and 300 mg dose every other week. At these concentrations, the mean trough concentrations ranged from 60.3 ± 35.1 mcg/mL to 79.9 ± 41.4 mcg/mL for 300 mg dose and from 29.2 ± 18.7 to 36.5 ± 22.2 mcg/mL for 200 mg dose administered every other week. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The estimated volume of distribution is 4.8 ± 1.3 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is limited data on the serum protein binding profile of dupilumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Being a monoclonal antibody, dupilumab is not expected to undergo significant hepatic metabolism. While the metabolism of dupilumab has not been characterized, it is speculated that dupilumab undergoes nonspecific degradation into smaller peptides and amino acids, as often observed with endogenous IgG. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Being a monoclonal antibody, dupilumab is not expected to undergo significant renal elimination. It is proposed that dupilumab is eliminated via parallel linear and nonlinear pathways. At higher concentrations, dupilumab is primarily cleared through a non-saturable proteolytic pathway. At lower concentrations, it undergoes a non-linear saturable IL-4R α target-mediated 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): There is limited human data on the half-life of dupilumab. In single-dose pharmacokinetic studies, the mean half-life of dupilumab following intravenous or subcutaneous administration ranged from 4.8 to 7 days in rats and 11.7 to 20.5 days in cynomolgus monkeys. In these studies, the mean half-life was comparable was comparable following intravenous and subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is limited data on the clearance of dupilumab. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited data on the overdose of dupilumab. As there is no specific treatment for dupilumab, close monitoring of the patient with appropriate symptomatic treatment is advised in case of suspected overdosage.[] •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Dupixent •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): Dupilumab is a monoclonal antibody used to treat moderate to severe atopic dermatitis, asthma, and nasal polyps accompanied by chronic rhinosinusitis in adolescents and 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 Durvalumab interact?

•Drug A: Abciximab •Drug B: Durvalumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Durvalumab. •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): Durvalumab is indicated for the treatment of adults with the following conditions: unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumour aberrations, in combination with tremelimumab and platinum-based chemotherapy. extensive-stage small cell lung cancer (ES-SCLC) in combination with etoposide and either carboplatin or cisplatin as first-line therapy. locally advanced or metastatic biliary tract cancer (BTC) in combination with gemcitabine and cisplatin. unresectable hepatocellular carcinoma (uHCC) in combination with tremelimumab. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Durvalumab is an anticancer antibody that works to promote the antitumour responses mediated by immune cells. By blocking the action of PD-L1, durvalumab exerts its anticancer effects by increasing T-cell activation, enhancing detection and ablation of tumour cells. In in vitro assays, durvalumab inhibited the activity of PD-L1 in a concentration-dependent manner. In co-engrafted human tumor and immune cell xenograft mouse models, durvalumab was effective in decreasing tumour size. Durvalumab does not mediate antibody-dependent cell-mediated 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): Because cancer cells express antigens that are recognized and taken up by antigen-presenting cells (APCs), the immune responses prime and activate cytotoxic T cells, and allow them to travel to the site of the tumour to destroy cancer cells. However, tumours often evade T cell-mediated immune responses to enhance their survival. Inflammatory mediators, such as IFN-gamma, induce the expression of programmed cell death ligand-1 (PD-L1), which is a type 1 transmembrane protein expressed on tumour cells and tumour-associated immune cells in the tumour microenvironment. PD-L1 acts as an immune checkpoint to regulate immune responses. PD-L1 is a ligand to PD-1, which is a cell surface receptor expressed on activated T cells in peripheral tissues following antigen exposure. Both PD-L1 and PD-1 are co-inhibitory molecules involved in blocking T cell-mediated immune responses. PD-L1 also interacts with CD-80, which is a receptor constitutively expressed by T cells and is upregulated early after T cell activation. The expression of PD-L1 is an adaptive immune response by tumour cells, resulting in the over-expression of the molecule in some cancers. PD-L1 interacts with PD-1 and CD80, which leads to blocked cytotoxic T cell activation, T cell proliferation, and cytokine production. By binding to PD-L1 and preventing its association with PD-1 and CD80, durvalumab activates the immune responses mediated by cytotoxic T cells that attack tumour cells. Durvalumab displays selective and high affinity toward PD-L1 but not PD-L2, which is a regulatory ligand expressed in tumour cells to a lesser extent and involved in regulating inflammation and differentiation of T cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): Durvalumab exhibits a dose-proportional pharmacokinetic profile that is non-linear at doses <3 mg/kg and linear at doses ≥3 mg/kg. Following intravenous administration in patients with solid tumours, the steady-state plasma concentrations were reached at approximately 16 weeks. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients receiving the dose range of ≥ 10 mg/kg every 2 weeks, the mean steady state volume of distribution (Vss) was 5.64 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is limited information on the serum protein binding profile of durvalumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Durvalumab is subject to protein catabolism via reticuloedothelial system or target-mediated disposition. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Durvalumab is primarily eliminated by protein catabolism. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Based on baseline clearance rate, the geometric mean terminal half-life is 18 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of durvalumab decreases over time, resulting in a mean steady-state clearance (CLss) of 8.2 mL/h following 365 days of initial drug administration. However, the decrease in CLss is not considered clinically relevant. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information about the overdose profile and LD 50 of durvalumab. In case of overdose, the patient should be closely monitored for drug-related adverse events, and appropriate symptomatic treatment should be immediately initiated. Based on the findings of clinical studies, durvalumab had a risk of causing immune-mediated reactions, such as pneumonitis, hepatitis, and other serious infections. In animal reproductive studies, durvalumab caused fetal harm and this fetal toxicity may be possible in humans. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Imfinzi •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): Durvalumab is an antineoplastic monoclonal antibody used to treat urothelial carcinoma and locally advanced, unresectable 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 Durvalumab interact? Information: •Drug A: Abciximab •Drug B: Durvalumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Durvalumab. •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): Durvalumab is indicated for the treatment of adults with the following conditions: unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumour aberrations, in combination with tremelimumab and platinum-based chemotherapy. extensive-stage small cell lung cancer (ES-SCLC) in combination with etoposide and either carboplatin or cisplatin as first-line therapy. locally advanced or metastatic biliary tract cancer (BTC) in combination with gemcitabine and cisplatin. unresectable hepatocellular carcinoma (uHCC) in combination with tremelimumab. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Durvalumab is an anticancer antibody that works to promote the antitumour responses mediated by immune cells. By blocking the action of PD-L1, durvalumab exerts its anticancer effects by increasing T-cell activation, enhancing detection and ablation of tumour cells. In in vitro assays, durvalumab inhibited the activity of PD-L1 in a concentration-dependent manner. In co-engrafted human tumor and immune cell xenograft mouse models, durvalumab was effective in decreasing tumour size. Durvalumab does not mediate antibody-dependent cell-mediated 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): Because cancer cells express antigens that are recognized and taken up by antigen-presenting cells (APCs), the immune responses prime and activate cytotoxic T cells, and allow them to travel to the site of the tumour to destroy cancer cells. However, tumours often evade T cell-mediated immune responses to enhance their survival. Inflammatory mediators, such as IFN-gamma, induce the expression of programmed cell death ligand-1 (PD-L1), which is a type 1 transmembrane protein expressed on tumour cells and tumour-associated immune cells in the tumour microenvironment. PD-L1 acts as an immune checkpoint to regulate immune responses. PD-L1 is a ligand to PD-1, which is a cell surface receptor expressed on activated T cells in peripheral tissues following antigen exposure. Both PD-L1 and PD-1 are co-inhibitory molecules involved in blocking T cell-mediated immune responses. PD-L1 also interacts with CD-80, which is a receptor constitutively expressed by T cells and is upregulated early after T cell activation. The expression of PD-L1 is an adaptive immune response by tumour cells, resulting in the over-expression of the molecule in some cancers. PD-L1 interacts with PD-1 and CD80, which leads to blocked cytotoxic T cell activation, T cell proliferation, and cytokine production. By binding to PD-L1 and preventing its association with PD-1 and CD80, durvalumab activates the immune responses mediated by cytotoxic T cells that attack tumour cells. Durvalumab displays selective and high affinity toward PD-L1 but not PD-L2, which is a regulatory ligand expressed in tumour cells to a lesser extent and involved in regulating inflammation and differentiation of T cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): Durvalumab exhibits a dose-proportional pharmacokinetic profile that is non-linear at doses <3 mg/kg and linear at doses ≥3 mg/kg. Following intravenous administration in patients with solid tumours, the steady-state plasma concentrations were reached at approximately 16 weeks. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients receiving the dose range of ≥ 10 mg/kg every 2 weeks, the mean steady state volume of distribution (Vss) was 5.64 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is limited information on the serum protein binding profile of durvalumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Durvalumab is subject to protein catabolism via reticuloedothelial system or target-mediated disposition. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Durvalumab is primarily eliminated by protein catabolism. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Based on baseline clearance rate, the geometric mean terminal half-life is 18 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance of durvalumab decreases over time, resulting in a mean steady-state clearance (CLss) of 8.2 mL/h following 365 days of initial drug administration. However, the decrease in CLss is not considered clinically relevant. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information about the overdose profile and LD 50 of durvalumab. In case of overdose, the patient should be closely monitored for drug-related adverse events, and appropriate symptomatic treatment should be immediately initiated. Based on the findings of clinical studies, durvalumab had a risk of causing immune-mediated reactions, such as pneumonitis, hepatitis, and other serious infections. In animal reproductive studies, durvalumab caused fetal harm and this fetal toxicity may be possible in humans. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Imfinzi •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): Durvalumab is an antineoplastic monoclonal antibody used to treat urothelial carcinoma and locally advanced, unresectable 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 Dydrogesterone interact?

•Drug A: Abciximab •Drug B: Dydrogesterone •Severity: MODERATE •Description: Dydrogesterone may decrease the anticoagulant activities of Abciximab. •Extended Description: Progestins affect hemostasis by exerting a procoagulant activity and are associated with a risk for thromboembolic disorders. While there is limited clinical evidence that progestins may interfere with the pharmacological activity of anticoagulants when co-administered, concurrent use of progestins with anticoagulants may potentially interfere with the anticoagulant actions. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%. •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): Metabolism is complete to a 20-dihydrodydrogesterone (DHD) metabolite. •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): Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No serious or unexpected toxicity has been observed with dydrogesterone. In acute toxicity studies, the LD50 doses in rats exceeded 4,640mg/kg for the oral route. •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): Didrogesterona Didrogesterone Dydrogesterona Dydrogestérone Dydrogesterone Dydrogesteronum Gestatron Hydrogesterone Hydrogestrone Isopregnenone •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dydrogesterone is a synthetic progesterone for menstrual cycle regulation, infertility treatment, prevention of miscarriage, and other conditions.

Progestins affect hemostasis by exerting a procoagulant activity and are associated with a risk for thromboembolic disorders. While there is limited clinical evidence that progestins may interfere with the pharmacological activity of anticoagulants when co-administered, concurrent use of progestins with anticoagulants may potentially interfere with the anticoagulant actions. The severity of the interaction is moderate.

Question: Does Abciximab and Dydrogesterone interact? Information: •Drug A: Abciximab •Drug B: Dydrogesterone •Severity: MODERATE •Description: Dydrogesterone may decrease the anticoagulant activities of Abciximab. •Extended Description: Progestins affect hemostasis by exerting a procoagulant activity and are associated with a risk for thromboembolic disorders. While there is limited clinical evidence that progestins may interfere with the pharmacological activity of anticoagulants when co-administered, concurrent use of progestins with anticoagulants may potentially interfere with the anticoagulant actions. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%. •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): Metabolism is complete to a 20-dihydrodydrogesterone (DHD) metabolite. •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): Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No serious or unexpected toxicity has been observed with dydrogesterone. In acute toxicity studies, the LD50 doses in rats exceeded 4,640mg/kg for the oral route. •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): Didrogesterona Didrogesterone Dydrogesterona Dydrogestérone Dydrogesterone Dydrogesteronum Gestatron Hydrogesterone Hydrogestrone Isopregnenone •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Dydrogesterone is a synthetic progesterone for menstrual cycle regulation, infertility treatment, prevention of miscarriage, and other conditions. Output: Progestins affect hemostasis by exerting a procoagulant activity and are associated with a risk for thromboembolic disorders. While there is limited clinical evidence that progestins may interfere with the pharmacological activity of anticoagulants when co-administered, concurrent use of progestins with anticoagulants may potentially interfere with the anticoagulant actions. The severity of the interaction is moderate.

Does Abciximab and Ebola Zaire vaccine (live, attenuated) interact?

•Drug A: Abciximab •Drug B: Ebola Zaire vaccine (live, attenuated) •Severity: MINOR •Description: The therapeutic efficacy of Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Abciximab. •Extended Description: Immunoglobulins suppress the immune response and may reduce the therapeutic effectiveness of live attenuated Ebola vaccine virus when co-administered in a short time frame, as vaccines work by eliciting an immune response. It is speculated that administration of immune globulins administered 3 months before or up to 1 month after the Ebola virus vaccine administration may interfere with the expected immune response. There is also a possibility of an infection, as live vaccines hold viral proteins and carry a risk of systemic infection, especially to individuals with profound immunosuppression caused by disease or 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

Immunoglobulins suppress the immune response and may reduce the therapeutic effectiveness of live attenuated Ebola vaccine virus when co-administered in a short time frame, as vaccines work by eliciting an immune response. It is speculated that administration of immune globulins administered 3 months before or up to 1 month after the Ebola virus vaccine administration may interfere with the expected immune response. There is also a possibility of an infection, as live vaccines hold viral proteins and carry a risk of systemic infection, especially to individuals with profound immunosuppression caused by disease or drugs. The severity of the interaction is minor.

Question: Does Abciximab and Ebola Zaire vaccine (live, attenuated) interact? Information: •Drug A: Abciximab •Drug B: Ebola Zaire vaccine (live, attenuated) •Severity: MINOR •Description: The therapeutic efficacy of Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Abciximab. •Extended Description: Immunoglobulins suppress the immune response and may reduce the therapeutic effectiveness of live attenuated Ebola vaccine virus when co-administered in a short time frame, as vaccines work by eliciting an immune response. It is speculated that administration of immune globulins administered 3 months before or up to 1 month after the Ebola virus vaccine administration may interfere with the expected immune response. There is also a possibility of an infection, as live vaccines hold viral proteins and carry a risk of systemic infection, especially to individuals with profound immunosuppression caused by disease or 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: Immunoglobulins suppress the immune response and may reduce the therapeutic effectiveness of live attenuated Ebola vaccine virus when co-administered in a short time frame, as vaccines work by eliciting an immune response. It is speculated that administration of immune globulins administered 3 months before or up to 1 month after the Ebola virus vaccine administration may interfere with the expected immune response. There is also a possibility of an infection, as live vaccines hold viral proteins and carry a risk of systemic infection, especially to individuals with profound immunosuppression caused by disease or drugs. The severity of the interaction is minor.

Does Abciximab and Eculizumab interact?

