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Does Abciximab and Estrone sulfate interact?

•Drug A: Abciximab •Drug B: Estrone sulfate •Severity: MODERATE •Description: Estrone sulfate 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): Estropipate is used for the treatment of moderate to severe vasomotor symptoms associated with the monopause, and moderate to severe symptoms of vulval and vaginal atrophy associated with the menopause. It is also used to treat hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and prevent 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): Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): 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): Estropipate is well absorbed through the skin and gastrointestinal tract. When applied for a local action, absorption is usually sufficient to cause systemic effects. •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 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): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Estrone 3-sulfate Estrone bisulfate Estrone hemisulfate Estrone hydrogen sulfate Estrone sulphate Estrone, hydrogen sulfate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estrone sulfate is an estrogen used as monotherapy or in several combination hormone replacement products for managing menopause symptoms and hormone disorders.

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 Estrone sulfate interact? Information: •Drug A: Abciximab •Drug B: Estrone sulfate •Severity: MODERATE •Description: Estrone sulfate 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): Estropipate is used for the treatment of moderate to severe vasomotor symptoms associated with the monopause, and moderate to severe symptoms of vulval and vaginal atrophy associated with the menopause. It is also used to treat hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and prevent 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): Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): 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): Estropipate is well absorbed through the skin and gastrointestinal tract. When applied for a local action, absorption is usually sufficient to cause systemic effects. •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 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): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Estrone 3-sulfate Estrone bisulfate Estrone hemisulfate Estrone hydrogen sulfate Estrone sulphate Estrone, hydrogen sulfate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estrone sulfate is an estrogen used as monotherapy or in several combination hormone replacement products for managing menopause symptoms and hormone disorders. 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 Estrone interact?

•Drug A: Abciximab •Drug B: Estrone •Severity: MINOR •Description: Estrone may increase the thrombogenic activities of Abciximab. •Extended Description: Therapeutic immune globulins have been associated with the risk for adverse thromboembolic events, oftentimes leading to withdrawal from therapy. The use of estrogen-containing preparations, such as oral contraceptives (OC), is also a well established risk factor for venous thrombosis. Co-administration of two agents may further elevate the risk for developing thrombotic disorders. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 management of perimenopausal and postmenopausal 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): Estrone, a synthetically prepared or naturally occurring steroidal estrogen obtained from pregnant equine urine, is the primary circulating estrogen after menopause. Estrone is naturally derived from the peripheral conversion of androstenedione by an aromatase enzyme found in adipose tissues and is converted to estradiol in peripheral tissues. The estrogenic potency of estrone is one third that of estradiol. Estropipate is piperazine-stabilized estrone sulfate. Estrone, and estropipate are used to treat abnormalities related to gonadotropin hormone dysfunction, vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated with menopause, and for the prevention of osteoporosis due to estrogen deficiency. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 enter the cells of responsive tissues (e.g. female organs, breasts, hypothalamus, pituitary) where they interact with estrogen receptors. Hormone-bound estrogen receptors dimerize, translocate to the nucleus of cells and bind to estrogen response elements (ERE) of genes. Binding to ERE alters the transcription rate of affected genes. 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) release from the anterior pituitary. •Absorption (Drug A): No absorption available •Absorption (Drug B): 43% •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% •Metabolism (Drug A): 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): 19 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include nausea and vomiting. Estrogen related side effects include nausea, breast tenderness, fluid retention and edema, headaches and/or migraines, chloasma and poor contact lens fit. Estrogen hormone deficiency is associated with breakthrough bleeding, hypomenorrhea, irritability, depression and menopausal symptoms. Withdrawal bleeds may occur in females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Estragyn •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Estrona Estrone Estronum Follicular hormone Folliculin Oestrone •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estrone is an estrogen used to treat perimenopausal and postmenopausal symptoms.

Therapeutic immune globulins have been associated with the risk for adverse thromboembolic events, oftentimes leading to withdrawal from therapy. The use of estrogen-containing preparations, such as oral contraceptives (OC), is also a well established risk factor for venous thrombosis. Co-administration of two agents may further elevate the risk for developing thrombotic disorders. The severity of the interaction is minor.

Question: Does Abciximab and Estrone interact? Information: •Drug A: Abciximab •Drug B: Estrone •Severity: MINOR •Description: Estrone may increase the thrombogenic activities of Abciximab. •Extended Description: Therapeutic immune globulins have been associated with the risk for adverse thromboembolic events, oftentimes leading to withdrawal from therapy. The use of estrogen-containing preparations, such as oral contraceptives (OC), is also a well established risk factor for venous thrombosis. Co-administration of two agents may further elevate the risk for developing thrombotic disorders. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 management of perimenopausal and postmenopausal 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): Estrone, a synthetically prepared or naturally occurring steroidal estrogen obtained from pregnant equine urine, is the primary circulating estrogen after menopause. Estrone is naturally derived from the peripheral conversion of androstenedione by an aromatase enzyme found in adipose tissues and is converted to estradiol in peripheral tissues. The estrogenic potency of estrone is one third that of estradiol. Estropipate is piperazine-stabilized estrone sulfate. Estrone, and estropipate are used to treat abnormalities related to gonadotropin hormone dysfunction, vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated with menopause, and for the prevention of osteoporosis due to estrogen deficiency. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 enter the cells of responsive tissues (e.g. female organs, breasts, hypothalamus, pituitary) where they interact with estrogen receptors. Hormone-bound estrogen receptors dimerize, translocate to the nucleus of cells and bind to estrogen response elements (ERE) of genes. Binding to ERE alters the transcription rate of affected genes. 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) release from the anterior pituitary. •Absorption (Drug A): No absorption available •Absorption (Drug B): 43% •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% •Metabolism (Drug A): 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): 19 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose include nausea and vomiting. Estrogen related side effects include nausea, breast tenderness, fluid retention and edema, headaches and/or migraines, chloasma and poor contact lens fit. Estrogen hormone deficiency is associated with breakthrough bleeding, hypomenorrhea, irritability, depression and menopausal symptoms. Withdrawal bleeds may occur in females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Estragyn •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Estrona Estrone Estronum Follicular hormone Folliculin Oestrone •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Estrone is an estrogen used to treat perimenopausal and postmenopausal symptoms. Output: Therapeutic immune globulins have been associated with the risk for adverse thromboembolic events, oftentimes leading to withdrawal from therapy. The use of estrogen-containing preparations, such as oral contraceptives (OC), is also a well established risk factor for venous thrombosis. Co-administration of two agents may further elevate the risk for developing thrombotic disorders. The severity of the interaction is minor.

Does Abciximab and Ethinylestradiol interact?

•Drug A: Abciximab •Drug B: Ethinylestradiol •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Ethinylestradiol 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): Ethinylestradiol is combined with other drugs for use as a contraceptive, premenstrual dysphoric disorder, moderate acne, moderate to severe vasomotor symptoms of menopause, prevention 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): Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation. It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects. Patients should be counselled regarding the risks of thrombotic events. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ethinylestradiol is a synthetic estrogenic compound. Use of estrogens have a number of effects on the body including reduced bone density. Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg. Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium. It also increases sex hormone binding globulin. •Absorption (Drug A): No absorption available •Absorption (Drug B): A 30µg oral dose of ethinylestradiol reaches a C max of 74.1±35.6pg/mL, with a T max of 1.5±0.5h, and an AUC of 487.4±166.6pg*h/mL. A 1.2mg dose delivered via a patch reaches a C max of 28.8±10.3pg/mL, with a T max of 86±31h, and an AUC of3895±1423pg*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): A 30µg oral dose has an apparent volume of distribution of 625.3±228.7L and a 1.2mg topical dose has an apparent volume of distribution of 11745.3±15934.8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Enthinylestradiol is 98.3-98.5% bound to albumin in serum but also exhibits binding 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): Ethinylestradiol can be glucuronidated by UGT1A1, UGT1A3, UGT1A4, UGT1A9, and UGT2B7. Ethinylestradiol is also sulfated by SULT1A1, SULT1A3, and SULT1E1. Ethinylestradiol can also be hydroxylated at positions 2, 4, 6, 7, and 16 by CYP3A4, CYP3A5, CYP2C8, CYP2C9, and CYP1A2. These hydroxylated metabolites can be methylated by catechol-O-methyltransferase. The methoxy metabolites can in turn be sulfated or glucuronidated. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ethinylestradiol is 59.2% eliminated in the urine and bile, while 2-3% is eliminated in the feces. Over 90% of ethinylestradiol is eliminated as the unchanged parent drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): A 30µg oral dose has a half life of 8.4±4.8h and a 1.2mg topical dose has a half life of 27.7±34.2h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ethinylestradiol has an intravenous clearance of 16.47L/h, and an estimated renal clearance of approximately 2.1L/h. A 30µg oral dose has a clearance of 58.0±19.8L/h and a 1.2mg topical dose has a clearance of 303.5±100.5L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Female patients experiencing and overdose may present with withdrawal bleeding, nausea, vomiting, breast tenderness, abdominal pain, drowsiness, and fatigue. Overdose should be treated with symptomatic and supportive care including monitoring for potassium concentrations, sodium concentrations, and signs of metabolic acidosis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Afirmelle 28 Day, Alesse, Altavera 28 Day, Alyacen 1/35, Alyacen 7/7/7, Amethia 91 Day, Amethyst, Annovera, Apri 28 Day, Aranelle 28, Ashlyna 91 Day, Aubra 28 Day, Aurovela, Aurovela Fe, Aviane 28, Ayuna 28 Day Pack, Azurette 28 Day, Balcoltra 28 Day, Balziva 28 Day, Bekyree 28 Day, Beyaz 28 Day, Blisovi 21 Fe 1.5/30 28 Day Pack, Blisovi 21 Fe 1/20 28 Day Pack, Blisovi 24 Fe 1/20 28 Day, Brevicon, Briellyn 28 Day, Camrese 91 Day, Camreselo 91 Day, Caziant 28 Day, Cesia 28 Day, Charlotte 24 Fe Chewable 28 Day, Chateal 28 Day, Cléo -35, Cryselle 28, Cyclafem 1/35 28 Day, Cyclafem 7/7/7 28 Day, Cyestra-35, Cyonanz 28 Day, Cyred 28 Day, Dasetta 1/35 28 Day, Dasetta 7/7/7 28 Day, Daysee 91 Day, Delyla 28 Day, Diane, Dolishale 28 Day, Elinest 28 Day, Eluryng, Emoquette, Enilloring, Enpresse 28 Day, Enskyce 28 Day, Estarylla 28 Day, Evra, Falmina 28 Day, Fayosim 91 Day, Femcon Fe 28 Day, Femhrt 0.5/2.5 28 Day, Femynor 28 Day, Finzala 24 Fe Chewable 28 Day, Freya, Fyavolv, Gemmily 28 Day, Gianvi 28-day, Hailey 1.5/30 21 Day, Hailey 24 Fe 28 Day, Hailey Fe 1.5/30 28 Day, Hailey Fe 1/20 28 Day, Iclevia 91 Day, Indayo, Introvale 91 Day, Isibloom 28 Day, Jaimiess 91 Day, Jasmiel 28 Day, Jinteli, Jolessa 91 Day, Joyeaux 28 Day, Juleber 28 Day, Junel 1.5/30 21 Day, Junel 1/20 21 Day, Junel Fe 1.5/30 28 Day, Junel Fe 1/20 28 Day, Junel Fe 24 1/20 28 Day, Kaitlib Fe 28 Day, Kalliga, Kariva 28 Day, Kelnor 1/35 28 Day, Kelnor 1/50 28 Day, Kurvelo, Larin 1.5/30, Larin 1/20, Larin 24 Fe 1/20, Larin Fe 1.5/30, Larin Fe 1/20, Layolis Fe 28, Leena 28 Day, Levonest 28 Day, Levora 0.15/30 28 Day, Linessa, Lo Loestrin Fe 28 Day, Lo Simpesse, Lo-zumandimine 28 Day, Lo/ovral 28 Day, LoJaimiess, Loestrin 1.5/30 21 Day, Loestrin 24 Fe 28 Day, Loestrin Fe 1/20 28 Day, Lolo, Lomedia 24 Fe, Loryna, Loseasonique, Low-ogestrel 28 Day, Lutera 28 Day, Marlissa 28 Day, Marvelon, Melodetta 24 Fe Chewable 28 Day, Merzee 28 Day, Mibelas 24 Fe Chewable 28 Day, Microgestin 1.5/30 21 Day, Microgestin 1/20 21 Day, Microgestin 24 Fe 28 Day, Microgestin Fe 1.5/30 28 Day, Microgestin Fe 1/20 28 Day, Mili 28 Day, Min-ovral, Minastrin 24 Fe Chewable 28 Day, Mircette 28 Day, Mono-linyah 28 Day, Mononessa 28 Day, Myzilra 28 Day, Necon 0.5/35 28 Day, Necon 1/35 28 Day, Necon 7/7/7 28 Day, Nexesta Fe 28 Day, Nikki 28 Day, Nortrel 1/35 21 Day, Nortrel 1/35 28 Day, Nortrel 7/7/7 28 Day, Nuvaring, Nylia 1/35 28 Day, Nylia 7/7/7 28 Day, Nymyo 28 Day, Ocella 28 Day, Orsythia 28 Day, Ortho Tri-cyclen 28 Day, Ortho Tri-cyclen Lo 28 Day, Ortho-novum 7/7/7 28 Day, Philith 28 Day, Pimtrea Pack, Pirmella 1/35 28 Day, Pirmella 7/7/7 28 Day, Portia 28 Day, Previfem 28 Day, Quartette 91 Day Pack, Reclipsen, Rhuzdah 28 Day, Rivelsa 91 Day, Safyral 28 Day, Seasonale, Seasonique, Select, Setlakin 91 Day, Simliya, Simpesse, Sprintec 28 Day, Sronyx 28 Day, Syeda 28 Day, Synphasic, Tarina 24 Fe 1/20 28 Day, Tarina Fe 1/20 28 Day, Taysofy 28 Day, Taytulla 28 Day, Tilia Fe, Tri Femynor 28 Day, Tri-LO- Estarylla 28 Day, Tri-LO-marzia 28-day, Tri-LO-mili, Tri-Lo-Sprintec, Tri-estarylla 28 Day, Tri-legest 28 Day, Tri-linyah, Tri-mili 28 Day, Tri-nymyo 28 Day Pack, Tri-previfem 28 Day, Tri-sprintec 28 Day, Tri-vylibra 28 Day, Tri-vylibra Lo 28 Day, Trinessa 28 Day, Trinessa Lo 28 Day, Triquilar, Trivora 28 Day, Turqoz 28 Day, Twirla 3 Count Weekly Patch, Tyblume 28 Day, Tydemy 28 Day, Velivet 28 Day, Vestura, Vienva 28 Day, Viorele 28 Day, Volnea 28 Day, Vyfemla 28 Day, Vylibra 28 Day, Wera 28 Day, Wymzya Fe 28 Day, Xulane, Yasmin, Yasmin 28 Day, Yaz 28 Day, Yaz Plus, Zafemy, Zarah, Zenchent, Zovia 1/35e 28 Day, Zovia 1/50e 28 Day, Zumandimine 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 17-ethinylestradiol 17alpha-Ethinyl estradiol Ethinyl estradiol Ethinylestradiol Ethinylestradiolum Ethinyloestradiol Ethynyl estradiol Etinilestradiol •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ethinylestradiol is an estradiol used as a contraceptive.

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 Ethinylestradiol interact? Information: •Drug A: Abciximab •Drug B: Ethinylestradiol •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Ethinylestradiol 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): Ethinylestradiol is combined with other drugs for use as a contraceptive, premenstrual dysphoric disorder, moderate acne, moderate to severe vasomotor symptoms of menopause, prevention 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): Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation. It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects. Patients should be counselled regarding the risks of thrombotic events. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ethinylestradiol is a synthetic estrogenic compound. Use of estrogens have a number of effects on the body including reduced bone density. Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg. Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium. It also increases sex hormone binding globulin. •Absorption (Drug A): No absorption available •Absorption (Drug B): A 30µg oral dose of ethinylestradiol reaches a C max of 74.1±35.6pg/mL, with a T max of 1.5±0.5h, and an AUC of 487.4±166.6pg*h/mL. A 1.2mg dose delivered via a patch reaches a C max of 28.8±10.3pg/mL, with a T max of 86±31h, and an AUC of3895±1423pg*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): A 30µg oral dose has an apparent volume of distribution of 625.3±228.7L and a 1.2mg topical dose has an apparent volume of distribution of 11745.3±15934.8L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Enthinylestradiol is 98.3-98.5% bound to albumin in serum but also exhibits binding 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): Ethinylestradiol can be glucuronidated by UGT1A1, UGT1A3, UGT1A4, UGT1A9, and UGT2B7. Ethinylestradiol is also sulfated by SULT1A1, SULT1A3, and SULT1E1. Ethinylestradiol can also be hydroxylated at positions 2, 4, 6, 7, and 16 by CYP3A4, CYP3A5, CYP2C8, CYP2C9, and CYP1A2. These hydroxylated metabolites can be methylated by catechol-O-methyltransferase. The methoxy metabolites can in turn be sulfated or glucuronidated. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ethinylestradiol is 59.2% eliminated in the urine and bile, while 2-3% is eliminated in the feces. Over 90% of ethinylestradiol is eliminated as the unchanged parent drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): A 30µg oral dose has a half life of 8.4±4.8h and a 1.2mg topical dose has a half life of 27.7±34.2h. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ethinylestradiol has an intravenous clearance of 16.47L/h, and an estimated renal clearance of approximately 2.1L/h. A 30µg oral dose has a clearance of 58.0±19.8L/h and a 1.2mg topical dose has a clearance of 303.5±100.5L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Female patients experiencing and overdose may present with withdrawal bleeding, nausea, vomiting, breast tenderness, abdominal pain, drowsiness, and fatigue. Overdose should be treated with symptomatic and supportive care including monitoring for potassium concentrations, sodium concentrations, and signs of metabolic acidosis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Afirmelle 28 Day, Alesse, Altavera 28 Day, Alyacen 1/35, Alyacen 7/7/7, Amethia 91 Day, Amethyst, Annovera, Apri 28 Day, Aranelle 28, Ashlyna 91 Day, Aubra 28 Day, Aurovela, Aurovela Fe, Aviane 28, Ayuna 28 Day Pack, Azurette 28 Day, Balcoltra 28 Day, Balziva 28 Day, Bekyree 28 Day, Beyaz 28 Day, Blisovi 21 Fe 1.5/30 28 Day Pack, Blisovi 21 Fe 1/20 28 Day Pack, Blisovi 24 Fe 1/20 28 Day, Brevicon, Briellyn 28 Day, Camrese 91 Day, Camreselo 91 Day, Caziant 28 Day, Cesia 28 Day, Charlotte 24 Fe Chewable 28 Day, Chateal 28 Day, Cléo -35, Cryselle 28, Cyclafem 1/35 28 Day, Cyclafem 7/7/7 28 Day, Cyestra-35, Cyonanz 28 Day, Cyred 28 Day, Dasetta 1/35 28 Day, Dasetta 7/7/7 28 Day, Daysee 91 Day, Delyla 28 Day, Diane, Dolishale 28 Day, Elinest 28 Day, Eluryng, Emoquette, Enilloring, Enpresse 28 Day, Enskyce 28 Day, Estarylla 28 Day, Evra, Falmina 28 Day, Fayosim 91 Day, Femcon Fe 28 Day, Femhrt 0.5/2.5 28 Day, Femynor 28 Day, Finzala 24 Fe Chewable 28 Day, Freya, Fyavolv, Gemmily 28 Day, Gianvi 28-day, Hailey 1.5/30 21 Day, Hailey 24 Fe 28 Day, Hailey Fe 1.5/30 28 Day, Hailey Fe 1/20 28 Day, Iclevia 91 Day, Indayo, Introvale 91 Day, Isibloom 28 Day, Jaimiess 91 Day, Jasmiel 28 Day, Jinteli, Jolessa 91 Day, Joyeaux 28 Day, Juleber 28 Day, Junel 1.5/30 21 Day, Junel 1/20 21 Day, Junel Fe 1.5/30 28 Day, Junel Fe 1/20 28 Day, Junel Fe 24 1/20 28 Day, Kaitlib Fe 28 Day, Kalliga, Kariva 28 Day, Kelnor 1/35 28 Day, Kelnor 1/50 28 Day, Kurvelo, Larin 1.5/30, Larin 1/20, Larin 24 Fe 1/20, Larin Fe 1.5/30, Larin Fe 1/20, Layolis Fe 28, Leena 28 Day, Levonest 28 Day, Levora 0.15/30 28 Day, Linessa, Lo Loestrin Fe 28 Day, Lo Simpesse, Lo-zumandimine 28 Day, Lo/ovral 28 Day, LoJaimiess, Loestrin 1.5/30 21 Day, Loestrin 24 Fe 28 Day, Loestrin Fe 1/20 28 Day, Lolo, Lomedia 24 Fe, Loryna, Loseasonique, Low-ogestrel 28 Day, Lutera 28 Day, Marlissa 28 Day, Marvelon, Melodetta 24 Fe Chewable 28 Day, Merzee 28 Day, Mibelas 24 Fe Chewable 28 Day, Microgestin 1.5/30 21 Day, Microgestin 1/20 21 Day, Microgestin 24 Fe 28 Day, Microgestin Fe 1.5/30 28 Day, Microgestin Fe 1/20 28 Day, Mili 28 Day, Min-ovral, Minastrin 24 Fe Chewable 28 Day, Mircette 28 Day, Mono-linyah 28 Day, Mononessa 28 Day, Myzilra 28 Day, Necon 0.5/35 28 Day, Necon 1/35 28 Day, Necon 7/7/7 28 Day, Nexesta Fe 28 Day, Nikki 28 Day, Nortrel 1/35 21 Day, Nortrel 1/35 28 Day, Nortrel 7/7/7 28 Day, Nuvaring, Nylia 1/35 28 Day, Nylia 7/7/7 28 Day, Nymyo 28 Day, Ocella 28 Day, Orsythia 28 Day, Ortho Tri-cyclen 28 Day, Ortho Tri-cyclen Lo 28 Day, Ortho-novum 7/7/7 28 Day, Philith 28 Day, Pimtrea Pack, Pirmella 1/35 28 Day, Pirmella 7/7/7 28 Day, Portia 28 Day, Previfem 28 Day, Quartette 91 Day Pack, Reclipsen, Rhuzdah 28 Day, Rivelsa 91 Day, Safyral 28 Day, Seasonale, Seasonique, Select, Setlakin 91 Day, Simliya, Simpesse, Sprintec 28 Day, Sronyx 28 Day, Syeda 28 Day, Synphasic, Tarina 24 Fe 1/20 28 Day, Tarina Fe 1/20 28 Day, Taysofy 28 Day, Taytulla 28 Day, Tilia Fe, Tri Femynor 28 Day, Tri-LO- Estarylla 28 Day, Tri-LO-marzia 28-day, Tri-LO-mili, Tri-Lo-Sprintec, Tri-estarylla 28 Day, Tri-legest 28 Day, Tri-linyah, Tri-mili 28 Day, Tri-nymyo 28 Day Pack, Tri-previfem 28 Day, Tri-sprintec 28 Day, Tri-vylibra 28 Day, Tri-vylibra Lo 28 Day, Trinessa 28 Day, Trinessa Lo 28 Day, Triquilar, Trivora 28 Day, Turqoz 28 Day, Twirla 3 Count Weekly Patch, Tyblume 28 Day, Tydemy 28 Day, Velivet 28 Day, Vestura, Vienva 28 Day, Viorele 28 Day, Volnea 28 Day, Vyfemla 28 Day, Vylibra 28 Day, Wera 28 Day, Wymzya Fe 28 Day, Xulane, Yasmin, Yasmin 28 Day, Yaz 28 Day, Yaz Plus, Zafemy, Zarah, Zenchent, Zovia 1/35e 28 Day, Zovia 1/50e 28 Day, Zumandimine 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 17-ethinylestradiol 17alpha-Ethinyl estradiol Ethinyl estradiol Ethinylestradiol Ethinylestradiolum Ethinyloestradiol Ethynyl estradiol Etinilestradiol •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ethinylestradiol is an estradiol used as a contraceptive. 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 Ethynodiol diacetate interact?

•Drug A: Abciximab •Drug B: Ethynodiol diacetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Ethynodiol diacetate 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 prevention of pregnancy in women who elect to use this product as a method of contraception. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ethynodiol Diacetate is used as a female contraceptive. Ethynodiol Diacetate is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Ethynodiol Diacetate tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Ethynodiol Diacetate will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 50-85% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kelnor 1/35 28 Day, Kelnor 1/50 28 Day, Zovia 1/35e 28 Day, Zovia 1/50e 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ethynodiol diacetate Etynodiol acetate Etynodiol diacetate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ethynodiol diacetate is an oral contraceptive used to prevent pregnancy.

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 Ethynodiol diacetate interact? Information: •Drug A: Abciximab •Drug B: Ethynodiol diacetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Ethynodiol diacetate 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 prevention of pregnancy in women who elect to use this product as a method of contraception. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ethynodiol Diacetate is used as a female contraceptive. Ethynodiol Diacetate is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Ethynodiol Diacetate tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Ethynodiol Diacetate will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 50-85% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kelnor 1/35 28 Day, Kelnor 1/50 28 Day, Zovia 1/35e 28 Day, Zovia 1/50e 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ethynodiol diacetate Etynodiol acetate Etynodiol diacetate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ethynodiol diacetate is an oral contraceptive used to prevent pregnancy. 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 Etodolac interact?

•Drug A: Abciximab •Drug B: Etodolac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Etodolac 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 acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in vivo. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss. •Absorption (Drug A): No absorption available •Absorption (Drug B): Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 390 mL/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): > 99% bound, primarily to albumin •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Etodolac is extensively metabolized in the liver. Renal elimination of etodolac and its metabolites is the primary route of excretion (72%). Metabolites found in urine (with percents of the administered dose) are: unchanged etodolac (1%), etodolac glucuronide (13%), hydroxylated metabolites (6-, 7-, and 8-OH; 5%), hydroxylated metabolite glucuronides (20%), and unidentified metabolites (33%). Fecal excretion accounts for 16% of its elimination. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Etodolac is extensively metabolized in the liver. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces (16% of dose). Approximately 1% of a etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Terminal t 1/2, 7.3 ± 4.0 hours. Distribution t 1/2, 0.71 ± 0.50 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral cl=49.1 mL/h/kg [Normal healthy adults] Oral cl=49.4 mL/h/kg [Healthy males (18-65 years)] Oral cl=35.7 mL/h/kg [Healthy females (27-65 years)] Oral cl=45.7 mL/h/kg [Eldery (>65 years)] Oral cl=58.3 mL/h/kg [Renal impairement (46-73 years)] Oral cl=42.0 mL/h/kg [Hepatic impairement (34-60 years)] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): 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 etodolac. Etodolac may increase blood pressure and/or cause fluid retention and edema. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lodine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Etodolac Étodolac Etodolaco Etodolacum Etodolic acid Etodolsäure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Etodolac is an NSAID used to treat osteoarthritis and rheumatoid arthritis, as well as acute 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 Etodolac interact? Information: •Drug A: Abciximab •Drug B: Etodolac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Etodolac 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 acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in vivo. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss. •Absorption (Drug A): No absorption available •Absorption (Drug B): Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 390 mL/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): > 99% bound, primarily to albumin •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Etodolac is extensively metabolized in the liver. Renal elimination of etodolac and its metabolites is the primary route of excretion (72%). Metabolites found in urine (with percents of the administered dose) are: unchanged etodolac (1%), etodolac glucuronide (13%), hydroxylated metabolites (6-, 7-, and 8-OH; 5%), hydroxylated metabolite glucuronides (20%), and unidentified metabolites (33%). Fecal excretion accounts for 16% of its elimination. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Etodolac is extensively metabolized in the liver. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces (16% of dose). Approximately 1% of a etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Terminal t 1/2, 7.3 ± 4.0 hours. Distribution t 1/2, 0.71 ± 0.50 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral cl=49.1 mL/h/kg [Normal healthy adults] Oral cl=49.4 mL/h/kg [Healthy males (18-65 years)] Oral cl=35.7 mL/h/kg [Healthy females (27-65 years)] Oral cl=45.7 mL/h/kg [Eldery (>65 years)] Oral cl=58.3 mL/h/kg [Renal impairement (46-73 years)] Oral cl=42.0 mL/h/kg [Hepatic impairement (34-60 years)] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): 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 etodolac. Etodolac may increase blood pressure and/or cause fluid retention and edema. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Lodine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Etodolac Étodolac Etodolaco Etodolacum Etodolic acid Etodolsäure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Etodolac is an NSAID used to treat osteoarthritis and rheumatoid arthritis, as well as acute 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 Etonogestrel interact?

•Drug A: Abciximab •Drug B: Etonogestrel •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Etonogestrel. •Extended Description: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Etonogestrel is administered in subdermal implants as long-acting reversible contraception. It is known to be effective in postpartum insertion including breastfeeding women. Etonogestrel is part of the long-acting contraceptive implants that prevent pregnancy. The implant's effect can remain for 5 years. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etonogestrel attains its therapeutic effect inhibiting fertility by impairing the release of the luteinizing hormone which is one of the most important reproductive hormones for ovulation. As well, etonogestrel is known to increase the viscosity of the cervical mucus hindering the passage of the spermatozoa and altering the lining in the uterus to prevent the implantation of the fertilized eggs in the endometrium. In clinical trials, etonogestrel was implanted and reported to avoid 100% of pregnancies over a three year period. When the implant was removed, normal periods were reinstalled within 90 days in 91% of the individuals. Fertility was established quickly with 20 reported pregnancies within 3 months of implant removal. The implants of etonogestrel release 40 mcg of etonogestrel daily and they usually provide a continuous contraception effect for 3 years. When the implant is administered, the failure rate is reported to be 0.1%. Some non-contraceptive effects are improved dysmenorrhea. All data of etonogestrel comes from patients between 80-130% of the body mass. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Etonogestrel binds with high affinity to the progesterone and estrogen receptors in the target organs. From the target organs, they include the female reproductive tract, mammary gland, hypothalamus, and pituitary. Once bound, this drug changes the synthesis of different proteins which in order decreases the level of gonadotropin-releasing hormone and the luteinizing hormone. •Absorption (Drug A): No absorption available •Absorption (Drug B): Vaginal administration of etonogestrel is known to be significantly absorbed through the vaginal epithelium but it does not increase the levels of etonogestrel in the urine. On the other hand, oral administration is absorbed in the GI tract and it goes through the first-pass metabolism. When etonogestrel is administered subdermally it is absorbed rapidly into the bloodstream and it presents a bioavailability of 82%. It is reported that the implant releases around 60 mcg per day in the first 3 months and then decreases steady reaching a concentration of 30 mcg at the end of year 2. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of etonogestrel is of around 201 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Etonogestrel is highly bound to plasma proteins being mainly albumin followed by sex-hormone binding globulin. The protein bound form of the etonogestrel represents around 96-99% of the administered dose. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Etonogestrel is highly metabolized in the liver by the action of the cytochrome isoenzyme 3A4 mainly by the presence of hydroxylation, sulfate conjugation and glucuronide conjugation reactions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of etonogestrel and its metabolites is mainly done renally. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 etonogestrel is reported to be of 25 hours which indicates a reversible contraceptive effect. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance rate of etonogestrel is reported to be of 7.5 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The reported LD50 of oral etonogestrel in the rat is reported to be higher than 2000 mg/kg. Overdosage can only happen when more than one implant is inserted. In cases of overdose, removal of the implant is recommended. There aren't reports relating etonogestrel with carcinogenesis, mutagenesis or impaired fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Eluryng, Enilloring, Implanon, Nexplanon, Nuvaring •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): Etonogestrel is a long-acting synthetic derived progestin contraceptive used in various devices such as contraceptive rings and intradermal implants.

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

Question: Does Abciximab and Etonogestrel interact? Information: •Drug A: Abciximab •Drug B: Etonogestrel •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Etonogestrel. •Extended Description: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Etonogestrel is administered in subdermal implants as long-acting reversible contraception. It is known to be effective in postpartum insertion including breastfeeding women. Etonogestrel is part of the long-acting contraceptive implants that prevent pregnancy. The implant's effect can remain for 5 years. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etonogestrel attains its therapeutic effect inhibiting fertility by impairing the release of the luteinizing hormone which is one of the most important reproductive hormones for ovulation. As well, etonogestrel is known to increase the viscosity of the cervical mucus hindering the passage of the spermatozoa and altering the lining in the uterus to prevent the implantation of the fertilized eggs in the endometrium. In clinical trials, etonogestrel was implanted and reported to avoid 100% of pregnancies over a three year period. When the implant was removed, normal periods were reinstalled within 90 days in 91% of the individuals. Fertility was established quickly with 20 reported pregnancies within 3 months of implant removal. The implants of etonogestrel release 40 mcg of etonogestrel daily and they usually provide a continuous contraception effect for 3 years. When the implant is administered, the failure rate is reported to be 0.1%. Some non-contraceptive effects are improved dysmenorrhea. All data of etonogestrel comes from patients between 80-130% of the body mass. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Etonogestrel binds with high affinity to the progesterone and estrogen receptors in the target organs. From the target organs, they include the female reproductive tract, mammary gland, hypothalamus, and pituitary. Once bound, this drug changes the synthesis of different proteins which in order decreases the level of gonadotropin-releasing hormone and the luteinizing hormone. •Absorption (Drug A): No absorption available •Absorption (Drug B): Vaginal administration of etonogestrel is known to be significantly absorbed through the vaginal epithelium but it does not increase the levels of etonogestrel in the urine. On the other hand, oral administration is absorbed in the GI tract and it goes through the first-pass metabolism. When etonogestrel is administered subdermally it is absorbed rapidly into the bloodstream and it presents a bioavailability of 82%. It is reported that the implant releases around 60 mcg per day in the first 3 months and then decreases steady reaching a concentration of 30 mcg at the end of year 2. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of etonogestrel is of around 201 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Etonogestrel is highly bound to plasma proteins being mainly albumin followed by sex-hormone binding globulin. The protein bound form of the etonogestrel represents around 96-99% of the administered dose. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Etonogestrel is highly metabolized in the liver by the action of the cytochrome isoenzyme 3A4 mainly by the presence of hydroxylation, sulfate conjugation and glucuronide conjugation reactions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The elimination of etonogestrel and its metabolites is mainly done renally. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 etonogestrel is reported to be of 25 hours which indicates a reversible contraceptive effect. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance rate of etonogestrel is reported to be of 7.5 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The reported LD50 of oral etonogestrel in the rat is reported to be higher than 2000 mg/kg. Overdosage can only happen when more than one implant is inserted. In cases of overdose, removal of the implant is recommended. There aren't reports relating etonogestrel with carcinogenesis, mutagenesis or impaired fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Eluryng, Enilloring, Implanon, Nexplanon, Nuvaring •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): Etonogestrel is a long-acting synthetic derived progestin contraceptive used in various devices such as contraceptive rings and intradermal implants. Output: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. The severity of the interaction is moderate.

Does Abciximab and Etoposide interact?

•Drug A: Abciximab •Drug B: Etoposide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Etoposide. •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 in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The disposition of etoposide is a biphasic process with a distribution half-life of 1.5 hours. It does not cross into cerebrospinal fluid well. Volume of distribution, steady state = 18 - 29 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 97% protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine. Etoposide also undergoes glutathione and glucuronide conjugation which are catalyzed by GSTT1/GSTP1 and UGT1A1, respectively. Prostaglandin synthases are also responsible for the conversion of etoposide to O-demethylated metabolites (quinone). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. 56% of the dose was in the urine, 45% of which was excreted as etoposide. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 4-11 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance = 33 - 48 mL/min [IV administration, adults] Mean renal clearance = 7 - 10 mL/min/m^2 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Etopophos, Vepesid •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Etoposide Etoposido Etoposidum trans-Etoposide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Etoposide is a podophyllotoxin derivative used to treat testicular and small cell lung 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 Etoposide interact? Information: •Drug A: Abciximab •Drug B: Etoposide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Etoposide. •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 in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The disposition of etoposide is a biphasic process with a distribution half-life of 1.5 hours. It does not cross into cerebrospinal fluid well. Volume of distribution, steady state = 18 - 29 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 97% protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine. Etoposide also undergoes glutathione and glucuronide conjugation which are catalyzed by GSTT1/GSTP1 and UGT1A1, respectively. Prostaglandin synthases are also responsible for the conversion of etoposide to O-demethylated metabolites (quinone). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. 56% of the dose was in the urine, 45% of which was excreted as etoposide. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 4-11 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance = 33 - 48 mL/min [IV administration, adults] Mean renal clearance = 7 - 10 mL/min/m^2 •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Etopophos, Vepesid •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Etoposide Etoposido Etoposidum trans-Etoposide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Etoposide is a podophyllotoxin derivative used to treat testicular and small cell lung 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 Etoricoxib interact?

•Drug A: Abciximab •Drug B: Etoricoxib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Etoricoxib is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability is 100% 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): 92% •Metabolism (Drug A): 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 CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 22 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): This reduced activity is the cause of reduced gastrointestinal toxicity, as demonstrated in several large clinical trials performed with different COXIB (see below links on NEJM and The Lancet). Some clinical trials and meta-analysis showed that treatment with COXIB lead to increased incidence of cardiovascular adverse events compared to placebo •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): Etoricoxib étoricoxib Etoricoxibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Etoricoxib is a selective COX-2 inhibitor used to relieve moderate post-surgical dental pain as a short-term treatment and inflammatory and painful symptoms of various forms of 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 Etoricoxib interact? Information: •Drug A: Abciximab •Drug B: Etoricoxib •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Etoricoxib is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1). •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability is 100% 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): 92% •Metabolism (Drug A): 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 CYP3A4. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 22 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): This reduced activity is the cause of reduced gastrointestinal toxicity, as demonstrated in several large clinical trials performed with different COXIB (see below links on NEJM and The Lancet). Some clinical trials and meta-analysis showed that treatment with COXIB lead to increased incidence of cardiovascular adverse events compared to placebo •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): Etoricoxib étoricoxib Etoricoxibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Etoricoxib is a selective COX-2 inhibitor used to relieve moderate post-surgical dental pain as a short-term treatment and inflammatory and painful symptoms of various forms of 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 Everolimus interact?

•Drug A: Abciximab •Drug B: Everolimus •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Everolimus. •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): Everolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Everolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, Cmax is dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in Cmax is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg dose range. Steady-state was achieved within 2 weeks following once-daily dosing. Dose Proportionality in Patients with SEGA (subependymal giant-cell astrocytomas) and TSC (tuberous sclerosis complex): In patients with SEGA and TSC, everolimus Cmin was approximately dose-proportional within the dose range from 1.35 mg/m2 to 14.4 mg/m2. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The blood-to-plasma ratio of everolimus is 17% to 73%. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): ~ 74% in both healthy patients and those with moderate hepatic impairment. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Everolimus is a substrate of CYP3A4 and PgP (phosphoglycolate phosphatase). Three monohydroxylated metabolites, two hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus were the 6 primary metabolites detected in human blood. In vitro, everolimus competitively inhibited the metabolism of CYP3A4 and was a mixed inhibitor of the CYP2D6 substrate dextromethorphan. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): ~30 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a 3 mg radiolabeled dose of everolimus, 80% of the radioactivity was recovered from the feces, while 5% was excreted in the urine. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): IC50 of 0.63 nM. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Afinitor, Votubia, Zortress •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Everolimus évérolimus •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Everolimus is a mammalian target of rapamycin (mTOR) kinase inhibitor used to treat various types of malignancies.

As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Everolimus interact? Information: •Drug A: Abciximab •Drug B: Everolimus •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Everolimus. •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): Everolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Everolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, Cmax is dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in Cmax is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg dose range. Steady-state was achieved within 2 weeks following once-daily dosing. Dose Proportionality in Patients with SEGA (subependymal giant-cell astrocytomas) and TSC (tuberous sclerosis complex): In patients with SEGA and TSC, everolimus Cmin was approximately dose-proportional within the dose range from 1.35 mg/m2 to 14.4 mg/m2. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The blood-to-plasma ratio of everolimus is 17% to 73%. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): ~ 74% in both healthy patients and those with moderate hepatic impairment. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Everolimus is a substrate of CYP3A4 and PgP (phosphoglycolate phosphatase). Three monohydroxylated metabolites, two hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus were the 6 primary metabolites detected in human blood. In vitro, everolimus competitively inhibited the metabolism of CYP3A4 and was a mixed inhibitor of the CYP2D6 substrate dextromethorphan. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): ~30 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a 3 mg radiolabeled dose of everolimus, 80% of the radioactivity was recovered from the feces, while 5% was excreted in the urine. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): IC50 of 0.63 nM. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Afinitor, Votubia, Zortress •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Everolimus évérolimus •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Everolimus is a mammalian target of rapamycin (mTOR) kinase inhibitor used to treat various types of malignancies. Output: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Does Abciximab and Evolocumab interact?

•Drug A: Abciximab •Drug B: Evolocumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Evolocumab. •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): Evolocumab is indicated in adult patients with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization. It is also indicated as an adjunct to diet, alone or in combination with other hypolipidemic treatments, in adults with primary hyperlipidemia (and in pediatric patients ≥10 years old with heterozygous familial hypercholesterolemia) to reduce LDL-C. In addition, it is indicated adjunctly to other hypolipidemic treatments in patients ≥10 years old with homozygous familiar hypercholesterolemia to reduce LDL-C. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Evolocumab is a human IgG monoclonal antibody which targets PCSK9 (proprotein convertase subtilisin/kexin type 9). PCSK9 is a serine protease produced by the liver which binds LDL receptors and creates a complex to be targeted for lysosomal degradation. LDL receptors typically bind LDL-cholesterol ("bad" cholesterol) for cellular reuptake, therefore the formation of these complexes with PCSK9 inhibits LDL receptor recycling to the cell surface, resulting in decreased cellular reuptake of LDL-C and increased levels of free LDL-C in the plasma. Individuals with familial hypercholesterolemia often may have "gain of function" mutations in the PCSK9 molecules in their body, resulting in increased LDL-C plasma levels and a consequent cardiovascular risk. Evolocumab is able to bind both the normal PCSK9 and the "gain of function" mutant, D374Y. The exact mechanism of the binding has not been published, however the precursor molecule, mAb1, is indicative of the interaction. The mAb1 molecule binds on the catalytic site of PCSK9 next to the binding site for the LDL receptor and creates hydrogen bonds and hydrophobic interactions, resulting in the steric inhibition of binding between PCSK9 and the LDL receptor. Because the formation of complexes between LDL receptor and PCSK9 are prevented, the internalized LDL receptors are less likely to be degrated by lysosomes and may recycle to the surface of the cell to serve their function of removing LDL from the blood. •Absorption (Drug A): No absorption available •Absorption (Drug B): Total bioavailability from subcutaneous injection was 82% in cynomolgus monkeys. •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): Evolocumab showed non-linear, dose-dependent clearance in healthy volunteers; clearance decreased with increasing dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Repatha •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): Evolocumab is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody used as an adjunct to LDL cholesterol reducing therapies, aiding in the prevention of cardiovascular events and cardiovascular revascularization procedures.

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 Evolocumab interact? Information: •Drug A: Abciximab •Drug B: Evolocumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Evolocumab. •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): Evolocumab is indicated in adult patients with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization. It is also indicated as an adjunct to diet, alone or in combination with other hypolipidemic treatments, in adults with primary hyperlipidemia (and in pediatric patients ≥10 years old with heterozygous familial hypercholesterolemia) to reduce LDL-C. In addition, it is indicated adjunctly to other hypolipidemic treatments in patients ≥10 years old with homozygous familiar hypercholesterolemia to reduce LDL-C. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Evolocumab is a human IgG monoclonal antibody which targets PCSK9 (proprotein convertase subtilisin/kexin type 9). PCSK9 is a serine protease produced by the liver which binds LDL receptors and creates a complex to be targeted for lysosomal degradation. LDL receptors typically bind LDL-cholesterol ("bad" cholesterol) for cellular reuptake, therefore the formation of these complexes with PCSK9 inhibits LDL receptor recycling to the cell surface, resulting in decreased cellular reuptake of LDL-C and increased levels of free LDL-C in the plasma. Individuals with familial hypercholesterolemia often may have "gain of function" mutations in the PCSK9 molecules in their body, resulting in increased LDL-C plasma levels and a consequent cardiovascular risk. Evolocumab is able to bind both the normal PCSK9 and the "gain of function" mutant, D374Y. The exact mechanism of the binding has not been published, however the precursor molecule, mAb1, is indicative of the interaction. The mAb1 molecule binds on the catalytic site of PCSK9 next to the binding site for the LDL receptor and creates hydrogen bonds and hydrophobic interactions, resulting in the steric inhibition of binding between PCSK9 and the LDL receptor. Because the formation of complexes between LDL receptor and PCSK9 are prevented, the internalized LDL receptors are less likely to be degrated by lysosomes and may recycle to the surface of the cell to serve their function of removing LDL from the blood. •Absorption (Drug A): No absorption available •Absorption (Drug B): Total bioavailability from subcutaneous injection was 82% in cynomolgus monkeys. •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): Evolocumab showed non-linear, dose-dependent clearance in healthy volunteers; clearance decreased with increasing dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Repatha •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): Evolocumab is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody used as an adjunct to LDL cholesterol reducing therapies, aiding in the prevention of cardiovascular events and cardiovascular revascularization procedures. 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 Factor IX Complex (Human) interact?

•Drug A: Abciximab •Drug B: Factor IX Complex (Human) •Severity: MAJOR •Description: The therapeutic efficacy of Factor IX Complex (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 Complex is indicated for the prevention and control of hemorrhagic episodes in hemophilia B patients. 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 or who require rapid reversal of therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): 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): Factor IX Complex is a sterile, lyophilized concentrate composed of a number of Vitamin K-dependent clotting factors found in functioning human plasma. Also known as prothrombin complex concentrate, products containing this complex often include Factor IX (antihemophilic factor B), Factor II (prothrombin), Factor X (Stuart-Prower Factor), and low levels of Factor VII (proconvertin) derived from human plasma. Many commercially available products also contain low levels of other antithrombotic proteins. For example, Kcentra(FDA) also contains the antithrombotic proteins C and S, while Bebulin VH (FDA) contains heparin. This complex of coagulation factors helps replenish clotting factors that may have been lost through warfarin therapy or through a congenital abnormality such as Hemophilia B. •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): Profilnine •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): Factor IX Complex (Human) is a Factor IX complex used to prevent and treat bleeding episodes in hemophilia B or vitamin K antagonist therapy.

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 Factor IX Complex (Human) interact? Information: •Drug A: Abciximab •Drug B: Factor IX Complex (Human) •Severity: MAJOR •Description: The therapeutic efficacy of Factor IX Complex (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 Complex is indicated for the prevention and control of hemorrhagic episodes in hemophilia B patients. 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 or who require rapid reversal of therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): 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): Factor IX Complex is a sterile, lyophilized concentrate composed of a number of Vitamin K-dependent clotting factors found in functioning human plasma. Also known as prothrombin complex concentrate, products containing this complex often include Factor IX (antihemophilic factor B), Factor II (prothrombin), Factor X (Stuart-Prower Factor), and low levels of Factor VII (proconvertin) derived from human plasma. Many commercially available products also contain low levels of other antithrombotic proteins. For example, Kcentra(FDA) also contains the antithrombotic proteins C and S, while Bebulin VH (FDA) contains heparin. This complex of coagulation factors helps replenish clotting factors that may have been lost through warfarin therapy or through a congenital abnormality such as Hemophilia B. •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): Profilnine •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): Factor IX Complex (Human) is a Factor IX complex used to prevent and treat bleeding episodes in hemophilia B or vitamin K antagonist therapy. 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 Factor XIII (human) interact?

•Drug A: Abciximab •Drug B: Factor XIII (human) •Severity: MAJOR •Description: The therapeutic efficacy of Factor XIII (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 XIII (Human), available as the commercially available product Corifact, is approved by the Food and Drug Administration for routine prophylactic treatment and peri-operative management of surgical bleeding in adult and pediatric patients with congenital FXIII deficiency. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Also known as Fibrin Stabilizing Factor (FSF), Factor XIII is an endogenously produced coagulation factor and the final enzyme within the blood coagulation cascade. Within the body, FXIII circulates as a heterotetramer composed of 2 A-subunits and 2 B-subunits (A2B2). When activated by thrombin at the site of injury, the FXIII pro-enzyme is cleaved resulting in activation of the catalytic A-subunit and dissociation from its carrier B-subunit. As a result, the active transglutaminase from subunit A cross-links fibrin and other proteins resulting in increased mechanical strength and resistance to fibrinolysis of the fibrin clot. This contributes to enhanced platelet and clot adhesion to injured tissue, thereby improving blood coagulation and maintenance of hemostasis. Exogenous replacement of Factor XIII is a cornerstone of treatment for bleeding associated with congenital Factor XIII deficiency. •Absorption (Drug A): No absorption available •Absorption (Drug B): Tmax = 1.7 ±1.44 hr Tmax = 1.72 hr Cmax = 0.9 ±0.20 units/mL (peak concentration at steady state) Cmax = 87.7% (peak concentration at steady state) •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Vss = 51.1 mL/kg (volume of distribution at steady state) •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): 6.6 ±2.29 days 6.6 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.25 ±0.09 mL/hr/kg 0.25 mL/hr/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Corifact was studied in an acute toxicity study in mice and rats at doses up to 3550 units per kg and 1420 units per kg, respectively. Repeat dose toxicity was studied in rats at daily doses up to 350 units per kg for a period of 14 days. No signs of toxicity were observed in the single dose and repeat dose studies. A local tolerance study in rabbits demonstrated no clinical or histopathological changes at the injection site after intravenous, intra-arterial or para-venous administration of Corifact. A thrombogenicity test was performed in rabbits at doses up to 350 units per kg. Corifact showed no thrombogenic potential at the doses tested. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Corifact •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): Factor XIII (human) is a purified form of Factor XIII that is used to prevent and treat surgical bleeding in patients with a Factor XIII deficiency.

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 Factor XIII (human) interact? Information: •Drug A: Abciximab •Drug B: Factor XIII (human) •Severity: MAJOR •Description: The therapeutic efficacy of Factor XIII (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 XIII (Human), available as the commercially available product Corifact, is approved by the Food and Drug Administration for routine prophylactic treatment and peri-operative management of surgical bleeding in adult and pediatric patients with congenital FXIII deficiency. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Also known as Fibrin Stabilizing Factor (FSF), Factor XIII is an endogenously produced coagulation factor and the final enzyme within the blood coagulation cascade. Within the body, FXIII circulates as a heterotetramer composed of 2 A-subunits and 2 B-subunits (A2B2). When activated by thrombin at the site of injury, the FXIII pro-enzyme is cleaved resulting in activation of the catalytic A-subunit and dissociation from its carrier B-subunit. As a result, the active transglutaminase from subunit A cross-links fibrin and other proteins resulting in increased mechanical strength and resistance to fibrinolysis of the fibrin clot. This contributes to enhanced platelet and clot adhesion to injured tissue, thereby improving blood coagulation and maintenance of hemostasis. Exogenous replacement of Factor XIII is a cornerstone of treatment for bleeding associated with congenital Factor XIII deficiency. •Absorption (Drug A): No absorption available •Absorption (Drug B): Tmax = 1.7 ±1.44 hr Tmax = 1.72 hr Cmax = 0.9 ±0.20 units/mL (peak concentration at steady state) Cmax = 87.7% (peak concentration at steady state) •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Vss = 51.1 mL/kg (volume of distribution at steady state) •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): 6.6 ±2.29 days 6.6 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.25 ±0.09 mL/hr/kg 0.25 mL/hr/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Corifact was studied in an acute toxicity study in mice and rats at doses up to 3550 units per kg and 1420 units per kg, respectively. Repeat dose toxicity was studied in rats at daily doses up to 350 units per kg for a period of 14 days. No signs of toxicity were observed in the single dose and repeat dose studies. A local tolerance study in rabbits demonstrated no clinical or histopathological changes at the injection site after intravenous, intra-arterial or para-venous administration of Corifact. A thrombogenicity test was performed in rabbits at doses up to 350 units per kg. Corifact showed no thrombogenic potential at the doses tested. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Corifact •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): Factor XIII (human) is a purified form of Factor XIII that is used to prevent and treat surgical bleeding in patients with a Factor XIII deficiency. 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 Fenoprofen interact?

•Drug A: Abciximab •Drug B: Fenoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Fenoprofen is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Also for the relief of mild to moderate pain. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fenoprofen is a propionic acid derivative with analgesic, antiinflammatory and antipyretic properties. Fenoprofen inhibits prostaglandin synthesis by decreasing the enzyme needed for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory action of fenoprofen has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenoprofen have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints. In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown fenoprofen to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with fenoprofen than in aspirin-treated patients. It is not known whether fenoprofen causes less peptic ulceration than does aspirin. In patients with pain, the analgesic action of fenoprofen has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Fenoprofen's exact mode of action is unknown, but it is thought that prostaglandin synthetase inhibition is involved. Fenoprofen has been shown to inhibit prostaglandin synthetase isolated from bovine seminal vesicles. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed under fasting conditions, and peak plasma levels of 50 µg/mL are achieved within 2 hours after oral administration of 600 mg doses. •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% 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): About 90% of a single oral dose is eliminated within 24 hours as fenoprofen glucuronide and 4'-hydroxyfenoprofen glucuronide, the major urinary metabolites of fenoprofen. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Plasma half-life is approximately 3 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose appear within several hours and generally involve the gastrointestinal and central nervous systems. They include dyspepsia, nausea, vomiting, abdominal pain, dizziness, headache, ataxia, tinnitus, tremor, drowsiness, and confusion. Hyperpyrexia, tachycardia, hypotension, and acute renal failure may occur rarely following overdose. Respiratory depression and metabolic acidosis have also been reported following overdose with certain NSAIDs. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fenortho, Nalfon •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fenoprofen Fénoprofène Fenoprofeno Fenoprofenum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fenoprofen is an anti-inflammatory analgesic used to treat mild to moderate pain in addition to the signs and symptoms of rheumatoid arthritis and osteoarthritis.

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 Fenoprofen interact? Information: •Drug A: Abciximab •Drug B: Fenoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Fenoprofen is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Also for the relief of mild to moderate pain. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fenoprofen is a propionic acid derivative with analgesic, antiinflammatory and antipyretic properties. Fenoprofen inhibits prostaglandin synthesis by decreasing the enzyme needed for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory action of fenoprofen has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenoprofen have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints. In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown fenoprofen to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with fenoprofen than in aspirin-treated patients. It is not known whether fenoprofen causes less peptic ulceration than does aspirin. In patients with pain, the analgesic action of fenoprofen has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Fenoprofen's exact mode of action is unknown, but it is thought that prostaglandin synthetase inhibition is involved. Fenoprofen has been shown to inhibit prostaglandin synthetase isolated from bovine seminal vesicles. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed under fasting conditions, and peak plasma levels of 50 µg/mL are achieved within 2 hours after oral administration of 600 mg doses. •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% 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): About 90% of a single oral dose is eliminated within 24 hours as fenoprofen glucuronide and 4'-hydroxyfenoprofen glucuronide, the major urinary metabolites of fenoprofen. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Plasma half-life is approximately 3 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overdose appear within several hours and generally involve the gastrointestinal and central nervous systems. They include dyspepsia, nausea, vomiting, abdominal pain, dizziness, headache, ataxia, tinnitus, tremor, drowsiness, and confusion. Hyperpyrexia, tachycardia, hypotension, and acute renal failure may occur rarely following overdose. Respiratory depression and metabolic acidosis have also been reported following overdose with certain NSAIDs. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fenortho, Nalfon •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fenoprofen Fénoprofène Fenoprofeno Fenoprofenum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fenoprofen is an anti-inflammatory analgesic used to treat mild to moderate pain in addition to the signs and symptoms of rheumatoid arthritis and osteoarthritis. 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 Fibrinogen human interact?

•Drug A: Abciximab •Drug B: Fibrinogen human •Severity: MAJOR •Description: The therapeutic efficacy of Fibrinogen 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): Human fibrinogen is used for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. In combination with thrombin, it is used indicated as an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fibrinogen replaces the missing, or low coagulation factor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340 kDa. The native molecule is a dimer and consists of three pairs of polypeptide chains (Aα, Bβ and γ). Fibrinogen is a physiological substrate of three enzymes: thrombin, factor XIIIa, and plasmin. During the coagulation process, thrombin cleaves the Aα and Bβ chains releasing fibrinopeptides A and B (FPA and FPB, respectively). FPA is separated rapidly and the remaining molecule is a soluble fibrin monomer (fibrin I). The slower removal of FPB results in formation of fibrin II that is capable of polymerization that occurs by aggregation of fibrin monomers. The resulting fibrin is stabilized in the presence of calcium ions and by activated factor XIII, which acts as a transglutaminase. Factor XIIIa-induced cross-linking of fibrin polymers renders the fibrin clot more elastic and more resistant to fibrinolysis. Cross-linked fibrin is the end result of the coagulation cascade, and provides tensile strength to a primary hemostatic platelet plug and structure to the vessel wall. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax is 140 mg/dL •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mean volume of distribution is 52.7 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): 78.7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.59 mL/h/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Artiss, Evarrest, Evicel, Fibryga, Riastap, Tachosil, Tisseel, Vistaseal •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): Fibrinogen human is a hemostatic agent used for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.