•Drug A: Abciximab •Drug B: Eculizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Eculizumab. •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): Eculizumab is indicated in the US to treat paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy, and neuromyelitis optica spectrum disorder (NMOSD). It is also indicated in EU to treat PNH in both adult and pediatric 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): Eculizumab is a monoclonal antibody that prevents the activation of terminal complement in some autoimmune conditions. Eculizumab has a long duration of action. Patients taking this medication should be vaccinated against Neisseria meningiditis as serious meningococcal infections have occurred in the past. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eculizumab is a monoclonal antibody that targets complement protein C5, preventing cleavage to C5a and C5b, and the formation of the terminal complement complex C5b-9. Inhibition of this complex prevents complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobunuria, complement mediated microangiopathy in atypical hemolytic uremic syndrome, and immune mediated inflammation and damage of the central nervous system in neuromyelitis optica spectrum disorder. •Absorption (Drug A): No absorption available •Absorption (Drug B): Eculizumab is administered by intravenous infusion so the bioavailability is 100%. This drug reaches a C max of 194±76µg/mL and C trough of 97±60µg/mL. The AUC was calculated to be 24,467.6µg*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of eculizumab is 5-8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Though protein binding data is scarce, eculizumab is unlikely to be protein bound as it is a monoclonal antibody. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Eculizumab is a monoclonal antibody and is expected to be metabolized to small peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies are not eliminated in the urine, and only a small amount is excreted in bile. Most monoclonal antibodies are catabolized in lysosomes to amino acids. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 eculizumab is 270-375h or 272±82h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pharmacokinetic properties in healthy patients have not been determined. In patients with rhematoid arthritis, there is an average clearance of 0.26mL/kg/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdoses of eculizumab are unlikely as it is administered under specialist supervision. In case of overdose, contact local poison control. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Soliris •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): Eculizumab is a recombinant humanized monoclonal antibody used to reduce the risk of hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

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 Eculizumab interact? Information: •Drug A: Abciximab •Drug B: Eculizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Eculizumab. •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): Eculizumab is indicated in the US to treat paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy, and neuromyelitis optica spectrum disorder (NMOSD). It is also indicated in EU to treat PNH in both adult and pediatric 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): Eculizumab is a monoclonal antibody that prevents the activation of terminal complement in some autoimmune conditions. Eculizumab has a long duration of action. Patients taking this medication should be vaccinated against Neisseria meningiditis as serious meningococcal infections have occurred in the past. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eculizumab is a monoclonal antibody that targets complement protein C5, preventing cleavage to C5a and C5b, and the formation of the terminal complement complex C5b-9. Inhibition of this complex prevents complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobunuria, complement mediated microangiopathy in atypical hemolytic uremic syndrome, and immune mediated inflammation and damage of the central nervous system in neuromyelitis optica spectrum disorder. •Absorption (Drug A): No absorption available •Absorption (Drug B): Eculizumab is administered by intravenous infusion so the bioavailability is 100%. This drug reaches a C max of 194±76µg/mL and C trough of 97±60µg/mL. The AUC was calculated to be 24,467.6µg*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of eculizumab is 5-8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Though protein binding data is scarce, eculizumab is unlikely to be protein bound as it is a monoclonal antibody. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Eculizumab is a monoclonal antibody and is expected to be metabolized to small peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibodies are not eliminated in the urine, and only a small amount is excreted in bile. Most monoclonal antibodies are catabolized in lysosomes to amino acids. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 eculizumab is 270-375h or 272±82h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Pharmacokinetic properties in healthy patients have not been determined. In patients with rhematoid arthritis, there is an average clearance of 0.26mL/kg/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdoses of eculizumab are unlikely as it is administered under specialist supervision. In case of overdose, contact local poison control. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Soliris •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): Eculizumab is a recombinant humanized monoclonal antibody used to reduce the risk of hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). 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 Edetic acid interact?

•Drug A: Abciximab •Drug B: Edetic acid •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Edetic acid. •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 the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and 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): Edetate calcium is a heavy metal chelating agent. The calcium in edetate calcium can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. In theory, 1 g of edetate calcium can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, edetate calcium also chelates and eliminates zinc from the body. Edetate calcium also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. Edetate calcium is relatively ineffective for use in treating mercury, gold or arsenic poisoning. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron metabolized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased. •Absorption (Drug A): No absorption available •Absorption (Drug B): Poorly absorbed from the gastrointestinal tract. Well absorbed following intramuscular injection. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Almost none of the compound is metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): It is excreted primarily by the kidney, with about 50% excreted in one hour and over 95% within 24 hours.2 Almost none of the compound is metabolized. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 edetate calcium disodium is 20 to 60 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dl did not cause any ill effects. Edetate calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning. Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of edetate calcium disodium may produce a more severe zinc deficiency. •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): Acide edetique Acide ethylenediaminetetracetique Acido edetico Acidum edeticum Edetic acid EDTA Ethylenediaminetetraacetate Ethylenediaminetetraacetic 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): Edetic acid is a chelating agent used to treat mercury and lead toxicity and some blood transfusion dependent anemias.

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 Edetic acid interact? Information: •Drug A: Abciximab •Drug B: Edetic acid •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Edetic acid. •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 the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and 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): Edetate calcium is a heavy metal chelating agent. The calcium in edetate calcium can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. In theory, 1 g of edetate calcium can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, edetate calcium also chelates and eliminates zinc from the body. Edetate calcium also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. Edetate calcium is relatively ineffective for use in treating mercury, gold or arsenic poisoning. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron metabolized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased. •Absorption (Drug A): No absorption available •Absorption (Drug B): Poorly absorbed from the gastrointestinal tract. Well absorbed following intramuscular injection. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Almost none of the compound is metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): It is excreted primarily by the kidney, with about 50% excreted in one hour and over 95% within 24 hours.2 Almost none of the compound is metabolized. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 edetate calcium disodium is 20 to 60 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dl did not cause any ill effects. Edetate calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning. Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of edetate calcium disodium may produce a more severe zinc deficiency. •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): Acide edetique Acide ethylenediaminetetracetique Acido edetico Acidum edeticum Edetic acid EDTA Ethylenediaminetetraacetate Ethylenediaminetetraacetic 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): Edetic acid is a chelating agent used to treat mercury and lead toxicity and some blood transfusion dependent anemias. 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 Edoxaban interact?

•Drug A: Abciximab •Drug B: Edoxaban •Severity: MAJOR •Description: The risk or severity of bleeding can be increased when Edoxaban is combined with Abciximab. •Extended Description: Edoxoaban is associated with a risk for serious bleeding, including serious and fatal bleeding events. Concomitant use of edoxoban with drugs affecting hemostasis, including other anticoagulant drugs, may increase the anticoagulant effect of those drugs due to an additive effect and 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): Edoxaban is indicated for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). However, it should not be used in patients with creatinine clearance (CrCL) > 95 mL/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg). It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, peak plasma edoxaban concentrations are observed within 1-2 hours. Absolute bioavailability is 62%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady state volume of distribution is 107 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro plasma protein binding is ~55%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Edoxaban is not extensively metabolized by CYP3A4 resulting in minimal drug-drug interactions. However, it does interact with drugs that inhibit p-gp (p-glycoprotein), which is used to transport edoxaban across the intestinal wall. Unchanged edoxaban is the predominant form in plasma. There is minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4. The predominant metabolite M-4, formed by hydrolysis, is human-specific and active and reaches less than 10% of the exposure of the parent compound in healthy subjects. Exposure to the other metabolites is less than 5% of exposure to edoxaban. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Edoxaban is eliminated primarily as unchanged drug in urine. Renal clearance (11 L/hour) accounts for approximately 50% of the total clearance of edoxaban (22 L/hour). Metabolism and biliary/intestinal excretion account for the remaining clearance. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 edoxaban following oral administration is 10 to 14 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 22 L/hr •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant. Edoxaban increases the risk of potentially fatal major bleeding such as intracranial hemorrhage and gastrointestinal bleeding. Patients should be educated on how to watch for signs of major and minor bleeding and when to seek medical help. Co-administration of other anti-coagulants, anti-platelets, or thrombolytics may increase the risk of bleeding and should therefore be avoided. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lixiana, Savaysa •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): Edoxaban is a novel oral anticoagulant used for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF).

Edoxoaban is associated with a risk for serious bleeding, including serious and fatal bleeding events. Concomitant use of edoxoban with drugs affecting hemostasis, including other anticoagulant drugs, may increase the anticoagulant effect of those drugs due to an additive effect and increase the risk of bleeding. The severity of the interaction is major.

Question: Does Abciximab and Edoxaban interact? Information: •Drug A: Abciximab •Drug B: Edoxaban •Severity: MAJOR •Description: The risk or severity of bleeding can be increased when Edoxaban is combined with Abciximab. •Extended Description: Edoxoaban is associated with a risk for serious bleeding, including serious and fatal bleeding events. Concomitant use of edoxoban with drugs affecting hemostasis, including other anticoagulant drugs, may increase the anticoagulant effect of those drugs due to an additive effect and 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): Edoxaban is indicated for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). However, it should not be used in patients with creatinine clearance (CrCL) > 95 mL/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg). It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, peak plasma edoxaban concentrations are observed within 1-2 hours. Absolute bioavailability is 62%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady state volume of distribution is 107 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro plasma protein binding is ~55%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Edoxaban is not extensively metabolized by CYP3A4 resulting in minimal drug-drug interactions. However, it does interact with drugs that inhibit p-gp (p-glycoprotein), which is used to transport edoxaban across the intestinal wall. Unchanged edoxaban is the predominant form in plasma. There is minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4. The predominant metabolite M-4, formed by hydrolysis, is human-specific and active and reaches less than 10% of the exposure of the parent compound in healthy subjects. Exposure to the other metabolites is less than 5% of exposure to edoxaban. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Edoxaban is eliminated primarily as unchanged drug in urine. Renal clearance (11 L/hour) accounts for approximately 50% of the total clearance of edoxaban (22 L/hour). Metabolism and biliary/intestinal excretion account for the remaining clearance. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 edoxaban following oral administration is 10 to 14 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): 22 L/hr •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant. Edoxaban increases the risk of potentially fatal major bleeding such as intracranial hemorrhage and gastrointestinal bleeding. Patients should be educated on how to watch for signs of major and minor bleeding and when to seek medical help. Co-administration of other anti-coagulants, anti-platelets, or thrombolytics may increase the risk of bleeding and should therefore be avoided. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lixiana, Savaysa •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): Edoxaban is a novel oral anticoagulant used for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). Output: Edoxoaban is associated with a risk for serious bleeding, including serious and fatal bleeding events. Concomitant use of edoxoban with drugs affecting hemostasis, including other anticoagulant drugs, may increase the anticoagulant effect of those drugs due to an additive effect and increase the risk of bleeding. The severity of the interaction is major.

Does Abciximab and Eflapegrastim interact?

•Drug A: Abciximab •Drug B: Eflapegrastim •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Eflapegrastim. •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): Eflapegrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eflapegrastim increases absolute neutrophil count (ANC) in a dose-dependent manner in both healthy subjects and cancer patients. In rat studies, it was associated with higher serum and bone marrow concentrations than pegfilgrastim, which translated to a significantly shorter duration of neutropenia when eflapegrastim was administered 24 hours post-chemotherapy compared to pegfilgrastim. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eflapegrastim is a recombinant human granulocyte-colony stimulating factor (rhG-CSF). Like endogenous G-CSF, eflapegrastim binds to G-CSF receptors on myeloid progenitor cells and neutrophils - this triggers signaling pathways that result in neutrophil differentiation, proliferation, migration, and survival. •Absorption (Drug A): No absorption available •Absorption (Drug B): The T max of eflapegrastim is dose-dependent and increases with increasing dose. Following administration of the recommended dosage in patients with breast cancer, the median T max of eflapegrastim-xnst is 25 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of eflapegrastim-xnst is 1.44 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): Eflapegrastim is likely metabolized via endogenous degradation following internalization by cells expressing G-CSF receptors. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following subcutaneous administration, eflapegrastim is not detectable 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): In patients with breast cancer, the geometric mean half-life of eflapegrastim-xnst is 36.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of eflapegrastim-xnst decreased with increasing dose, suggesting target-mediated clearance by neutrophils. With repeat dosing clearance appears to increase, potentially due to the subsequent increase in circulating neutrophils. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): An overdose of eflapegrastim may result in leukocytosis and bone pain. In the event of an overdose, the patient should be monitored for adverse effects and general supportive measures should be implemented as necessary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rolvedon •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): Eflapegrastim is a form of recombinant human granulocyte colony stimulating factor used to induce the production of granulocytes and lower infection risk after myelosuppressive 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 Eflapegrastim interact? Information: •Drug A: Abciximab •Drug B: Eflapegrastim •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Eflapegrastim. •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): Eflapegrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eflapegrastim increases absolute neutrophil count (ANC) in a dose-dependent manner in both healthy subjects and cancer patients. In rat studies, it was associated with higher serum and bone marrow concentrations than pegfilgrastim, which translated to a significantly shorter duration of neutropenia when eflapegrastim was administered 24 hours post-chemotherapy compared to pegfilgrastim. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eflapegrastim is a recombinant human granulocyte-colony stimulating factor (rhG-CSF). Like endogenous G-CSF, eflapegrastim binds to G-CSF receptors on myeloid progenitor cells and neutrophils - this triggers signaling pathways that result in neutrophil differentiation, proliferation, migration, and survival. •Absorption (Drug A): No absorption available •Absorption (Drug B): The T max of eflapegrastim is dose-dependent and increases with increasing dose. Following administration of the recommended dosage in patients with breast cancer, the median T max of eflapegrastim-xnst is 25 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of eflapegrastim-xnst is 1.44 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): Eflapegrastim is likely metabolized via endogenous degradation following internalization by cells expressing G-CSF receptors. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following subcutaneous administration, eflapegrastim is not detectable 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): In patients with breast cancer, the geometric mean half-life of eflapegrastim-xnst is 36.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of eflapegrastim-xnst decreased with increasing dose, suggesting target-mediated clearance by neutrophils. With repeat dosing clearance appears to increase, potentially due to the subsequent increase in circulating neutrophils. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): An overdose of eflapegrastim may result in leukocytosis and bone pain. In the event of an overdose, the patient should be monitored for adverse effects and general supportive measures should be implemented as necessary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Rolvedon •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): Eflapegrastim is a form of recombinant human granulocyte colony stimulating factor used to induce the production of granulocytes and lower infection risk after myelosuppressive 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 Eftrenonacog alfa interact?

•Drug A: Abciximab •Drug B: Eftrenonacog alfa •Severity: MAJOR •Description: The therapeutic efficacy of Eftrenonacog 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): Indicated for the treatment and prophylaxis of bleeding in patients of all age with haemophilia B (congenital factor IX 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): In two multinational, phase III studies in previously treated children, adolescents and adults with severe haemophilia B, eftrenonacog alfa prophylaxis resulted in low median annualized bleeding rates (ABRs), and was associated with reductions in median weekly factor consumption and dosing frequency compared with pre-study FIX regimens. The extension of those studies demonstrated effectiveness in the treatment of bleeding episodes and when used in the perioperative setting in all age groups. In animal models, a single intravenous dose of eftrenonacog alfa displayed half values approximately three- to four-fold longer than those seen with recombinant FIX. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 coagulation protein factor IX (FIX) is a vitamin K-dependent coagulation factor and one of the critical serine proteases involved in the coagulation cascade. Upon activation by factor XIa in the intrinsic coagulation pathway and by the factor VII/tissue factor complex in the extrinsic pathway, factor IX, in combination with factor VIII, activates factor X. Activated factor X mediates the conversion of prothrombin to thrombin which sequentially leads to thrombin converting fibrinogen into fibrin. A blood clot is then formed. With a mutation in the gene encoding the coagulation protein factor IX (FIX), patients with hemophilia B have factor IX deficiency and are at high risk for recurrent bleeding episodes. Eftrenonacog alfa is composed of a single molecule of recombinant FIX (rFIX) covalently fused to the dimeric Fc domain of immunoglobulin (Ig) G1 (rFIXFc). It serves as a replacement therapy to increase the plasma levels of factor IX thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies. The Fc region of human immunoglobulin G1 binds with the neonatal Fc receptor which is expressed throughout life as part of a naturally occurring pathway that protects immunoglobulins from lysosomal degradation by cycling these proteins back into circulation, resulting in their long plasma half-life. The binding of eftrenonacog alfa to the neonatal Fc receptor delays degradation and recycles the fusion protein back into circulation for increased plasma half life and prolonged therapeutic action. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean peak plasma concentration (Cmax) was 46.10 IU/dL. The mean area under the FIX activity time curve (AUC) was 31.58 Uxh/dL per IU/kg. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean AUC ranged from 22.71 to 29.50 Uxh/dL per IU/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean volume of distribution at steady-state (Vss) was 303.4 mL/kg. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean Vss ranged from 289 to 365.1 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): The Fc domain of eftrenonacog alfa is expected to undergo lysosomal degradation while the remaining recombinant FIX (rFIX) portion is expected to be metabolized by the same pathway as endogenous factor IX. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Eftrenonacog alfa is expected to undergo renal clearance. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean terminal half life (t1/2) was 77.6 hours. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean t1/2 ranged from 66.49 to 82.22 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean clearance (CL) was 3.17 mL/h/kg. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, mean CL ranged from 3.390 to 4.365 mL/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Based on findings from a rabbit thrombogenicity test and rat or monkey repeated-dose toxicity studies, eftrenonacog alfa displays no special hazards for humans. Studies to investigate the genotoxicity, carcinogenicity, toxicity to reproduction or embryo-foetal development have not been conducted. Eftrenonacog alfa has shown to cross the placenta in small amounts according to a mouse placental transfer study. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alprolix •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): Eftrenonacog alfa is a recombinant Factor IX used to treat and prevent bleeding in hemophilia B.