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 Fibrinogen human interact? Information: •Drug A: Abciximab •Drug B: Fibrinogen human •Severity: MAJOR •Description: The therapeutic efficacy of Fibrinogen 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): Human fibrinogen is used for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. In combination with thrombin, it is used indicated as an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fibrinogen replaces the missing, or low coagulation factor. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340 kDa. The native molecule is a dimer and consists of three pairs of polypeptide chains (Aα, Bβ and γ). Fibrinogen is a physiological substrate of three enzymes: thrombin, factor XIIIa, and plasmin. During the coagulation process, thrombin cleaves the Aα and Bβ chains releasing fibrinopeptides A and B (FPA and FPB, respectively). FPA is separated rapidly and the remaining molecule is a soluble fibrin monomer (fibrin I). The slower removal of FPB results in formation of fibrin II that is capable of polymerization that occurs by aggregation of fibrin monomers. The resulting fibrin is stabilized in the presence of calcium ions and by activated factor XIII, which acts as a transglutaminase. Factor XIIIa-induced cross-linking of fibrin polymers renders the fibrin clot more elastic and more resistant to fibrinolysis. Cross-linked fibrin is the end result of the coagulation cascade, and provides tensile strength to a primary hemostatic platelet plug and structure to the vessel wall. •Absorption (Drug A): No absorption available •Absorption (Drug B): Cmax is 140 mg/dL •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mean volume of distribution is 52.7 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): 78.7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.59 mL/h/kg •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Artiss, Evarrest, Evicel, Fibryga, Riastap, Tachosil, Tisseel, Vistaseal •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): Fibrinogen human is a hemostatic agent used for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. 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 Floctafenine interact?

•Drug A: Abciximab •Drug B: Floctafenine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Floctafenine 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): No indication available •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Floctafenine is an anti-inflammatory analgesic used to manage mild to moderate acute 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 Floctafenine interact? Information: •Drug A: Abciximab •Drug B: Floctafenine •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Floctafenine 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): No indication available •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Floctafenine is an anti-inflammatory analgesic used to manage mild to moderate acute 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 Floxuridine interact?

•Drug A: Abciximab •Drug B: Floxuridine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Floxuridine. •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 palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Floxuridine is an anti-metabolite or a pyrimidine analog that works by disrupting the process S-phase of cell division, selectively targeting rapidly dividing cells. Due to the structural similarities, antimetabolites act as pyrimidine-like molecules and prevent normal pyrimidines from being incorporated into DNA. After successful biotransformation, floxuridine is converted into an active component, flurouracil, which blocks the enzyme which converts cytosine nucleosides into the deoxy derivative. Flurouracil also physically prevents the incorporation of thymidine nucleotides into the DNA strand by taking their place, further preventing DNA 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): Floxuridine rapidly undergoes catabolism to form 5-fluorouracil, which is the active component of the drug. 5-Fluorouracil primarily works by interfering with DNA synthesis; however, it may also inhibit the formation of fraudulent RNA via physical incorporation into the RNA. It is also an inhibitor of riboside phophorylase, preventing the utilization of pre-formed uracil in RNA synthesis. Floxuridine can also form 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP), which is the monophosphate of floxuridine that inhibits thymidylate synthetase that plays a role in the methylation of deoxyuridylic acid to thymidylic acid during DNA synthesis. FUDR-MP thus interferes with DNA synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hepatic. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Floxuridine can be excreted as unchanged drug, urea, fluorouracil, a-fluoro-bureidopropionic acid, dihydrofluorouracil, a-fluoro-b-guanidopropionic acid and a-fluoro-b-alanine via the kidneys. Floxuridine may also be excreted as respiratory carbon dioxide. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat LD 50: 215 mg/kg. Signs of overdose include nausea, vomiting, diarrhea, gastrointestinal ulceration and bleeding, and bone marrow depression (including thrombocytopenia, leukopenia and agranulocytosis). •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): 5-Fluorodeoxyuridine 5FDU Deoxyfluorouridine Floxiridina Floxuridin Floxuridine Floxuridinum Fluorodeoxyuridine Fluoruridine deoxyribose •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Floxuridine is an antimetabolite used as palliative management for liver metastases of gastrointestinal malignancy.

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 Floxuridine interact? Information: •Drug A: Abciximab •Drug B: Floxuridine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Floxuridine. •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 palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Floxuridine is an anti-metabolite or a pyrimidine analog that works by disrupting the process S-phase of cell division, selectively targeting rapidly dividing cells. Due to the structural similarities, antimetabolites act as pyrimidine-like molecules and prevent normal pyrimidines from being incorporated into DNA. After successful biotransformation, floxuridine is converted into an active component, flurouracil, which blocks the enzyme which converts cytosine nucleosides into the deoxy derivative. Flurouracil also physically prevents the incorporation of thymidine nucleotides into the DNA strand by taking their place, further preventing DNA 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): Floxuridine rapidly undergoes catabolism to form 5-fluorouracil, which is the active component of the drug. 5-Fluorouracil primarily works by interfering with DNA synthesis; however, it may also inhibit the formation of fraudulent RNA via physical incorporation into the RNA. It is also an inhibitor of riboside phophorylase, preventing the utilization of pre-formed uracil in RNA synthesis. Floxuridine can also form 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP), which is the monophosphate of floxuridine that inhibits thymidylate synthetase that plays a role in the methylation of deoxyuridylic acid to thymidylic acid during DNA synthesis. FUDR-MP thus interferes with DNA synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hepatic. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Floxuridine can be excreted as unchanged drug, urea, fluorouracil, a-fluoro-bureidopropionic acid, dihydrofluorouracil, a-fluoro-b-guanidopropionic acid and a-fluoro-b-alanine via the kidneys. Floxuridine may also be excreted as respiratory carbon dioxide. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat LD 50: 215 mg/kg. Signs of overdose include nausea, vomiting, diarrhea, gastrointestinal ulceration and bleeding, and bone marrow depression (including thrombocytopenia, leukopenia and agranulocytosis). •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): 5-Fluorodeoxyuridine 5FDU Deoxyfluorouridine Floxiridina Floxuridin Floxuridine Floxuridinum Fluorodeoxyuridine Fluoruridine deoxyribose •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Floxuridine is an antimetabolite used as palliative management for liver metastases of gastrointestinal malignancy. 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 Flucytosine interact?

•Drug A: Abciximab •Drug B: Flucytosine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Flucytosine. •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 (in combination with amphotericin B) of serious infections caused by susceptible strains of Candida (septicemia, endocarditis and urinary system infections) and/or Cryptococcus (meningitis and pulmonary 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): Flucytosine is an antimetabolite that acts as an antifungal agent with in vitro and in vivo activity against Candida and Cryptococcus. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. Antifungal synergism between Ancobon and polyene antibiotics, particularly amphotericin B, has been reported. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly and virtually completely absorbed following oral administration. Bioavailability 78% to 89%. •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): 28-31% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Flucytosine is deaminated, possibly by gut bacteria or by the fungal targets, to 5-fluorouracil, the active metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Flucytosine is excreted via the kidneys by means of glomerular filtration without significant tubular reabsorption. A small portion of the dose 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): 2.4 to 4.8 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat: LD 50 = >15 gm/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ancobon •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): Flucytosine is an antifungal indicated only to treat severe infections throughout the body caused by susceptible strains of Candida or Cryptococcus.

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 Flucytosine interact? Information: •Drug A: Abciximab •Drug B: Flucytosine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Flucytosine. •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 (in combination with amphotericin B) of serious infections caused by susceptible strains of Candida (septicemia, endocarditis and urinary system infections) and/or Cryptococcus (meningitis and pulmonary 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): Flucytosine is an antimetabolite that acts as an antifungal agent with in vitro and in vivo activity against Candida and Cryptococcus. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. Antifungal synergism between Ancobon and polyene antibiotics, particularly amphotericin B, has been reported. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly and virtually completely absorbed following oral administration. Bioavailability 78% to 89%. •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): 28-31% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Flucytosine is deaminated, possibly by gut bacteria or by the fungal targets, to 5-fluorouracil, the active metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Flucytosine is excreted via the kidneys by means of glomerular filtration without significant tubular reabsorption. A small portion of the dose 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): 2.4 to 4.8 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat: LD 50 = >15 gm/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ancobon •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): Flucytosine is an antifungal indicated only to treat severe infections throughout the body caused by susceptible strains of Candida or Cryptococcus. 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 Fludarabine interact?

•Drug A: Abciximab •Drug B: Fludarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Fludarabine. •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 adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the 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): Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability is 55% 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): 19-29% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): 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): 20 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 117-145 mL/min [patients with B-cell CLL receiving IV administration of a single dose of 40 mg/m^2. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fludara •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fludarabina Fludarabine Fludarabinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fludarabine is a purine analog antimetabolite that inhibits DNA synthesis.

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 Fludarabine interact? Information: •Drug A: Abciximab •Drug B: Fludarabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Fludarabine. •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 adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the 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): Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted. •Absorption (Drug A): No absorption available •Absorption (Drug B): Bioavailability is 55% 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): 19-29% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): 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): 20 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): 117-145 mL/min [patients with B-cell CLL receiving IV administration of a single dose of 40 mg/m^2. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fludara •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fludarabina Fludarabine Fludarabinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fludarabine is a purine analog antimetabolite that inhibits DNA synthesis. 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 Fluorouracil interact?

•Drug A: Abciximab •Drug B: Fluorouracil •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Fluorouracil. •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 topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas, renal cell, and carcinoid. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): 28-100% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 8-12% •Metabolism (Drug A): 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. The catabolic metabolism of fluorouracil results in degradation products ( e.g., CO2, urea and α-fluoro-ß-alanine) which are inactive. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Seven percent to 20% of the parent drug is excreted unchanged in the urine in 6 hours; of this over 90% is excreted in the first hour. The remaining percentage of the administered dose is metabolized, primarily in the liver. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 10-20 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =230mg/kg (orally in mice) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Actikerall, Carac, Efudex, Fluoroplex, Tolak •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-Fluoracil 5-Fluorouracil 5-Fluracil 5-FU Fluoro Uracil Fluorouracil Fluorouracilo Fluorouracilum Fluouracil •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fluorouracil is a pyrimidine analog used to treat basal cell carcinomas, and as an injection in palliative cancer treatment.

As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Fluorouracil interact? Information: •Drug A: Abciximab •Drug B: Fluorouracil •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Fluorouracil. •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 topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas, renal cell, and carcinoid. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): 28-100% •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 8-12% •Metabolism (Drug A): 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. The catabolic metabolism of fluorouracil results in degradation products ( e.g., CO2, urea and α-fluoro-ß-alanine) which are inactive. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Seven percent to 20% of the parent drug is excreted unchanged in the urine in 6 hours; of this over 90% is excreted in the first hour. The remaining percentage of the administered dose is metabolized, primarily in the liver. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 10-20 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =230mg/kg (orally in mice) •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Actikerall, Carac, Efudex, Fluoroplex, Tolak •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-Fluoracil 5-Fluorouracil 5-Fluracil 5-FU Fluoro Uracil Fluorouracil Fluorouracilo Fluorouracilum Fluouracil •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fluorouracil is a pyrimidine analog used to treat basal cell carcinomas, and as an injection in palliative cancer treatment. Output: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Does Abciximab and Fluoxetine interact?

•Drug A: Abciximab •Drug B: Fluoxetine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Fluoxetine 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): Fluoxetine is indicated for both acute and maintenance treatment of major depressive disorder, obsessive compulsive disorder, and bulimia nervosa; however, it is only indicated for acute treatment of panic disorder independent of whether agoraphobia is present. Fluoxetine may also be used in combination with olanzapine to treat depression related to Bipolar I Disorder, and treatment resistant depression. Fluoxetine is additionally indicated for the treatment of female patients with premenstrual dysphoric disorder (PMDD). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas. However, fluoxetine binds with relatively poor affinity to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors which explains why it has a far more desirable adverse effect profile compared to earlier developed classes of antidepressants such as tricyclic antidepressants. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 monoaminergic hypothesis of depression emerged in 1965 and linked depression with dysfunction of neurotransmitters such as noradrenaline and serotonin. Indeed, low levels of serotonin have been observed in the cerebrospinal fluid of patients diagnosed with depression. As a result of this hypothesis, drugs that modulate levels of serotonin such as fluoxetine were developed. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and as the name suggests, it exerts it's therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. As a result, levels of 5-hydroxytryptamine (5-HT) are increased in various parts of the brain. Further, fluoxetine has high affinity for 5-HT transporters, weak affinity for noradrenaline transporters and no affinity for dopamine transporters indicating that it is 5-HT selective. Fluoxetine interacts to a degree with the 5-HT 2C receptor and it has been suggested that through this mechanism, it is able to increase noradrenaline and dopamine levels in the prefrontal cortex. •Absorption (Drug A): No absorption available •Absorption (Drug B): The oral bioavailability of fluoxetine is <90% as a result of hepatic first pass metabolism. In a bioequivalence study, the Cmax of fluoxetine 20 mg for the established reference formulation was 11.754 ng/mL while the Cmax for the proposed generic formulation was 11.786 ng/ml. Fluoxetine is very lipophilic and highly plasma protein bound, allowing the drug and it's active metabolite, norfluoxetine, to be distributed to the brain. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of fluoxetine and it's metabolite varies between 20 to 42 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 94% of fluoxetine is plasma protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Fluoxetine is metabolized to norfluoxetine by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 upon ingestion. Although all of the mentioned enzymes contribute to N-demethylation of fluoxetine, CYP2D6, CYP2C9 and CYP3A4 appear to be the major contributing enzymes for phase I metabolism. In addition, there is evidence to suggest that CYP2C19 and CYP3A4 mediate O-dealkylation of fluoxetine and norfluoxetine to produce para-trifluoromethylphenol which is subsequently metabolized to hippuric acid. Both fluoxetine and norfluoxetine undergo glucuronidation to facilitate excretion. Notably, both the parent drug and active metabolite inhibit CYP2D6 isozymes, and as a result patients who are being treated with fluoxetine are susceptible to drug interactions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Fluoxetine is primarily eliminated 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 fluoxetine is significant with the elimination half-life of the parent drug averaging 1-3 days after acute administration, and 4-6 days after chronic administration. Further, the elimination half life of it's active metabolite, norfluoxetine, ranges from 4-16 days after both acute and chronic administration. The half-life of fluoxetine should be considered when switching patients from fluoxetine to another antidepressant since marked accumulation occurs after chronic use. Fluoxetine's long half-life may even be beneficial when discontinuing the drug since the risk of withdrawal is minimized. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance value of fluoxetine in healthy patients is reported to be 9.6 ml/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In a report that included 234 fluoxetine overdose cases, it was concluded that symptoms resulting from fluoxetine overdose were generally minor and short in duration. The most common overdose adverse effects included drowsiness, tremor, tachycardia, nausea and vomiting, and providing the patient with aggressive supportive care was the recommended intervention. Despite this evidence, more severe adverse effects have been linked to fluoxetine ingestion although most of these reports involved co-ingestion with other substances or drugs as well as other factors. For example, there is a case report that details a patient who ingested 1400 mg of fluoxetine in a suicide attempt and as a result, experienced a generalized seizure three hours later. In a separate case, a 14 year old patient ingested 1.2 g of fluoxetine and subsequently experienced tonic/clonic seizures, symptoms consistent with serotonin syndrome, and rhabdomyolysis, although the patient did not experience sustained renal injury. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Prozac, Sarafem, Symbyax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fluoxetin Fluoxetina Fluoxétine Fluoxetine Fluoxetinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fluoxetine is a selective serotonin reuptake inhibitor used to treat major depressive disorder, bulimia, OCD, premenstrual dysphoric disorder, panic disorder, and bipolar I.

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 Fluoxetine interact? Information: •Drug A: Abciximab •Drug B: Fluoxetine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Fluoxetine 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): Fluoxetine is indicated for both acute and maintenance treatment of major depressive disorder, obsessive compulsive disorder, and bulimia nervosa; however, it is only indicated for acute treatment of panic disorder independent of whether agoraphobia is present. Fluoxetine may also be used in combination with olanzapine to treat depression related to Bipolar I Disorder, and treatment resistant depression. Fluoxetine is additionally indicated for the treatment of female patients with premenstrual dysphoric disorder (PMDD). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas. However, fluoxetine binds with relatively poor affinity to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors which explains why it has a far more desirable adverse effect profile compared to earlier developed classes of antidepressants such as tricyclic antidepressants. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 monoaminergic hypothesis of depression emerged in 1965 and linked depression with dysfunction of neurotransmitters such as noradrenaline and serotonin. Indeed, low levels of serotonin have been observed in the cerebrospinal fluid of patients diagnosed with depression. As a result of this hypothesis, drugs that modulate levels of serotonin such as fluoxetine were developed. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and as the name suggests, it exerts it's therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. As a result, levels of 5-hydroxytryptamine (5-HT) are increased in various parts of the brain. Further, fluoxetine has high affinity for 5-HT transporters, weak affinity for noradrenaline transporters and no affinity for dopamine transporters indicating that it is 5-HT selective. Fluoxetine interacts to a degree with the 5-HT 2C receptor and it has been suggested that through this mechanism, it is able to increase noradrenaline and dopamine levels in the prefrontal cortex. •Absorption (Drug A): No absorption available •Absorption (Drug B): The oral bioavailability of fluoxetine is <90% as a result of hepatic first pass metabolism. In a bioequivalence study, the Cmax of fluoxetine 20 mg for the established reference formulation was 11.754 ng/mL while the Cmax for the proposed generic formulation was 11.786 ng/ml. Fluoxetine is very lipophilic and highly plasma protein bound, allowing the drug and it's active metabolite, norfluoxetine, to be distributed to the brain. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of fluoxetine and it's metabolite varies between 20 to 42 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Approximately 94% of fluoxetine is plasma protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Fluoxetine is metabolized to norfluoxetine by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 upon ingestion. Although all of the mentioned enzymes contribute to N-demethylation of fluoxetine, CYP2D6, CYP2C9 and CYP3A4 appear to be the major contributing enzymes for phase I metabolism. In addition, there is evidence to suggest that CYP2C19 and CYP3A4 mediate O-dealkylation of fluoxetine and norfluoxetine to produce para-trifluoromethylphenol which is subsequently metabolized to hippuric acid. Both fluoxetine and norfluoxetine undergo glucuronidation to facilitate excretion. Notably, both the parent drug and active metabolite inhibit CYP2D6 isozymes, and as a result patients who are being treated with fluoxetine are susceptible to drug interactions. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Fluoxetine is primarily eliminated 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 fluoxetine is significant with the elimination half-life of the parent drug averaging 1-3 days after acute administration, and 4-6 days after chronic administration. Further, the elimination half life of it's active metabolite, norfluoxetine, ranges from 4-16 days after both acute and chronic administration. The half-life of fluoxetine should be considered when switching patients from fluoxetine to another antidepressant since marked accumulation occurs after chronic use. Fluoxetine's long half-life may even be beneficial when discontinuing the drug since the risk of withdrawal is minimized. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance value of fluoxetine in healthy patients is reported to be 9.6 ml/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In a report that included 234 fluoxetine overdose cases, it was concluded that symptoms resulting from fluoxetine overdose were generally minor and short in duration. The most common overdose adverse effects included drowsiness, tremor, tachycardia, nausea and vomiting, and providing the patient with aggressive supportive care was the recommended intervention. Despite this evidence, more severe adverse effects have been linked to fluoxetine ingestion although most of these reports involved co-ingestion with other substances or drugs as well as other factors. For example, there is a case report that details a patient who ingested 1400 mg of fluoxetine in a suicide attempt and as a result, experienced a generalized seizure three hours later. In a separate case, a 14 year old patient ingested 1.2 g of fluoxetine and subsequently experienced tonic/clonic seizures, symptoms consistent with serotonin syndrome, and rhabdomyolysis, although the patient did not experience sustained renal injury. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Prozac, Sarafem, Symbyax •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Fluoxetin Fluoxetina Fluoxétine Fluoxetine Fluoxetinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Fluoxetine is a selective serotonin reuptake inhibitor used to treat major depressive disorder, bulimia, OCD, premenstrual dysphoric disorder, panic disorder, and bipolar I. 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 Flurbiprofen interact?

•Drug A: Abciximab •Drug B: Flurbiprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Flurbiprofen 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): Flurbiprofen tablets are indicated for the acute or long-term symptomatic treatment of rheumatoid arthritis, osteorarthritis and anklosing spondylitis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Topical ophthalmic formulations may be used pre-operatively to prevent intraoperative miosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of the propionic acid class, is structually and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen, and has similar pharmacological actions to other prototypica NSAIAs. Flurbiprofen exhibits antiinflammatory, analgesic, and antipyretic activities. The commercially available flurbiprofen is a racemic mixture of (+)S- and (-) R-enantiomers. The S-enantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Fluribiprofen is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations are reached 0.5 - 4 hours after oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 14 L [Normal Healthy Adults] 12 L [Geriatric Arthritis Patients] 10 L [End Stage Renal Disease Patients] 14 L [Alcoholic Cirrhosis Patients] 0.12 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): > 99% bound, primarily to albumin. Binds to a different primary binding site on albumin than anticoagulants, sulfonamides and phenytoin. •Metabolism (Drug A): 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. Cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4’-hydroxy-flurbiprofen. The 4’-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Flurbiprofen is poorly excreted into human milk. Following dosing with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Renal elimination is a significant pathway of elimination of flurbiprofen 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): R-flurbiprofen, 4.7 hours; S-flurbiprofen, 5.7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =10 mg/kg (orally in dogs). 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 flurbiprofen. Flurbiprofen may increase blood pressure and/or cause fluid retention and edema. Use caution in patients with fluid retention or heart failure. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) may occur. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Although rarely documented in the case of flurbiprofen, oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. •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): Flurbiprofen Flurbiprofene Flurbiprofeno Flurbiprofenum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Flurbiprofen 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 Flurbiprofen interact? Information: •Drug A: Abciximab •Drug B: Flurbiprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Flurbiprofen 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): Flurbiprofen tablets are indicated for the acute or long-term symptomatic treatment of rheumatoid arthritis, osteorarthritis and anklosing spondylitis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Topical ophthalmic formulations may be used pre-operatively to prevent intraoperative miosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of the propionic acid class, is structually and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen, and has similar pharmacological actions to other prototypica NSAIAs. Flurbiprofen exhibits antiinflammatory, analgesic, and antipyretic activities. The commercially available flurbiprofen is a racemic mixture of (+)S- and (-) R-enantiomers. The S-enantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Fluribiprofen is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations are reached 0.5 - 4 hours after oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 14 L [Normal Healthy Adults] 12 L [Geriatric Arthritis Patients] 10 L [End Stage Renal Disease Patients] 14 L [Alcoholic Cirrhosis Patients] 0.12 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): > 99% bound, primarily to albumin. Binds to a different primary binding site on albumin than anticoagulants, sulfonamides and phenytoin. •Metabolism (Drug A): 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. Cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4’-hydroxy-flurbiprofen. The 4’-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Flurbiprofen is poorly excreted into human milk. Following dosing with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Renal elimination is a significant pathway of elimination of flurbiprofen 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): R-flurbiprofen, 4.7 hours; S-flurbiprofen, 5.7 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =10 mg/kg (orally in dogs). 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 flurbiprofen. Flurbiprofen may increase blood pressure and/or cause fluid retention and edema. Use caution in patients with fluid retention or heart failure. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) may occur. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Although rarely documented in the case of flurbiprofen, oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. •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): Flurbiprofen Flurbiprofene Flurbiprofeno Flurbiprofenum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Flurbiprofen 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 Fluvoxamine interact?

•Drug A: Abciximab •Drug B: Fluvoxamine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Fluvoxamine 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 predominantly for the management of depression and for Obsessive Compulsive Disorder (OCD). Has also been used in the management of bulimia nervosa. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Moreover, apart from binding to σ1 receptors, fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT 1A, 5HT 1B, 5HT 2 ), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. Furthermore, some studies have demonstrated that the chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors (as has been observed with other drugs effective in the treatment of major depressive disorder), while others suggest the opposite. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 action of fluvoxamine has not been fully determined, but appears to be linked to its inhibition of CNS neuronal uptake of serotonin. Fluvoxamine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT 1A autoreceptors. Studies have also demonstrated that fluvoxamine has virtually no affinity for α 1 - or α 2 -adrenergic, β-adrenergic, muscarinic, dopamine D 2, histamine H 1, GABA-benzodiazepine, opiate, 5-HT 1, or 5-HT 2 receptors, despite having an affinity for binding to σ1 receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed, bioavailability of fluvoxamine maleate is 53%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 25 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): ~77-80% (plasma protein). •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Fluvoxamine is metabolized extensively by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nine metabolites were identified following a 5 mg radio labelled dose of fluvoxamine maleate, constituting approximately 85% of the urinary excretion products of fluvoxamine. The main human metabolite was fluvoxamine acid which, together with its N-acetylated analog, accounted for about 60% of the urinary excretion products. Approximately 2% of fluvoxamine was excreted in urine unchanged. Following a 14C-labelled oral dose of fluvoxamine maleate (5 mg), an average of 94% of drug-related products was recovered in the urine within 71 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): 15.6 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Fluvoxamine is a member of antidepressants that possess an increased risk compared to placebo of suicidal thinking and behaviour (suicidality) in children, adolescents, and young adults (ages including and and below 24) in short-term studies of major depressive disorder and other psychiatric disorders. Fluvoxamine maleate tablets are not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). Side effects include anorexia, constipation, dry mouth, headache, nausea, nervousness, skin rash, sleep problems, somnolence, liver toxicity, mania, increase urination, seizures, sweating increase, tremors, or Tourette's syndrome. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Luvox •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): Fluvoxamine is a selective serotonin-reuptake inhibitor used to treat obsessive-compulsive disorder.

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

Question: Does Abciximab and Fluvoxamine interact? Information: •Drug A: Abciximab •Drug B: Fluvoxamine •Severity: MODERATE •Description: The risk or severity of hemorrhage can be increased when Fluvoxamine 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 predominantly for the management of depression and for Obsessive Compulsive Disorder (OCD). Has also been used in the management of bulimia nervosa. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Moreover, apart from binding to σ1 receptors, fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT 1A, 5HT 1B, 5HT 2 ), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. Furthermore, some studies have demonstrated that the chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors (as has been observed with other drugs effective in the treatment of major depressive disorder), while others suggest the opposite. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 action of fluvoxamine has not been fully determined, but appears to be linked to its inhibition of CNS neuronal uptake of serotonin. Fluvoxamine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT 1A autoreceptors. Studies have also demonstrated that fluvoxamine has virtually no affinity for α 1 - or α 2 -adrenergic, β-adrenergic, muscarinic, dopamine D 2, histamine H 1, GABA-benzodiazepine, opiate, 5-HT 1, or 5-HT 2 receptors, despite having an affinity for binding to σ1 receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well absorbed, bioavailability of fluvoxamine maleate is 53%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 25 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): ~77-80% (plasma protein). •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Fluvoxamine is metabolized extensively by the liver. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Nine metabolites were identified following a 5 mg radio labelled dose of fluvoxamine maleate, constituting approximately 85% of the urinary excretion products of fluvoxamine. The main human metabolite was fluvoxamine acid which, together with its N-acetylated analog, accounted for about 60% of the urinary excretion products. Approximately 2% of fluvoxamine was excreted in urine unchanged. Following a 14C-labelled oral dose of fluvoxamine maleate (5 mg), an average of 94% of drug-related products was recovered in the urine within 71 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): 15.6 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Fluvoxamine is a member of antidepressants that possess an increased risk compared to placebo of suicidal thinking and behaviour (suicidality) in children, adolescents, and young adults (ages including and and below 24) in short-term studies of major depressive disorder and other psychiatric disorders. Fluvoxamine maleate tablets are not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). Side effects include anorexia, constipation, dry mouth, headache, nausea, nervousness, skin rash, sleep problems, somnolence, liver toxicity, mania, increase urination, seizures, sweating increase, tremors, or Tourette's syndrome. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Luvox •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): Fluvoxamine is a selective serotonin-reuptake inhibitor used to treat obsessive-compulsive disorder. Output: It has been reported that concomitant administration of antiplatelet agents and SSRI is associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Fondaparinux interact?

•Drug A: Abciximab •Drug B: Fondaparinux •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Fondaparinux. •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): Approved for: (1) prophylaxis of VTE for up to one month post surgery in patients undergoing orthopedic surgery of the lower limbs such as hip fracture, hip replacement and knee surgery; (2) prophylaxis of VTE patients undergoing abdominal surgery who are at high risk of thromboembolic complications (e.g. patients undergoing abdominal cancer surgery); (3) treatment of acute DVT and PE; (4) management of UA and NSTEMI for the prevention of death and subsequent myocardial infarction (MI); and (5) management of STEMI for the prevention of death and myocardial reinfarction in patients who are managed with thrombolytics or who are initially to receive no form of reperfusion therapy. Fondaparinux should not be used as the sole anticoagulant during percutaneous coronary intervention (PCI) due to an increased risk of guiding catheter thrombosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%). At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure. As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients. However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux. •Absorption (Drug A): No absorption available •Absorption (Drug B): 100% bioavailability when administered subcutaneously •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 7 - 11 L (healthy adults), distributed primarily in blood •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 94% in vitro protein binding specifically to ATIII •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Not metabolized •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 17-21 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): As with other anticoagulants, the main concern is increased bleed risk. The risk of hemorrhage may increase with decreased renal function, body mass less than 50 kg, and moderate to severe hepatic function. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Arixtra •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): Fondaparinux is an anticoagulant used to prevent venous thromboembolism, to treat deep vein thrombosis, and to improve survival following 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 Fondaparinux interact? Information: •Drug A: Abciximab •Drug B: Fondaparinux •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Fondaparinux. •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): Approved for: (1) prophylaxis of VTE for up to one month post surgery in patients undergoing orthopedic surgery of the lower limbs such as hip fracture, hip replacement and knee surgery; (2) prophylaxis of VTE patients undergoing abdominal surgery who are at high risk of thromboembolic complications (e.g. patients undergoing abdominal cancer surgery); (3) treatment of acute DVT and PE; (4) management of UA and NSTEMI for the prevention of death and subsequent myocardial infarction (MI); and (5) management of STEMI for the prevention of death and myocardial reinfarction in patients who are managed with thrombolytics or who are initially to receive no form of reperfusion therapy. Fondaparinux should not be used as the sole anticoagulant during percutaneous coronary intervention (PCI) due to an increased risk of guiding catheter thrombosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%). At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure. As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients. However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux. •Absorption (Drug A): No absorption available •Absorption (Drug B): 100% bioavailability when administered subcutaneously •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 7 - 11 L (healthy adults), distributed primarily in blood •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 94% in vitro protein binding specifically to ATIII •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Not metabolized •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 17-21 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): As with other anticoagulants, the main concern is increased bleed risk. The risk of hemorrhage may increase with decreased renal function, body mass less than 50 kg, and moderate to severe hepatic function. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Arixtra •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): Fondaparinux is an anticoagulant used to prevent venous thromboembolism, to treat deep vein thrombosis, and to improve survival following 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 Fremanezumab interact?

•Drug A: Abciximab •Drug B: Fremanezumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Fremanezumab. •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): Fremanezumab 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): Fremanezumab is a subcutaneous injection that targets the calcitonin gene-related peptide (CGRP) ligand, preventing its binding to the CGRP receptor. It possesses a long duration of action requiring only monthly or quarterly administration and appears well-tolerated 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): Studies dating back to 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after administration of antimigraine therapy such as sumatriptan. Moreover, research has shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For these reasons, and despite the fact that their role in migraine headaches has not been entirely elucidated, CGRP and its receptors have become desirable targets for antimigraine therapies. Fremanezumab is a humanized monoclonal antibody directed against endogenous CGRP - it interferes with the activity of CGRP, preventing its downstream effects and ultimately mitigating the development of migraine headaches. •Absorption (Drug A): No absorption available •Absorption (Drug B): Geometric mean ratios (GMRs) for Cmax for Japanese and Caucasian study subjects were 0.91, 1.04, and 1.14 for 225 mg, 675 mg, and 900 mg doses of fremanezumab. GMRs for AUC (0-inf) were 0.96, 1.09, and 0.98, respectively. Mean Tmax in a range of 5 to 11 days were similar across doses for both ethnicities as well. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Fremanezumab has an apparent volume of distribution of approximately 6 liters which indicates very little distribution into tissue. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Data regarding protein binding of fremanezumab are 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): Like other monoclonal antibodies, fremanezumab is expected to undergo enzymatic proteolysis into smaller peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibody agents like fremanezumab 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 mean half-life recorded for fremanezumab was similar across doses for Japanese and Caucasian study subjects and was estimated to be approximately 31-39 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of fremanezumab is 0.141 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Information regarding overdose of fremanezumab is not readily available. The most common adverse events that led to discontinuation of fremanezumab therapy were injection site reactions including erythema, induration, and pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ajovy •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): Fremanezumab is a humanized monoclonal antibody directed against human calcitonin-gene related peptide 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 Fremanezumab interact? Information: •Drug A: Abciximab •Drug B: Fremanezumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Fremanezumab. •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): Fremanezumab 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): Fremanezumab is a subcutaneous injection that targets the calcitonin gene-related peptide (CGRP) ligand, preventing its binding to the CGRP receptor. It possesses a long duration of action requiring only monthly or quarterly administration and appears well-tolerated 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): Studies dating back to 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after administration of antimigraine therapy such as sumatriptan. Moreover, research has shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For these reasons, and despite the fact that their role in migraine headaches has not been entirely elucidated, CGRP and its receptors have become desirable targets for antimigraine therapies. Fremanezumab is a humanized monoclonal antibody directed against endogenous CGRP - it interferes with the activity of CGRP, preventing its downstream effects and ultimately mitigating the development of migraine headaches. •Absorption (Drug A): No absorption available •Absorption (Drug B): Geometric mean ratios (GMRs) for Cmax for Japanese and Caucasian study subjects were 0.91, 1.04, and 1.14 for 225 mg, 675 mg, and 900 mg doses of fremanezumab. GMRs for AUC (0-inf) were 0.96, 1.09, and 0.98, respectively. Mean Tmax in a range of 5 to 11 days were similar across doses for both ethnicities as well. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Fremanezumab has an apparent volume of distribution of approximately 6 liters which indicates very little distribution into tissue. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Data regarding protein binding of fremanezumab are 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): Like other monoclonal antibodies, fremanezumab is expected to undergo enzymatic proteolysis into smaller peptides and amino acids. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibody agents like fremanezumab 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 mean half-life recorded for fremanezumab was similar across doses for Japanese and Caucasian study subjects and was estimated to be approximately 31-39 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of fremanezumab is 0.141 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Information regarding overdose of fremanezumab is not readily available. The most common adverse events that led to discontinuation of fremanezumab therapy were injection site reactions including erythema, induration, and pain. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ajovy •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): Fremanezumab is a humanized monoclonal antibody directed against human calcitonin-gene related peptide 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 Galcanezumab interact?

•Drug A: Abciximab •Drug B: Galcanezumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Galcanezumab. •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): Galcanezumab is indicated in adults for the preventive treatment of migraine and the treatment of episodic cluster headache. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Galcanezumab is administered as a subcutaneous injection. During clinical trials, it was noted that galcanezumab therapy significantly reduced the mean number of migraine headache days and a good tolerability profile. Additionally, post hoc efficacy analyses showed that 32% of patients given galcanezumab responded to treatment, compared to 18% in the placebo group.. Hypersensitivity reactions, including dyspnea, urticaria, and rash, have been reported in patients using galcanezumab. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Galcanezumab is a humanized monoclonal antibody that targets and binds 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. Also, research has shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For these reasons, binding to CGRP to interfere with its activity was specifically designed as the mechanism of action for galcanezumab, in order to reverse the migraine-inducing activity of natural CGRP. By binding to natural endogenous CGRP, galcanezumab interferes with its activities by making it unable to bind to CGRP receptors. Moreover, studies have shown that humanized monoclonal antibodies against CGRP have successfully reduced the frequency of migraine headaches in early clinical trials as a preventative therapeutic. •Absorption (Drug A): No absorption available •Absorption (Drug B): Galcanezumab follows a linear pharmacokinetic profile, with a Cmax and AUC 0-∞ considered to be dose-proportional between 1 and 600 mg. After a single dose of galcanezumab-gnlm administered subcutaneously, the time to maximum concentration was 5 days. In a group of healthy subjects (n=7) given four biweekly doses of galcanezumab, T max was 3 days, C max was 37,210 ng/mL and the AUC was 1,959,000 ng⋅day/mL. The injection site location does not appear to significantly influence the absorption of this drug. Galcanezumab is expected to have a subcutaneous bioavailability between 50% and 100%, similar to other monoclonal antibodies. Renal and hepatic impairment are not expected to have an effect on the pharmacokinetics of galcanezumab. A population analysis has shown that pharmacokinetic parameters are not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), while body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of galcanezumab is 7.3 L, with 34% inter-individual variability. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Readily accessible data regarding the protein binding of galcanezumab 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): After administration, galcanezumab is expected to be degraded into small peptides and amino acids by proteolysis, in a process similar to the one followed by endogenous immunoglobulins. Galcanezumab is not believed to be metabolized by liver enzymes, making drug-drug interactions relatively unlikely. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibody agents like galcanezumab are generally eliminated via intracellular catabolism, followed by fluid-phase or receptor-mediated endocytosis. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Between 1 and 600 mg of galcanezumab, the mean serum half-life ranged from 25 to 30 days. On average, the elimination half-life of galcanezumab was approximately 27 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of galcanezumab is 0.008 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding galcanezumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nasopharyngitis, hematuria, and contact dermatitis. Symptomatic and supportive measures are recommended. Additional adverse effects reported in healthy subjects receiving a single high dose of galcanezumab (600 mg) were diarrhea, vomiting and high levels of alanine aminotransferase. Studies evaluating the carcinogenic potential or genetic toxicology of galcanezumab have not yet been conducted. No adverse effects were observed in male rats given galcanezumab (0, 30, or 250 mg/kg) subcutaneously before or during mating. The highest dose given to male rats corresponded to 8 or 4 times the recommended human dose for migraine (120 mg) or episodic cluster headache (300 mg), respectively. Female rats given 0, 30, 100 or 250 mg/kg of galcanezumab did not show adverse effects on fertility either. The highest dose given to female rats corresponded to 38 or 18 times the recommended human dose for migraine (120 mg) or episodic cluster headache (300 mg), respectively. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Emgality •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): Galcanezumab is a calcitonin-gene related peptide antagonist used to prevent migraines and treat cluster headaches.

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 Galcanezumab interact? Information: •Drug A: Abciximab •Drug B: Galcanezumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Galcanezumab. •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): Galcanezumab is indicated in adults for the preventive treatment of migraine and the treatment of episodic cluster headache. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Galcanezumab is administered as a subcutaneous injection. During clinical trials, it was noted that galcanezumab therapy significantly reduced the mean number of migraine headache days and a good tolerability profile. Additionally, post hoc efficacy analyses showed that 32% of patients given galcanezumab responded to treatment, compared to 18% in the placebo group.. Hypersensitivity reactions, including dyspnea, urticaria, and rash, have been reported in patients using galcanezumab. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Galcanezumab is a humanized monoclonal antibody that targets and binds 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. Also, research has shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For these reasons, binding to CGRP to interfere with its activity was specifically designed as the mechanism of action for galcanezumab, in order to reverse the migraine-inducing activity of natural CGRP. By binding to natural endogenous CGRP, galcanezumab interferes with its activities by making it unable to bind to CGRP receptors. Moreover, studies have shown that humanized monoclonal antibodies against CGRP have successfully reduced the frequency of migraine headaches in early clinical trials as a preventative therapeutic. •Absorption (Drug A): No absorption available •Absorption (Drug B): Galcanezumab follows a linear pharmacokinetic profile, with a Cmax and AUC 0-∞ considered to be dose-proportional between 1 and 600 mg. After a single dose of galcanezumab-gnlm administered subcutaneously, the time to maximum concentration was 5 days. In a group of healthy subjects (n=7) given four biweekly doses of galcanezumab, T max was 3 days, C max was 37,210 ng/mL and the AUC was 1,959,000 ng⋅day/mL. The injection site location does not appear to significantly influence the absorption of this drug. Galcanezumab is expected to have a subcutaneous bioavailability between 50% and 100%, similar to other monoclonal antibodies. Renal and hepatic impairment are not expected to have an effect on the pharmacokinetics of galcanezumab. A population analysis has shown that pharmacokinetic parameters are not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), while body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of galcanezumab is 7.3 L, with 34% inter-individual variability. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Readily accessible data regarding the protein binding of galcanezumab 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): After administration, galcanezumab is expected to be degraded into small peptides and amino acids by proteolysis, in a process similar to the one followed by endogenous immunoglobulins. Galcanezumab is not believed to be metabolized by liver enzymes, making drug-drug interactions relatively unlikely. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Monoclonal antibody agents like galcanezumab are generally eliminated via intracellular catabolism, followed by fluid-phase or receptor-mediated endocytosis. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Between 1 and 600 mg of galcanezumab, the mean serum half-life ranged from 25 to 30 days. On average, the elimination half-life of galcanezumab was approximately 27 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of galcanezumab is 0.008 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding galcanezumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nasopharyngitis, hematuria, and contact dermatitis. Symptomatic and supportive measures are recommended. Additional adverse effects reported in healthy subjects receiving a single high dose of galcanezumab (600 mg) were diarrhea, vomiting and high levels of alanine aminotransferase. Studies evaluating the carcinogenic potential or genetic toxicology of galcanezumab have not yet been conducted. No adverse effects were observed in male rats given galcanezumab (0, 30, or 250 mg/kg) subcutaneously before or during mating. The highest dose given to male rats corresponded to 8 or 4 times the recommended human dose for migraine (120 mg) or episodic cluster headache (300 mg), respectively. Female rats given 0, 30, 100 or 250 mg/kg of galcanezumab did not show adverse effects on fertility either. The highest dose given to female rats corresponded to 38 or 18 times the recommended human dose for migraine (120 mg) or episodic cluster headache (300 mg), respectively. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Emgality •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): Galcanezumab is a calcitonin-gene related peptide antagonist used to prevent migraines and treat cluster headaches. 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 Gemcitabine interact?

•Drug A: Abciximab •Drug B: Gemcitabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Gemcitabine. •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): Gemcitabine is a chemotherapeutic agent used as monotherapy or in combination with other anticancer agents. In combination with carboplatin, it is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. Gemcitabine in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. In combination with cisplatin, gemcitabine is indicated for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC). Dual therapy with cisplatin is also used to treat patients with Stage IV (locally advanced or metastatic) transitional cell carcinoma (TCC) of the bladder. Gemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine is indicated for patients previously treated with fluorouracil. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary. Gemcitabine demonstrated cytotoxic effects against a broad range of cancer cell lines in vitro. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer. Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage. Gemcitabine inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months. In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months. Gemcitabine causes dose-limiting myelosuppression, such as anemia, leukopenia, neutropenia, and thrombocytopenia; however, events leading to discontinuation tend to occur less than 1% of the patients. Gemcitabine can elevate ALT, AST and alkaline phosphatase 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): Gemcitabine is a potent and specific deoxycytidine analog. After uptake into malignant cells, gemcitabine is phosphorylated by deoxycytidine kinase to form gemcitabine monophosphate, which is then converted to the active compounds, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These active metabolites are nucleosides that mediate antitumour effects. dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, thereby competitively inhibiting DNA chain elongation. The non-terminal position of dFdCTP in the DNA chain prevents detection of dFdCTP in the chain and repair by proof-reading 3′5′-exonuclease: this process is referred to as "masked DNA chain termination." Incorporation of dFdCTP into the DNA chain ultimately leads to chain termination, DNA fragmentation, and apoptotic cell death of malignant cells. Gemcitabine has self-potentiating pharmacological actions that can increase the probability of successful incorporation of gemcitabine triphosphate into the DNA chain: dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate dCTP for DNA synthesis. Since dFdCDP reduces the levels of dCTP, there is less competition for gemcitabine triphosphate for incorporation into DNA. Gemcitabine can also reduce metabolism and elimination of active metabolites from the target ce1l, prolonging high intracellular concentrations of the active metabolites. Such self-potentiating effects are not present with cytarabine. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peak plasma concentrations of gemcitabine range from 10 to 40 mg/L following a 30-minute intravenous infusion, and are reached at 15 to 30 minutes. One study showed that steady-state concentrations of gemcitabine showed a linear relationship to dose over the dose range 53 to 1000 mg/m. Gemcitabine triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. In one study, the C max of gemcitabine triphosphate in peripheral blood mononuclear cells occurred within 30 minutes of the end of the infusion period and increased increased proportionally with gemcitabine doses of up to 350 mg/m. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with various solid tumours, the volume of distribution increased with infusion length. The volume of distribution of gemcitabine was 50 L/m following infusions lasting less than 70 minutes. For long infusions, the volume of distribution rose to 370 L/m. Gemcitabine triphosphate, the active metabolite of gemcitabine, accumulates and retains in solid tumour cells in vitro and in vivo. It is not extensively distributed to tissues after short infusions that last less than 70 minutes. It is not known whether gemcitabine crosses the blood-brain barrier, but gemcitabine is widely distributed into tissues, including ascitic fluid. In rats, placental and lacteal transfer occurred rapidly at five to 15 minutes following drug administration. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Gemcitabine plasma protein binding is less than 10%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Following administration and uptake into cancer cells, gemcitabine is initially phosphorylated by deoxycytidine kinase (dCK), and to a lower extent, the extra-mitochondrial thymidine kinase 2 to form gemcitabine monophosphate (dFdCMP). dFdCMP is subsequently phosphorylated by nucleoside kinases to form active metabolites, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). Gemcitabine is also deaminated intracellularly and extracellularly by cytidine deaminase to its inactive metabolite 2′,2′-difluorodeoxyuridine or 2´-deoxy-2´,2´-difluorouridine (dFdU). Deamination occurs in the blood, liver, kidneys, and other tissues, and this metabolic pathway accounts for most of drug clearance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Gemcitabine mainly undergoes renal excretion. Within a week following administration of a single dose of 1000 mg/m infused over 30 minutes, about 92-98% of the dose was recovered in urine where 89% of the recovered dose was excreted as difluorodeoxyuridine (dFdU) and less than 10% as gemcitabine. Monophosphate, diphosphate, or triphosphate metabolites of gemcitabine are not detectable in urine. In a single-dose study, about 1% of the administered dose was recovered 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): Following intravenous infusions lasting less than 70 minutes, the terminal half-life ranged from 0.7 to 1.6 hours. Following infusions ranging from 70 to 285 minutes, the terminal half-life ranged from 4.1 to 10.6 hours. Females tend to have longer half-lives than male patients. Gemcitabine triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. The terminal half-life of gemcitabine triphosphate, the active metabolite, from mononuclear cells ranges from 1.7 to 19.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following intravenous infusions lasting less than 70 minutes, clearance ranged from 41 to 92 L/h/m in males and ranged from 31 to 69 L/h/m in females. Clearance decreases with age. Females have about 30% lower clearance than male patients. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 is 333 mg/kg in mice and >500 mg/kg in rats. The dermal LD 50 in rabbits is >1000 mg/kg. There is no known antidote for gemcitabine overdose. In a dose-escalation study, patients were administered a single dose of gemcitabine as high as 5700 mg/m administered by intravenous infusion over 30 minutes every two weeks: main observed toxicities were myelosuppression, paresthesia, and severe rash. In the event of a suspected drug overdose, blood counts should be monitored, and patients should be provided with supportive therapy, as necessary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gemzar •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Gemcitabin Gemcitabina Gemcitabine Gemcitabinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Gemcitabine is a nucleoside metabolic inhibitor used as adjunct therapy in the treatment of certain types of ovarian cancer, non-small cell lung carcinoma, metastatic breast cancer, and as a single agent for pancreatic 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 Gemcitabine interact? Information: •Drug A: Abciximab •Drug B: Gemcitabine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Gemcitabine. •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): Gemcitabine is a chemotherapeutic agent used as monotherapy or in combination with other anticancer agents. In combination with carboplatin, it is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. Gemcitabine in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. In combination with cisplatin, gemcitabine is indicated for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC). Dual therapy with cisplatin is also used to treat patients with Stage IV (locally advanced or metastatic) transitional cell carcinoma (TCC) of the bladder. Gemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine is indicated for patients previously treated with fluorouracil. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary. Gemcitabine demonstrated cytotoxic effects against a broad range of cancer cell lines in vitro. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer. Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage. Gemcitabine inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months. In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months. Gemcitabine causes dose-limiting myelosuppression, such as anemia, leukopenia, neutropenia, and thrombocytopenia; however, events leading to discontinuation tend to occur less than 1% of the patients. Gemcitabine can elevate ALT, AST and alkaline phosphatase 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): Gemcitabine is a potent and specific deoxycytidine analog. After uptake into malignant cells, gemcitabine is phosphorylated by deoxycytidine kinase to form gemcitabine monophosphate, which is then converted to the active compounds, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These active metabolites are nucleosides that mediate antitumour effects. dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, thereby competitively inhibiting DNA chain elongation. The non-terminal position of dFdCTP in the DNA chain prevents detection of dFdCTP in the chain and repair by proof-reading 3′5′-exonuclease: this process is referred to as "masked DNA chain termination." Incorporation of dFdCTP into the DNA chain ultimately leads to chain termination, DNA fragmentation, and apoptotic cell death of malignant cells. Gemcitabine has self-potentiating pharmacological actions that can increase the probability of successful incorporation of gemcitabine triphosphate into the DNA chain: dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate dCTP for DNA synthesis. Since dFdCDP reduces the levels of dCTP, there is less competition for gemcitabine triphosphate for incorporation into DNA. Gemcitabine can also reduce metabolism and elimination of active metabolites from the target ce1l, prolonging high intracellular concentrations of the active metabolites. Such self-potentiating effects are not present with cytarabine. •Absorption (Drug A): No absorption available •Absorption (Drug B): Peak plasma concentrations of gemcitabine range from 10 to 40 mg/L following a 30-minute intravenous infusion, and are reached at 15 to 30 minutes. One study showed that steady-state concentrations of gemcitabine showed a linear relationship to dose over the dose range 53 to 1000 mg/m. Gemcitabine triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. In one study, the C max of gemcitabine triphosphate in peripheral blood mononuclear cells occurred within 30 minutes of the end of the infusion period and increased increased proportionally with gemcitabine doses of up to 350 mg/m. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In patients with various solid tumours, the volume of distribution increased with infusion length. The volume of distribution of gemcitabine was 50 L/m following infusions lasting less than 70 minutes. For long infusions, the volume of distribution rose to 370 L/m. Gemcitabine triphosphate, the active metabolite of gemcitabine, accumulates and retains in solid tumour cells in vitro and in vivo. It is not extensively distributed to tissues after short infusions that last less than 70 minutes. It is not known whether gemcitabine crosses the blood-brain barrier, but gemcitabine is widely distributed into tissues, including ascitic fluid. In rats, placental and lacteal transfer occurred rapidly at five to 15 minutes following drug administration. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Gemcitabine plasma protein binding is less than 10%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Following administration and uptake into cancer cells, gemcitabine is initially phosphorylated by deoxycytidine kinase (dCK), and to a lower extent, the extra-mitochondrial thymidine kinase 2 to form gemcitabine monophosphate (dFdCMP). dFdCMP is subsequently phosphorylated by nucleoside kinases to form active metabolites, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). Gemcitabine is also deaminated intracellularly and extracellularly by cytidine deaminase to its inactive metabolite 2′,2′-difluorodeoxyuridine or 2´-deoxy-2´,2´-difluorouridine (dFdU). Deamination occurs in the blood, liver, kidneys, and other tissues, and this metabolic pathway accounts for most of drug clearance. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Gemcitabine mainly undergoes renal excretion. Within a week following administration of a single dose of 1000 mg/m infused over 30 minutes, about 92-98% of the dose was recovered in urine where 89% of the recovered dose was excreted as difluorodeoxyuridine (dFdU) and less than 10% as gemcitabine. Monophosphate, diphosphate, or triphosphate metabolites of gemcitabine are not detectable in urine. In a single-dose study, about 1% of the administered dose was recovered 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): Following intravenous infusions lasting less than 70 minutes, the terminal half-life ranged from 0.7 to 1.6 hours. Following infusions ranging from 70 to 285 minutes, the terminal half-life ranged from 4.1 to 10.6 hours. Females tend to have longer half-lives than male patients. Gemcitabine triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. The terminal half-life of gemcitabine triphosphate, the active metabolite, from mononuclear cells ranges from 1.7 to 19.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following intravenous infusions lasting less than 70 minutes, clearance ranged from 41 to 92 L/h/m in males and ranged from 31 to 69 L/h/m in females. Clearance decreases with age. Females have about 30% lower clearance than male patients. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 is 333 mg/kg in mice and >500 mg/kg in rats. The dermal LD 50 in rabbits is >1000 mg/kg. There is no known antidote for gemcitabine overdose. In a dose-escalation study, patients were administered a single dose of gemcitabine as high as 5700 mg/m administered by intravenous infusion over 30 minutes every two weeks: main observed toxicities were myelosuppression, paresthesia, and severe rash. In the event of a suspected drug overdose, blood counts should be monitored, and patients should be provided with supportive therapy, as necessary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gemzar •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Gemcitabin Gemcitabina Gemcitabine Gemcitabinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Gemcitabine is a nucleoside metabolic inhibitor used as adjunct therapy in the treatment of certain types of ovarian cancer, non-small cell lung carcinoma, metastatic breast cancer, and as a single agent for pancreatic 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 Gemtuzumab ozogamicin interact?

•Drug A: Abciximab •Drug B: Gemtuzumab ozogamicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Gemtuzumab ozogamicin. •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): Indicated for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic 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): Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in site-specific DNA double strand breaks via formation of a p-benzene diradical. Eventually, cell death is induced. •Absorption (Drug A): No absorption available •Absorption (Drug B): In pediatric patients receiving a dose level of 9mg/m^2, the peak plasma concentration (Cmax) was approximately 3.47±1.04 mg/L with the AUC of 136 ±107 mg * h/L. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady state (Vss) was approximately 6.5 ± 5.5 L in pediatric patients receiving a dose level of 9mg/m^2. •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): Metabolic studies indicate hydrolytic release of the calicheamicin derivative from gemtuzumab ozogamicin. The drug is most likely removed by opsonization via the reticuloendothelial system. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In pediatric patients receiving a dose level of 9mg/m^2, the half life was approximately 64±44 h after the first dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance rate was approximately 0.12±0.15 L/h/m^2 in pediatric patients receiving a dose level of 9mg/m^2. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Mylotarg •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): Gemtuzumab ozogamicin is a monoclonal anti-CD33 antibody used to treat CD33-positive acute myeloid 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 Gemtuzumab ozogamicin interact? Information: •Drug A: Abciximab •Drug B: Gemtuzumab ozogamicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Gemtuzumab ozogamicin. •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): Indicated for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic 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): Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in site-specific DNA double strand breaks via formation of a p-benzene diradical. Eventually, cell death is induced. •Absorption (Drug A): No absorption available •Absorption (Drug B): In pediatric patients receiving a dose level of 9mg/m^2, the peak plasma concentration (Cmax) was approximately 3.47±1.04 mg/L with the AUC of 136 ±107 mg * h/L. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady state (Vss) was approximately 6.5 ± 5.5 L in pediatric patients receiving a dose level of 9mg/m^2. •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): Metabolic studies indicate hydrolytic release of the calicheamicin derivative from gemtuzumab ozogamicin. The drug is most likely removed by opsonization via the reticuloendothelial system. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In pediatric patients receiving a dose level of 9mg/m^2, the half life was approximately 64±44 h after the first dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance rate was approximately 0.12±0.15 L/h/m^2 in pediatric patients receiving a dose level of 9mg/m^2. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Mylotarg •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): Gemtuzumab ozogamicin is a monoclonal anti-CD33 antibody used to treat CD33-positive acute myeloid 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 Ginkgo biloba interact?

•Drug A: Abciximab •Drug B: Ginkgo biloba •Severity: MINOR •Description: Ginkgo biloba may increase the anticoagulant activities of Abciximab. •Extended Description: Cases of bleeding, including serious bleeding events, have occurred with ginkgo biloba.4 Key constituents of ginkgo biloba, such as flavones and terpene lactones, were shown to possess anticoagulant and antiplatelet activities. For example, ginkgolide B displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. A strong causal relationship between ginkgo biloba use and anticoagulant effects has not been established, and some evidence suggests that the short-term use of ginkgo might not significantly lead to anticoagulant effects. Additionally, drug interaction studies looking at the relationship between ginkgo biloba and anticoagulant agents were not conducted; however, concurrent administration of anticoagulants with ginkgo may present an additional 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. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in 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

Cases of bleeding, including serious bleeding events, have occurred with ginkgo biloba.4 Key constituents of ginkgo biloba, such as flavones and terpene lactones, were shown to possess anticoagulant and antiplatelet activities. For example, ginkgolide B displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. A strong causal relationship between ginkgo biloba use and anticoagulant effects has not been established, and some evidence suggests that the short-term use of ginkgo might not significantly lead to anticoagulant effects. Additionally, drug interaction studies looking at the relationship between ginkgo biloba and anticoagulant agents were not conducted; however, concurrent administration of anticoagulants with ginkgo may present an additional risk of bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Ginkgo biloba interact? Information: •Drug A: Abciximab •Drug B: Ginkgo biloba •Severity: MINOR •Description: Ginkgo biloba may increase the anticoagulant activities of Abciximab. •Extended Description: Cases of bleeding, including serious bleeding events, have occurred with ginkgo biloba.4 Key constituents of ginkgo biloba, such as flavones and terpene lactones, were shown to possess anticoagulant and antiplatelet activities. For example, ginkgolide B displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. A strong causal relationship between ginkgo biloba use and anticoagulant effects has not been established, and some evidence suggests that the short-term use of ginkgo might not significantly lead to anticoagulant effects. Additionally, drug interaction studies looking at the relationship between ginkgo biloba and anticoagulant agents were not conducted; however, concurrent administration of anticoagulants with ginkgo may present an additional 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. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in 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: Cases of bleeding, including serious bleeding events, have occurred with ginkgo biloba.4 Key constituents of ginkgo biloba, such as flavones and terpene lactones, were shown to possess anticoagulant and antiplatelet activities. For example, ginkgolide B displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. A strong causal relationship between ginkgo biloba use and anticoagulant effects has not been established, and some evidence suggests that the short-term use of ginkgo might not significantly lead to anticoagulant effects. Additionally, drug interaction studies looking at the relationship between ginkgo biloba and anticoagulant agents were not conducted; however, concurrent administration of anticoagulants with ginkgo may present an additional risk of bleeding. The severity of the interaction is minor.