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 Eftrenonacog alfa interact? Information: •Drug A: Abciximab •Drug B: Eftrenonacog alfa •Severity: MAJOR •Description: The therapeutic efficacy of Eftrenonacog 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): Indicated for the treatment and prophylaxis of bleeding in patients of all age with haemophilia B (congenital factor IX 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): In two multinational, phase III studies in previously treated children, adolescents and adults with severe haemophilia B, eftrenonacog alfa prophylaxis resulted in low median annualized bleeding rates (ABRs), and was associated with reductions in median weekly factor consumption and dosing frequency compared with pre-study FIX regimens. The extension of those studies demonstrated effectiveness in the treatment of bleeding episodes and when used in the perioperative setting in all age groups. In animal models, a single intravenous dose of eftrenonacog alfa displayed half values approximately three- to four-fold longer than those seen with recombinant FIX. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 coagulation protein factor IX (FIX) is a vitamin K-dependent coagulation factor and one of the critical serine proteases involved in the coagulation cascade. Upon activation by factor XIa in the intrinsic coagulation pathway and by the factor VII/tissue factor complex in the extrinsic pathway, factor IX, in combination with factor VIII, activates factor X. Activated factor X mediates the conversion of prothrombin to thrombin which sequentially leads to thrombin converting fibrinogen into fibrin. A blood clot is then formed. With a mutation in the gene encoding the coagulation protein factor IX (FIX), patients with hemophilia B have factor IX deficiency and are at high risk for recurrent bleeding episodes. Eftrenonacog alfa is composed of a single molecule of recombinant FIX (rFIX) covalently fused to the dimeric Fc domain of immunoglobulin (Ig) G1 (rFIXFc). It serves as a replacement therapy to increase the plasma levels of factor IX thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies. The Fc region of human immunoglobulin G1 binds with the neonatal Fc receptor which is expressed throughout life as part of a naturally occurring pathway that protects immunoglobulins from lysosomal degradation by cycling these proteins back into circulation, resulting in their long plasma half-life. The binding of eftrenonacog alfa to the neonatal Fc receptor delays degradation and recycles the fusion protein back into circulation for increased plasma half life and prolonged therapeutic action. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean peak plasma concentration (Cmax) was 46.10 IU/dL. The mean area under the FIX activity time curve (AUC) was 31.58 Uxh/dL per IU/kg. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean AUC ranged from 22.71 to 29.50 Uxh/dL per IU/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean volume of distribution at steady-state (Vss) was 303.4 mL/kg. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean Vss ranged from 289 to 365.1 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): The Fc domain of eftrenonacog alfa is expected to undergo lysosomal degradation while the remaining recombinant FIX (rFIX) portion is expected to be metabolized by the same pathway as endogenous factor IX. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Eftrenonacog alfa is expected to undergo renal clearance. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean terminal half life (t1/2) was 77.6 hours. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean t1/2 ranged from 66.49 to 82.22 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean clearance (CL) was 3.17 mL/h/kg. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, mean CL ranged from 3.390 to 4.365 mL/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Based on findings from a rabbit thrombogenicity test and rat or monkey repeated-dose toxicity studies, eftrenonacog alfa displays no special hazards for humans. Studies to investigate the genotoxicity, carcinogenicity, toxicity to reproduction or embryo-foetal development have not been conducted. Eftrenonacog alfa has shown to cross the placenta in small amounts according to a mouse placental transfer study. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alprolix •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): Eftrenonacog alfa is a recombinant Factor IX used to treat and prevent bleeding in hemophilia B. 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 Elotuzumab interact?

•Drug A: Abciximab •Drug B: Elotuzumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Elotuzumab. •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 in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior 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): 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): Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor activity in vitro and in vivo. •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): The clearance of elotuzumab decreased from a geometric mean (CV%) of 17.5 (21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended dosage). Based on a population PK model, when elotuzumab is given in combination with lenalidomide and dexamethasone, approximately 97% of the maximum steady-state concentration is predicted to be eliminated with a geometric mean (CV%) of 82.4 (48%) days. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Empliciti •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): Elotuzumab is an antineoplastic agent and SLAMF7-directed immunostimulatory antibody used for the treatment of refractory multiple myeloma 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 Elotuzumab interact? Information: •Drug A: Abciximab •Drug B: Elotuzumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Elotuzumab. •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 in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior 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): 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): Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor activity in vitro and in vivo. •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): The clearance of elotuzumab decreased from a geometric mean (CV%) of 17.5 (21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended dosage). Based on a population PK model, when elotuzumab is given in combination with lenalidomide and dexamethasone, approximately 97% of the maximum steady-state concentration is predicted to be eliminated with a geometric mean (CV%) of 82.4 (48%) days. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Empliciti •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): Elotuzumab is an antineoplastic agent and SLAMF7-directed immunostimulatory antibody used for the treatment of refractory multiple myeloma 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 Emapalumab interact?

•Drug A: Abciximab •Drug B: Emapalumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Emapalumab. •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): Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure. This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement. In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Emapalumab acts by binding and neutralizing interferon-gamma. The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity. It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface. HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients. •Absorption (Drug A): No absorption available •Absorption (Drug B): In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively. •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 are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Emapalumab presents a target-mediated clearance that is dependent on interferon-gamma production. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gamifant •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): Emapalumab is an interferon gamma blocking antibody used to treat primary hemophagocytic lymphohistiocytosis.

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 Emapalumab interact? Information: •Drug A: Abciximab •Drug B: Emapalumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Emapalumab. •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): Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure. This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement. In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Emapalumab acts by binding and neutralizing interferon-gamma. The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity. It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface. HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients. •Absorption (Drug A): No absorption available •Absorption (Drug B): In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively. •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 are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Emapalumab presents a target-mediated clearance that is dependent on interferon-gamma production. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gamifant •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): Emapalumab is an interferon gamma blocking antibody used to treat primary hemophagocytic lymphohistiocytosis. 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 Emicizumab interact?

•Drug A: Abciximab •Drug B: Emicizumab •Severity: MAJOR •Description: The therapeutic efficacy of Emicizumab 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): The main function of Emicizumab is the prevention of bleeding episodes. Thus, Emicizumab is approved for the routine prophylaxis to prevent or reduce the frequency of bleeding episodes of adult and pediatric patients with hemophilia A with or without Factor VIII inhibitors. Hemophilia A is a deficiency of coagulation Factor VIII which causes a serious bleeding disorder. The standard treatment is done with the administration of recombinant or serum-deriver Factor VIII which induces the formation of anti-factor VIII alloantibodies (Factor VIII inhibitors) and renders the standard treatment ineffective. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Emicizumab mimics the function of coagulation factor VIII, therefore it binds to the activated form of Factor IX (Factor IXa). This binding forms a complex that will later bind to the X factor of the coagulation factor. The ability of Emicizumab to interact with both factors (Factor IXa and Factor X) activates the coagulation cascade that will subsequently lead to the segmentation of fibrinogen into fibrin and the formation of blood clots. The effect of Emicizumab is translated into the restoration of the blood coagulation process and, therefore, in the reduction of hemorrhagic episodes. The activity of emicizumab can also produce changes in activated clotting time (ACT), activated partial thromboplastin time (aPTT) and one-step Factor VIII activity. In addition, the unique bispecific structure of Emicizumab prevents the formation of Factor VIII inhibitors or their effect. In the first clinical trials, emicizumab was tried on previously treated adult and pediatric patients of hemophilia A with FVIII inhibitors. In this trials, the annualized bleeding rate requiring treatment with coagulation factors was reduced by 87% when compared to untreated patients. Those clinical trials were followed by a second round on previously treated patients of severe hemophilia A without FVIII inhibitors. In this trial, the annualized bleed rate was reduced by 96% when compared to untreated 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): Emicizumab exerts its action by performing the function of the coagulation Factor VIII without presenting a structural homology. It presents a dual specificity which allows it to bind to both the Factor IXa and Factor X, performing the required bridging activity for the launch of the coagulation cascade. •Absorption (Drug A): No absorption available •Absorption (Drug B): Subcutaneous administration of Emicizumab presents a very high bioavailability ranging from 80.4% to 93.1% when administered subcutaneously in a dose of 1 mg/kg. In clinical trials, at the same dose, Emicizumab presented a linear exposure which concentration peaked 1-2 weeks after administration and presented a profile framed by a Cmax of 5.92 mcg/ml and an AUC of 304 mcg day/ml. After subcutaneous administration, the absorption half-life was 1.7 days and the pharmacokinetic profile seemed to be shared when the medication was administered in the abdomen, upper arm, and thigh. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution is 11.4 L when administered subcutaneously and there are reports indicating that this value can increase with increasing body weight. When emicizumab is administered intravenously, the volume of distribution at steady state is 106 ml/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): As emicizumab is a monoclonal antibody acting on the bloodstream, the determination of protein binding studies is not required. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Emicizumab is a monoclonal antibody and thus, it is thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of Emicizumab was monophasic in clinical trials. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Emcicizumab presents a long half-life ranging from 27.8 to 34.4 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance is 0.24 L/day when administered in multiple subcutaneous injections and there are reports indicating that this value can increase with increasing body weight. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The administration of Emicizumab has reported cases of microangiopathy and thrombotic events with concomitant use of activated prothrombin complex concentrate at doses higher of 100 U/kg/24 hours. There are also reports of injection site reaction, headaches and arthralgia. Genotoxicity and carcinogenicity studies have not been performed as it is not expected that emicizumab can have any interaction with DNA, or chromosomal material. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hemlibra •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): Emicizumab is an antibody against Factor IXa and Factor X used to treat 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 Emicizumab interact? Information: •Drug A: Abciximab •Drug B: Emicizumab •Severity: MAJOR •Description: The therapeutic efficacy of Emicizumab 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): The main function of Emicizumab is the prevention of bleeding episodes. Thus, Emicizumab is approved for the routine prophylaxis to prevent or reduce the frequency of bleeding episodes of adult and pediatric patients with hemophilia A with or without Factor VIII inhibitors. Hemophilia A is a deficiency of coagulation Factor VIII which causes a serious bleeding disorder. The standard treatment is done with the administration of recombinant or serum-deriver Factor VIII which induces the formation of anti-factor VIII alloantibodies (Factor VIII inhibitors) and renders the standard treatment ineffective. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Emicizumab mimics the function of coagulation factor VIII, therefore it binds to the activated form of Factor IX (Factor IXa). This binding forms a complex that will later bind to the X factor of the coagulation factor. The ability of Emicizumab to interact with both factors (Factor IXa and Factor X) activates the coagulation cascade that will subsequently lead to the segmentation of fibrinogen into fibrin and the formation of blood clots. The effect of Emicizumab is translated into the restoration of the blood coagulation process and, therefore, in the reduction of hemorrhagic episodes. The activity of emicizumab can also produce changes in activated clotting time (ACT), activated partial thromboplastin time (aPTT) and one-step Factor VIII activity. In addition, the unique bispecific structure of Emicizumab prevents the formation of Factor VIII inhibitors or their effect. In the first clinical trials, emicizumab was tried on previously treated adult and pediatric patients of hemophilia A with FVIII inhibitors. In this trials, the annualized bleeding rate requiring treatment with coagulation factors was reduced by 87% when compared to untreated patients. Those clinical trials were followed by a second round on previously treated patients of severe hemophilia A without FVIII inhibitors. In this trial, the annualized bleed rate was reduced by 96% when compared to untreated 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): Emicizumab exerts its action by performing the function of the coagulation Factor VIII without presenting a structural homology. It presents a dual specificity which allows it to bind to both the Factor IXa and Factor X, performing the required bridging activity for the launch of the coagulation cascade. •Absorption (Drug A): No absorption available •Absorption (Drug B): Subcutaneous administration of Emicizumab presents a very high bioavailability ranging from 80.4% to 93.1% when administered subcutaneously in a dose of 1 mg/kg. In clinical trials, at the same dose, Emicizumab presented a linear exposure which concentration peaked 1-2 weeks after administration and presented a profile framed by a Cmax of 5.92 mcg/ml and an AUC of 304 mcg day/ml. After subcutaneous administration, the absorption half-life was 1.7 days and the pharmacokinetic profile seemed to be shared when the medication was administered in the abdomen, upper arm, and thigh. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution is 11.4 L when administered subcutaneously and there are reports indicating that this value can increase with increasing body weight. When emicizumab is administered intravenously, the volume of distribution at steady state is 106 ml/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): As emicizumab is a monoclonal antibody acting on the bloodstream, the determination of protein binding studies is not required. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Emicizumab is a monoclonal antibody and thus, it is thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of Emicizumab was monophasic in clinical trials. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Emcicizumab presents a long half-life ranging from 27.8 to 34.4 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance is 0.24 L/day when administered in multiple subcutaneous injections and there are reports indicating that this value can increase with increasing body weight. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The administration of Emicizumab has reported cases of microangiopathy and thrombotic events with concomitant use of activated prothrombin complex concentrate at doses higher of 100 U/kg/24 hours. There are also reports of injection site reaction, headaches and arthralgia. Genotoxicity and carcinogenicity studies have not been performed as it is not expected that emicizumab can have any interaction with DNA, or chromosomal material. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hemlibra •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): Emicizumab is an antibody against Factor IXa and Factor X used to treat 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 Enoxaparin interact?