Does Abciximab and Glofitamab interact?

•Drug A: Abciximab •Drug B: Glofitamab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Glofitamab. •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): Glofitamab is indicated in Canada for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma (PMBCL), who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy. This indication has been authorized pending the results of trials designed to verify glofitamab's clinical benefit. The FDA approved glofitamab under accelerated approval for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. Glofitamab was also approved by the EMA to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In clinical trials, 10/152 patients exposed to glofitamab experienced a prolonged QTc interval (post-baseline QTc >450 ms), although only one of these cases was determined to be clinically significant and no patients were required to discontinue treatment due to QTc prolongation. Glofitamab can cause cytokine release syndrome (CRS) which may be serious or life-threatening in some patients. To limit the risk of CRS, prescribing information states that all patients must receive pre-treatment with obinutuzumab seven days prior to beginning treatment with glofitamab. In addition, patients should be well-hydrated and should receive a premedication regimen comprising a glucocorticoid, analgesic/antipyretic, and/or antihistamine, dependent on the patient and the cycle. The dose of glofitamab should be titrated gradually and according to prescribing information to further limit the risk of CRS, and patients should be monitored for 10 hours following the first infusion and as required thereafter. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Glofitamab is a bispecific monoclonal antibody targeted towards CD20 surface antigens - found on B-cells - and CD3 protein complexes found on the surface of T-cells. It binds bivalently to CD20 and monovalently to CD3, thereby creating an immunological synapse that serves to recruit T-cells to CD20-expressing B-cells. This simultaneous binding allows for potent T-cell activation and proliferation which ultimately results in the lysis of the target B-cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): According to population pharmacokinetic analysis, the geometric mean C max of glofitamab on day 1 after the first infusion of 2.5 mg was 0.674 µg/mL. At the end of cycle 2 - following the step-up dosing to a final dose of 30 mg - the geometric mean C max was estimated via population pharmacokinetic modeling to be 7.67 µg/mL. Non-compartmental analysis following a single dose of 10 mg showed a geometric mean C max of 2.34 µg/mL, T max of 8.05, and AUC inf of 244 hr*µg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous administration, population pharmacokinetic modeling estimated the central and peripheral volumes of distribution to be 3.33 L and 2.18 L, respectively, with an intercompartmental clearance of 0.674 L/day. •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 glofitamab has not been directly studied. As with other therapeutic antibodies, it is likely metabolized primarily via catabolism to 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 transition from non-linear to linear clearance phase was estimated to take approximately 1.56 days, after which the effective linear half-life of glofitamab is approximately 6.54 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Glofitamab's serum concentration-time data are best described by a two-compartment model and both time-independent and time-varying clearance parameters. Population pharmacokinetic modeling estimated a time-independent clearance parameter of 0.602 L/day, and an initial time-varying clearance parameter of 0.396 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There was no experience with overdosage of glofitamab in clinical trials. •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): Glofitamab •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Glofitamab is a bispecific monoclonal antibody directed against CD20 and CD3 which is used for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . The severity of the interaction is minor.

Question: Does Abciximab and Glofitamab interact? Information: •Drug A: Abciximab •Drug B: Glofitamab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Glofitamab. •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): Glofitamab is indicated in Canada for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma (PMBCL), who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy. This indication has been authorized pending the results of trials designed to verify glofitamab's clinical benefit. The FDA approved glofitamab under accelerated approval for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. Glofitamab was also approved by the EMA to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In clinical trials, 10/152 patients exposed to glofitamab experienced a prolonged QTc interval (post-baseline QTc >450 ms), although only one of these cases was determined to be clinically significant and no patients were required to discontinue treatment due to QTc prolongation. Glofitamab can cause cytokine release syndrome (CRS) which may be serious or life-threatening in some patients. To limit the risk of CRS, prescribing information states that all patients must receive pre-treatment with obinutuzumab seven days prior to beginning treatment with glofitamab. In addition, patients should be well-hydrated and should receive a premedication regimen comprising a glucocorticoid, analgesic/antipyretic, and/or antihistamine, dependent on the patient and the cycle. The dose of glofitamab should be titrated gradually and according to prescribing information to further limit the risk of CRS, and patients should be monitored for 10 hours following the first infusion and as required thereafter. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Glofitamab is a bispecific monoclonal antibody targeted towards CD20 surface antigens - found on B-cells - and CD3 protein complexes found on the surface of T-cells. It binds bivalently to CD20 and monovalently to CD3, thereby creating an immunological synapse that serves to recruit T-cells to CD20-expressing B-cells. This simultaneous binding allows for potent T-cell activation and proliferation which ultimately results in the lysis of the target B-cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): According to population pharmacokinetic analysis, the geometric mean C max of glofitamab on day 1 after the first infusion of 2.5 mg was 0.674 µg/mL. At the end of cycle 2 - following the step-up dosing to a final dose of 30 mg - the geometric mean C max was estimated via population pharmacokinetic modeling to be 7.67 µg/mL. Non-compartmental analysis following a single dose of 10 mg showed a geometric mean C max of 2.34 µg/mL, T max of 8.05, and AUC inf of 244 hr*µg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous administration, population pharmacokinetic modeling estimated the central and peripheral volumes of distribution to be 3.33 L and 2.18 L, respectively, with an intercompartmental clearance of 0.674 L/day. •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 glofitamab has not been directly studied. As with other therapeutic antibodies, it is likely metabolized primarily via catabolism to 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 transition from non-linear to linear clearance phase was estimated to take approximately 1.56 days, after which the effective linear half-life of glofitamab is approximately 6.54 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Glofitamab's serum concentration-time data are best described by a two-compartment model and both time-independent and time-varying clearance parameters. Population pharmacokinetic modeling estimated a time-independent clearance parameter of 0.602 L/day, and an initial time-varying clearance parameter of 0.396 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There was no experience with overdosage of glofitamab in clinical trials. •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): Glofitamab •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Glofitamab is a bispecific monoclonal antibody directed against CD20 and CD3 which is used for the treatment of relapsed or refractory diffuse large B-cell lymphoma. Output: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . The severity of the interaction is minor.

Does Abciximab and Glucosamine interact?

•Drug A: Abciximab •Drug B: Glucosamine •Severity: MODERATE •Description: Glucosamine may increase the antiplatelet activities of Abciximab. •Extended Description: Several studies suggest that glucosamine may increase antiplatelet effects.3,1,2 When combined with antiplatelet drugs, the additive antiplatelet effects of glucosamine and drugs that inhibit platelet activity or function may increase the risk of bleeding •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Glucosamine is generally used over the counter in the symptomatic treatment of osteoarthritis and joint pain, frequently combined with chondroitin sulfate and/or 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): The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time. •Absorption (Drug A): No absorption available •Absorption (Drug B): In a pharmacokinetic study, glucosamine was 88.7% absorption by the gastrointestinal tract. Absolute oral bioavailability was 44%, likely due to the hepatic first-pass effect. In a pharmacokinetic study of 12 healthy adults receiving oral crystalline glucosamine, plasma levels increased up to 30 times the baseline levels and Cmax was 10 microM with a 1,500 mg once-daily dose. Tmax was about 3 hours. AUC was 20,216 ± 5021 after a 15,000 mg dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Results of a pharmacokinetic study of 12 healthy volunteers receiving three daily consecutive oral administrations of glucosamine sulfate soluble powder demonstrated glucosamine distribution to extravascular compartments. Human pharmacokinetic data for glucosamine is limited in the literature, however, a large animal model study of horses revealed a mean apparent volume of distribution of 15.4 L/kg. Concentrations of glucosamine ranged from 9-15 microM after an intravenous dose, and 0.3-0.7 microM after nasogastric dosing. These concentrations remained in the range of 0.1-0.7 microM in the majority of horses 12 hours after dosing, suggesting effectiveness of a once-daily dose. In rats and dogs, radioactivity from a C-14 labeled dose of glucosamine is detected in the liver, kidneys, articular cartilage, and other areas. •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): Glucosamine undergoes metabolism in the liver. Metabolism information for glucosamine is limited in the literature. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Fecal excretion of glucosamine in a pharmacokinetic study was 11.3% within 120 hours after administration. Urinary elimination was found to be 1.19% within the first 8 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): The estimated half-life for glucosamine is 15 hours after an oral dose. After a bolus intravenous injection of 1005 mg crystalline glucosamine sulfate, the parent drug has an apparent half life of 1.11 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 of glucosamine in rats is >5000 mg/kg. Symptoms of an overdose with glucosamine may include nausea, vomiting, abdominal pain, and diarrhea (common side effects of this drug). Severe and life-threatening hypersensitivity reactions to glucosamine may occur in patients with a shellfish allergy or asthma. •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): Chitosamine D-Glucosamine Glucosamina Glucosamine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Glucosamine is a common ingredient in nutritional supplements used for the relief of joint pain.

Several studies suggest that glucosamine may increase antiplatelet effects.3,1,2 When combined with antiplatelet drugs, the additive antiplatelet effects of glucosamine and drugs that inhibit platelet activity or function may increase the risk of bleeding The severity of the interaction is moderate.

Question: Does Abciximab and Glucosamine interact? Information: •Drug A: Abciximab •Drug B: Glucosamine •Severity: MODERATE •Description: Glucosamine may increase the antiplatelet activities of Abciximab. •Extended Description: Several studies suggest that glucosamine may increase antiplatelet effects.3,1,2 When combined with antiplatelet drugs, the additive antiplatelet effects of glucosamine and drugs that inhibit platelet activity or function may increase the risk of bleeding •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Glucosamine is generally used over the counter in the symptomatic treatment of osteoarthritis and joint pain, frequently combined with chondroitin sulfate and/or 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): The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time. •Absorption (Drug A): No absorption available •Absorption (Drug B): In a pharmacokinetic study, glucosamine was 88.7% absorption by the gastrointestinal tract. Absolute oral bioavailability was 44%, likely due to the hepatic first-pass effect. In a pharmacokinetic study of 12 healthy adults receiving oral crystalline glucosamine, plasma levels increased up to 30 times the baseline levels and Cmax was 10 microM with a 1,500 mg once-daily dose. Tmax was about 3 hours. AUC was 20,216 ± 5021 after a 15,000 mg dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Results of a pharmacokinetic study of 12 healthy volunteers receiving three daily consecutive oral administrations of glucosamine sulfate soluble powder demonstrated glucosamine distribution to extravascular compartments. Human pharmacokinetic data for glucosamine is limited in the literature, however, a large animal model study of horses revealed a mean apparent volume of distribution of 15.4 L/kg. Concentrations of glucosamine ranged from 9-15 microM after an intravenous dose, and 0.3-0.7 microM after nasogastric dosing. These concentrations remained in the range of 0.1-0.7 microM in the majority of horses 12 hours after dosing, suggesting effectiveness of a once-daily dose. In rats and dogs, radioactivity from a C-14 labeled dose of glucosamine is detected in the liver, kidneys, articular cartilage, and other areas. •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): Glucosamine undergoes metabolism in the liver. Metabolism information for glucosamine is limited in the literature. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Fecal excretion of glucosamine in a pharmacokinetic study was 11.3% within 120 hours after administration. Urinary elimination was found to be 1.19% within the first 8 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): The estimated half-life for glucosamine is 15 hours after an oral dose. After a bolus intravenous injection of 1005 mg crystalline glucosamine sulfate, the parent drug has an apparent half life of 1.11 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 of glucosamine in rats is >5000 mg/kg. Symptoms of an overdose with glucosamine may include nausea, vomiting, abdominal pain, and diarrhea (common side effects of this drug). Severe and life-threatening hypersensitivity reactions to glucosamine may occur in patients with a shellfish allergy or asthma. •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): Chitosamine D-Glucosamine Glucosamina Glucosamine •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Glucosamine is a common ingredient in nutritional supplements used for the relief of joint pain. Output: Several studies suggest that glucosamine may increase antiplatelet effects.3,1,2 When combined with antiplatelet drugs, the additive antiplatelet effects of glucosamine and drugs that inhibit platelet activity or function may increase the risk of bleeding The severity of the interaction is moderate.

Does Abciximab and Golimumab interact?

•Drug A: Abciximab •Drug B: Golimumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Golimumab. •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): Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) in patients 2 years old and above with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS) or in combination with methotrexate, and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. It is also indicated (v) for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) 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): Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFα is associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. •Absorption (Drug A): No absorption available •Absorption (Drug B): After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 μg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding was not quantified. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolism of golimumab has yet to be determined. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The route of elimination for golimumab has yet to be determined. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Golimumab has a long half-life of about 2 weeks. •Clearance (Drug A): No clearance available •Clearance (Drug B): After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Simponi •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): Golimumab is a TNFα inhibitor used in the symptomatic treatment of various active inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.

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 Golimumab interact? Information: •Drug A: Abciximab •Drug B: Golimumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Golimumab. •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): Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) in patients 2 years old and above with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS) or in combination with methotrexate, and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. It is also indicated (v) for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) 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): Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFα is associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. •Absorption (Drug A): No absorption available •Absorption (Drug B): After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 μg/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding was not quantified. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolism of golimumab has yet to be determined. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The route of elimination for golimumab has yet to be determined. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Golimumab has a long half-life of about 2 weeks. •Clearance (Drug A): No clearance available •Clearance (Drug B): After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Simponi •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): Golimumab is a TNFα inhibitor used in the symptomatic treatment of various active inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. 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 Guselkumab interact?

•Drug A: Abciximab •Drug B: Guselkumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Guselkumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Guselkumab is shown to reduce serum levels of IL-17A, IL-17F and IL-22. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Guselkumab targets the p19 alpha subunit of IL-23. While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmune inflammatory skin diseases. Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatory cytokines and chemokines via stimulation of immune cells such as Th17 cells. Thus, guselkumab blocks the abnormally-heightened signalling of inflammatory cascades that promote epidermal abnormalities including keratinocyte hyperproliferation and psoriatic plaque formation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a 100mg subcutaneous administration, the peak plasma concentration (Cmax) of guselkumab is 8.09 ± 3.68 mcg/mL which is reached after approximately 5.5 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution is 13.5 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Like other human IgG monoclonal antibodies, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Like other human IgG monoclonal antibodies, guselkumab is expected to be both renally and fecally excreted as smaller peptide units. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 half-life of guselkumab is approximately 15 to 18 days in subjects with plaque psoriasis. •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance in subjects with plaque psoriasis is 0.516 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Animal studies to assess the effect of guselkumab on carcinogenesis, mutagenesis and impairment on fertility have not been conducted. When subcutaneously injected into guinea pigs, the doses of guselkumab up to 100mg/kg twice-weekly demonstrated no effects on fertility parameters. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tremfya •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): Guselkumab is a monoclonal antibody used to treat moderate to severe 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 Guselkumab interact? Information: •Drug A: Abciximab •Drug B: Guselkumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Guselkumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Guselkumab is shown to reduce serum levels of IL-17A, IL-17F and IL-22. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Guselkumab targets the p19 alpha subunit of IL-23. While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmune inflammatory skin diseases. Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatory cytokines and chemokines via stimulation of immune cells such as Th17 cells. Thus, guselkumab blocks the abnormally-heightened signalling of inflammatory cascades that promote epidermal abnormalities including keratinocyte hyperproliferation and psoriatic plaque formation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a 100mg subcutaneous administration, the peak plasma concentration (Cmax) of guselkumab is 8.09 ± 3.68 mcg/mL which is reached after approximately 5.5 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution is 13.5 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Like other human IgG monoclonal antibodies, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Like other human IgG monoclonal antibodies, guselkumab is expected to be both renally and fecally excreted as smaller peptide units. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 half-life of guselkumab is approximately 15 to 18 days in subjects with plaque psoriasis. •Clearance (Drug A): No clearance available •Clearance (Drug B): Apparent clearance in subjects with plaque psoriasis is 0.516 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Animal studies to assess the effect of guselkumab on carcinogenesis, mutagenesis and impairment on fertility have not been conducted. When subcutaneously injected into guinea pigs, the doses of guselkumab up to 100mg/kg twice-weekly demonstrated no effects on fertility parameters. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tremfya •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): Guselkumab is a monoclonal antibody used to treat moderate to severe 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 Hemin interact?

•Drug A: Abciximab •Drug B: Hemin •Severity: MAJOR •Description: Hemin may increase the anticoagulant activities of Abciximab. •Extended Description: Various studies have found that hemin is capable of demonstrating an anticoagulant effect [31427, 31428, 31429] as well as evidence of bleeding [31428, 31329] in patients administered the medication. Since an anticoagulant effect is also principal to the action of anticoagulant medications, concomitant use with hemin is not recommended because of the risk of enhancing the anticoagulant effect that is shared between hemin and other anticoagulant medications and therefore increasing the chances for dangerous bleeding events. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used in the management of porphyria attacks, particularly in acute intermittent porphyria. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Panhematin •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): Hemin is an iron-containing porphyrin injection used for the relief of recurrent attacks of acute intermittent porphyria (AIP) associated with the menstrual cycle when carbohydrate therapy is not effective.

Various studies have found that hemin is capable of demonstrating an anticoagulant effect [31427, 31428, 31429] as well as evidence of bleeding [31428, 31329] in patients administered the medication. Since an anticoagulant effect is also principal to the action of anticoagulant medications, concomitant use with hemin is not recommended because of the risk of enhancing the anticoagulant effect that is shared between hemin and other anticoagulant medications and therefore increasing the chances for dangerous bleeding events. The severity of the interaction is major.

Question: Does Abciximab and Hemin interact? Information: •Drug A: Abciximab •Drug B: Hemin •Severity: MAJOR •Description: Hemin may increase the anticoagulant activities of Abciximab. •Extended Description: Various studies have found that hemin is capable of demonstrating an anticoagulant effect [31427, 31428, 31429] as well as evidence of bleeding [31428, 31329] in patients administered the medication. Since an anticoagulant effect is also principal to the action of anticoagulant medications, concomitant use with hemin is not recommended because of the risk of enhancing the anticoagulant effect that is shared between hemin and other anticoagulant medications and therefore increasing the chances for dangerous bleeding events. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Used in the management of porphyria attacks, particularly in acute intermittent porphyria. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Panhematin •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): Hemin is an iron-containing porphyrin injection used for the relief of recurrent attacks of acute intermittent porphyria (AIP) associated with the menstrual cycle when carbohydrate therapy is not effective. Output: Various studies have found that hemin is capable of demonstrating an anticoagulant effect [31427, 31428, 31429] as well as evidence of bleeding [31428, 31329] in patients administered the medication. Since an anticoagulant effect is also principal to the action of anticoagulant medications, concomitant use with hemin is not recommended because of the risk of enhancing the anticoagulant effect that is shared between hemin and other anticoagulant medications and therefore increasing the chances for dangerous bleeding events. The severity of the interaction is major.

Does Abciximab and Heparin interact?

•Drug A: Abciximab •Drug B: Heparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Heparin. •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): Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and as an adjunct antithrombin therapy in patients with unstable angina and/or non-Q wave myocardial infarctions (i.e. non-ST elevated acute coronary artery syndrome) who are on platelet glycoprotein (IIb/IIIa) receptor inhibitors. Additionally, it is used to prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Unfractionated heparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3000 to 30,000 daltons. Heparin is obtained from liver, lung, mast cells, and other cells of vertebrates. Heparin is a well-known and commonly used anticoagulant which has antithrombotic properties. Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Small amounts of heparin in combination with antithrombin III, a heparin cofactor,) can inhibit thrombosis by inactivating Factor Xa and thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Heparin prolongs several coagulation tests. Of all the coagulation tests, activated partial prothrombin time (aPTT) is the most clinically important value. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate factors IX, XI, XII and plasmin. The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not a thrombolytic or fibrinolytic. It prevents progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics. •Absorption (Drug A): No absorption available •Absorption (Drug B): Heparin is not absorbed through the gastrointestinal tract and is therefore administered via a parenteral route. Peak plasma concentration and the onset of action are achieved immediately after intravenous administration. Plasma heparin concentrations may be increased and activated partial thromboplastin times (aPTTs) may be more prolonged in geriatric adults (older than 60 years of age) compared with younger adults. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution is 0.07 L/kg. Although heparin does not distribute into adipose tissues, clinicians should use actual body weight in obese patients to account for extra vasculature. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases, and lipoproteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Heparin does not undergo enzymatic degradation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Heparin undergoes biphasic clearance, a) rapid saturable clearance (zero-order process due to binding to proteins, endothelial cells, and macrophages), and b) slower first-order elimination. Low doses of heparin are cleared mostly by a saturable, rapid, zero-order process. Slower first-order elimination usually occurs with very high doses of heparin and is dependent on renal function. High-molecular-weight moieties are cleared more rapidly than lower molecular-weight moieties. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 is dose-dependent, and it ranges from 0.5 to 2 h. For the purpose of choosing a protamine dose, heparin can be assumed to have a half-life of about 30 minutes after intravenous injection. The plasma half-life of heparin increases from about 30 min after an IV bolus of 25 units/kg to 60 minutes with a 100 unit/kg dose or to about 150 minutes with a 400 unit/kg dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance in adults receiving a bolus dose of 75 units/kg and preterm newborns receiving a bolus dose of 100 units/kg were calculated to be 0.43 ml/kg/min and 1.49 ml/kg/min respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In mouse, the median lethal dose is greater than 5000 mg/kg. Another side effect is heparin-induced thrombocytopenia (HIT syndrome). Platelet counts usually do not fall until between days 5 and 12 of heparin therapy. HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors. It can progress to thrombotic complications such as arterial thrombosis, gangrene, stroke, myocardial infarction and disseminated intravascular coagulation. Symptoms of overdose may show excessive prolongation of aPTT or by bleeding, which may be internal or external, major or minor. Therapeutic doses of heparin give for at least 4 months have been associated with osteoporosis and spontaneous vertebral fractures. Osteoporosis may be reversible once heparin is discontinued. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., about 100–400 mg/kg daily) of benzyl alcohol in these neonates. Its use is principally associated with the use of bacteriostatic 0.9% sodium chloride intravascular flush or endotracheal tube lavage solutions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Defencath, Heparin Leo •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): Heparin is an anticoagulant indicated for thromboprophylaxis and to treat thrombosis associated with a variety of conditions such as pulmonary embolism and atrial fibrillation.

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 Heparin interact? Information: •Drug A: Abciximab •Drug B: Heparin •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Heparin. •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): Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and as an adjunct antithrombin therapy in patients with unstable angina and/or non-Q wave myocardial infarctions (i.e. non-ST elevated acute coronary artery syndrome) who are on platelet glycoprotein (IIb/IIIa) receptor inhibitors. Additionally, it is used to prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Unfractionated heparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3000 to 30,000 daltons. Heparin is obtained from liver, lung, mast cells, and other cells of vertebrates. Heparin is a well-known and commonly used anticoagulant which has antithrombotic properties. Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Small amounts of heparin in combination with antithrombin III, a heparin cofactor,) can inhibit thrombosis by inactivating Factor Xa and thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Heparin prolongs several coagulation tests. Of all the coagulation tests, activated partial prothrombin time (aPTT) is the most clinically important value. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate factors IX, XI, XII and plasmin. The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not a thrombolytic or fibrinolytic. It prevents progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics. •Absorption (Drug A): No absorption available •Absorption (Drug B): Heparin is not absorbed through the gastrointestinal tract and is therefore administered via a parenteral route. Peak plasma concentration and the onset of action are achieved immediately after intravenous administration. Plasma heparin concentrations may be increased and activated partial thromboplastin times (aPTTs) may be more prolonged in geriatric adults (older than 60 years of age) compared with younger adults. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution is 0.07 L/kg. Although heparin does not distribute into adipose tissues, clinicians should use actual body weight in obese patients to account for extra vasculature. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases, and lipoproteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Heparin does not undergo enzymatic degradation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Heparin undergoes biphasic clearance, a) rapid saturable clearance (zero-order process due to binding to proteins, endothelial cells, and macrophages), and b) slower first-order elimination. Low doses of heparin are cleared mostly by a saturable, rapid, zero-order process. Slower first-order elimination usually occurs with very high doses of heparin and is dependent on renal function. High-molecular-weight moieties are cleared more rapidly than lower molecular-weight moieties. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 is dose-dependent, and it ranges from 0.5 to 2 h. For the purpose of choosing a protamine dose, heparin can be assumed to have a half-life of about 30 minutes after intravenous injection. The plasma half-life of heparin increases from about 30 min after an IV bolus of 25 units/kg to 60 minutes with a 100 unit/kg dose or to about 150 minutes with a 400 unit/kg dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance in adults receiving a bolus dose of 75 units/kg and preterm newborns receiving a bolus dose of 100 units/kg were calculated to be 0.43 ml/kg/min and 1.49 ml/kg/min respectively. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In mouse, the median lethal dose is greater than 5000 mg/kg. Another side effect is heparin-induced thrombocytopenia (HIT syndrome). Platelet counts usually do not fall until between days 5 and 12 of heparin therapy. HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors. It can progress to thrombotic complications such as arterial thrombosis, gangrene, stroke, myocardial infarction and disseminated intravascular coagulation. Symptoms of overdose may show excessive prolongation of aPTT or by bleeding, which may be internal or external, major or minor. Therapeutic doses of heparin give for at least 4 months have been associated with osteoporosis and spontaneous vertebral fractures. Osteoporosis may be reversible once heparin is discontinued. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., about 100–400 mg/kg daily) of benzyl alcohol in these neonates. Its use is principally associated with the use of bacteriostatic 0.9% sodium chloride intravascular flush or endotracheal tube lavage solutions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Defencath, Heparin Leo •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): Heparin is an anticoagulant indicated for thromboprophylaxis and to treat thrombosis associated with a variety of conditions such as pulmonary embolism and atrial fibrillation. 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 Hepatitis B immune globulin interact?

•Drug A: Abciximab •Drug B: Hepatitis B immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Hepatitis B immune globulin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Investigated for use/treatment in hepatitis (viral, B), liver transplant surgery, and pediatric indications. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection, but has also led to marked reduction in liver cancer. •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): Hepagam B, Hyperhep B, Nabi-HB •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): Hepatitis B immune globulin is an injection of immunoglobulin G (IgG) antibodies to prevent the development of chronic Hepatitis B infection.

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 Hepatitis B immune globulin interact? Information: •Drug A: Abciximab •Drug B: Hepatitis B immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Hepatitis B immune globulin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Investigated for use/treatment in hepatitis (viral, B), liver transplant surgery, and pediatric indications. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection, but has also led to marked reduction in liver cancer. •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): Hepagam B, Hyperhep B, Nabi-HB •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): Hepatitis B immune globulin is an injection of immunoglobulin G (IgG) antibodies to prevent the development of chronic Hepatitis B infection. 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 Human cytomegalovirus immune globulin interact?

•Drug A: Abciximab •Drug B: Human cytomegalovirus immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Human cytomegalovirus immune globulin. •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): It is used to prevent cytomegalovirus (CMV) disease after organ transplant. Cytomegalovirus Immune Globulin Intravenous (Human) is indicated for the prophylaxis of cytomegalovirus disease associated with transplantation of kidney, lung, liver, pancreas, and heart. In transplants of these organs other than the kidney from CMV seropositive donors into seronegative recipients, prophylactic CMV-IGIV should be considered in combination with ganciclovir. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): CytoGam (cytomegalovirus immune globulin) contains IgG antibodies representing those of the large number of normal individuals who have contributed to the plasma pools from which the product was derived. The globulin contains a relatively high concentration of antibodies which are directed against cytomegalovirus (CMV). In the case of persons who may possibly be exposed to CMV, CytoGam can increase the relevant antibodies to levels sufficient to prevent or reduce the incidence of serious CMV disease. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): CMV—IGIV mainly consists of immunoglobulin G (IgG), specifically subclasses IgG1 and IgG3. IgG1 and IgG3 play important roles in viral neutralization in addition to tissue protection and complement activation. Immunoglobulins, such as CMV-IGIV, inhibit extracellular viruses from infecting their specific target cells. Viral neutralization decreases the capacity of viruses to spread from an extracellular location to an intracellular location. CMV-IGIV inhibits infection of cells with CMV due to the fact that the virus is prevented from accessing key cell membrane targets, or because of interference with uncoating or entry. Cytogam inhibits these process. •Absorption (Drug A): No absorption available •Absorption (Drug B): Protection derived from Cytomegalovirus immune globulin (CMV-IGIV) has a rapid onset, imparting relevant CMV antibody concentrations immediately after infusion. The duration of action of CMV-IGIV is 1—3 months. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): IgG is distributed from the plasma to various other body compartments. •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): Cytomegalovirus immune globulin (CMV-IGIV) is administered by the intravenous (IV) route. CMV—IGIV is primarily comprised of immunoglobulin G (IgG), specifically subclasses IgG1 and IgG3. Immunoglobulin catabolism occurs mainly in the plasma, however, the liver may also play a role. IgG metabolism appears to be a multicompartmental, first-order process. Higher IgG concentrations increase the rate of metabolism and shorten its half-life. IgG metabolism is likely a multicompartmental, first-order process. •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): IgG1 has a half-life of 23—25 days, whereas, the half-life of IgG3 is only 9 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): CMV-IGIV is made from human plasma and, like other plasma products, carries the possibility for transmission of blood-borne viral agents and possibly, the Creutzfeldt-Jakob disease (CJD) prion. The risk of transmission of recognized blood-borne viruses is considered low due to the viral inactivation and removal properties in the Cohn-Oncley cold ethanol. Renal Failure Renal dysfunction, acute renal failure (ARF), acute tubular necrosis (ATN), proximal tubular nephropathy, osmotic nephrosis, and death reported in patients receiving IGIV. Increases in blood urea nitrogen (BUN) and serum creatinine have occurred as soon as 1–2 days following IGIV treatment and this has progressed to oliguria or anuria. TRALI (transfusion-associated lung injury) TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. It typically occurs within 1-6 hours after transfusion of the immunoglobulin. Patients with TRALI should be managed using oxygen therapy combined with ventilatory support. Hemolysis Immune Globulin Intravenous (Human) (IGIV) products may contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, sometimes, hemolysis. Hemolytic anemia may develop after IGIV therapy due to enhanced red blood cell sequestration. * Thrombotic events * Patients at risk include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity. The possible risks and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom IGIV administration is being considered. Baseline assessment of blood viscosity are an important consideration for patients at risk for blood hyperviscosity. Aseptic meningitis syndrome An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with Immune Globulin Intravenous (Human) (IGIV) treatment. The syndrome normally begins within several hours to 2 days after treatment. This syndrome is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cu.mm., predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL. Patients experiencing such symptoms and signs must receive a thorough neurological assessment, including CSF studies, to rule out other possible causes of meningitis. This condition may occur more frequently in association with high doses (2 g/kg or greater) of IGIV treatment. Discontinuation of IGIV treatment has been followed by the remission of aseptic meningitis syndrome within several days without long-term sequelae. Cytomegalovirus immune globulin (CMV-IGIV) is categorized in FDA pregnancy risk category C. No well-controlled studies have been completed in pregnant women and it is unknown whether CMV-IGIV may cause female harm or negatively affect the reproductive system. According to the Advisory Committee on Immunization Practices, administration of immune globulin to pregnant women results in no known risk to the fetus. No data are available from the manufacturer regarding the use of cytomegalovirus immune globulin (CMV-IGIV) while breastfeeding and it is unknown whether CMV-IGIV is excreted in breast milk. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cytogam •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): Human cytomegalovirus immune globulin is a solution of immune globulin G against cytomegalovirus used to prevent transmission of cytomegalovirus after organ transplants.

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 Human cytomegalovirus immune globulin interact? Information: •Drug A: Abciximab •Drug B: Human cytomegalovirus immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Human cytomegalovirus immune globulin. •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): It is used to prevent cytomegalovirus (CMV) disease after organ transplant. Cytomegalovirus Immune Globulin Intravenous (Human) is indicated for the prophylaxis of cytomegalovirus disease associated with transplantation of kidney, lung, liver, pancreas, and heart. In transplants of these organs other than the kidney from CMV seropositive donors into seronegative recipients, prophylactic CMV-IGIV should be considered in combination with ganciclovir. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): CytoGam (cytomegalovirus immune globulin) contains IgG antibodies representing those of the large number of normal individuals who have contributed to the plasma pools from which the product was derived. The globulin contains a relatively high concentration of antibodies which are directed against cytomegalovirus (CMV). In the case of persons who may possibly be exposed to CMV, CytoGam can increase the relevant antibodies to levels sufficient to prevent or reduce the incidence of serious CMV disease. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): CMV—IGIV mainly consists of immunoglobulin G (IgG), specifically subclasses IgG1 and IgG3. IgG1 and IgG3 play important roles in viral neutralization in addition to tissue protection and complement activation. Immunoglobulins, such as CMV-IGIV, inhibit extracellular viruses from infecting their specific target cells. Viral neutralization decreases the capacity of viruses to spread from an extracellular location to an intracellular location. CMV-IGIV inhibits infection of cells with CMV due to the fact that the virus is prevented from accessing key cell membrane targets, or because of interference with uncoating or entry. Cytogam inhibits these process. •Absorption (Drug A): No absorption available •Absorption (Drug B): Protection derived from Cytomegalovirus immune globulin (CMV-IGIV) has a rapid onset, imparting relevant CMV antibody concentrations immediately after infusion. The duration of action of CMV-IGIV is 1—3 months. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): IgG is distributed from the plasma to various other body compartments. •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): Cytomegalovirus immune globulin (CMV-IGIV) is administered by the intravenous (IV) route. CMV—IGIV is primarily comprised of immunoglobulin G (IgG), specifically subclasses IgG1 and IgG3. Immunoglobulin catabolism occurs mainly in the plasma, however, the liver may also play a role. IgG metabolism appears to be a multicompartmental, first-order process. Higher IgG concentrations increase the rate of metabolism and shorten its half-life. IgG metabolism is likely a multicompartmental, first-order process. •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): IgG1 has a half-life of 23—25 days, whereas, the half-life of IgG3 is only 9 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): CMV-IGIV is made from human plasma and, like other plasma products, carries the possibility for transmission of blood-borne viral agents and possibly, the Creutzfeldt-Jakob disease (CJD) prion. The risk of transmission of recognized blood-borne viruses is considered low due to the viral inactivation and removal properties in the Cohn-Oncley cold ethanol. Renal Failure Renal dysfunction, acute renal failure (ARF), acute tubular necrosis (ATN), proximal tubular nephropathy, osmotic nephrosis, and death reported in patients receiving IGIV. Increases in blood urea nitrogen (BUN) and serum creatinine have occurred as soon as 1–2 days following IGIV treatment and this has progressed to oliguria or anuria. TRALI (transfusion-associated lung injury) TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. It typically occurs within 1-6 hours after transfusion of the immunoglobulin. Patients with TRALI should be managed using oxygen therapy combined with ventilatory support. Hemolysis Immune Globulin Intravenous (Human) (IGIV) products may contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, sometimes, hemolysis. Hemolytic anemia may develop after IGIV therapy due to enhanced red blood cell sequestration. * Thrombotic events * Patients at risk include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity. The possible risks and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom IGIV administration is being considered. Baseline assessment of blood viscosity are an important consideration for patients at risk for blood hyperviscosity. Aseptic meningitis syndrome An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with Immune Globulin Intravenous (Human) (IGIV) treatment. The syndrome normally begins within several hours to 2 days after treatment. This syndrome is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cu.mm., predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL. Patients experiencing such symptoms and signs must receive a thorough neurological assessment, including CSF studies, to rule out other possible causes of meningitis. This condition may occur more frequently in association with high doses (2 g/kg or greater) of IGIV treatment. Discontinuation of IGIV treatment has been followed by the remission of aseptic meningitis syndrome within several days without long-term sequelae. Cytomegalovirus immune globulin (CMV-IGIV) is categorized in FDA pregnancy risk category C. No well-controlled studies have been completed in pregnant women and it is unknown whether CMV-IGIV may cause female harm or negatively affect the reproductive system. According to the Advisory Committee on Immunization Practices, administration of immune globulin to pregnant women results in no known risk to the fetus. No data are available from the manufacturer regarding the use of cytomegalovirus immune globulin (CMV-IGIV) while breastfeeding and it is unknown whether CMV-IGIV is excreted in breast milk. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Cytogam •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): Human cytomegalovirus immune globulin is a solution of immune globulin G against cytomegalovirus used to prevent transmission of cytomegalovirus after organ transplants. 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 Human immunoglobulin G interact?

•Drug A: Abciximab •Drug B: Human immunoglobulin G •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Human immunoglobulin G 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): Human immunoglobulin G is indicated for the following conditions: Primary Immunodeficiency for the treatment of primary immunodeficiency in adult and pediatric patients in combination with hyaluronidase (human recombinant) for the treatment of primary immunodeficiency in patients ≥2 years of age. Immune Thrombocytopenic Purpura (ITP) for the treatment of acute or chronic immune thrombocytopenic purpura in adult and pediatric patients Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for the treatment of CIDP in adult patients in combination with hyaluronidase (human recombinant) as a maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) Multifocal Motor Neuropathy (MMN) for maintenance therapy to improve muscle strength and disability in adult patients with MMN Prophylaxis of Bacterial Infection for the prevention of bacterial infections in patients with hypogammaglobulinemia and/or B-cell chronic lymphocytic leukemia Coronary Artery Aneurysm Associated With Kawasaki Syndrome for the prevention of coronary artery aneurysms in pediatric patients with Kawasaki syndrome Dermatomyositis for the treatment of dermatomyositis in adult 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): Used as a replacement therapy in inherited humoral immunodeficiency disorders such as severe combined immunodeficiency syndrome, x-linked agammaglobulinemia, and Wiskott-Aldrich Syndrome. The immunoglobulins target, bind and kill bacterial cells as well as viral particles. IgG is the monomeric immunoglobulin of which there are four subclasses (IgG1, IgG2, IgG3 and IgG4) in differing abundances (66%, 23%, 7% and 4%). IgAs represent about 15% of the immunoglobulins in the blood. These target inhaled or ingested pathogens. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): IVIg interacts with a number of different components of the immune system, including cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also impacts different effector cells of the immune system (B and T lymphocytes, dendritic cells, etc.) and regulates a wide range of genes. Its main mechanism of actions are believed to be Fc-dependent and F(ab')2-dependent. IVIg competitively blocks gamma Fc receptors, preventing the binding and ingestion of phagocytes and suppressing platelet depletion. IVIg contains a number of different antobodies, which prevent infection by attaching to the surface of invading pathogens and aiding in their disposal before they can infect cells. Antibodies remove pathogens via complement activation, agglutination or precipitation, pathogen receptor blocking, macrophage “tagging” or neutralization (via binding) of pathogen toxins. Intact IVIg and F(ab′)2 fragments of IVIg can also neutralize the activity of various autoantibodies. By triggering the production of interleukin-1 receptor antagonist, IVIg modulates of the production of cytokines and cytokine antagonists. It also prevents the generation of the C5b-9 membrane attack complex and subsequent complement-mediated tissue damage by binding active complement components. •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): >20 hours (mammalian reticulocytes, in vitro). •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): Alyglo, Asceniv, Bivigam, Cuvitru, Flebogamma, Gamastan, Gammagard, Gammaked, Gammaplex, Gamunex, Hizentra, Hyqvia 5 G / 50 Ml Kit, Igivnex, Kiovig, Octagam, Panzyga, Privigen, Xembify •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): Human immunoglobulin G is a purified form of human immunoglobulin G and other proteins used to treat immunodeficiency and a wide variety of autoimmune disorders.

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 Human immunoglobulin G interact? Information: •Drug A: Abciximab •Drug B: Human immunoglobulin G •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Human immunoglobulin G 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): Human immunoglobulin G is indicated for the following conditions: Primary Immunodeficiency for the treatment of primary immunodeficiency in adult and pediatric patients in combination with hyaluronidase (human recombinant) for the treatment of primary immunodeficiency in patients ≥2 years of age. Immune Thrombocytopenic Purpura (ITP) for the treatment of acute or chronic immune thrombocytopenic purpura in adult and pediatric patients Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for the treatment of CIDP in adult patients in combination with hyaluronidase (human recombinant) as a maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) Multifocal Motor Neuropathy (MMN) for maintenance therapy to improve muscle strength and disability in adult patients with MMN Prophylaxis of Bacterial Infection for the prevention of bacterial infections in patients with hypogammaglobulinemia and/or B-cell chronic lymphocytic leukemia Coronary Artery Aneurysm Associated With Kawasaki Syndrome for the prevention of coronary artery aneurysms in pediatric patients with Kawasaki syndrome Dermatomyositis for the treatment of dermatomyositis in adult 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): Used as a replacement therapy in inherited humoral immunodeficiency disorders such as severe combined immunodeficiency syndrome, x-linked agammaglobulinemia, and Wiskott-Aldrich Syndrome. The immunoglobulins target, bind and kill bacterial cells as well as viral particles. IgG is the monomeric immunoglobulin of which there are four subclasses (IgG1, IgG2, IgG3 and IgG4) in differing abundances (66%, 23%, 7% and 4%). IgAs represent about 15% of the immunoglobulins in the blood. These target inhaled or ingested pathogens. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): IVIg interacts with a number of different components of the immune system, including cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also impacts different effector cells of the immune system (B and T lymphocytes, dendritic cells, etc.) and regulates a wide range of genes. Its main mechanism of actions are believed to be Fc-dependent and F(ab')2-dependent. IVIg competitively blocks gamma Fc receptors, preventing the binding and ingestion of phagocytes and suppressing platelet depletion. IVIg contains a number of different antobodies, which prevent infection by attaching to the surface of invading pathogens and aiding in their disposal before they can infect cells. Antibodies remove pathogens via complement activation, agglutination or precipitation, pathogen receptor blocking, macrophage “tagging” or neutralization (via binding) of pathogen toxins. Intact IVIg and F(ab′)2 fragments of IVIg can also neutralize the activity of various autoantibodies. By triggering the production of interleukin-1 receptor antagonist, IVIg modulates of the production of cytokines and cytokine antagonists. It also prevents the generation of the C5b-9 membrane attack complex and subsequent complement-mediated tissue damage by binding active complement components. •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): >20 hours (mammalian reticulocytes, in vitro). •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): Alyglo, Asceniv, Bivigam, Cuvitru, Flebogamma, Gamastan, Gammagard, Gammaked, Gammaplex, Gamunex, Hizentra, Hyqvia 5 G / 50 Ml Kit, Igivnex, Kiovig, Octagam, Panzyga, Privigen, Xembify •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): Human immunoglobulin G is a purified form of human immunoglobulin G and other proteins used to treat immunodeficiency and a wide variety of autoimmune disorders. 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 Human Rho(D) immune globulin interact?

•Drug A: Abciximab •Drug B: Human Rho(D) immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Human Rho(D) immune globulin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for suppression of rhesus (Rh) isoimmunization in nonsensitized Rho (D)-negative women with an Rh-incompatible pregnancy, or in Rho (D)-negative individuals transfused with Rh0(D)-positive red blood cells (RBCs) or blood components containing Rh0(D)-positive RBCs. Also indicated in Rh0(D)-positive, non-splenectomized adult patients with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): 15000 international unit (IU) contains sufficient anti-Rho (D) to effectively suppress the immunizing potential of approximately 17mL of Rho (D) (D-positive) red blood cells. Human Rho(D) immune globulin therapy prevents immunization to Rho (D)-positive red blood cells (RBC) by inducing antibody-mediated immunosuppression (AMIS) effectively clearing Rho-positive RBCs by rapidly binding to them. This prevents Rho-negative mothers to produce alloantibodies to paternally inherited RhD antigen expressed on fetal erythrocytes and cause haemolytic diseases of the newborn. Rho immune globulin increase platelet counts and reduce bleeding in Rho-positive patients with ITP by inhibiting autoantibody-mediated platelet clearance. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 Rho(D) immune globulin therapy is unclear. It is suggested that Rho immune globulin predominantly prevents the antibody response during incompatible pregnancy by accelerating the phagocytosis of RBC's and clearance from the circulation before the recognition by the immune system. IgG-opsonized RBCs may interact with activating IgG receptors (FcγRs) on effector cells and elicit phagocytosis via mononuclear phagocytic system, primarily by macrophages. IgG may also stimulate complement activation on the RBC surface, followed by RBC lysis or complement receptor-mediated phagocytosis but to smaller extent. Rho-specific IgG may inhibit the late stages of B cell activation by being internalized with Rho antigen by B cells, which alters the antigen processing and presentation. In response to the IgG-antigen complex formation, the immune globulin enhances the presentation of specific peptides and proliferation of epitope-specific T cells. Therapeutic efficacy of Rho (D) immune globulin in chronic immune thrombocytopenic purpura (ITP) may be explained by FcR blockade as well as the increase in the platelet count by substituting antibody-coated RBCs for antibodycoated platelets. In vitro studies of cytokine expression in human monocytes and granulocytes exposed to anti-D coated red blood cells have demonstrated enhanced secretion of interleukin 1 receptor antagonist resulting in down-regulation of FcγR mediated phagocytosis. Murine models show that RBC-specific antibodies can increase platelet counts by down-regulating FcγRIIIa on splenic macrophage, which is an opposing effect as predicted in intravenous Rho IgG. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients undergoing therapy for Rh isoimmunization suppression, Rho(D) immune globulin titers were detected in all women up to at least 9 weeks following either intravenous or intramuscular administration. Following intravenous administration of a single 1500 IU (300 mcg) dose, peak serum levels of Rh0(D) immune globulin ranged from 62 to 84 ng/mL after first day. The levels ranged from 7 to 46 ng/mL and were achieved between 2 and 7 days following intramuscular injection. The absolute bioavailability achieved following IM administration is 69%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): A single dose of 300ug Rho(D) Immune Globulin through intramuscular injection displays a Vd of 8.59L. •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): Rho (D) immune globulin is expected to undergo nonspecific catabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Human immune globulin and the fragments can be detected in feces and 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 is 16 ± 4 days following IV administration and 18 ± 5 days following IM administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean systemic clearance following IV administration is 0.20 ±0.03 mL/min. Mean apparent clearance following IM administration is 0.29 ± 0.12 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Most serious adverse reactions in patients with ITP include intravascular hemolysis, anemia, acute renal insufficiency, and death. In patients treated for Rh isoimmunization suppression, common adverse effects include nausea, dizziness, headache, pain at injection site and malaise. Common adverse effects in patients with ITP include chills, pyrexia, mild extravascular hemolysis and headache. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hyperrho, Micrhogam, Rhogam, Rhophylac, Winrho •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): Human Rho(D) immune globulin is a solution of antibodies used to prevent isoimmunization of Rho(D) negative patients exposed to Rho(D) positive blood in pregnancy or transfusion.

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 Human Rho(D) immune globulin interact? Information: •Drug A: Abciximab •Drug B: Human Rho(D) immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Human Rho(D) immune globulin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for suppression of rhesus (Rh) isoimmunization in nonsensitized Rho (D)-negative women with an Rh-incompatible pregnancy, or in Rho (D)-negative individuals transfused with Rh0(D)-positive red blood cells (RBCs) or blood components containing Rh0(D)-positive RBCs. Also indicated in Rh0(D)-positive, non-splenectomized adult patients with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): 15000 international unit (IU) contains sufficient anti-Rho (D) to effectively suppress the immunizing potential of approximately 17mL of Rho (D) (D-positive) red blood cells. Human Rho(D) immune globulin therapy prevents immunization to Rho (D)-positive red blood cells (RBC) by inducing antibody-mediated immunosuppression (AMIS) effectively clearing Rho-positive RBCs by rapidly binding to them. This prevents Rho-negative mothers to produce alloantibodies to paternally inherited RhD antigen expressed on fetal erythrocytes and cause haemolytic diseases of the newborn. Rho immune globulin increase platelet counts and reduce bleeding in Rho-positive patients with ITP by inhibiting autoantibody-mediated platelet clearance. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 Rho(D) immune globulin therapy is unclear. It is suggested that Rho immune globulin predominantly prevents the antibody response during incompatible pregnancy by accelerating the phagocytosis of RBC's and clearance from the circulation before the recognition by the immune system. IgG-opsonized RBCs may interact with activating IgG receptors (FcγRs) on effector cells and elicit phagocytosis via mononuclear phagocytic system, primarily by macrophages. IgG may also stimulate complement activation on the RBC surface, followed by RBC lysis or complement receptor-mediated phagocytosis but to smaller extent. Rho-specific IgG may inhibit the late stages of B cell activation by being internalized with Rho antigen by B cells, which alters the antigen processing and presentation. In response to the IgG-antigen complex formation, the immune globulin enhances the presentation of specific peptides and proliferation of epitope-specific T cells. Therapeutic efficacy of Rho (D) immune globulin in chronic immune thrombocytopenic purpura (ITP) may be explained by FcR blockade as well as the increase in the platelet count by substituting antibody-coated RBCs for antibodycoated platelets. In vitro studies of cytokine expression in human monocytes and granulocytes exposed to anti-D coated red blood cells have demonstrated enhanced secretion of interleukin 1 receptor antagonist resulting in down-regulation of FcγR mediated phagocytosis. Murine models show that RBC-specific antibodies can increase platelet counts by down-regulating FcγRIIIa on splenic macrophage, which is an opposing effect as predicted in intravenous Rho IgG. •Absorption (Drug A): No absorption available •Absorption (Drug B): In patients undergoing therapy for Rh isoimmunization suppression, Rho(D) immune globulin titers were detected in all women up to at least 9 weeks following either intravenous or intramuscular administration. Following intravenous administration of a single 1500 IU (300 mcg) dose, peak serum levels of Rh0(D) immune globulin ranged from 62 to 84 ng/mL after first day. The levels ranged from 7 to 46 ng/mL and were achieved between 2 and 7 days following intramuscular injection. The absolute bioavailability achieved following IM administration is 69%. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): A single dose of 300ug Rho(D) Immune Globulin through intramuscular injection displays a Vd of 8.59L. •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): Rho (D) immune globulin is expected to undergo nonspecific catabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Human immune globulin and the fragments can be detected in feces and 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 is 16 ± 4 days following IV administration and 18 ± 5 days following IM administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): Mean systemic clearance following IV administration is 0.20 ±0.03 mL/min. Mean apparent clearance following IM administration is 0.29 ± 0.12 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Most serious adverse reactions in patients with ITP include intravascular hemolysis, anemia, acute renal insufficiency, and death. In patients treated for Rh isoimmunization suppression, common adverse effects include nausea, dizziness, headache, pain at injection site and malaise. Common adverse effects in patients with ITP include chills, pyrexia, mild extravascular hemolysis and headache. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Hyperrho, Micrhogam, Rhogam, Rhophylac, Winrho •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): Human Rho(D) immune globulin is a solution of antibodies used to prevent isoimmunization of Rho(D) negative patients exposed to Rho(D) positive blood in pregnancy or transfusion. 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 Human varicella-zoster immune globulin interact?

•Drug A: Abciximab •Drug B: Human varicella-zoster immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Human varicella-zoster immune globulin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for preventing and reducing the severity of chicken pox (varicella zoster virus) infections in high risk individuals within 4 days of exposure to varicella zoster virus. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Varicella zoster immune globuline provides passive immunization for non-immune individuals exposed to VZV, reducing the severity of varicella 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): Immunoglobulins are derived from human plasma and synthesized from plasma cells that recognize a broad spectrum of specific antigenic determinants. Derived from a pool of healthy human plasma, Human Varicella-Zoster Immune Globulin is a solvent/detergent-treated sterile lyophilized preparation of purified human immune globulin G (IgG) containing antibodies to varicella zoster virus. The anti-VZV antibodies in VariZIG™ are thought to bind to proteins on the varicella virus; thereby, preventing or reducing the severity and progression of varicella infections. •Absorption (Drug A): No absorption available •Absorption (Drug B): Intravenous administration of varicella zoster antibodies tends to persist for 6 weeks or longer. Following intramuscular administration of varicella immune globulin products, varicella antibodies are detectable within 2-3 days. The peak levels of varicella antibodies is expected to occur within 3-7 days of VariZIG administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous administration of varicella zoster VZIG, anti-varicella zoster antibodies are expected to be quickly distributed between plasma and extravascular spaces with complete and immediate bioavailability. Intramuscular administration achieves nearly 100% bioavailability. •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): Immune globulins are metabolized in the reticuloendothelial system. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Human Varicella-Zoster Immunoglobulin has a half-life of about 18-24 days following intravenous administration and 24-30 days following intramuscular administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Since the drug was prepared from human plasma pool, it may contain other infectious agents such as viruses and Creutzfeldt-Jakob disease (vCJD) agent. Hypersensitivity reactions such as allergic or anaphylactic reactions may occur. More common adverse effects include pain at injection site, headache, and rash. Rare adverse effects from immune globulin intravenous therapy include thrombotic events, renal dysfunction and acute renal failure, and noncardiogenic pulmonary edema. An LD50 was not determined, as the maximal dose used did not kill any experimental animals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Varizig •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): Human varicella-zoster immune globulin is a solution of antibodies used for post exposure prophylaxis of varicella infections in high risk populations, as well as to reduce the severity of infections.

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 Human varicella-zoster immune globulin interact? Information: •Drug A: Abciximab •Drug B: Human varicella-zoster immune globulin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Human varicella-zoster immune globulin. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for preventing and reducing the severity of chicken pox (varicella zoster virus) infections in high risk individuals within 4 days of exposure to varicella zoster virus. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Varicella zoster immune globuline provides passive immunization for non-immune individuals exposed to VZV, reducing the severity of varicella 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): Immunoglobulins are derived from human plasma and synthesized from plasma cells that recognize a broad spectrum of specific antigenic determinants. Derived from a pool of healthy human plasma, Human Varicella-Zoster Immune Globulin is a solvent/detergent-treated sterile lyophilized preparation of purified human immune globulin G (IgG) containing antibodies to varicella zoster virus. The anti-VZV antibodies in VariZIG™ are thought to bind to proteins on the varicella virus; thereby, preventing or reducing the severity and progression of varicella infections. •Absorption (Drug A): No absorption available •Absorption (Drug B): Intravenous administration of varicella zoster antibodies tends to persist for 6 weeks or longer. Following intramuscular administration of varicella immune globulin products, varicella antibodies are detectable within 2-3 days. The peak levels of varicella antibodies is expected to occur within 3-7 days of VariZIG administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous administration of varicella zoster VZIG, anti-varicella zoster antibodies are expected to be quickly distributed between plasma and extravascular spaces with complete and immediate bioavailability. Intramuscular administration achieves nearly 100% bioavailability. •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): Immune globulins are metabolized in the reticuloendothelial system. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Human Varicella-Zoster Immunoglobulin has a half-life of about 18-24 days following intravenous administration and 24-30 days following intramuscular administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Since the drug was prepared from human plasma pool, it may contain other infectious agents such as viruses and Creutzfeldt-Jakob disease (vCJD) agent. Hypersensitivity reactions such as allergic or anaphylactic reactions may occur. More common adverse effects include pain at injection site, headache, and rash. Rare adverse effects from immune globulin intravenous therapy include thrombotic events, renal dysfunction and acute renal failure, and noncardiogenic pulmonary edema. An LD50 was not determined, as the maximal dose used did not kill any experimental animals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Varizig •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): Human varicella-zoster immune globulin is a solution of antibodies used for post exposure prophylaxis of varicella infections in high risk populations, as well as to reduce the severity of infections. 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 Hydrochlorothiazide interact?

•Drug A: Abciximab •Drug B: Hydrochlorothiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydrochlorothiazide. •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): Hydrochlorothiazide is indicated alone or in combination for the management of edema associated with congestive heart failure, hepatic cirrhosis, nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and corticosteroid and estrogen therapy. Hydrochlorothiazide is also indicated alone or in combination for the management 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): Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4). Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water. Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water. •Absorption (Drug A): No absorption available •Absorption (Drug B): An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a T max of 1-5 hours, and a C max of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, C max is 20% lower, and T max increases from 1.6 to 2.9 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Hydrochlorothiazide is 40-68% protein bound in plasma. Hydrochlorothiazide has been shown to bind to 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): Hydrochlorothiazide is not metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 hydrochlorothiazide is 5.6-14.8h. •Clearance (Drug A): No clearance available •Clearance (Drug B): The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 of hydrochlorothiazide is >10g/kg in mice and rats. Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Accuretic, Actelsar Hct, Aldactazide, Altace HCT, Atacand, Atacand Hct, Avalide, Benicar Hct, Diovan Hct, Exforge Hct, Hyzaar, Ifirmacombi, Karvezide, Lopressor Hct, Lotensin Hct, Maxzide, Micardis-hct, Olmetec Plus, Tekturna Hct, Teveten HCT, Tribenzor, Urozide, Vaseretic, Viskazide, Zestoretic, Ziac •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): Hydrochlorothiazide is a thiazide diuretic used to treat edema associated with a number of conditions, and hypertension.