•Drug A: Abciximab •Drug B: Enoxaparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Enoxaparin. •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): Enoxaparin is indicated for the prevention of ischemic complications in unstable angina and in non Q-wave myocardial infarction; it is indicated in conjunction with percutaneous intervention and/or other treatment for the management of acute ST elevation myocardial infarction. Enoxaparin is also indicated in the prophylaxis of DVT in abdominal surgery, hip replacement, knee replacement, or medical patients with severely restricted mobility during acute illness. Additionally, enoxaparin is indicated for the inpatient treatment of DVT with or without pulmonary embolism and the treatment of outpatient DVT without pulmonary embolism. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): This drug has an immediate onset of action. Enoxaparin increases Thrombin Time (TT) and activated partial thromboplastin time (aPTT), preventing and reducing thromboembolic complications such as DVT, pulmonary embolism, and ischemic cardiac complications. Administered at 1.5 mg/kg subcutaneously in a pharmacodynamic study, enoxaparin led to a higher ratio of anti-Factor Xa to anti-Factor IIa activity (mean ±SD, 14.0±3.1) (based on areas under anti-Factor activity versus time curves) when compared to that of heparin (mean ±SD, 1.22±0.13). Increases in the TT and aPTT were 1.8 times those of the control group. Enoxaparin at 1 mg/kg subcutaneously every 12 hours led to aPTT values of 45 seconds or less in most patients. Average aPTT prolongation time on Day 1 was approximately 16% higher than on Day 4 of enoxaparin therapy. Caution is advised during treatment with enoxaparin - the risk of hemorrhage and thrombocytopenia is increased. In pregnant women with prosthetic mechanic heart valves, the risk of thromboembolism is increased. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Enoxaparin binds to antithrombin III, a serine protease inhibitor, forming a complex that irreversibly inactivates factor Xa, which is frequently used to monitor anticoagulation in the clinical setting. Following factor Xa inactivation, enoxaparin is released and binds to other anti-thrombin molecules. Factor IIa (thrombin) is directly inhibited by enoxaparin, however with less potency than unfractionated heparin (UFH). Due to the cascade of effects resulting from enoxaparin binding, thrombin is unable to convert fibrinogen to fibrin and form a clot, preventing thromboembolic events. •Absorption (Drug A): No absorption available •Absorption (Drug B): Mean absolute bioavailability of enoxaparin, after 1-2 mg/kg given subcutaneously is approximately 100% in healthy volunteers. The absorption of enoxaparin is proportional to the dose, demonstrating linear absorption. The average maximum plasma anti-Xa activity is reached 3 to 5 hours after a subcutaneous injection. A 30 mg IV bolus preceding an immediate 1 mg/kg SC every twice a day led to maximum anti-Factor Xa levels of 1.16 IU/mL. Steady-state is reached within 3-4 days of treatment with a Cmax of 1.2 IU/mL. The AUC under the thrombin generation curve was 305 +/- 48. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of enoxaparin is approximately 4-5L, similar to normal blood volume. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Enoxaparin binds to antithrombin III. The percentage of plasma protein binding for enoxaparin 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): Enoxaparin is mainly metabolized by the liver via desulfation and/or depolymerization to lower and less potent molecular weight metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Enoxaparin is mainly excreted by the kidneys. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of enoxaparin is about 4 hours after a single dose administered subcutaneously and about 7 hours after several doses. One source mentions a half-life ranging from 1 hour to 4.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance of enoxaparin is 0.74 L/h after a 1.5 mg/kg intravenous infusion over 6 hours; clearance of enoxaparin is significantly decreased in patients with severe renal impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 for enoxaparin in mice is >5000 mg/kg; the subcutaneous LD50 of enoxaparin in mice is >2500 mg/kg. Accidental overdose after the administration of enoxaparin may cause hemorrhage. Enoxaparin administered by injection is mainly neutralized by gradual intravenous injection of a 1% protamine sulfate solution. The dose of protamine sulfate should be equal to the dose of enoxaparin administered: 1 mg protamine sulfate for 1 mg enoxaparin, of enoxaparin was administered in the previous 8 hours. If a minimum of 12 hours has passed since the last enoxaparin dose, protamine may not be necessary; it is important to avoid an overdose with protamine, as fatal reactions may occur. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lovenox •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): Enoxaparin is a low molecular weight heparin used for the prophylaxis of deep vein thrombosis and ischemic complications of 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 Enoxaparin interact? Information: •Drug A: Abciximab •Drug B: Enoxaparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Enoxaparin. •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): Enoxaparin is indicated for the prevention of ischemic complications in unstable angina and in non Q-wave myocardial infarction; it is indicated in conjunction with percutaneous intervention and/or other treatment for the management of acute ST elevation myocardial infarction. Enoxaparin is also indicated in the prophylaxis of DVT in abdominal surgery, hip replacement, knee replacement, or medical patients with severely restricted mobility during acute illness. Additionally, enoxaparin is indicated for the inpatient treatment of DVT with or without pulmonary embolism and the treatment of outpatient DVT without pulmonary embolism. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): This drug has an immediate onset of action. Enoxaparin increases Thrombin Time (TT) and activated partial thromboplastin time (aPTT), preventing and reducing thromboembolic complications such as DVT, pulmonary embolism, and ischemic cardiac complications. Administered at 1.5 mg/kg subcutaneously in a pharmacodynamic study, enoxaparin led to a higher ratio of anti-Factor Xa to anti-Factor IIa activity (mean ±SD, 14.0±3.1) (based on areas under anti-Factor activity versus time curves) when compared to that of heparin (mean ±SD, 1.22±0.13). Increases in the TT and aPTT were 1.8 times those of the control group. Enoxaparin at 1 mg/kg subcutaneously every 12 hours led to aPTT values of 45 seconds or less in most patients. Average aPTT prolongation time on Day 1 was approximately 16% higher than on Day 4 of enoxaparin therapy. Caution is advised during treatment with enoxaparin - the risk of hemorrhage and thrombocytopenia is increased. In pregnant women with prosthetic mechanic heart valves, the risk of thromboembolism is increased. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Enoxaparin binds to antithrombin III, a serine protease inhibitor, forming a complex that irreversibly inactivates factor Xa, which is frequently used to monitor anticoagulation in the clinical setting. Following factor Xa inactivation, enoxaparin is released and binds to other anti-thrombin molecules. Factor IIa (thrombin) is directly inhibited by enoxaparin, however with less potency than unfractionated heparin (UFH). Due to the cascade of effects resulting from enoxaparin binding, thrombin is unable to convert fibrinogen to fibrin and form a clot, preventing thromboembolic events. •Absorption (Drug A): No absorption available •Absorption (Drug B): Mean absolute bioavailability of enoxaparin, after 1-2 mg/kg given subcutaneously is approximately 100% in healthy volunteers. The absorption of enoxaparin is proportional to the dose, demonstrating linear absorption. The average maximum plasma anti-Xa activity is reached 3 to 5 hours after a subcutaneous injection. A 30 mg IV bolus preceding an immediate 1 mg/kg SC every twice a day led to maximum anti-Factor Xa levels of 1.16 IU/mL. Steady-state is reached within 3-4 days of treatment with a Cmax of 1.2 IU/mL. The AUC under the thrombin generation curve was 305 +/- 48. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of enoxaparin is approximately 4-5L, similar to normal blood volume. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Enoxaparin binds to antithrombin III. The percentage of plasma protein binding for enoxaparin 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): Enoxaparin is mainly metabolized by the liver via desulfation and/or depolymerization to lower and less potent molecular weight metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Enoxaparin is mainly excreted by the kidneys. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of enoxaparin is about 4 hours after a single dose administered subcutaneously and about 7 hours after several doses. One source mentions a half-life ranging from 1 hour to 4.5 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance of enoxaparin is 0.74 L/h after a 1.5 mg/kg intravenous infusion over 6 hours; clearance of enoxaparin is significantly decreased in patients with severe renal impairment. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 for enoxaparin in mice is >5000 mg/kg; the subcutaneous LD50 of enoxaparin in mice is >2500 mg/kg. Accidental overdose after the administration of enoxaparin may cause hemorrhage. Enoxaparin administered by injection is mainly neutralized by gradual intravenous injection of a 1% protamine sulfate solution. The dose of protamine sulfate should be equal to the dose of enoxaparin administered: 1 mg protamine sulfate for 1 mg enoxaparin, of enoxaparin was administered in the previous 8 hours. If a minimum of 12 hours has passed since the last enoxaparin dose, protamine may not be necessary; it is important to avoid an overdose with protamine, as fatal reactions may occur. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lovenox •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): Enoxaparin is a low molecular weight heparin used for the prophylaxis of deep vein thrombosis and ischemic complications of 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 Epirubicin interact?

•Drug A: Abciximab •Drug B: Epirubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Epirubicin. •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 use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast 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): Epirubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Epirubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Epirubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): 100% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 21 ± 2 L/kg [60 mg/m2 Dose] 27 ± 11 L/kg [75 mg/m2 Dose] 23 ± 7 L/kg [120 mg/m2 Dose] 21 ± 7 L/kg [150 mg/m2 Dose] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 77% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Extensively and rapidly metabolized in the liver. Epirubicin is also metabolized by other organs and cells, including red blood cells. The four main metabolic routes are: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol exhibits in vitro cytoxic activity (~10% that of epirubicin), but it is unlikely to reach sufficient concentrations in vivo to produce cytotoxic effects. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Epirubicin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary 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): Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively •Clearance (Drug A): No clearance available •Clearance (Drug B): 65 +/- 8 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 60 mg/m2] 83 +/- 14 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 75 mg/m2] 65 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 120 mg/m2] 69 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 150 mg/m2] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): bone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ellence, Pharmorubicin PFS •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): Epirubicin is an anthracycline topoisomerase II inhibitor used as an adjuvant to treating axillary node metastases in patients who have undergone surgical resection of primary 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 Epirubicin interact? Information: •Drug A: Abciximab •Drug B: Epirubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Epirubicin. •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 use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast 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): Epirubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Epirubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Epirubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): 100% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 21 ± 2 L/kg [60 mg/m2 Dose] 27 ± 11 L/kg [75 mg/m2 Dose] 23 ± 7 L/kg [120 mg/m2 Dose] 21 ± 7 L/kg [150 mg/m2 Dose] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 77% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Extensively and rapidly metabolized in the liver. Epirubicin is also metabolized by other organs and cells, including red blood cells. The four main metabolic routes are: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol exhibits in vitro cytoxic activity (~10% that of epirubicin), but it is unlikely to reach sufficient concentrations in vivo to produce cytotoxic effects. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Epirubicin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary 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): Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively •Clearance (Drug A): No clearance available •Clearance (Drug B): 65 +/- 8 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 60 mg/m2] 83 +/- 14 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 75 mg/m2] 65 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 120 mg/m2] 69 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 150 mg/m2] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): bone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ellence, Pharmorubicin PFS •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): Epirubicin is an anthracycline topoisomerase II inhibitor used as an adjuvant to treating axillary node metastases in patients who have undergone surgical resection of primary 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 Epoprostenol interact?

•Drug A: Abciximab •Drug B: Epoprostenol •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Epoprostenol. •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 the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional 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): Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI2) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A2 binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists. •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): 357 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): Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; the in vivo half-life of epoprostenol in humans is therefore expected to be no greater than 6 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of epoprostenol. Single intravenous doses at 10 and 50 mg/kg (2703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Flolan, Veletri •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Epoprostenol Prostacyclin Prostaglandin I2 Prostaglandin X Vasocyclin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Epoprostenol is a vasodilator and platelet aggregation inhibitor used for the management of primary pulmonary hypertension and pulmonary hypertension in patients with heart failure.

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 Epoprostenol interact? Information: •Drug A: Abciximab •Drug B: Epoprostenol •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Epoprostenol. •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 the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional 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): Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI2) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A2 binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists. •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): 357 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): Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; the in vivo half-life of epoprostenol in humans is therefore expected to be no greater than 6 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of epoprostenol. Single intravenous doses at 10 and 50 mg/kg (2703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Flolan, Veletri •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Epoprostenol Prostacyclin Prostaglandin I2 Prostaglandin X Vasocyclin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Epoprostenol is a vasodilator and platelet aggregation inhibitor used for the management of primary pulmonary hypertension and pulmonary hypertension in patients with heart failure. 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 Eptifibatide interact?

•Drug A: Abciximab •Drug B: Eptifibatide •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Eptifibatide is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 myocardial infarction and acute coronary syndrome. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eptifibatide is an anti-coagulant that selectively and reversibly blocks the platelet glycoprotein IIb/IIIa receptor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen, von Willebrand factor, and other adhesive ligands. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner. •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): Approximately 25% •Metabolism (Drug A): 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 major metabolites have been detected in human plasma. Deamidated eptifibatide and other, more polar metabolites have been detected in 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): Approximately 2.5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 55 mL/kg/h [patients with coronary artery disease] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Integrilin •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): Eptifibatide is a peptide-based antagonist for glycoprotein IIb/IIIa used in the medical management of myocardial infarction and as an adjunct to percutaneous coronary intervention.

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 Eptifibatide interact? Information: •Drug A: Abciximab •Drug B: Eptifibatide •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Eptifibatide is combined with Abciximab. •Extended Description: Both antiplatelet agents and anticoagulants are associated with a risk of bleeding when administered alone. The concomitant use of these agents may further increase the risk for fatal and non-fatal bleeding events, including gastrointestinal hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 myocardial infarction and acute coronary syndrome. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eptifibatide is an anti-coagulant that selectively and reversibly blocks the platelet glycoprotein IIb/IIIa receptor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen, von Willebrand factor, and other adhesive ligands. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner. •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): Approximately 25% •Metabolism (Drug A): 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 major metabolites have been detected in human plasma. Deamidated eptifibatide and other, more polar metabolites have been detected in 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): Approximately 2.5 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 55 mL/kg/h [patients with coronary artery disease] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Integrilin •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): Eptifibatide is a peptide-based antagonist for glycoprotein IIb/IIIa used in the medical management of myocardial infarction and as an adjunct to percutaneous coronary intervention. 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 Eptinezumab interact?

•Drug A: Abciximab •Drug B: Eptinezumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Eptinezumab. •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): Eptinezumab is indicated for the preventive treatment of migraine 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): Eptinezumab is experimentally administered as an intravenous infusion and/or subcutaneous injection. During Phase 3 clinical trials, it was noted that patients with episodic migraine who on average had 8.6 days of migraine per month demonstrated significant reductions in migraine frequency over weeks 1-12, associated with the 300mg dose arm. Additionally, 29.7% of patients achieved a 75% or greater reduction in migraine days from baseline, compared to 16.2% for placebo (p<0.0007). Moreover, a post hoc analysis revealed that those patients achieving a 75% or greater response rate had over an eight-fold increase in days between migraines. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eptinezumab is a fully-humanized IgG1 antibody manufactured and designed specifically to bind both alpha and beta forms of the human calcitonin gene-related peptide (CGRP). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy. Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the form and mechanism of action for eptinezumab. The binding of eptinezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. •Absorption (Drug A): No absorption available •Absorption (Drug B): Eptinezumab is the only potent and selective and anti-calcitonin gene-related peptide (CGRP) monoclonal antibody administered by quarterly infusion for migraine prevention delivering 100% bioavailability by way of the intravenous route of administration to immediately inhibit CGRP. With an intravenous dose of eptinezumab 1000 mg, the mean maximum concentration of 336.4 ug/mL (SD 79.9) occurred after 4.8 hours after the start of the 1 hour infusion. The mean exposure to free eptinezumab, as characterized by area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and from time zero to infinity were 8245 days per ug per mL (SD 2619) and 8722 days per ug per mL (SD 2522), respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central volume of distribution for eptinezumab is approximately 3.7 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Readily accessible data regarding the protein binding of eptinezumab is 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): Monoclonal antibody agents like eptinezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibody agents like eptinezumab are generally not eliminated via hepatic, renal, or biliary routes. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The plasma half-life after an intravenous infusion is approximately 27 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of eptinezumab is 0.006 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequent adverse events associated with eptinezumab use include upper respiratory tract infection, urinary tract infection, fatigue, back pain, arthralgia, and nausea and vomiting. No data regarding overdosage has been reported yet. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Vyepti •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): Eptinezumab is a monoclonal antibody directed against CGRP infused every 3 months for the preventive treatment of migraine 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 Eptinezumab interact? Information: •Drug A: Abciximab •Drug B: Eptinezumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Eptinezumab. •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): Eptinezumab is indicated for the preventive treatment of migraine 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): Eptinezumab is experimentally administered as an intravenous infusion and/or subcutaneous injection. During Phase 3 clinical trials, it was noted that patients with episodic migraine who on average had 8.6 days of migraine per month demonstrated significant reductions in migraine frequency over weeks 1-12, associated with the 300mg dose arm. Additionally, 29.7% of patients achieved a 75% or greater reduction in migraine days from baseline, compared to 16.2% for placebo (p<0.0007). Moreover, a post hoc analysis revealed that those patients achieving a 75% or greater response rate had over an eight-fold increase in days between migraines. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eptinezumab is a fully-humanized IgG1 antibody manufactured and designed specifically to bind both alpha and beta forms of the human calcitonin gene-related peptide (CGRP). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy. Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the form and mechanism of action for eptinezumab. The binding of eptinezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example. •Absorption (Drug A): No absorption available •Absorption (Drug B): Eptinezumab is the only potent and selective and anti-calcitonin gene-related peptide (CGRP) monoclonal antibody administered by quarterly infusion for migraine prevention delivering 100% bioavailability by way of the intravenous route of administration to immediately inhibit CGRP. With an intravenous dose of eptinezumab 1000 mg, the mean maximum concentration of 336.4 ug/mL (SD 79.9) occurred after 4.8 hours after the start of the 1 hour infusion. The mean exposure to free eptinezumab, as characterized by area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and from time zero to infinity were 8245 days per ug per mL (SD 2619) and 8722 days per ug per mL (SD 2522), respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The central volume of distribution for eptinezumab is approximately 3.7 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Readily accessible data regarding the protein binding of eptinezumab is 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): Monoclonal antibody agents like eptinezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibody agents like eptinezumab are generally not eliminated via hepatic, renal, or biliary routes. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The plasma half-life after an intravenous infusion is approximately 27 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of eptinezumab is 0.006 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequent adverse events associated with eptinezumab use include upper respiratory tract infection, urinary tract infection, fatigue, back pain, arthralgia, and nausea and vomiting. No data regarding overdosage has been reported yet. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Vyepti •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): Eptinezumab is a monoclonal antibody directed against CGRP infused every 3 months for the preventive treatment of migraine 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 Erenumab interact?

•Drug A: Abciximab •Drug B: Erenumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Erenumab. •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): Erenumab is indicated for the preventative treatment of migraine 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): As a human monoclonal antibody designed to specifically bind with and antagonize the calcitonin gene-related peptide (CGRP) receptor, there is the possibility that erenumab could interfere with natural activities of CGRP that may not be immediately or directly associated with migraines. For example, at peripheral synapses, CGRP released from trigeminal terminals results in vasodilation by way of CGRP receptor on smooth muscle cells of meningeal and cerebral blood vessels, making CGRP a potent general arterial vasodilator. Antagonism of CGRP receptors responsible for such vasodilation could theoretically result in vasoconstriction and raises in blood pressure. In a randomised, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab (140 mg intravenous, single dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone, however. Please note that erenumab is indicated for subcutaneous use only, though. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Erenumab is a human monoclonal antibody that has been designed to bind specifically to the calcitonin gene-related peptide (CGRP) receptor and antagonize the CGRP receptor function. Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy. Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For all these reasons, the binding and antagonism of CGRP receptors was designed to be mechanism of action for erenumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. CGRP and its receptor are expressed in both the peripheral and the central nervous system. In addition to playing a role in cranial nociception, CGRP is also a potent general arterial vasodilator. At peripheral synapses, CGRP released from trigeminal terminals results in vasodilation via CGRP receptors on the smooth muscle cells of meningeal and cerebral blood vessels. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single subcutaneous dose of 70 mg or 140 mg erenumab administered to healthy adults, the median peak serum concentrations were attained in about 6 days, and the estimated absolute bioavailability was approximately 82%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be approximately 3.86 (0.77) L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Readily accessible data regarding the protein binding of erenumab is not available, although it is reported that erenumab is capable of 50% to 99% total inhibition of calcitonin gene-related peptide receptors with dosages of 255 ng/mL and 1134 ng/mL, 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): Erenumab CGRP antibodies demonstrate a low risk for drug-drug interactions and hepatotoxicity since they are predominantly metabolized by degradation into peptides and single amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Two elimination phases are observed for erenumab. At low concentrations, the elimination is mainly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab is primarily through a non-specific, non-saturable proteolytic pathway. These phases correspond to studies that demonstrated two parallel elimination pathways: (a) a slow non-specific elimination pathway through the hepatic reticuloendothelial system, and (b) a rapid saturable elimination pathway mediated by degradation or internalization of the erenumab-receptor complex. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Erenumab exhibits non-linear kinetics as a result of binding to the CGRP receptor. Lower than 2-fold accumulation was recorded in trough serum concentrations (Cmin) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once-monthly and 140 mg once-monthly doses. Serum trough concentrations approached steady state by 3 months of dosing. The effective half-life of erenumab was observed to be 28 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Certain studies show that the population estimate of linear clearance is independent of erenumab concentrations and stays approximately constant at 0.214 L/day (95% CI: 0.191–0.243). In contrast, the nonlinear clearance is dependent on the target receptor density and the amount of erenumab bound to the receptors. Nevertheless, the maximal nonlinear clearance was observed to be about 1.84L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common side effects of erenumab include pain, redness, or swelling at the injection site, and constipation. Information regarding overdosage is not available. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aimovig •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): Erenumab is a calcitonin-gene related peptide antagonist used to prevent migraines.

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 Erenumab interact? Information: •Drug A: Abciximab •Drug B: Erenumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Erenumab. •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): Erenumab is indicated for the preventative treatment of migraine 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): As a human monoclonal antibody designed to specifically bind with and antagonize the calcitonin gene-related peptide (CGRP) receptor, there is the possibility that erenumab could interfere with natural activities of CGRP that may not be immediately or directly associated with migraines. For example, at peripheral synapses, CGRP released from trigeminal terminals results in vasodilation by way of CGRP receptor on smooth muscle cells of meningeal and cerebral blood vessels, making CGRP a potent general arterial vasodilator. Antagonism of CGRP receptors responsible for such vasodilation could theoretically result in vasoconstriction and raises in blood pressure. In a randomised, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab (140 mg intravenous, single dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone, however. Please note that erenumab is indicated for subcutaneous use only, though. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Erenumab is a human monoclonal antibody that has been designed to bind specifically to the calcitonin gene-related peptide (CGRP) receptor and antagonize the CGRP receptor function. Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy. Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For all these reasons, the binding and antagonism of CGRP receptors was designed to be mechanism of action for erenumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. CGRP and its receptor are expressed in both the peripheral and the central nervous system. In addition to playing a role in cranial nociception, CGRP is also a potent general arterial vasodilator. At peripheral synapses, CGRP released from trigeminal terminals results in vasodilation via CGRP receptors on the smooth muscle cells of meningeal and cerebral blood vessels. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single subcutaneous dose of 70 mg or 140 mg erenumab administered to healthy adults, the median peak serum concentrations were attained in about 6 days, and the estimated absolute bioavailability was approximately 82%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be approximately 3.86 (0.77) L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Readily accessible data regarding the protein binding of erenumab is not available, although it is reported that erenumab is capable of 50% to 99% total inhibition of calcitonin gene-related peptide receptors with dosages of 255 ng/mL and 1134 ng/mL, 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): Erenumab CGRP antibodies demonstrate a low risk for drug-drug interactions and hepatotoxicity since they are predominantly metabolized by degradation into peptides and single amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Two elimination phases are observed for erenumab. At low concentrations, the elimination is mainly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab is primarily through a non-specific, non-saturable proteolytic pathway. These phases correspond to studies that demonstrated two parallel elimination pathways: (a) a slow non-specific elimination pathway through the hepatic reticuloendothelial system, and (b) a rapid saturable elimination pathway mediated by degradation or internalization of the erenumab-receptor complex. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Erenumab exhibits non-linear kinetics as a result of binding to the CGRP receptor. Lower than 2-fold accumulation was recorded in trough serum concentrations (Cmin) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once-monthly and 140 mg once-monthly doses. Serum trough concentrations approached steady state by 3 months of dosing. The effective half-life of erenumab was observed to be 28 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Certain studies show that the population estimate of linear clearance is independent of erenumab concentrations and stays approximately constant at 0.214 L/day (95% CI: 0.191–0.243). In contrast, the nonlinear clearance is dependent on the target receptor density and the amount of erenumab bound to the receptors. Nevertheless, the maximal nonlinear clearance was observed to be about 1.84L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common side effects of erenumab include pain, redness, or swelling at the injection site, and constipation. Information regarding overdosage is not available. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aimovig •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): Erenumab is a calcitonin-gene related peptide antagonist used to prevent migraines. 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 Eribulin interact?

•Drug A: Abciximab •Drug B: Eribulin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Eribulin. •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 patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic 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): Linear •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. [FDA] •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): 43 L/m2 to 114 L/m2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 49 to 65%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): There are no major human metabolites of eribulin, CYP3A4 negligibly metabolizes eribulin in vitro. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Eribulin is eliminated primarily in feces 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): about 40 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 1.16 L/hr/m2 to 2.42 L/hr/m2 (dose range of 0.25 mg/m2 to 4.0 mg/m2). [FDA] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent). [Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.] Single doses of 0.75 mg/kg were lethal to rats and two doses of 0.075 mg/kg were lethal to dogs. The no-observed-adverse-effect level (NOAEL) in rats and dogs were 0.015 and 0.0045 mg/kg/day, respectively. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Halaven •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): Eribulin is a microtubule inhibitor used to treat metastatic breast cancer and metastatic or unresectable liposarcoma.

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 Eribulin interact? Information: •Drug A: Abciximab •Drug B: Eribulin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Eribulin. •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 patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic 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): Linear •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. [FDA] •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): 43 L/m2 to 114 L/m2 •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 49 to 65%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): There are no major human metabolites of eribulin, CYP3A4 negligibly metabolizes eribulin in vitro. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Eribulin is eliminated primarily in feces 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): about 40 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 1.16 L/hr/m2 to 2.42 L/hr/m2 (dose range of 0.25 mg/m2 to 4.0 mg/m2). [FDA] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent). [Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.] Single doses of 0.75 mg/kg were lethal to rats and two doses of 0.075 mg/kg were lethal to dogs. The no-observed-adverse-effect level (NOAEL) in rats and dogs were 0.015 and 0.0045 mg/kg/day, respectively. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Halaven •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): Eribulin is a microtubule inhibitor used to treat metastatic breast cancer and metastatic or unresectable liposarcoma. 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 Erythromycin interact?

•Drug A: Abciximab •Drug B: Erythromycin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Erythromycin is combined with Abciximab. •Extended Description: Erythromycin may increase the bleeding tendency associated with anticoagulant agents, according to several reports.1,3,2,6 The mechanism behind this interaction is likely the fact that erythromycin is a CYP3A4 inhibitor which may decrease the metabolism of various anticoagulants, potentiating their bleeding risk. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Erythromycin is indicated in the treatment of infections caused by susceptible strains of various bacteria. The indications for erythromycin have been summarized by body system below: Respiratory infections Mild to moderate upper respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae, or Haemophilus influenzae (when used concomitantly with appropriate doses of sulfonamides) can be treated with erythromycin. Mild to moderate lower-respiratory tract infections due to susceptible strains of Streptococcus pneumoniae or Streptococcus pyogenes may also be treated. Erythromycin treats listeriosis caused by Listeria monocytogenes may also be treated with erythromycin. Erythromycin is indicated to treat pertussis (whooping cough) caused by Bordetella pertussis. It is effective in eliminating the causative organism from the nasopharynx of infected individuals, rendering them noninfectious. Clinical studies suggest that erythromycin may aid in the prevention of pertussis infection for individuals who have been exposed to the bacteria. Respiratory tract infections due to Mycoplasma pneumoniae may also be treated with erythromycin. Despite the fact that no controlled clinical efficacy studies have been conducted to this date, in vitro and certain preliminary clinical study results indicate that erythromycin may be an effective treatment in Legionnaires’ Disease. Finally, erythromycin is indicated to treat diphtheria and other infections due to Corynebacterium diphtheriae, as an adjunct to antitoxin, to prevent carrier status and to eradicate the organism in existing carriers. In addition to the prevention of diphtheria, erythromycin can be used to prevent rheumatic fever in penicillin intolerant patients. Skin infections Mild to moderate skin or skin structure infections caused by Streptococcus pyogenes or Staphylococcus aureus may be treated with erythromycin, however, resistant staphylococcal organisms may emerge. Erythromycin can also be used to treat erythrasma, an infectious condition caused by Corynebacterium minutissimum. Gastrointestinal infections Intestinal amebiasis caused by Entamoeba histolytica can be treated with oral erythromycin. Extraenteric amebiasis warrants treatment with other antimicrobial drugs. Genital infections/STIs Erythromycin can be used as an alternative drug in treating acute pelvic inflammatory disease caused by N. gonorrheae in female patients who have demonstrated hypersensitivity or intolerance to penicillin. Syphilis, caused by Treponema pallidum, can be treated with erythromycin. It serves as an alternative treatment for primary syphilis in patients who have demonstrated penicillin hypersensitivity. Erythromycin can also be used in the primary stage of primary syphilis. Another approved indication of erythromycin is to treat chlamydial infections that cause conjunctivitis of the newborn, pneumonia of infancy, and urogenital infections occurring in pregnancy. It is indicated as an alternative option to tetracyclines for the treatment of uncomplicated rectal, urethral and endocervical infections in adults caused by Chlamydia trachomatis. Erythromycin can be used in nongonococcal urethritis can be used when tetracyclines cannot be administered. Finally, erythromycin is indicated to treat nongonococcal urethritis due to Ureaplasma urealyticum. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Macrolides, such as erythromycin, stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections. Erythromycin does not exert effects on nucleic acid synthesis. This drug has been shown to be active against most strains of the following microorganisms, effectively treating both in vitro and clinical infections. Despite this, it is important to perform bacterial susceptibility testing before administering this antibiotic, as resistance is a common issue that may affect treatment. A note on antimicrobial resistance, pseudomembranous colitis, and hepatotoxicity Many strains of Haemophilus influenzae are resistant to erythromycin alone but are found to be susceptible to erythromycin and sulfonamides used in combination. It is important to note that Staphylococci that are resistant to erythromycin may emerge during erythromycin and/or sulfonamide therapy. Pseudomembranous colitis has been reported with most antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, the physician should consider this diagnosis in patients with diarrhea after the administration of antibacterial agents. Erythromycin can cause hepatic dysfunction, cholestatic jaundice, and abnormal liver transaminases, particularly when erythromycin estolate is administered. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Erythromycin acts by inhibition of protein synthesis by binding to the 23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible bacterial organisms. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. This results in the control of various bacterial infections. The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities. •Absorption (Drug A): No absorption available •Absorption (Drug B): Orally administered erythromycin is readily absorbed. Food intake does not appear to exert effects on serum concentrations of erythromycin. Some interindividual variation exists in terms of erythromycin absorption, which may impact absorption to varying degrees. The Cmax of erythromycin is 1.8 mcg/L and the Tmax is 1.2 hours. The serum AUC of erythromycin after the administration of a 500mg oral dose was 7.3±3.9 mg.h/l in one pharmacokinetic study. Erythromycin is well known for a bioavailability that is variable (18-45%) after oral administration and its susceptibility to broken down under acidic conditions. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Erythromycin is found in most body fluids and accumulates in leucocytes and inflammatory liquid. Spinal fluid concentrations of erythromycin are low, however, the diffusion of erythromycin through the blood-brain barrier increases in meningitis, likely due to the presence of inflamed tissues which are easily penetrated. Erythromycin crosses the placenta. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Erythromycin demonstrates 93% serum protein binding in the erythromycin propionate form. Another resource indicates that erythromycin protein binding ranges from 80 to 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): Hepatic first-pass metabolism contributes significantly to erythromycin metabolism after an oral dose. Erythromycin is partially metabolized by CYP3A4 enzyme to N-desmethylerythromycin. Erythromycin is also hydrolyzed to anhydro forms (anhydroerythromycin [AHE] and other metabolites), and this process is promoted by acidic conditions. AHE is inactive against microbes but inhibits hepatic drug oxidation and is therefore considered to be an important contributor to erythromycin drug-drug interactions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In patients with normal liver function, erythromycin concentrates in the liver and is then excreted in the bile. Under 5% of the orally administered dose of erythromycin is found excreted in the urine. A high percentage of absorbed erythromycin is not accounted for, but is likely metabolized. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 oral erythromycin was 3.5 hours according to one study and ranged between 2.4-3.1 hours in another study. Repetitive dosing of erythromycin leads to increased elimination half-life. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of erythromycin in healthy subjects was 0.53 ± 0.13 l/h/kg after a 125mg intravenous dose. In a clinical study of healthy patients and patients with liver cirrhosis, clearance of erythromycin was significantly reduced in those with severe liver cirrhosis. The clearance in cirrhotic patients was 42.2 ± 10.1 l h–1 versus 113.2 ± 44.2 l h-1 in healthy patients. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 The oral LD50 of erythromycin in rats is 9272 mg/kg. Overdose information Symptoms of overdose may include diarrhea, nausea, stomach cramps, and vomiting. Erythromycin should immediately be discontinued in cases of overdose. Rapid elimination of unabsorbed drug should be attempted. Supportive measures should be initiated. Erythromycin is not adequately removed by peritoneal dialysis or hemodialysis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aktipak, Apo-Erythro-S, Benzamycin, E.E.S., Ery, Ery-tab, Erygel, Eryped, Erythro, Erythrocin, Erythrocin Stearate •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Abomacetin Eritromicina Erythromycin Erythromycin A Erythromycin C érythromycine Erythromycinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Erythromycin is a macrolide antibiotic used to treat and prevent a variety of bacterial infections.

Erythromycin may increase the bleeding tendency associated with anticoagulant agents, according to several reports.1,3,2,6 The mechanism behind this interaction is likely the fact that erythromycin is a CYP3A4 inhibitor which may decrease the metabolism of various anticoagulants, potentiating their bleeding risk. The severity of the interaction is moderate.