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 Hydrochlorothiazide interact? Information: •Drug A: Abciximab •Drug B: Hydrochlorothiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydrochlorothiazide. •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): Hydrochlorothiazide is indicated alone or in combination for the management of edema associated with congestive heart failure, hepatic cirrhosis, nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and corticosteroid and estrogen therapy. Hydrochlorothiazide is also indicated alone or in combination for the management 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): Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4). Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water. Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water. •Absorption (Drug A): No absorption available •Absorption (Drug B): An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a T max of 1-5 hours, and a C max of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, C max is 20% lower, and T max increases from 1.6 to 2.9 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Hydrochlorothiazide is 40-68% protein bound in plasma. Hydrochlorothiazide has been shown to bind to 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): Hydrochlorothiazide is not metabolized. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 hydrochlorothiazide is 5.6-14.8h. •Clearance (Drug A): No clearance available •Clearance (Drug B): The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 of hydrochlorothiazide is >10g/kg in mice and rats. Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Accuretic, Actelsar Hct, Aldactazide, Altace HCT, Atacand, Atacand Hct, Avalide, Benicar Hct, Diovan Hct, Exforge Hct, Hyzaar, Ifirmacombi, Karvezide, Lopressor Hct, Lotensin Hct, Maxzide, Micardis-hct, Olmetec Plus, Tekturna Hct, Teveten HCT, Tribenzor, Urozide, Vaseretic, Viskazide, Zestoretic, Ziac •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): Hydrochlorothiazide is a thiazide diuretic used to treat edema associated with a number of conditions, and hypertension. 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 Hydroflumethiazide interact?

•Drug A: Abciximab •Drug B: Hydroflumethiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydroflumethiazide. •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): Used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Also used in the management of hypertension either as the sole therapeutic agent or to enhance the effect 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): Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit 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. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron. •Absorption (Drug A): No absorption available •Absorption (Drug B): Hydroflumethiazide is incompletely but fairly rapidly 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): 74% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Essentially unchanged •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): It appears to have a biphasic biological half-life with an estimated alpha-phase of about 2 hours and an estimated beta-phase of about 17 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdoses lead to diuresis, lethargy progressing to coma, with minimal cardiorespiratory depression and with or without significant serum electrolyte changes or dehydration. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Saluron •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): Hydroflumethiazide is a thiazide diuretic used to treat hypertension as well as edema due to congestive heart failure and liver cirrhosis.

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 Hydroflumethiazide interact? Information: •Drug A: Abciximab •Drug B: Hydroflumethiazide •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydroflumethiazide. •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): Used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Also used in the management of hypertension either as the sole therapeutic agent or to enhance the effect 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): Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit 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. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron. •Absorption (Drug A): No absorption available •Absorption (Drug B): Hydroflumethiazide is incompletely but fairly rapidly 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): 74% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Essentially unchanged •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): It appears to have a biphasic biological half-life with an estimated alpha-phase of about 2 hours and an estimated beta-phase of about 17 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Overdoses lead to diuresis, lethargy progressing to coma, with minimal cardiorespiratory depression and with or without significant serum electrolyte changes or dehydration. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Saluron •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): Hydroflumethiazide is a thiazide diuretic used to treat hypertension as well as edema due to congestive heart failure and liver cirrhosis. 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 Hydroxyprogesterone caproate interact?

•Drug A: Abciximab •Drug B: Hydroxyprogesterone caproate •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydroxyprogesterone caproate. •Extended Description: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Hydroxyprogesterone caproate was previously indicated in the US for the prevention of spontaneous preterm births in singleton pregnancies in women with a history of spontaneous preterm birth. This indication was revoked by the FDA in April 2023. Hydroxyprogesterone caproate remains indicated in other jurisdictions for the management of primary and secondary amenorrhea, corpus luteum insufficiency, and for the prevention of preterm birth. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 specific pharmacodynamic studies have been performed to assess hydroxyprogesterone caproate injections. However, the mechanism of action is likely related to increased interaction between progesterone and progesterone receptors. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The mechanism by which progesterone prevents preterm birth is not well understood, but many pathways are likely involved. Progesterone plays a vital role in regulation of the female reproductive system and is important for successful implantation of the embryo and maintenance of pregnancy. It acts by binding to progesterone receptors in the uterus, ovaries, breasts and in the central nervous system. These receptors exist in 2 isoforms, PR-A and PR-B. Progesterone binding to these receptors ultimately leads to regulation of gene transcription. This results in an anti-inflammatory effect which blunts the proinflammatory state that occurs with initiation of labor, and maintains uterine queiscence by stabilizing progesterone acting on the myometrium. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of 17-hydroxyprogesteron caproate is slow, occurring over a long period of time. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Hydroxyprogesterone caproate has a high volume of distribution. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Hydroxyprogesterone caproate is extensively protein bound in the 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): The main enzymes involved in metabolism of hydroxyprogesterone caproate are cytochrome P450 (CYP) 3A4 and to a lesser extent CYP3A5. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following intramuscular injection, approximately 50% of hydroxyprogesterone caproate metabolites are eliminated in the feces, while approximately 30% of metabolites are eliminated 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): Half-life = 16 days (±6 days). •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance is highly variable from patient to patient. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Injection site pain is the most common adverse effect associated with hydroxyprogesterone caproate. Other commonly reported adverse effects include: injection site swelling, urticaria, pruritus, injection site pruritus, nausea, injection site nodule, and diarrhea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Makena •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Caproate d'hydroxyprogesterone Caproato de hidroxiprogesterona Hydroxyprogesterone caproate Hydroxyprogesterone hexanoate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Hydroxyprogesterone caproate is a synthetic progestin used for the prevention of spontaneous preterm births in singleton pregnancies in women who have previously had a spontaneous preterm birth.

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

Question: Does Abciximab and Hydroxyprogesterone caproate interact? Information: •Drug A: Abciximab •Drug B: Hydroxyprogesterone caproate •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydroxyprogesterone caproate. •Extended Description: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Hydroxyprogesterone caproate was previously indicated in the US for the prevention of spontaneous preterm births in singleton pregnancies in women with a history of spontaneous preterm birth. This indication was revoked by the FDA in April 2023. Hydroxyprogesterone caproate remains indicated in other jurisdictions for the management of primary and secondary amenorrhea, corpus luteum insufficiency, and for the prevention of preterm birth. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 specific pharmacodynamic studies have been performed to assess hydroxyprogesterone caproate injections. However, the mechanism of action is likely related to increased interaction between progesterone and progesterone receptors. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The mechanism by which progesterone prevents preterm birth is not well understood, but many pathways are likely involved. Progesterone plays a vital role in regulation of the female reproductive system and is important for successful implantation of the embryo and maintenance of pregnancy. It acts by binding to progesterone receptors in the uterus, ovaries, breasts and in the central nervous system. These receptors exist in 2 isoforms, PR-A and PR-B. Progesterone binding to these receptors ultimately leads to regulation of gene transcription. This results in an anti-inflammatory effect which blunts the proinflammatory state that occurs with initiation of labor, and maintains uterine queiscence by stabilizing progesterone acting on the myometrium. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of 17-hydroxyprogesteron caproate is slow, occurring over a long period of time. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Hydroxyprogesterone caproate has a high volume of distribution. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Hydroxyprogesterone caproate is extensively protein bound in the 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): The main enzymes involved in metabolism of hydroxyprogesterone caproate are cytochrome P450 (CYP) 3A4 and to a lesser extent CYP3A5. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following intramuscular injection, approximately 50% of hydroxyprogesterone caproate metabolites are eliminated in the feces, while approximately 30% of metabolites are eliminated 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): Half-life = 16 days (±6 days). •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance is highly variable from patient to patient. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Injection site pain is the most common adverse effect associated with hydroxyprogesterone caproate. Other commonly reported adverse effects include: injection site swelling, urticaria, pruritus, injection site pruritus, nausea, injection site nodule, and diarrhea. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Makena •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Caproate d'hydroxyprogesterone Caproato de hidroxiprogesterona Hydroxyprogesterone caproate Hydroxyprogesterone hexanoate •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Hydroxyprogesterone caproate is a synthetic progestin used for the prevention of spontaneous preterm births in singleton pregnancies in women who have previously had a spontaneous preterm birth. Output: Systemic hormonal contraceptives, such as the subject drug, are known to increase the risk of venous thromboembolism (VTE).4,1,3 While specific data regarding the concomitant use of hormonal contraceptives and anticoagulants is sparse, it follows that the procoagulant effects of hormonal contraceptives may oppose the therapeutic effects of anticoagulants, lowering their efficacy and increasing the risk of clotting. The estrogen component of combined hormonal contraceptives appears to the be the primary culprit in their induction of hypercoagulability - its effects appear to be driven by alterations to procoagulant proteins (i.e. clotting factors) and an induced resistance to activated protein C (APC), an endogenous anticoagulant. While it was previously thought that first-pass metabolism of oral contraceptives through the liver was responsible for their prothrombotic effect, more recent studies have suggested that alternative routes of administration (i.e. routes that bypass first-pass metabolism) do not improve the risk of clotting, and this is reflected in the FDA labeling for these non-oral contraceptive options. Progestin-only contraceptives do not appear to carry the same risk of thrombotic events as do estrogen-containing contraceptives. This interaction is likely to be more significant in patients with other risk factors for hormonal contraceptive-induced thrombotic events, such as smoking, age >35, obesity, and hypertension. The severity of the interaction is moderate.

Does Abciximab and Hydroxyurea interact?

•Drug A: Abciximab •Drug B: Hydroxyurea •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Hydroxyurea. •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): Hydroxyurea is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 correlation between hydroxyurea concentrations, reduction of crisis rate, and increase in HbF, is not known. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism by which hydroxyurea produces its antineoplastic effects cannot, at present, be described. However, the reports of various studies in rat and human tissue cultures lend support to the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis, by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. Hydroxyurea probably acts by decreasing the rate of conversion of ribonucleotides and deoxyribonucleotides. This effect is particularly apparent in cells with a high rate of proliferation. Particularly, hydroxyurea reduces the tyrosyl free radical at the active site of the M2 via a one-electron transfer reaction through the –NH2-OH moiety. Three mechanisms have been postulated for the potentiation of the therapeutic effects of irradiation by hydroxyurea on squamous cell (epidermoid) carcinomas of the head and neck. In vitro studies utilizing Chinese hamster cells suggest that hydroxyurea is lethal to normally radioresistant S-stage cells and holds other cells of the cell cycle in the G1 or pre-DNA synthesis stage where they are most susceptible to the effects of irradiation. The third mechanism of action has been theorized on the basis of in vitro studies of HeLa cells: it appears that hydroxyurea, by inhibition of DNA synthesis, hinders the normal repair process of cells damaged but not killed by irradiation, thereby decreasing their survival rate; there is no alteration of RNA and protein syntheses. Another proposed mechanism of action of hydroxyurea is the elevation of HbF concentrations in Sickle Cell Disease patients. HbF interferes with the polymerization of HbS (sickle haemoglobin) and thus impedes the sickling of red blood cell. Recently, hydroxyurea has shown to be associated with the generation of nitric oxide, suggesting that nitric oxide stimulates cyclic guanosine monophosphates (cGMP) production, which then activates a protein kinase and increases the production of HbF. Other known pharmacological effects of hydroxycarbamide which may contribute to its beneficial effects in Sickle Cell Disease include decrease of neutrophils, improved deformability of sickled cells, and altered adhesion of red blood cells to the endothelium. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration hydroxyurea is readily absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 2 hours and by 24 hours the serum concentrations are virtually zero. Bioavailability is complete or nearly complete in cancer patients. After oral administration of 20 mg/kg of hydroxyurea, a rapid absorption is observed with peak plasma levels of about 30 mg/L occurring after 0.75 and 1.2 h in children and adult patients with sickle cell syndrome, respectively. The total exposure up to 24 h post-dose is 124 mg.h/L in children and adolescents and 135 mg.h/L in adult patients. The oral bioavailability of hydroxyurea is almost complete as assessed in indications other than sickle cell syndrome. In a comparative bioavailability study in healthy adult volunteers (n=28), 500 mg of hydroxyurea oral solution was demonstrated to be bioequivalent to the reference 500 mg capsule, with respect to both the peak concentration and area under the curve. There was a statistically significant reduction in time to peak concentration with hydroxyurea oral solution compared to the reference 500 mg capsule (0.5 versus 0.75 hours, p = 0.0467), indicating a faster rate of absorption.[L47137 In a study of children with Sickle Cell Disease, liquid and capsule formulations resulted in similar area under the curve, peak concentrations, and half-life. The largest difference in the pharmacokinetic profile was a trend towards a shorter time to peak concentration following ingestion of the liquid compared with the capsule, but that difference did not reach statistical significance (0.74 versus 0.97 hours, p = 0.14). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Hydroxyurea distributes rapidly throughout the human body, enters the cerebrospinal fluid, appears in peritoneal fluid and ascites, and concentrates in leukocytes and erythrocytes. The estimated volume of distribution of hydroxycarbamide approximates total body water. The volume of distribution following oral dosing of hydroxycarbamide is approximately equal to total body water: adult values of 0.48 – 0.90 L/kg have been reported, whilst in children a population estimate of 0.7 L/kg has been reported. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The extent of protein binding of hydroxyurea is unknown. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation to acetohydroxamic acid by urease found in intestinal bacteria. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): A significant fraction of hydroxycarbamide is eliminated by nonrenal (mainly hepatic) mechanisms. In adults, the urinary recovery of unchanged drug is reported to be approximately 37% of the oral dose when renal function is normal. In children, the fraction of hydroxyurea excreted unchanged into the urine comprised about 50%. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In adult cancer patients, hydroxyurea was eliminated with a half-life of approximately 2-3 hours. In a single-dose study in children with Sickle Cell Disease, the mean half-life was reported to be 1.7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total body clearance of hydroxyurea in adult patients with Sickle Cell Disease is 0.17 L/h/kg. The respective value in children was similar, 0.22 L/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, mouse: LD 50 = 7330 mg/kg; Oral, rat: LD 50 = 5760 mg/kg Hydroxyurea can cause fetal harm based on findings from animal studies and the drug’s mechanism of action. There are no studies on the use of Hydroxyurea in pregnant women and limited available data on SIKLOS use during pregnancy are insufficient to inform drug-associated risks. Drugs that affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents. In animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m² basis. In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Advise pregnant women of the potential risk to a fetus. Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed. In patients with sickle cell anemia, neutropenia was reported in isolated cases of hydroxyurea overdose (1.43 times and 8.57 times the maximum recommended dose of 35 mg/kg b.w./day). Monitor blood counts weekly until recovery. Treatment of overdose consists of gastric lavage, followed by symptomatic treatment and control of bone marrow function. Conventional long-term studies to evaluate the carcinogenic potential of hydroxyurea have not been performed. However, hydroxyurea is presumed to be a transspecies carcinogen. Intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months in female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype. Hydroxyurea administered to male rats at 60 mg/kg /day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Droxia, Hydrea, Siklos •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): Hydroxyurea is an antimetabolite used to treat sickle cell anemia crisis, resistant chronic myeloid leukemia, and Locally advanced squamous cell carcinomas of the head and neck (excluding the lip).

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 Hydroxyurea interact? Information: •Drug A: Abciximab •Drug B: Hydroxyurea •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Hydroxyurea. •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): Hydroxyurea is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 correlation between hydroxyurea concentrations, reduction of crisis rate, and increase in HbF, is not known. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism by which hydroxyurea produces its antineoplastic effects cannot, at present, be described. However, the reports of various studies in rat and human tissue cultures lend support to the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis, by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. Hydroxyurea probably acts by decreasing the rate of conversion of ribonucleotides and deoxyribonucleotides. This effect is particularly apparent in cells with a high rate of proliferation. Particularly, hydroxyurea reduces the tyrosyl free radical at the active site of the M2 via a one-electron transfer reaction through the –NH2-OH moiety. Three mechanisms have been postulated for the potentiation of the therapeutic effects of irradiation by hydroxyurea on squamous cell (epidermoid) carcinomas of the head and neck. In vitro studies utilizing Chinese hamster cells suggest that hydroxyurea is lethal to normally radioresistant S-stage cells and holds other cells of the cell cycle in the G1 or pre-DNA synthesis stage where they are most susceptible to the effects of irradiation. The third mechanism of action has been theorized on the basis of in vitro studies of HeLa cells: it appears that hydroxyurea, by inhibition of DNA synthesis, hinders the normal repair process of cells damaged but not killed by irradiation, thereby decreasing their survival rate; there is no alteration of RNA and protein syntheses. Another proposed mechanism of action of hydroxyurea is the elevation of HbF concentrations in Sickle Cell Disease patients. HbF interferes with the polymerization of HbS (sickle haemoglobin) and thus impedes the sickling of red blood cell. Recently, hydroxyurea has shown to be associated with the generation of nitric oxide, suggesting that nitric oxide stimulates cyclic guanosine monophosphates (cGMP) production, which then activates a protein kinase and increases the production of HbF. Other known pharmacological effects of hydroxycarbamide which may contribute to its beneficial effects in Sickle Cell Disease include decrease of neutrophils, improved deformability of sickled cells, and altered adhesion of red blood cells to the endothelium. •Absorption (Drug A): No absorption available •Absorption (Drug B): After oral administration hydroxyurea is readily absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 2 hours and by 24 hours the serum concentrations are virtually zero. Bioavailability is complete or nearly complete in cancer patients. After oral administration of 20 mg/kg of hydroxyurea, a rapid absorption is observed with peak plasma levels of about 30 mg/L occurring after 0.75 and 1.2 h in children and adult patients with sickle cell syndrome, respectively. The total exposure up to 24 h post-dose is 124 mg.h/L in children and adolescents and 135 mg.h/L in adult patients. The oral bioavailability of hydroxyurea is almost complete as assessed in indications other than sickle cell syndrome. In a comparative bioavailability study in healthy adult volunteers (n=28), 500 mg of hydroxyurea oral solution was demonstrated to be bioequivalent to the reference 500 mg capsule, with respect to both the peak concentration and area under the curve. There was a statistically significant reduction in time to peak concentration with hydroxyurea oral solution compared to the reference 500 mg capsule (0.5 versus 0.75 hours, p = 0.0467), indicating a faster rate of absorption.[L47137 In a study of children with Sickle Cell Disease, liquid and capsule formulations resulted in similar area under the curve, peak concentrations, and half-life. The largest difference in the pharmacokinetic profile was a trend towards a shorter time to peak concentration following ingestion of the liquid compared with the capsule, but that difference did not reach statistical significance (0.74 versus 0.97 hours, p = 0.14). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Hydroxyurea distributes rapidly throughout the human body, enters the cerebrospinal fluid, appears in peritoneal fluid and ascites, and concentrates in leukocytes and erythrocytes. The estimated volume of distribution of hydroxycarbamide approximates total body water. The volume of distribution following oral dosing of hydroxycarbamide is approximately equal to total body water: adult values of 0.48 – 0.90 L/kg have been reported, whilst in children a population estimate of 0.7 L/kg has been reported. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The extent of protein binding of hydroxyurea is unknown. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation to acetohydroxamic acid by urease found in intestinal bacteria. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): A significant fraction of hydroxycarbamide is eliminated by nonrenal (mainly hepatic) mechanisms. In adults, the urinary recovery of unchanged drug is reported to be approximately 37% of the oral dose when renal function is normal. In children, the fraction of hydroxyurea excreted unchanged into the urine comprised about 50%. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In adult cancer patients, hydroxyurea was eliminated with a half-life of approximately 2-3 hours. In a single-dose study in children with Sickle Cell Disease, the mean half-life was reported to be 1.7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The total body clearance of hydroxyurea in adult patients with Sickle Cell Disease is 0.17 L/h/kg. The respective value in children was similar, 0.22 L/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, mouse: LD 50 = 7330 mg/kg; Oral, rat: LD 50 = 5760 mg/kg Hydroxyurea can cause fetal harm based on findings from animal studies and the drug’s mechanism of action. There are no studies on the use of Hydroxyurea in pregnant women and limited available data on SIKLOS use during pregnancy are insufficient to inform drug-associated risks. Drugs that affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents. In animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m² basis. In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Advise pregnant women of the potential risk to a fetus. Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed. In patients with sickle cell anemia, neutropenia was reported in isolated cases of hydroxyurea overdose (1.43 times and 8.57 times the maximum recommended dose of 35 mg/kg b.w./day). Monitor blood counts weekly until recovery. Treatment of overdose consists of gastric lavage, followed by symptomatic treatment and control of bone marrow function. Conventional long-term studies to evaluate the carcinogenic potential of hydroxyurea have not been performed. However, hydroxyurea is presumed to be a transspecies carcinogen. Intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months in female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype. Hydroxyurea administered to male rats at 60 mg/kg /day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Droxia, Hydrea, Siklos •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): Hydroxyurea is an antimetabolite used to treat sickle cell anemia crisis, resistant chronic myeloid leukemia, and Locally advanced squamous cell carcinomas of the head and neck (excluding the lip). 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 Ibalizumab interact?

•Drug A: Abciximab •Drug B: Ibalizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ibalizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with ≥10 antiretroviral medications. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 4.8 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): Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient). •Clearance (Drug A): No clearance available •Clearance (Drug B): Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trogarzo •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): Ibalizumab is a CD4-specific antibody used to treat HIV infections.

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 Ibalizumab interact? Information: •Drug A: Abciximab •Drug B: Ibalizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ibalizumab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with ≥10 antiretroviral medications. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 4.8 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): Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient). •Clearance (Drug A): No clearance available •Clearance (Drug B): Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Trogarzo •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): Ibalizumab is a CD4-specific antibody used to treat HIV infections. 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 Ibritumomab tiuxetan interact?

•Drug A: Abciximab •Drug B: Ibritumomab tiuxetan •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ibritumomab tiuxetan. •Extended Description: Antiplatelet agents may agents exert an additive effect on the anticoagulant actions of ibritumomab tiuxetan, which may cause bleeding or thrombocytopenia. This increases the risk of bleeding complications due to thrombocytopenia. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of non-Hodgkin's 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): Ibritumomab is a murine monoclonal antibody against CD20 that has been radiolabeled with yttrium-90. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via production of beta particles. •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): Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines) •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Most likely removed by opsonization via the reticuloendothelial system when bound to B cells, or by human antimurine antibody production •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 0.8 hours (mammalian reticulocytes, in vitro) •Clearance (Drug A): No clearance available •Clearance (Drug B): Approximately 7.2% of injected dose of yttrium Y 90 ibritumomab tiuxetan is excreted in urine within 7 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): Zevalin •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): Ibritumomab tiuxetan is a monoclonal anti-CD20 antibody used to treat B-cell non-Hodgkin's lymphoma via a conjugated radioactive isotope.

Antiplatelet agents may agents exert an additive effect on the anticoagulant actions of ibritumomab tiuxetan, which may cause bleeding or thrombocytopenia. This increases the risk of bleeding complications due to thrombocytopenia. The severity of the interaction is moderate.

Question: Does Abciximab and Ibritumomab tiuxetan interact? Information: •Drug A: Abciximab •Drug B: Ibritumomab tiuxetan •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ibritumomab tiuxetan. •Extended Description: Antiplatelet agents may agents exert an additive effect on the anticoagulant actions of ibritumomab tiuxetan, which may cause bleeding or thrombocytopenia. This increases the risk of bleeding complications due to thrombocytopenia. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For treatment of non-Hodgkin's 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): Ibritumomab is a murine monoclonal antibody against CD20 that has been radiolabeled with yttrium-90. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via production of beta particles. •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): Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines) •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Most likely removed by opsonization via the reticuloendothelial system when bound to B cells, or by human antimurine antibody production •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 0.8 hours (mammalian reticulocytes, in vitro) •Clearance (Drug A): No clearance available •Clearance (Drug B): Approximately 7.2% of injected dose of yttrium Y 90 ibritumomab tiuxetan is excreted in urine within 7 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): Zevalin •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): Ibritumomab tiuxetan is a monoclonal anti-CD20 antibody used to treat B-cell non-Hodgkin's lymphoma via a conjugated radioactive isotope. Output: Antiplatelet agents may agents exert an additive effect on the anticoagulant actions of ibritumomab tiuxetan, which may cause bleeding or thrombocytopenia. This increases the risk of bleeding complications due to thrombocytopenia. The severity of the interaction is moderate.

Does Abciximab and Ibrutinib interact?

•Drug A: Abciximab •Drug B: Ibrutinib •Severity: MINOR •Description: The risk or severity of bleeding and hemorrhage can be increased when Ibrutinib is combined with Abciximab. •Extended Description: Fatal bleeding events and grade 3 or higher bleeding events including subdural hematoma, gastrointestinal bleeding, hematuria and post procedural hemorrhage have been observed with ibrutinib therapy. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with ibrutinib. While the mechanism for the bleeding events of ibrutinib is not clearly understood, co-adminsitereing ibrutininb with drugs with potential to cause bleeding, such as anticoagulants, may increase the risk for non-fatal or fatal bleeding and hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ibrutinib is indicated for the treatment of the following conditions. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) In the US, it is used in adult patients with or without 17p deletion. In Europe and Canada, it is used as a single agent or combined with rituximab, obinutuzumab, or venetoclax in previously untreated CLL patients. In patients who have received at least one prior therapy, it is used as a single agent or in combination with bendamustine and rituximab. Waldenström's macroglobulinemia It is used alone or with rituximab. In Europe, it is approved for patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemoimmunotherapy. Chronic graft-versus-host disease (cGVHD) In the US, it is approved in patients aged one year and older after the prior failure of one or more lines of systemic therapy. In Canada, it is approved in adults with steroid-dependent or refractory cGVHD. Mantle cell lymphoma (MCL) In Europe and Canada, ibrutinib is also indicated to treat relapsed or refractory MCL in adults. Marginal zone lymphoma (MZL) In Canada, it is approved for adults who require systemic therapy and have received at least one prior anti-CD20-based 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 vitro studies have shown an induction of CLL cell apoptosis even in presence of prosurvival factors. It has also been reported an inhibition of CLL cell survival and proliferation as well as an impaired in cell migration and a reduction in the secretion of chemokines such as CCL3 and CCL4. The latter effect has been shown to produce regression in xenograft mouse models. Clinical studies for relapsed/refractory CLL in phase I and II showed an approximate 71% of overall response rate.. In the case of relapsed/refractory mantle cell lymphoma, approximately 70% of the tested patients presented a partial or complete response.. In clinical trials for relapsed/refractory diffuse large B-cell lymphoma, a partial response was found in between 15-20% of the patients studied; while for patients with relapsed/refractory Waldenstrom's macroglobulinemia, a partial response was observed in over 75% of the patients tested. Finally, for patients with relapsed/refractory follicular lymphoma, a partial to complete response was obtained in approximately 54% of the 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): Ibrutinib is an inhibitor of Bruton’s tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue in the active site of BTK (Cys481), leading to its inhibition. The inhibition of BTK plays a role in the B-cell receptor signaling and thus, the presence of ibrutinib prevents the phosphorylation of downstream substrates such as PLC-γ. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ibrutinib is rapidly absorbed after oral administration and it presents a Cmax, tmax and AUC of approximately 35 ng/ml, 1-2 hour and 953 mg.h/ml respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady-state of ibrutinib is in approximately 10,000 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Irreversible plasma protein binding increases gradually over time and reaches 25% of the administered dose 8 hours after initial administration. From the plasma proteins, ibrutinib has been shown to be mainly bound to albumin and to bind to α1 AGP. The irreversible protein binding of ibrutinib to plasma proteins can account for 97.3% of the administered dose. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Three metabolic pathways have been identified according to the possible metabolites. These pathways are the hydroxylation of the phenyl group (M35), the opening of the piperidine with a reduction of the primary alcohol (M34) and the oxidation to a carboxylic acid and epoxidation of the ethylene followed by a hydrolysis to the formation of dihydrodiol (PCI-45227). The latter metabolite presents also 15 times lower inhibitory activity against BTK. The metabolism of ibrutinib is mainly performed by CYP3A5 and CYP3A4. and in a minor extent it is seen to be performed by CYP2D6. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The cumulative excretion of ibrutinib in urine is of about 7.8% of the administered dose and most of this excretion is found during the first 24 hours after administration. In feces, the cumulative excretion accounts for 80% of the administered dose and the excretion occurs within 48 hours of the initial administration. The total excretion of ibrutinib during the first 168 hours after initial administration accounts for 88.5% 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 elimination half-life of ibrutinib is of approximately 4-6 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with normal renal function, the clearance rate is in the range of 112-159 ml/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ibrutinib was not showed to present a mutagenic potential in bacterial assays, nor clastogenic in chromosome aberration assays in mammalian cells or in bone marrow micronucleus assays in mice. Carcinogenicity or effects on fertility have not been determined. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Imbruvica •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ibrutinib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ibrutinib is an antineoplastic agent used to treat chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia.

Fatal bleeding events and grade 3 or higher bleeding events including subdural hematoma, gastrointestinal bleeding, hematuria and post procedural hemorrhage have been observed with ibrutinib therapy. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with ibrutinib. While the mechanism for the bleeding events of ibrutinib is not clearly understood, co-adminsitereing ibrutininb with drugs with potential to cause bleeding, such as anticoagulants, may increase the risk for non-fatal or fatal bleeding and hemorrhage. The severity of the interaction is minor.