Question: Does Abciximab and Erythromycin interact? Information: •Drug A: Abciximab •Drug B: Erythromycin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Erythromycin is combined with Abciximab. •Extended Description: Erythromycin may increase the bleeding tendency associated with anticoagulant agents, according to several reports.1,3,2,6 The mechanism behind this interaction is likely the fact that erythromycin is a CYP3A4 inhibitor which may decrease the metabolism of various anticoagulants, potentiating their bleeding risk. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Erythromycin is indicated in the treatment of infections caused by susceptible strains of various bacteria. The indications for erythromycin have been summarized by body system below: Respiratory infections Mild to moderate upper respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae, or Haemophilus influenzae (when used concomitantly with appropriate doses of sulfonamides) can be treated with erythromycin. Mild to moderate lower-respiratory tract infections due to susceptible strains of Streptococcus pneumoniae or Streptococcus pyogenes may also be treated. Erythromycin treats listeriosis caused by Listeria monocytogenes may also be treated with erythromycin. Erythromycin is indicated to treat pertussis (whooping cough) caused by Bordetella pertussis. It is effective in eliminating the causative organism from the nasopharynx of infected individuals, rendering them noninfectious. Clinical studies suggest that erythromycin may aid in the prevention of pertussis infection for individuals who have been exposed to the bacteria. Respiratory tract infections due to Mycoplasma pneumoniae may also be treated with erythromycin. Despite the fact that no controlled clinical efficacy studies have been conducted to this date, in vitro and certain preliminary clinical study results indicate that erythromycin may be an effective treatment in Legionnaires’ Disease. Finally, erythromycin is indicated to treat diphtheria and other infections due to Corynebacterium diphtheriae, as an adjunct to antitoxin, to prevent carrier status and to eradicate the organism in existing carriers. In addition to the prevention of diphtheria, erythromycin can be used to prevent rheumatic fever in penicillin intolerant patients. Skin infections Mild to moderate skin or skin structure infections caused by Streptococcus pyogenes or Staphylococcus aureus may be treated with erythromycin, however, resistant staphylococcal organisms may emerge. Erythromycin can also be used to treat erythrasma, an infectious condition caused by Corynebacterium minutissimum. Gastrointestinal infections Intestinal amebiasis caused by Entamoeba histolytica can be treated with oral erythromycin. Extraenteric amebiasis warrants treatment with other antimicrobial drugs. Genital infections/STIs Erythromycin can be used as an alternative drug in treating acute pelvic inflammatory disease caused by N. gonorrheae in female patients who have demonstrated hypersensitivity or intolerance to penicillin. Syphilis, caused by Treponema pallidum, can be treated with erythromycin. It serves as an alternative treatment for primary syphilis in patients who have demonstrated penicillin hypersensitivity. Erythromycin can also be used in the primary stage of primary syphilis. Another approved indication of erythromycin is to treat chlamydial infections that cause conjunctivitis of the newborn, pneumonia of infancy, and urogenital infections occurring in pregnancy. It is indicated as an alternative option to tetracyclines for the treatment of uncomplicated rectal, urethral and endocervical infections in adults caused by Chlamydia trachomatis. Erythromycin can be used in nongonococcal urethritis can be used when tetracyclines cannot be administered. Finally, erythromycin is indicated to treat nongonococcal urethritis due to Ureaplasma urealyticum. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Macrolides, such as erythromycin, stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections. Erythromycin does not exert effects on nucleic acid synthesis. This drug has been shown to be active against most strains of the following microorganisms, effectively treating both in vitro and clinical infections. Despite this, it is important to perform bacterial susceptibility testing before administering this antibiotic, as resistance is a common issue that may affect treatment. A note on antimicrobial resistance, pseudomembranous colitis, and hepatotoxicity Many strains of Haemophilus influenzae are resistant to erythromycin alone but are found to be susceptible to erythromycin and sulfonamides used in combination. It is important to note that Staphylococci that are resistant to erythromycin may emerge during erythromycin and/or sulfonamide therapy. Pseudomembranous colitis has been reported with most antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, the physician should consider this diagnosis in patients with diarrhea after the administration of antibacterial agents. Erythromycin can cause hepatic dysfunction, cholestatic jaundice, and abnormal liver transaminases, particularly when erythromycin estolate is administered. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Erythromycin acts by inhibition of protein synthesis by binding to the 23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible bacterial organisms. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. This results in the control of various bacterial infections. The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities. •Absorption (Drug A): No absorption available •Absorption (Drug B): Orally administered erythromycin is readily absorbed. Food intake does not appear to exert effects on serum concentrations of erythromycin. Some interindividual variation exists in terms of erythromycin absorption, which may impact absorption to varying degrees. The Cmax of erythromycin is 1.8 mcg/L and the Tmax is 1.2 hours. The serum AUC of erythromycin after the administration of a 500mg oral dose was 7.3±3.9 mg.h/l in one pharmacokinetic study. Erythromycin is well known for a bioavailability that is variable (18-45%) after oral administration and its susceptibility to broken down under acidic conditions. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Erythromycin is found in most body fluids and accumulates in leucocytes and inflammatory liquid. Spinal fluid concentrations of erythromycin are low, however, the diffusion of erythromycin through the blood-brain barrier increases in meningitis, likely due to the presence of inflamed tissues which are easily penetrated. Erythromycin crosses the placenta. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Erythromycin demonstrates 93% serum protein binding in the erythromycin propionate form. Another resource indicates that erythromycin protein binding ranges from 80 to 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): Hepatic first-pass metabolism contributes significantly to erythromycin metabolism after an oral dose. Erythromycin is partially metabolized by CYP3A4 enzyme to N-desmethylerythromycin. Erythromycin is also hydrolyzed to anhydro forms (anhydroerythromycin [AHE] and other metabolites), and this process is promoted by acidic conditions. AHE is inactive against microbes but inhibits hepatic drug oxidation and is therefore considered to be an important contributor to erythromycin drug-drug interactions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In patients with normal liver function, erythromycin concentrates in the liver and is then excreted in the bile. Under 5% of the orally administered dose of erythromycin is found excreted in the urine. A high percentage of absorbed erythromycin is not accounted for, but is likely metabolized. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 oral erythromycin was 3.5 hours according to one study and ranged between 2.4-3.1 hours in another study. Repetitive dosing of erythromycin leads to increased elimination half-life. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of erythromycin in healthy subjects was 0.53 ± 0.13 l/h/kg after a 125mg intravenous dose. In a clinical study of healthy patients and patients with liver cirrhosis, clearance of erythromycin was significantly reduced in those with severe liver cirrhosis. The clearance in cirrhotic patients was 42.2 ± 10.1 l h–1 versus 113.2 ± 44.2 l h-1 in healthy patients. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 The oral LD50 of erythromycin in rats is 9272 mg/kg. Overdose information Symptoms of overdose may include diarrhea, nausea, stomach cramps, and vomiting. Erythromycin should immediately be discontinued in cases of overdose. Rapid elimination of unabsorbed drug should be attempted. Supportive measures should be initiated. Erythromycin is not adequately removed by peritoneal dialysis or hemodialysis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Aktipak, Apo-Erythro-S, Benzamycin, E.E.S., Ery, Ery-tab, Erygel, Eryped, Erythro, Erythrocin, Erythrocin Stearate •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Abomacetin Eritromicina Erythromycin Erythromycin A Erythromycin C érythromycine Erythromycinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Erythromycin is a macrolide antibiotic used to treat and prevent a variety of bacterial infections. Output: Erythromycin may increase the bleeding tendency associated with anticoagulant agents, according to several reports.1,3,2,6 The mechanism behind this interaction is likely the fact that erythromycin is a CYP3A4 inhibitor which may decrease the metabolism of various anticoagulants, potentiating their bleeding risk. The severity of the interaction is moderate.

Does Abciximab and Escitalopram interact?

•Drug A: Abciximab •Drug B: Escitalopram •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Escitalopram is combined with Abciximab. •Extended Description: Platelets release serotonin in response to injury, triggering vasoconstriction and eventually hemostasis. As a selective serotonin re-uptake inhibitor (SSRI), escitalopram can inhibit the re-uptake of serotonin into platelets in much the same way it inhibits re-uptake into pre-synaptic neurons - this decrease in available platelet serotonin can result in a diminished clotting response and increased risk of bleeding. The combination of escitalopram with other agents that can increase the risk of bleeding may potentiate the baseline risk associated with SSRI use. SSRIs may also affect clotting ability via action the glycogen IIb/IIIa surface receptor (involved in platelet aggregation) or up-regulation of glycogen synthase kinase 3-beta (GSK3B) on 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): Escitalopram is indicated for the acute and maintenance treatment of major depressive disorder (MDD) in adults and pediatric patients 12 years old and older and for the acute treatment of generalized anxiety disorder (GAD) in adults and pediatric patients 7 years old and older. It is additionally indicated for symptomatic relief of obsessive-compulsive disorder (OCD) in Canada. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Escitalopram belongs to a class of medications called selective serotonin re-uptake inhibitors (SSRIs). These agents cause an increase in serotonin levels in neuronal synapses by preventing the re-uptake of serotonin (5-HT) into the presynaptic terminals of serotonergic neurons. As compared to other SSRIs, it appears to have a relatively quick onset of effect due to its potency. SSRIs as a class have been associated with abnormal bleeding, particularly in patients receiving concomitant therapy with other medications affecting hemostasis, and with the development of serotonin syndrome. Use escitalopram with caution in patients with a higher-than-baseline risk of bleeding and in patients receiving concomitant therapy with other serotonergic drugs. Escitalopram may also cause a discontinuation syndrome with abrupt removal of the drug, and should be slowly tapered if discontinuation of therapy is warranted. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Escitalopram, like other selective serotonin re-uptake inhibitors, enhances serotonergic activity by binding to the orthosteric (i.e. primary) binding site on the serotonin transporter (SERT), the same site to which endogenous 5-HT binds, and thus prevents the re-uptake of serotonin into the presynaptic neuron. Escitalopram, along with paroxetine, is also considered an allosteric serotonin re-uptake inhibitor - it binds to a secondary allosteric site on the SERT molecule to more strongly inhibit 5-HT re-uptake. Its combination of orthosteric and allosteric activity on SERT allows for greater extracellular 5-HT levels, a faster onset of action, and greater efficacy as compared to other SSRIs. The sustained elevation of synaptic 5-HT eventually causes desensitization of 5-HT 1A auto-receptors, which normally shut down endogenous 5-HT release in the presence of excess 5-HT - this desensitization may be necessary for the full clinical effect of SSRIs and may be responsible for their typically prolonged onset of action. Escitalopram has shown little-to-no binding affinity at a number of other receptors, such as histamine and muscarinic receptors, and minor activity at these off-targets may explain some of its adverse effects. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of escitalopram following oral administration is expected to be almost complete, with an estimated absolute bioavailability of approximately 80%. T max occurs after about 4-5 hours. C max and AUC appear to follow dose proportionality - at steady state, patients receiving 10mg of escitalopram daily had a C max of 21 ng/mL and a 24h AUC of approximately 360 ng*h/mL, while patients receiving 30mg daily had a roughly 3-fold increase in both C max and 24h AUC, comparatively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Escitalopram appears to distribute extensively into tissues, with an apparent volume of distribution of approximately 12-26 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Escitalopram exhibits relatively low protein binding at approximately 55-56%. •Metabolism (Drug A): 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 escitalopram is mainly hepatic, mediated primarily by CYP2C19 and CYP3A4 and, to a lesser extent, CYP2D6. Oxidative N-demethylation by the CYP enzyme system results in S-desmethylcitalopram (S-DCT) and S-didesmethylcitalopram (S-DDCT) - these metabolites do not contribute to the pharmacologic activity of escitalopram, and exist in the plasma in small quantities relative to the parent compound (28-31% and <5%, respectively). There is also some evidence that escitalopram is metabolized to a propionic acid metabolite by monoamine oxidase A and B in the brain, and that these enzymes constitute the major route of escitalopram metabolism in the brain. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After oral administration of escitalopram, approximately 8% of the total dose is eliminated in the urine as unchanged escitalopram and 10% is eliminated in the urine as S-desmethylcitalopram. The apparent hepatic clearance of escitalopram amounts to approximately 90% of the total 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 elimination half-life of escitalopram is 27-32 hours, though this is increased by approximately 50% in the elderly and doubled in patients with reduced hepatic function. The elimination half-life of escitalopram's primary metabolite, S-desmethylcitalopram, is approximately 54 hours at steady state. •Clearance (Drug A): No clearance available •Clearance (Drug B): The oral plasma clearance of escitalopram is 600 mL/min, of which approximately 7% is due to renal clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose may include CNS effects (dizziness, convulsions, coma, somnolence), gastrointestinal distress (nausea, vomiting), and/or cardiac abnormalities (hypotension, tachycardia, ECG changes). There is no specific antidote for escitalopram overdose. Management of overdose should focus on monitoring for cardiac abnormalities and changes to vital signs as well as treatment with supportive measures as indicated. As escitalopram is highly distributed into tissue following oral administration, forced diuresis, dialysis, and other methods of extracting drug from plasma are unlikely to be beneficial. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cipralex, Lexapro •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-Citalopram Escitalopram Escitalopramum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Escitalopram is a selective serotonin re-uptake inhibitor used in the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and other select psychiatric disorders such as obsessive-compulsive disorder (OCD).

Platelets release serotonin in response to injury, triggering vasoconstriction and eventually hemostasis. As a selective serotonin re-uptake inhibitor (SSRI), escitalopram can inhibit the re-uptake of serotonin into platelets in much the same way it inhibits re-uptake into pre-synaptic neurons - this decrease in available platelet serotonin can result in a diminished clotting response and increased risk of bleeding. The combination of escitalopram with other agents that can increase the risk of bleeding may potentiate the baseline risk associated with SSRI use. SSRIs may also affect clotting ability via action the glycogen IIb/IIIa surface receptor (involved in platelet aggregation) or up-regulation of glycogen synthase kinase 3-beta (GSK3B) on platelets. The severity of the interaction is moderate.

Question: Does Abciximab and Escitalopram interact? Information: •Drug A: Abciximab •Drug B: Escitalopram •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Escitalopram is combined with Abciximab. •Extended Description: Platelets release serotonin in response to injury, triggering vasoconstriction and eventually hemostasis. As a selective serotonin re-uptake inhibitor (SSRI), escitalopram can inhibit the re-uptake of serotonin into platelets in much the same way it inhibits re-uptake into pre-synaptic neurons - this decrease in available platelet serotonin can result in a diminished clotting response and increased risk of bleeding. The combination of escitalopram with other agents that can increase the risk of bleeding may potentiate the baseline risk associated with SSRI use. SSRIs may also affect clotting ability via action the glycogen IIb/IIIa surface receptor (involved in platelet aggregation) or up-regulation of glycogen synthase kinase 3-beta (GSK3B) on 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): Escitalopram is indicated for the acute and maintenance treatment of major depressive disorder (MDD) in adults and pediatric patients 12 years old and older and for the acute treatment of generalized anxiety disorder (GAD) in adults and pediatric patients 7 years old and older. It is additionally indicated for symptomatic relief of obsessive-compulsive disorder (OCD) in Canada. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Escitalopram belongs to a class of medications called selective serotonin re-uptake inhibitors (SSRIs). These agents cause an increase in serotonin levels in neuronal synapses by preventing the re-uptake of serotonin (5-HT) into the presynaptic terminals of serotonergic neurons. As compared to other SSRIs, it appears to have a relatively quick onset of effect due to its potency. SSRIs as a class have been associated with abnormal bleeding, particularly in patients receiving concomitant therapy with other medications affecting hemostasis, and with the development of serotonin syndrome. Use escitalopram with caution in patients with a higher-than-baseline risk of bleeding and in patients receiving concomitant therapy with other serotonergic drugs. Escitalopram may also cause a discontinuation syndrome with abrupt removal of the drug, and should be slowly tapered if discontinuation of therapy is warranted. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Escitalopram, like other selective serotonin re-uptake inhibitors, enhances serotonergic activity by binding to the orthosteric (i.e. primary) binding site on the serotonin transporter (SERT), the same site to which endogenous 5-HT binds, and thus prevents the re-uptake of serotonin into the presynaptic neuron. Escitalopram, along with paroxetine, is also considered an allosteric serotonin re-uptake inhibitor - it binds to a secondary allosteric site on the SERT molecule to more strongly inhibit 5-HT re-uptake. Its combination of orthosteric and allosteric activity on SERT allows for greater extracellular 5-HT levels, a faster onset of action, and greater efficacy as compared to other SSRIs. The sustained elevation of synaptic 5-HT eventually causes desensitization of 5-HT 1A auto-receptors, which normally shut down endogenous 5-HT release in the presence of excess 5-HT - this desensitization may be necessary for the full clinical effect of SSRIs and may be responsible for their typically prolonged onset of action. Escitalopram has shown little-to-no binding affinity at a number of other receptors, such as histamine and muscarinic receptors, and minor activity at these off-targets may explain some of its adverse effects. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of escitalopram following oral administration is expected to be almost complete, with an estimated absolute bioavailability of approximately 80%. T max occurs after about 4-5 hours. C max and AUC appear to follow dose proportionality - at steady state, patients receiving 10mg of escitalopram daily had a C max of 21 ng/mL and a 24h AUC of approximately 360 ng*h/mL, while patients receiving 30mg daily had a roughly 3-fold increase in both C max and 24h AUC, comparatively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Escitalopram appears to distribute extensively into tissues, with an apparent volume of distribution of approximately 12-26 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Escitalopram exhibits relatively low protein binding at approximately 55-56%. •Metabolism (Drug A): 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 escitalopram is mainly hepatic, mediated primarily by CYP2C19 and CYP3A4 and, to a lesser extent, CYP2D6. Oxidative N-demethylation by the CYP enzyme system results in S-desmethylcitalopram (S-DCT) and S-didesmethylcitalopram (S-DDCT) - these metabolites do not contribute to the pharmacologic activity of escitalopram, and exist in the plasma in small quantities relative to the parent compound (28-31% and <5%, respectively). There is also some evidence that escitalopram is metabolized to a propionic acid metabolite by monoamine oxidase A and B in the brain, and that these enzymes constitute the major route of escitalopram metabolism in the brain. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After oral administration of escitalopram, approximately 8% of the total dose is eliminated in the urine as unchanged escitalopram and 10% is eliminated in the urine as S-desmethylcitalopram. The apparent hepatic clearance of escitalopram amounts to approximately 90% of the total 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 elimination half-life of escitalopram is 27-32 hours, though this is increased by approximately 50% in the elderly and doubled in patients with reduced hepatic function. The elimination half-life of escitalopram's primary metabolite, S-desmethylcitalopram, is approximately 54 hours at steady state. •Clearance (Drug A): No clearance available •Clearance (Drug B): The oral plasma clearance of escitalopram is 600 mL/min, of which approximately 7% is due to renal clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose may include CNS effects (dizziness, convulsions, coma, somnolence), gastrointestinal distress (nausea, vomiting), and/or cardiac abnormalities (hypotension, tachycardia, ECG changes). There is no specific antidote for escitalopram overdose. Management of overdose should focus on monitoring for cardiac abnormalities and changes to vital signs as well as treatment with supportive measures as indicated. As escitalopram is highly distributed into tissue following oral administration, forced diuresis, dialysis, and other methods of extracting drug from plasma are unlikely to be beneficial. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cipralex, Lexapro •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-Citalopram Escitalopram Escitalopramum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Escitalopram is a selective serotonin re-uptake inhibitor used in the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and other select psychiatric disorders such as obsessive-compulsive disorder (OCD). Output: Platelets release serotonin in response to injury, triggering vasoconstriction and eventually hemostasis. As a selective serotonin re-uptake inhibitor (SSRI), escitalopram can inhibit the re-uptake of serotonin into platelets in much the same way it inhibits re-uptake into pre-synaptic neurons - this decrease in available platelet serotonin can result in a diminished clotting response and increased risk of bleeding. The combination of escitalopram with other agents that can increase the risk of bleeding may potentiate the baseline risk associated with SSRI use. SSRIs may also affect clotting ability via action the glycogen IIb/IIIa surface receptor (involved in platelet aggregation) or up-regulation of glycogen synthase kinase 3-beta (GSK3B) on platelets. The severity of the interaction is moderate.

Does Abciximab and Esterified estrogens interact?

•Drug A: Abciximab •Drug B: Esterified estrogens •Severity: MODERATE •Description: Esterified estrogens may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Esterified estrogens are indicated to replace estrogen in women with ovarian failure or other conditions that cause a lack of natural estrogen in the body. It is also indicated for the treatment of symptoms of breast cancer in both men and women. In men it can be used for the treatment of advanced prostate cancer. It is also indicated for the treatment of menopausal symptoms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estrogens are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estradiol is the principle intracellular human estrogen and is more potent than estrone and estriol at the receptor level; it is the primary estrogen secreted prior to menopause. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone, and follicle-stimulating hormone through a negative feedback system; estrogen replacement reduces elevated levels of these hormones. •Absorption (Drug A): No absorption available •Absorption (Drug B): Readily absorbed after oral administration. High concentrations of estrone are achieved with oral administration, whereas higher concentrations of estradiol are generally achieved after percutaneous absorption. Although vaginal products (such as gel, rings, etc.) are administered locally, they achieve high serum concentrations. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentration in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 95-98% of estradiol is bound loosely to albumin or tightly to sex hormone binding globulin. •Metabolism (Drug A): 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; partial metabolism via CYP3A4 enzymes; estradiol is reversibly converted to estrone and estriol; oral estradiol also undergoes enterohepatic recirculation by conjugation in the liver, followed by excretion of sulfate and glucuronide conjugates into the bile, then hydrolysis in the intestine and estrogen reabsorption. Sulfate conjugates are the primary form found in postmenopausal women. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mainly urinary as estradiol, estrone, estriol, and their glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Half-life varies, it is in the range 1-2 hr. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is variation in the clearance rate depends on each estrogen individual: estradiol-17β: 580 L/day/m2 estrone: 4050 L/day/m2 estriol: 1110 L/day/m2 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 IP 325 mg/Kg (rat). LD50 IV 1740 mg/Kg (mouse). LD50 oral >5000 mg/Kg (rat). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Covaryx, Menest •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Esterified estrogens Estrogens, esterified Estrogens,esterified •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Esterified estrogens is a female hormone used to treat conditions related to estrogen deficiency and moderate to severe vasomotor menopausal symptoms in women.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Esterified estrogens interact? Information: •Drug A: Abciximab •Drug B: Esterified estrogens •Severity: MODERATE •Description: Esterified estrogens may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Esterified estrogens are indicated to replace estrogen in women with ovarian failure or other conditions that cause a lack of natural estrogen in the body. It is also indicated for the treatment of symptoms of breast cancer in both men and women. In men it can be used for the treatment of advanced prostate cancer. It is also indicated for the treatment of menopausal symptoms. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estrogens are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estradiol is the principle intracellular human estrogen and is more potent than estrone and estriol at the receptor level; it is the primary estrogen secreted prior to menopause. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone, and follicle-stimulating hormone through a negative feedback system; estrogen replacement reduces elevated levels of these hormones. •Absorption (Drug A): No absorption available •Absorption (Drug B): Readily absorbed after oral administration. High concentrations of estrone are achieved with oral administration, whereas higher concentrations of estradiol are generally achieved after percutaneous absorption. Although vaginal products (such as gel, rings, etc.) are administered locally, they achieve high serum concentrations. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentration in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 95-98% of estradiol is bound loosely to albumin or tightly to sex hormone binding globulin. •Metabolism (Drug A): 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; partial metabolism via CYP3A4 enzymes; estradiol is reversibly converted to estrone and estriol; oral estradiol also undergoes enterohepatic recirculation by conjugation in the liver, followed by excretion of sulfate and glucuronide conjugates into the bile, then hydrolysis in the intestine and estrogen reabsorption. Sulfate conjugates are the primary form found in postmenopausal women. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mainly urinary as estradiol, estrone, estriol, and their glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Half-life varies, it is in the range 1-2 hr. •Clearance (Drug A): No clearance available •Clearance (Drug B): There is variation in the clearance rate depends on each estrogen individual: estradiol-17β: 580 L/day/m2 estrone: 4050 L/day/m2 estriol: 1110 L/day/m2 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 IP 325 mg/Kg (rat). LD50 IV 1740 mg/Kg (mouse). LD50 oral >5000 mg/Kg (rat). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Covaryx, Menest •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Esterified estrogens Estrogens, esterified Estrogens,esterified •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Esterified estrogens is a female hormone used to treat conditions related to estrogen deficiency and moderate to severe vasomotor menopausal symptoms in women. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Does Abciximab and Estradiol acetate interact?

•Drug A: Abciximab •Drug B: Estradiol acetate •Severity: MODERATE •Description: Estradiol acetate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Femring is indicated for the treatment of vasomotor and urogenital symptoms associated with menopause. Use of Femring (estradiol acetate) has been shown to improve symptoms caused by atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular 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): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause, which are primarily caused by a loss of estrogenic activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Drug delivery from Femring is rapid for the first hour and then declines to a relatively constant rate for the remainder of the 3-month dosing interval. Estradiol acetate is rapidly hydrolyzed to estradiol which is absorbed through the vaginal mucosa as evidenced by the mean time to maximum concentration (tmax) for estradiol of about 1 hour (range 0.25 to 1.5 hrs). Following the maximum concentration (Cmax=1129pg/mL), serum estradiol decreases rapidly such that by 24 to 48 hours postdose, serum estradiol concentrations are relatively constant through the end of the 3-month dosing interval. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Estrogens circulate in the blood largely (>95%) bound to sex hormone binding globulin (SHBG) and 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): Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Can cause nausea and vomiting, and withdrawal bleeding may occur in females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Femring •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Estradiol 3-acetate Estradiol 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): Estradiol acetate is an estrogen used to treat vasomotor symptoms and moderate to severe vulvar and vaginal atrophy from menopause.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Estradiol acetate interact? Information: •Drug A: Abciximab •Drug B: Estradiol acetate •Severity: MODERATE •Description: Estradiol acetate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Femring is indicated for the treatment of vasomotor and urogenital symptoms associated with menopause. Use of Femring (estradiol acetate) has been shown to improve symptoms caused by atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular 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): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause, which are primarily caused by a loss of estrogenic activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Drug delivery from Femring is rapid for the first hour and then declines to a relatively constant rate for the remainder of the 3-month dosing interval. Estradiol acetate is rapidly hydrolyzed to estradiol which is absorbed through the vaginal mucosa as evidenced by the mean time to maximum concentration (tmax) for estradiol of about 1 hour (range 0.25 to 1.5 hrs). Following the maximum concentration (Cmax=1129pg/mL), serum estradiol decreases rapidly such that by 24 to 48 hours postdose, serum estradiol concentrations are relatively constant through the end of the 3-month dosing interval. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Estrogens circulate in the blood largely (>95%) bound to sex hormone binding globulin (SHBG) and 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): Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Can cause nausea and vomiting, and withdrawal bleeding may occur in females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Femring •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Estradiol 3-acetate Estradiol 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): Estradiol acetate is an estrogen used to treat vasomotor symptoms and moderate to severe vulvar and vaginal atrophy from menopause. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Does Abciximab and Estradiol benzoate interact?

•Drug A: Abciximab •Drug B: Estradiol benzoate •Severity: MODERATE •Description: Estradiol benzoate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Estradiol benzoate is not currently available in any FDA or Health Canada approved products. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. •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): Estrogens circulate in the blood largely (>95%) bound to sex hormone binding globulin (SHBG) and 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): Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450. •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): Estradiol benzoate is an estrogen indicated in combination with progesterone for the treatment of irregular menstruation.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Estradiol benzoate interact? Information: •Drug A: Abciximab •Drug B: Estradiol benzoate •Severity: MODERATE •Description: Estradiol benzoate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Estradiol benzoate is not currently available in any FDA or Health Canada approved products. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. •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): Estrogens circulate in the blood largely (>95%) bound to sex hormone binding globulin (SHBG) and 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): Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450. •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): Estradiol benzoate is an estrogen indicated in combination with progesterone for the treatment of irregular menstruation. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Does Abciximab and Estradiol cypionate interact?

•Drug A: Abciximab •Drug B: Estradiol cypionate •Severity: MODERATE •Description: Estradiol cypionate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Depo-Estradiol intramuscular depot injection is indicated for the treatment of moderate to severe vasomotor symptoms and hypoestrogenism due to hypogonadism. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular 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): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause and of hypoestrogenism, which are primarily caused by a loss of estrogenic activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and 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): Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Depo-estradiol •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): Estradiol cypionate is an estradiol prodrug used to treat vasomotor symptoms and hypoestrogenisms from hypogonadism.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Estradiol cypionate interact? Information: •Drug A: Abciximab •Drug B: Estradiol cypionate •Severity: MODERATE •Description: Estradiol cypionate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Depo-Estradiol intramuscular depot injection is indicated for the treatment of moderate to severe vasomotor symptoms and hypoestrogenism due to hypogonadism. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular 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): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause and of hypoestrogenism, which are primarily caused by a loss of estrogenic activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and 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): Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Depo-estradiol •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): Estradiol cypionate is an estradiol prodrug used to treat vasomotor symptoms and hypoestrogenisms from hypogonadism. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Does Abciximab and Estradiol valerate interact?

•Drug A: Abciximab •Drug B: Estradiol valerate •Severity: MODERATE •Description: Estradiol valerate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Estradiol valerate is commercially available as an intramuscular injection as the product Delestrogen and is indicated for the treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and for the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Estradiol valerate is also available in combination with Dienogest as the commercially available product Natazia used for the prevention of pregnancy and for the treatment of heavy menstrual 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): Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular 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): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause, which are primarily caused by a loss of estrogenic activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): IM Injection: When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. Natazia: After oral administration of estradiol valerate, cleavage to 17β-estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites, estrone and other metabolites. Maximum serum estradiol concentrations of 73.3 pg/mL are reached at a median of approximately 6 hours (range: 1.5–12 hours) and the area under the estradiol concentration curve [AUC(0–24h)] was 1301 pg·h/mL after single ingestion of a tablet containing 3 mg estradiol valerate under fasted condition on Day 1 of the 28-day sequential regimen. •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): Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Delestrogen, Natazia •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): Estradiol valerate is an estradiol prodrug used to treat some effects of menopause, hypoestrogenism, androgen dependant carcinoma of the prostate, and in combination products for endometriosis and contraception.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Estradiol valerate interact? Information: •Drug A: Abciximab •Drug B: Estradiol valerate •Severity: MODERATE •Description: Estradiol valerate may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Estradiol valerate is commercially available as an intramuscular injection as the product Delestrogen and is indicated for the treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and for the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Estradiol valerate is also available in combination with Dienogest as the commercially available product Natazia used for the prevention of pregnancy and for the treatment of heavy menstrual 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): Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular 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): Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause, which are primarily caused by a loss of estrogenic activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): IM Injection: When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. Natazia: After oral administration of estradiol valerate, cleavage to 17β-estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites, estrone and other metabolites. Maximum serum estradiol concentrations of 73.3 pg/mL are reached at a median of approximately 6 hours (range: 1.5–12 hours) and the area under the estradiol concentration curve [AUC(0–24h)] was 1301 pg·h/mL after single ingestion of a tablet containing 3 mg estradiol valerate under fasted condition on Day 1 of the 28-day sequential regimen. •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): Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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): Delestrogen, Natazia •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): Estradiol valerate is an estradiol prodrug used to treat some effects of menopause, hypoestrogenism, androgen dependant carcinoma of the prostate, and in combination products for endometriosis and contraception. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Does Abciximab and Estradiol interact?

•Drug A: Abciximab •Drug B: Estradiol •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Estradiol 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): Estradiol is indicated in various preparations for the treatment of moderate to severe vasomotor symptoms and vulvar and vaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure, and for the prevention of postmenopausal osteoporosis. It is also used for the treatment of breast cancer (only for palliation therapy) in certain men or women with metastatic disease, and for the treatment of androgen-dependent prostate cancer (only for palliation therapy). It is also used in combination with other hormones as a component of oral contraceptive pills for preventing pregnancy (most commonly as Ethinylestradiol, a synthetic form of estradiol). A note on duration of treatment Recommendations for treatment of menopausal symptoms changed drastically following the release of results and early termination of the Women's Health Initiative (WHI) studies in 2002 as concerns were raised regarding estrogen use. Specifically, the combined estrogen–progestin group was discontinued after about 5 years of follow up due to a statistically significant increase in invasive breast cancer and in cardiovascular events. Following extensive critique of the WHI results, Hormone Replacement Therapy (HRT) is now recommended to be used only for a short period (for 3-5 years postmenopause) in low doses, and in women without a history of breast cancer or increased risk of cardiovascular or thromboembolic disease. Estrogen for postmenopausal symptoms should always be given with a progestin component due to estrogen's stimulatory effects on the endometrium; in women with an intact uterus, unopposed estrogen has been shown to promote the growth of the endometrium which can lead to endometrial hyperplasia and possibly cancer over the long-term. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia). Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption and may have beneficial effects on the plasma lipid profile. Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland. A note on hyper-coagulable state, cardiovascular health, and blood pressure Estradiol may cause an increased risk of cardiovascular disease, DVT, and stroke, and its use should be avoided in patients at high risk of these conditions. Estrogen induces a hyper-coagulable state, which is also associated with both estrogen-containing oral contraceptive (OC) use and pregnancy. Although estrogen causes an increase in levels of plasma renin and angiotensin. Estrogen-induced increases in angiotensin, causing sodium retention, which is likely to be the mechanism causing hypertension after oral contraceptive 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): Estrogen is found in the the breast, uterine, ovarian, skin, prostate, bone, fat, and brain tissues. The main source of estrogen in adult women during the reproductive period of life is the ovarian follicle, which secretes 70 to 500 mcg of estradiol each day. After menopause, however, the majority of endogenous estrogen is produced by transformation of androstenedione (which is secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women. Estradiol, however, is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, the higher estrone concentration in postmenopausal population, can cause various undesirable effects. These effects may include hot flashes, chills, vaginal dryness, mood swings, irregular menstruation, and chills, in addition to sleep problems. Estradiol workings by binding to subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). It also exerts potent agonism of G Protein-coupled estrogen receptor (GPER), which is recognized an important regulator of this drug's rapid effects. Once the estrogen receptor has bound to its ligand, it enters the nucleus of the target cell, regulating gene transcription and formation of of messenger RNA. This mRNA makes contact with ribosomes producing specific proteins that express the effect of estradiol upon the target cell. Agonism of estrogen receptors increases pro-estrogenic effects, leading to the relief of vasomotor and urogenital symptoms of a postmenopausal or low estradiol state. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absorption of several formulations of estradiol is described below: Oral tablets and injections First-pass metabolism in the gastrointestinal tract rapidly breaks down estradiol tablets before entering the systemic circulation. The bioavailability of oral estrogens is said to be 2-10% due to significant first-pass effects. The esterification of estradiol improves the administration (such as with estradiol valerate) or to sustain release from intramuscular depot injections (including estradiol cypionate ) via higher lipophilicity. After absorption, the esters are cleaved, which leads to the release of endogenous estradiol, or 17β-estradiol. Transdermal preparations The transdermal preparations slowly release estradiol through intact skin, which sustains circulating levels of estradiol during a 1 week period of time. Notably, the bioavailability of estradiol after transdermal administration is about 20 times higher than after oral administration. Transdermal estradiol avoids first pass metabolism effects that reduce bioavailability. Administration via the buttock leads to a Cmax of about 174 pg/mL compared to 147 pg/mL via the abdomen. Spray preparations After daily administration, the spray formulations of estradiol reach steady state within 7-8 days. After 3 sprays daily, Cmax is about 54 pg/mL with a Tmax of 20 hours. AUC is about 471 pg•hr/mL. Vaginal ring and cream preparations Estradiol is efficiently absorbed through the mucous membranes of the vagina. The vaginal administration of estrogens evades first-pass metabolism. Tmax after vaginal ring delivery ranges from 0.5 to 1 hour. Cmax is about 63 pg/mL. The vaginal cream preparation has a Cmax of estradiol (a component of Premarin vaginal estrogen conjugate cream) was a Cmax of 12.8 ± 16.6 pg/mL, Tmax of 8.5 ± 6.2 hours, with an AUC of 231 ± 285 pg•hr/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Estrogens administered exogenously distribute in a similar fashion to endogenous estrogens. They can be found throughout the body, especially in the sex hormone target organs, such as the breast, ovaries and uterus. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): More than 95% of estrogens are found to circulate in the blood bound to sex hormone binding globulin (SHBG) and 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): Exogenously administered estrogens are metabolized in the same fashion as endogenous estrogens. Metabolic transformation occurs primarily in the liver and intestine. Estradiol is metabolized to estrone, and both are converted to estriol, which is later excreted in the urine. Sulfate and glucuronide conjugation estrogens also take place in the liver. Biliary secretion of metabolic conjugates are released into the intestine, and estrogen hydrolysis in the gut occurs, followed by reabsorption. The CYP3A4 hepatic cytochrome enzyme is heavily involved in the metabolism of estradiol. CYP1A2 also plays a role. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol is excreted in the urine with both glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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-lives for various estrogen products post oral or intravenous administration has been reported to range from 1-12 hours. One pharmacokinetic study of oral estradiol valerate administration in postmenopausal women revealed a terminal elimination half-life of 16.9 ± 6.0 h. A pharmacokinetic study of intravenous estradiol administration in postmenopausal women showed an elimination half-life of 27.45 ± 5.65 minutes. The half-life of estradiol appears to vary by route of administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): In one pharmacokinetic study, the clearance of orally administered micronized estradiol in postmenopausal women was 29.9±15.5 mL/min/kg. Another study revealed a clearance of intravenously administered estradiol was 1.3 mL/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The NOAEL (no-observed-adverse-effect-level) oral toxicity of estradiol after 90 day in rats was 0.003 mg/kg/day for blood, female reproductive, and male reproductive, endocrine, and liver toxicity. Oral TDLO of ethinyl estradiol is 21 mg/kg/21D intermittent, woman) with an oral LD50 of 960 mg/kg in the rat. There is limited information in the literature regarding estrogen overdose. Estradiol overdose likely leads to the occurrence of estrogen-associated adverse effects, including nausea, vomiting, abdominal pain, breast tenderness, venous thrombosis, and vaginal bleeding. It is generally recommend to discontinue estradiol treatment and offer supportive care in the case of an overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Activella 1/0.5 28 Day, Activelle, Amabelz 0.5/0.1 28 Day, Angeliq 0.25/0.5 28 Day, Bijuva, Climara, Climara Pro, Combipatch, Divigel, Dotti, Elestrin, Estalis, Estrace, Estradot, Estring, Estrogel, Etyqa 0.5/0.1 28 Day, Evamist, Imvexxy 4 Mcg Starter Pack, Lopreeza 1/0.5 28 Day, Lyllana, Menostar, Mimvey, Minivelle, Myfembree, Oesclim, Oriahnn 28 Day Kit, Prefest 30 Day, Vagifem, Vivelle, Yuvafem •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 17beta oestradiol beta-Estradiol cis-Estradiol Estradiol Estradiol-17beta Estradiolum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estradiol is an estrogenic steroid used to treat vasomotor symptoms of vulvar and vaginal atrophy in menopause, hypoestrogenism, prevention of postmenopausal osteoporosis, treatment of breast cancer, and advanced androgen-dependent carcinoma of the prostate.

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 Estradiol interact? Information: •Drug A: Abciximab •Drug B: Estradiol •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Estradiol 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): Estradiol is indicated in various preparations for the treatment of moderate to severe vasomotor symptoms and vulvar and vaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure, and for the prevention of postmenopausal osteoporosis. It is also used for the treatment of breast cancer (only for palliation therapy) in certain men or women with metastatic disease, and for the treatment of androgen-dependent prostate cancer (only for palliation therapy). It is also used in combination with other hormones as a component of oral contraceptive pills for preventing pregnancy (most commonly as Ethinylestradiol, a synthetic form of estradiol). A note on duration of treatment Recommendations for treatment of menopausal symptoms changed drastically following the release of results and early termination of the Women's Health Initiative (WHI) studies in 2002 as concerns were raised regarding estrogen use. Specifically, the combined estrogen–progestin group was discontinued after about 5 years of follow up due to a statistically significant increase in invasive breast cancer and in cardiovascular events. Following extensive critique of the WHI results, Hormone Replacement Therapy (HRT) is now recommended to be used only for a short period (for 3-5 years postmenopause) in low doses, and in women without a history of breast cancer or increased risk of cardiovascular or thromboembolic disease. Estrogen for postmenopausal symptoms should always be given with a progestin component due to estrogen's stimulatory effects on the endometrium; in women with an intact uterus, unopposed estrogen has been shown to promote the growth of the endometrium which can lead to endometrial hyperplasia and possibly cancer over the long-term. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia). Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption and may have beneficial effects on the plasma lipid profile. Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland. A note on hyper-coagulable state, cardiovascular health, and blood pressure Estradiol may cause an increased risk of cardiovascular disease, DVT, and stroke, and its use should be avoided in patients at high risk of these conditions. Estrogen induces a hyper-coagulable state, which is also associated with both estrogen-containing oral contraceptive (OC) use and pregnancy. Although estrogen causes an increase in levels of plasma renin and angiotensin. Estrogen-induced increases in angiotensin, causing sodium retention, which is likely to be the mechanism causing hypertension after oral contraceptive 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): Estrogen is found in the the breast, uterine, ovarian, skin, prostate, bone, fat, and brain tissues. The main source of estrogen in adult women during the reproductive period of life is the ovarian follicle, which secretes 70 to 500 mcg of estradiol each day. After menopause, however, the majority of endogenous estrogen is produced by transformation of androstenedione (which is secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women. Estradiol, however, is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, the higher estrone concentration in postmenopausal population, can cause various undesirable effects. These effects may include hot flashes, chills, vaginal dryness, mood swings, irregular menstruation, and chills, in addition to sleep problems. Estradiol workings by binding to subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). It also exerts potent agonism of G Protein-coupled estrogen receptor (GPER), which is recognized an important regulator of this drug's rapid effects. Once the estrogen receptor has bound to its ligand, it enters the nucleus of the target cell, regulating gene transcription and formation of of messenger RNA. This mRNA makes contact with ribosomes producing specific proteins that express the effect of estradiol upon the target cell. Agonism of estrogen receptors increases pro-estrogenic effects, leading to the relief of vasomotor and urogenital symptoms of a postmenopausal or low estradiol state. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absorption of several formulations of estradiol is described below: Oral tablets and injections First-pass metabolism in the gastrointestinal tract rapidly breaks down estradiol tablets before entering the systemic circulation. The bioavailability of oral estrogens is said to be 2-10% due to significant first-pass effects. The esterification of estradiol improves the administration (such as with estradiol valerate) or to sustain release from intramuscular depot injections (including estradiol cypionate ) via higher lipophilicity. After absorption, the esters are cleaved, which leads to the release of endogenous estradiol, or 17β-estradiol. Transdermal preparations The transdermal preparations slowly release estradiol through intact skin, which sustains circulating levels of estradiol during a 1 week period of time. Notably, the bioavailability of estradiol after transdermal administration is about 20 times higher than after oral administration. Transdermal estradiol avoids first pass metabolism effects that reduce bioavailability. Administration via the buttock leads to a Cmax of about 174 pg/mL compared to 147 pg/mL via the abdomen. Spray preparations After daily administration, the spray formulations of estradiol reach steady state within 7-8 days. After 3 sprays daily, Cmax is about 54 pg/mL with a Tmax of 20 hours. AUC is about 471 pg•hr/mL. Vaginal ring and cream preparations Estradiol is efficiently absorbed through the mucous membranes of the vagina. The vaginal administration of estrogens evades first-pass metabolism. Tmax after vaginal ring delivery ranges from 0.5 to 1 hour. Cmax is about 63 pg/mL. The vaginal cream preparation has a Cmax of estradiol (a component of Premarin vaginal estrogen conjugate cream) was a Cmax of 12.8 ± 16.6 pg/mL, Tmax of 8.5 ± 6.2 hours, with an AUC of 231 ± 285 pg•hr/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Estrogens administered exogenously distribute in a similar fashion to endogenous estrogens. They can be found throughout the body, especially in the sex hormone target organs, such as the breast, ovaries and uterus. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): More than 95% of estrogens are found to circulate in the blood bound to sex hormone binding globulin (SHBG) and 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): Exogenously administered estrogens are metabolized in the same fashion as endogenous estrogens. Metabolic transformation occurs primarily in the liver and intestine. Estradiol is metabolized to estrone, and both are converted to estriol, which is later excreted in the urine. Sulfate and glucuronide conjugation estrogens also take place in the liver. Biliary secretion of metabolic conjugates are released into the intestine, and estrogen hydrolysis in the gut occurs, followed by reabsorption. The CYP3A4 hepatic cytochrome enzyme is heavily involved in the metabolism of estradiol. CYP1A2 also plays a role. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Estradiol is excreted in the urine with both glucuronide and sulfate conjugates. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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-lives for various estrogen products post oral or intravenous administration has been reported to range from 1-12 hours. One pharmacokinetic study of oral estradiol valerate administration in postmenopausal women revealed a terminal elimination half-life of 16.9 ± 6.0 h. A pharmacokinetic study of intravenous estradiol administration in postmenopausal women showed an elimination half-life of 27.45 ± 5.65 minutes. The half-life of estradiol appears to vary by route of administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): In one pharmacokinetic study, the clearance of orally administered micronized estradiol in postmenopausal women was 29.9±15.5 mL/min/kg. Another study revealed a clearance of intravenously administered estradiol was 1.3 mL/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The NOAEL (no-observed-adverse-effect-level) oral toxicity of estradiol after 90 day in rats was 0.003 mg/kg/day for blood, female reproductive, and male reproductive, endocrine, and liver toxicity. Oral TDLO of ethinyl estradiol is 21 mg/kg/21D intermittent, woman) with an oral LD50 of 960 mg/kg in the rat. There is limited information in the literature regarding estrogen overdose. Estradiol overdose likely leads to the occurrence of estrogen-associated adverse effects, including nausea, vomiting, abdominal pain, breast tenderness, venous thrombosis, and vaginal bleeding. It is generally recommend to discontinue estradiol treatment and offer supportive care in the case of an overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Activella 1/0.5 28 Day, Activelle, Amabelz 0.5/0.1 28 Day, Angeliq 0.25/0.5 28 Day, Bijuva, Climara, Climara Pro, Combipatch, Divigel, Dotti, Elestrin, Estalis, Estrace, Estradot, Estring, Estrogel, Etyqa 0.5/0.1 28 Day, Evamist, Imvexxy 4 Mcg Starter Pack, Lopreeza 1/0.5 28 Day, Lyllana, Menostar, Mimvey, Minivelle, Myfembree, Oesclim, Oriahnn 28 Day Kit, Prefest 30 Day, Vagifem, Vivelle, Yuvafem •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 17beta oestradiol beta-Estradiol cis-Estradiol Estradiol Estradiol-17beta Estradiolum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estradiol is an estrogenic steroid used to treat vasomotor symptoms of vulvar and vaginal atrophy in menopause, hypoestrogenism, prevention of postmenopausal osteoporosis, treatment of breast cancer, and advanced androgen-dependent carcinoma of the prostate. 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 Estriol interact?

•Drug A: Abciximab •Drug B: Estriol •Severity: MODERATE •Description: Estriol may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Used as a test to determine the general health of an unborn fetus. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Estriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta. If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. The drug interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estriol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. •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): ORAL (LD50): Acute: >2000 mg/kg [Rat]. •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): 16-alpha-Hydroxyestradiol 16alpha-hydroxyestradiol Estriol Oestriol Östriol Trihydroxyestrin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estriol is a weak estrogen used to treat vaginal dryness and estrogen deficiency conditions, such as vaginitis and vulvar itching.

Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.

Question: Does Abciximab and Estriol interact? Information: •Drug A: Abciximab •Drug B: Estriol •Severity: MODERATE •Description: Estriol may decrease the anticoagulant activities of Abciximab. •Extended Description: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those 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): Used as a test to determine the general health of an unborn fetus. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Estriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta. If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. The drug interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estriol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. •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): ORAL (LD50): Acute: >2000 mg/kg [Rat]. •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): 16-alpha-Hydroxyestradiol 16alpha-hydroxyestradiol Estriol Oestriol Östriol Trihydroxyestrin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estriol is a weak estrogen used to treat vaginal dryness and estrogen deficiency conditions, such as vaginitis and vulvar itching. Output: Estrogens activate the coagulation pathway via increasing plasma fibrinogen and the activity of coagulation factors such as factors VII and X. Co-administration of estrogens with anticoagulant agents may interfere with the anticoagulant actions of those agents. The severity of the interaction is moderate.