Question: Does Abciximab and Ibrutinib interact? Information: •Drug A: Abciximab •Drug B: Ibrutinib •Severity: MINOR •Description: The risk or severity of bleeding and hemorrhage can be increased when Ibrutinib is combined with Abciximab. •Extended Description: Fatal bleeding events and grade 3 or higher bleeding events including subdural hematoma, gastrointestinal bleeding, hematuria and post procedural hemorrhage have been observed with ibrutinib therapy. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with ibrutinib. While the mechanism for the bleeding events of ibrutinib is not clearly understood, co-adminsitereing ibrutininb with drugs with potential to cause bleeding, such as anticoagulants, may increase the risk for non-fatal or fatal bleeding and hemorrhage. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Ibrutinib is indicated for the treatment of the following conditions. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) In the US, it is used in adult patients with or without 17p deletion. In Europe and Canada, it is used as a single agent or combined with rituximab, obinutuzumab, or venetoclax in previously untreated CLL patients. In patients who have received at least one prior therapy, it is used as a single agent or in combination with bendamustine and rituximab. Waldenström's macroglobulinemia It is used alone or with rituximab. In Europe, it is approved for patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemoimmunotherapy. Chronic graft-versus-host disease (cGVHD) In the US, it is approved in patients aged one year and older after the prior failure of one or more lines of systemic therapy. In Canada, it is approved in adults with steroid-dependent or refractory cGVHD. Mantle cell lymphoma (MCL) In Europe and Canada, ibrutinib is also indicated to treat relapsed or refractory MCL in adults. Marginal zone lymphoma (MZL) In Canada, it is approved for adults who require systemic therapy and have received at least one prior anti-CD20-based 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 vitro studies have shown an induction of CLL cell apoptosis even in presence of prosurvival factors. It has also been reported an inhibition of CLL cell survival and proliferation as well as an impaired in cell migration and a reduction in the secretion of chemokines such as CCL3 and CCL4. The latter effect has been shown to produce regression in xenograft mouse models. Clinical studies for relapsed/refractory CLL in phase I and II showed an approximate 71% of overall response rate.. In the case of relapsed/refractory mantle cell lymphoma, approximately 70% of the tested patients presented a partial or complete response.. In clinical trials for relapsed/refractory diffuse large B-cell lymphoma, a partial response was found in between 15-20% of the patients studied; while for patients with relapsed/refractory Waldenstrom's macroglobulinemia, a partial response was observed in over 75% of the patients tested. Finally, for patients with relapsed/refractory follicular lymphoma, a partial to complete response was obtained in approximately 54% of the 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): Ibrutinib is an inhibitor of Bruton’s tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue in the active site of BTK (Cys481), leading to its inhibition. The inhibition of BTK plays a role in the B-cell receptor signaling and thus, the presence of ibrutinib prevents the phosphorylation of downstream substrates such as PLC-γ. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ibrutinib is rapidly absorbed after oral administration and it presents a Cmax, tmax and AUC of approximately 35 ng/ml, 1-2 hour and 953 mg.h/ml respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady-state of ibrutinib is in approximately 10,000 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Irreversible plasma protein binding increases gradually over time and reaches 25% of the administered dose 8 hours after initial administration. From the plasma proteins, ibrutinib has been shown to be mainly bound to albumin and to bind to α1 AGP. The irreversible protein binding of ibrutinib to plasma proteins can account for 97.3% of the administered dose. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Three metabolic pathways have been identified according to the possible metabolites. These pathways are the hydroxylation of the phenyl group (M35), the opening of the piperidine with a reduction of the primary alcohol (M34) and the oxidation to a carboxylic acid and epoxidation of the ethylene followed by a hydrolysis to the formation of dihydrodiol (PCI-45227). The latter metabolite presents also 15 times lower inhibitory activity against BTK. The metabolism of ibrutinib is mainly performed by CYP3A5 and CYP3A4. and in a minor extent it is seen to be performed by CYP2D6. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The cumulative excretion of ibrutinib in urine is of about 7.8% of the administered dose and most of this excretion is found during the first 24 hours after administration. In feces, the cumulative excretion accounts for 80% of the administered dose and the excretion occurs within 48 hours of the initial administration. The total excretion of ibrutinib during the first 168 hours after initial administration accounts for 88.5% 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 elimination half-life of ibrutinib is of approximately 4-6 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with normal renal function, the clearance rate is in the range of 112-159 ml/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Ibrutinib was not showed to present a mutagenic potential in bacterial assays, nor clastogenic in chromosome aberration assays in mammalian cells or in bone marrow micronucleus assays in mice. Carcinogenicity or effects on fertility have not been determined. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Imbruvica •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ibrutinib •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ibrutinib is an antineoplastic agent used to treat chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia. Output: Fatal bleeding events and grade 3 or higher bleeding events including subdural hematoma, gastrointestinal bleeding, hematuria and post procedural hemorrhage have been observed with ibrutinib therapy. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with ibrutinib. While the mechanism for the bleeding events of ibrutinib is not clearly understood, co-adminsitereing ibrutininb with drugs with potential to cause bleeding, such as anticoagulants, may increase the risk for non-fatal or fatal bleeding and hemorrhage. The severity of the interaction is minor.

Does Abciximab and Ibuprofen interact?

•Drug A: Abciximab •Drug B: Ibuprofen •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Ibuprofen 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): Ibuprofen is the most commonly used and prescribed NSAID. It is a very common over-the-counter medication widely used as an analgesic, anti-inflammatory and antipyretic. The use of ibuprofen and its enantiomer Dexibuprofen in a racemic mix is common for the management of mild to moderate pain related to dysmenorrhea, headache, migraine, postoperative dental pain, spondylitis, osteoarthritis, rheumatoid arthritis, and soft tissue disorder. Due to its activity against prostaglandin and thromboxane synthesis, ibuprofen has been attributed to alteration of platelet function and prolongation of gestation and labour. As ibuprofen is a widely used medication, the main therapeutic indications are: Patent Ductus Arteriosus - it is a neonatal condition wherein the ductus arteriosus (blood vessel that connects the main pulmonary artery to the proximal descending aorta) fails to close after birth causing severe risk of heart failure. The prostaglandin inhibition of ibuprofen has been studied for the treatment of this condition as it is known that prostaglandin E2 is responsible for keeping the ductus arteriosus open. Rheumatoid- and osteo-arthritis - ibuprofen is very commonly used in the symptomatic treatment of inflammatory, musculoskeletal and rheumatic disorders. Cystic fibrosis - the use of high dosages of ibuprofen has been proven to decrease inflammation and decreasing polymorphonuclear cell influx in the lungs. Orthostatic hypotension - ibuprofen can induce sodium retention and antagonize the effect of diuretics which has been reported to be beneficial for patients with severe orthostatic hypotension. Dental pain - ibuprofen is used to manage acute and chronic orofacial pain. Pain - ibuprofen is widely used to reduce minor aches and pains as well as to reduce fever and manage dysmenorrhea. It is very commonly used for the relief of acute indications such as fever and tension headaches. It is also used to manage mild to moderate pain and moderate to severe pain as an adjunct to opioid analgesics. Investigational uses - efforts have been put into developing ibuprofen for the prophylaxis of Alzheimer's disease, Parkinson disease, and 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): Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials. The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region. The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen. The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. Ibuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility. As well, it has been reported to reduce significantly the fever and the pain caused by migraines. This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system. In the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time. On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition. The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway. Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. •Absorption (Drug A): No absorption available •Absorption (Drug B): It is very well absorbed orally and the peak serum concentration can be attained in 1 to 2 hours after extravascular administration. When ibuprofen is administered immediately after a meal there is a slight reduction in the absorption rate but there is no change in the extent of the absorption. When orally administered, the absorption of ibuprofen in adults is very rapidly done in the upper GI tract. The average Cmax, Tmax and AUC ranges around 20 mcg/ml, 2 h and 70 mcg.h/ml. These parameters can vary depending on the enantiomer form, route, and dose of administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of ibuprofen is of 0.1 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ibuprofen dosage is more than 99% bound to plasma proteins and site II of purified albumin, binding appears to be saturable and becomes non-linear at concentrations exceeding 20 mcg/ml. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ibuprofen is rapidly metabolized and biotransformed in the liver to the formation of major metabolites which are the hydroxylated and carboxylated derivatives. As soon as it is absorbed, the R-enantiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer in vivo by the activity of alpha-methylacyl-CoA racemase. Ibuprofen metabolism can be divided in phase I which is represented by the hydroxylation of the isobutyl chains for the formation of 2 or 3-hydroxy derivatives followed by oxidation to 2-carboxy-ibuprofen and p-carboxy-2-propionate. These oxidative reactions are performed by the activity of the cytochrome P450 isoforms CYP 2C9, CYP 2C19 and CYP 2C8. Therefore, these enzymes participate in the oxidation of the alkyl side chain to hydroxyl and carboxyl derivatives. From this enzymes, the major catalyst in the formation of oxidative metabolites is the isoform CYP 2C9. The metabolic phase I is followed by a phase II in which the oxidative metabolites may be conjugated to glucuronide prior to excretion. This activity forms phenolic and acyl glucuronides. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ibuprofen is rapidly metabolized and eliminated in the urine thus, this via accounts for more than 90% of the administered dose. It is completely eliminated in 24 hours after the last dose and almost all the administered dose goes through metabolism, representing about 99% of the eliminated dose. The biliary excretion of unchanged drug and active phase II metabolites represents 1% of the administered dose. In summary, ibuprofen is excreted as metabolites or their conjugates. The elimination of ibuprofen is not impaired by old age or the presence of renal impairment. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The serum half-life of ibuprofen is 1.2-2 hours. In patients with a compromised liver function, the half-life can be prolonged to 3.1-3.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance rate ranges between 3-13 L/h depending on the route of administration, enantiomer type and dosage. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The symptoms of overdose are presented in individuals that consumed more than 99 mg/kg. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients). The reported LD50 of ibuprofen is of 636 mg/kg in rat, 740 mg/kg in mouse and 495 mg/kg in guinea pig. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Addaprin, Advil, Advil Cold and Sinus, Advil Congestion Relief, Advil PM, Advil Sinus Congestion and Pain, Alivio, Caldolor, Cedaprin, Children's Ibuprofen, Combogesic, Diphen, Duexis, Ibu, Ibutab, Junior Strength Motrin, Motrin, Motrin PM, Neoprofen, Nuprin, Pedea, Proprinal, Reprexain, Sudafed PE Head Congestion Plus Pain, Vicoprofen, Wal-profen Congestion Relief and Pain •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ibuprofen Ibuprofene Ibuprofeno Ibuprofenum Ibuprophen •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ibuprofen is an NSAID and non-selective COX inhibitor used to treat mild-moderate pain, fever, 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 Ibuprofen interact? Information: •Drug A: Abciximab •Drug B: Ibuprofen •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Ibuprofen 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): Ibuprofen is the most commonly used and prescribed NSAID. It is a very common over-the-counter medication widely used as an analgesic, anti-inflammatory and antipyretic. The use of ibuprofen and its enantiomer Dexibuprofen in a racemic mix is common for the management of mild to moderate pain related to dysmenorrhea, headache, migraine, postoperative dental pain, spondylitis, osteoarthritis, rheumatoid arthritis, and soft tissue disorder. Due to its activity against prostaglandin and thromboxane synthesis, ibuprofen has been attributed to alteration of platelet function and prolongation of gestation and labour. As ibuprofen is a widely used medication, the main therapeutic indications are: Patent Ductus Arteriosus - it is a neonatal condition wherein the ductus arteriosus (blood vessel that connects the main pulmonary artery to the proximal descending aorta) fails to close after birth causing severe risk of heart failure. The prostaglandin inhibition of ibuprofen has been studied for the treatment of this condition as it is known that prostaglandin E2 is responsible for keeping the ductus arteriosus open. Rheumatoid- and osteo-arthritis - ibuprofen is very commonly used in the symptomatic treatment of inflammatory, musculoskeletal and rheumatic disorders. Cystic fibrosis - the use of high dosages of ibuprofen has been proven to decrease inflammation and decreasing polymorphonuclear cell influx in the lungs. Orthostatic hypotension - ibuprofen can induce sodium retention and antagonize the effect of diuretics which has been reported to be beneficial for patients with severe orthostatic hypotension. Dental pain - ibuprofen is used to manage acute and chronic orofacial pain. Pain - ibuprofen is widely used to reduce minor aches and pains as well as to reduce fever and manage dysmenorrhea. It is very commonly used for the relief of acute indications such as fever and tension headaches. It is also used to manage mild to moderate pain and moderate to severe pain as an adjunct to opioid analgesics. Investigational uses - efforts have been put into developing ibuprofen for the prophylaxis of Alzheimer's disease, Parkinson disease, and 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): Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials. The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region. The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen. The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. Ibuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility. As well, it has been reported to reduce significantly the fever and the pain caused by migraines. This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system. In the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time. On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition. The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway. Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. •Absorption (Drug A): No absorption available •Absorption (Drug B): It is very well absorbed orally and the peak serum concentration can be attained in 1 to 2 hours after extravascular administration. When ibuprofen is administered immediately after a meal there is a slight reduction in the absorption rate but there is no change in the extent of the absorption. When orally administered, the absorption of ibuprofen in adults is very rapidly done in the upper GI tract. The average Cmax, Tmax and AUC ranges around 20 mcg/ml, 2 h and 70 mcg.h/ml. These parameters can vary depending on the enantiomer form, route, and dose of administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of ibuprofen is of 0.1 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ibuprofen dosage is more than 99% bound to plasma proteins and site II of purified albumin, binding appears to be saturable and becomes non-linear at concentrations exceeding 20 mcg/ml. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ibuprofen is rapidly metabolized and biotransformed in the liver to the formation of major metabolites which are the hydroxylated and carboxylated derivatives. As soon as it is absorbed, the R-enantiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer in vivo by the activity of alpha-methylacyl-CoA racemase. Ibuprofen metabolism can be divided in phase I which is represented by the hydroxylation of the isobutyl chains for the formation of 2 or 3-hydroxy derivatives followed by oxidation to 2-carboxy-ibuprofen and p-carboxy-2-propionate. These oxidative reactions are performed by the activity of the cytochrome P450 isoforms CYP 2C9, CYP 2C19 and CYP 2C8. Therefore, these enzymes participate in the oxidation of the alkyl side chain to hydroxyl and carboxyl derivatives. From this enzymes, the major catalyst in the formation of oxidative metabolites is the isoform CYP 2C9. The metabolic phase I is followed by a phase II in which the oxidative metabolites may be conjugated to glucuronide prior to excretion. This activity forms phenolic and acyl glucuronides. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ibuprofen is rapidly metabolized and eliminated in the urine thus, this via accounts for more than 90% of the administered dose. It is completely eliminated in 24 hours after the last dose and almost all the administered dose goes through metabolism, representing about 99% of the eliminated dose. The biliary excretion of unchanged drug and active phase II metabolites represents 1% of the administered dose. In summary, ibuprofen is excreted as metabolites or their conjugates. The elimination of ibuprofen is not impaired by old age or the presence of renal impairment. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The serum half-life of ibuprofen is 1.2-2 hours. In patients with a compromised liver function, the half-life can be prolonged to 3.1-3.4 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance rate ranges between 3-13 L/h depending on the route of administration, enantiomer type and dosage. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The symptoms of overdose are presented in individuals that consumed more than 99 mg/kg. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients). The reported LD50 of ibuprofen is of 636 mg/kg in rat, 740 mg/kg in mouse and 495 mg/kg in guinea pig. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Addaprin, Advil, Advil Cold and Sinus, Advil Congestion Relief, Advil PM, Advil Sinus Congestion and Pain, Alivio, Caldolor, Cedaprin, Children's Ibuprofen, Combogesic, Diphen, Duexis, Ibu, Ibutab, Junior Strength Motrin, Motrin, Motrin PM, Neoprofen, Nuprin, Pedea, Proprinal, Reprexain, Sudafed PE Head Congestion Plus Pain, Vicoprofen, Wal-profen Congestion Relief and Pain •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ibuprofen Ibuprofene Ibuprofeno Ibuprofenum Ibuprophen •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ibuprofen is an NSAID and non-selective COX inhibitor used to treat mild-moderate pain, fever, 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 Icosapent ethyl interact?

•Drug A: Abciximab •Drug B: Icosapent ethyl •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Icosapent ethyl 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): Icosapent ethyl is indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalizing in adult patients with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease or who have diabetes mellitus and ≥2 other risk factors for cardiovascular disease. It is also indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Icosapent ethyl is de-esterfied, converted into active EPA, and then absorbed in the small intestine. It reaches peak plasma concentration in 5 hours post-oral administration. Very little (<1%) is left circulating in the plasma as EPA incorporates into phospholipids, TG's, and cholesteryl esters. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Steady state volume of distribution of active EPA is 88 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): Once converted into active EPA, it is hepatically metabolized into acetyl Coenzyme A via beta-oxidation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Icosapent ethyl is not renally excreted •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half life of EPA is 89 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total plasma clearance, EPA = 684 mL/hr •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Icosapent ethyl is generally well tolerated and adverse effects are unrelated to treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Vascepa •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): E-EPA Eicosapentaenoic acid ethyl ester Ethyl eicosapentaenoate Ethyl icosapentate Ethyl-EPA Icosapent ethyl Timnodonic acid ethyl ester •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Icosapent ethyl is an ethyl ester of eicosapentaenoic acid (EPA) that reduces synthesis and enhances clearance of triglycerides that is used to treat patients with severe hypertriglyceridemia.

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 Icosapent ethyl interact? Information: •Drug A: Abciximab •Drug B: Icosapent ethyl •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Icosapent ethyl 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): Icosapent ethyl is indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalizing in adult patients with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease or who have diabetes mellitus and ≥2 other risk factors for cardiovascular disease. It is also indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Icosapent ethyl is de-esterfied, converted into active EPA, and then absorbed in the small intestine. It reaches peak plasma concentration in 5 hours post-oral administration. Very little (<1%) is left circulating in the plasma as EPA incorporates into phospholipids, TG's, and cholesteryl esters. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Steady state volume of distribution of active EPA is 88 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): Once converted into active EPA, it is hepatically metabolized into acetyl Coenzyme A via beta-oxidation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Icosapent ethyl is not renally excreted •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half life of EPA is 89 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total plasma clearance, EPA = 684 mL/hr •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Icosapent ethyl is generally well tolerated and adverse effects are unrelated to treatment. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Vascepa •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): E-EPA Eicosapentaenoic acid ethyl ester Ethyl eicosapentaenoate Ethyl icosapentate Ethyl-EPA Icosapent ethyl Timnodonic acid ethyl ester •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Icosapent ethyl is an ethyl ester of eicosapentaenoic acid (EPA) that reduces synthesis and enhances clearance of triglycerides that is used to treat patients with severe hypertriglyceridemia. 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 Icosapent interact?

•Drug A: Abciximab •Drug B: Icosapent •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Icosapent 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): EPA can be used for lowering elevated triglycerides in those who are hyperglyceridemic. In addition, EPA may play a therapeutic role in patients with cystic fibrosis by reducing disease severity and may play a similar role in type 2 diabetics in slowing the progression of diabetic nephropathy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eicosanoids are chemical messengers derived from 20-carbon polyunsaturated fatty acids that play critical roles in immune and inflammatory responses. Both 20-carbon omega-6 fatty acids (arachidonic acid) and 20-carbon omega-3 fatty acids (EPA) can be found in cell membranes. During an inflammatory response, arachidonic acid and EPA are metabolized by enzymes known as cyclooxygenases and lipoxygenases to form eicosanoids. Increasing omega-3 fatty acid intake increases the EPA content of cell membranes and decreases the arachidonic acid content, resulting in higher proportions of eicosanoids derived from EPA. Physiologic responses to arachidonic acid-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and clotting than eicosanoids derived from arachidonic acid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The anti-inflammatory, antithrombotic and immunomodulatory actions of EPA is probably due to its role in eicosanoid physiology and biochemistry. Most eicosanoids are produced by the metabolism of omega-3 fatty acids, specifically, arachidonic acid. These eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2) stimulate leukocyte chemotaxis, platelet aggregation and vasoconstriction. They are thrombogenic and artherogenic. On the other hand, EPA is metabolized to leukotriene B5 (LTB5) and thromboxane A3 (TXA3), which are eicosanoids that promote vasodilation, inhibit platelet aggregation and leukocyte chemotaxis and are anti-artherogenic and anti-thrombotic. The triglyceride-lowering effect of EPA results from inhibition of lipogenesis and stimulation of fatty acid oxidation. Fatty acid oxidation of EPA occurs mainly in the mitochondria. EPA is a substrate for Prostaglandin-endoperoxide synthase 1 and 2. It also appears to affect the function and bind to the Carbohydrate responsive element binding protein (ChREBP) and to a fatty acid receptor (G-coupled receptor) known as GP40. •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): Animi-3 With Vitamin D •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Eicosapentaenoic acid Icosapent Icosapentaenoic acid Icosapento Icosapentum Timnodonic 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): Icosapent is a polyunsaturated fatty acid, usually found in fish oils, that is used in many supplements.

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 Icosapent interact? Information: •Drug A: Abciximab •Drug B: Icosapent •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Icosapent 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): EPA can be used for lowering elevated triglycerides in those who are hyperglyceridemic. In addition, EPA may play a therapeutic role in patients with cystic fibrosis by reducing disease severity and may play a similar role in type 2 diabetics in slowing the progression of diabetic nephropathy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Eicosanoids are chemical messengers derived from 20-carbon polyunsaturated fatty acids that play critical roles in immune and inflammatory responses. Both 20-carbon omega-6 fatty acids (arachidonic acid) and 20-carbon omega-3 fatty acids (EPA) can be found in cell membranes. During an inflammatory response, arachidonic acid and EPA are metabolized by enzymes known as cyclooxygenases and lipoxygenases to form eicosanoids. Increasing omega-3 fatty acid intake increases the EPA content of cell membranes and decreases the arachidonic acid content, resulting in higher proportions of eicosanoids derived from EPA. Physiologic responses to arachidonic acid-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and clotting than eicosanoids derived from arachidonic acid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The anti-inflammatory, antithrombotic and immunomodulatory actions of EPA is probably due to its role in eicosanoid physiology and biochemistry. Most eicosanoids are produced by the metabolism of omega-3 fatty acids, specifically, arachidonic acid. These eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2) stimulate leukocyte chemotaxis, platelet aggregation and vasoconstriction. They are thrombogenic and artherogenic. On the other hand, EPA is metabolized to leukotriene B5 (LTB5) and thromboxane A3 (TXA3), which are eicosanoids that promote vasodilation, inhibit platelet aggregation and leukocyte chemotaxis and are anti-artherogenic and anti-thrombotic. The triglyceride-lowering effect of EPA results from inhibition of lipogenesis and stimulation of fatty acid oxidation. Fatty acid oxidation of EPA occurs mainly in the mitochondria. EPA is a substrate for Prostaglandin-endoperoxide synthase 1 and 2. It also appears to affect the function and bind to the Carbohydrate responsive element binding protein (ChREBP) and to a fatty acid receptor (G-coupled receptor) known as GP40. •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): Animi-3 With Vitamin D •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Eicosapentaenoic acid Icosapent Icosapentaenoic acid Icosapento Icosapentum Timnodonic 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): Icosapent is a polyunsaturated fatty acid, usually found in fish oils, that is used in many supplements. 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 Idarubicin interact?

•Drug A: Abciximab •Drug B: Idarubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Idarubicin. •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 myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Idarubicin 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. Idarubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Idarubicin 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): Idarubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Idarubicin 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): 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): 97% •Metabolism (Drug A): 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 drug is eliminated predominately by biliary and to a lesser extent by renal excretion, mostly in the form of idarubicinol. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 22 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): Idamycin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4-Demethoxydaunorubicin Idarubicin Idarubicina Idarubicine Idarubicinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Idarubicin is an anthracycline antineoplastic agent used to treat acute myeloid leukemia (AML) in adults.

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 Idarubicin interact? Information: •Drug A: Abciximab •Drug B: Idarubicin •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Idarubicin. •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 myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Idarubicin 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. Idarubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Idarubicin 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): Idarubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Idarubicin 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): 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): 97% •Metabolism (Drug A): 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 drug is eliminated predominately by biliary and to a lesser extent by renal excretion, mostly in the form of idarubicinol. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 22 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): Idamycin •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 4-Demethoxydaunorubicin Idarubicin Idarubicina Idarubicine Idarubicinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Idarubicin is an anthracycline antineoplastic agent used to treat acute myeloid leukemia (AML) in adults. 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 Idarucizumab interact?

•Drug A: Abciximab •Drug B: Idarucizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Idarucizumab. •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 use in patients treated with Dabigatran when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures and in life-threatening or uncontrolled 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): 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): Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect. •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): 8.9 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): Several pathways have been described that may contribute to the metabolism of antibodies. All of these pathways involve biodegradation of the antibody to smaller molecules, i.e., small peptides or amino acids which are then reabsorbed and incorporated in the general protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After intravenous administration of 5 g idarucizumab, 32.1% (gCV 60.0%) of the dose was recovered in urine within a collection period of 6 hours and less than 1% in the following 18 hours. The remaining part of the dose is assumed to be eliminated via protein catabolism, mainly in the kidney. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): initial half-life: 47 minutes terminal half-life: 10.3 h •Clearance (Drug A): No clearance available •Clearance (Drug B): 47.0 mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In healthy volunteers, the most frequently reported adverse reactions in greater than or equal to 5% of subjects treated with idarucizumab was headache. In patients, the most frequently reported adverse reactions in greater than or equal to 5% of patients treated with idarucizumab were hypokalemia, delirium, constipation, pyrexia, and pneumonia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Praxbind •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): Idarucizumab is an antibody that binds dabigatran for the reversal of anticoagulant effects of dabigatran.

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 Idarucizumab interact? Information: •Drug A: Abciximab •Drug B: Idarucizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Idarucizumab. •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 use in patients treated with Dabigatran when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures and in life-threatening or uncontrolled 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): 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): Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect. •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): 8.9 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): Several pathways have been described that may contribute to the metabolism of antibodies. All of these pathways involve biodegradation of the antibody to smaller molecules, i.e., small peptides or amino acids which are then reabsorbed and incorporated in the general protein synthesis. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): After intravenous administration of 5 g idarucizumab, 32.1% (gCV 60.0%) of the dose was recovered in urine within a collection period of 6 hours and less than 1% in the following 18 hours. The remaining part of the dose is assumed to be eliminated via protein catabolism, mainly in the kidney. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): initial half-life: 47 minutes terminal half-life: 10.3 h •Clearance (Drug A): No clearance available •Clearance (Drug B): 47.0 mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In healthy volunteers, the most frequently reported adverse reactions in greater than or equal to 5% of subjects treated with idarucizumab was headache. In patients, the most frequently reported adverse reactions in greater than or equal to 5% of patients treated with idarucizumab were hypokalemia, delirium, constipation, pyrexia, and pneumonia. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Praxbind •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): Idarucizumab is an antibody that binds dabigatran for the reversal of anticoagulant effects of dabigatran. 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 Ifosfamide interact?

•Drug A: Abciximab •Drug B: Ifosfamide •Severity: MAJOR •Description: The risk or severity of bleeding can be increased when Ifosfamide is combined with Abciximab. •Extended Description: It is reported that ifosfamide, due to its mechanism of action, can produce a significant reduction in the platelet number generating severe thrombocytopenia. This effect can derive from a high risk of bleeding events. When this agent is combined with anticoagulant agents, there is a high risk of bleeding events that can be very severe. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer. Also used as a component of various chemotherapeutic regimens for the treatment of cervical cancer, as well as in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas. Other indications include treatment of osteosarcoma, bladder cancer, ovarian cancer. small cell lung cancer, and non-Hodgkin's 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): Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase 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): The exact mechanism of ifosfamide has not been determined, but appears to be similar to other alkylating agents. Ifosfamide requires biotransformation in the liver by mixed-function oxidases (cytochrome P450 system) before it becomes active. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily through the alkylation of DNA, done by attaching the N-7 position of guanine to its reactive electrophilic groups. The formation of inter and intra strand cross-links in the DNA results in 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): Ifosfamide volume of distribution (Vd) approximates the total body water volume, suggesting that distribution takes place with minimal tissue binding. Following intravenous administration of 1.5 g/m2 over 0.5 hour once daily for 5 days to 15 patients with neoplastic disease, the median Vd of ifosfamide was 0.64 L/kg on Day 1 and 0.72 L/kg on Day 5. When given to pediatric patients, the volume of distribution was 21±1.6 L/m^2. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ifosfamide shows little 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): Primarily hepatic. Ifosfamide is metabolized through two metabolic pathways: ring oxidation ("activation") to form the active metabolite, 4-hydroxy-ifosfamide and side-chain oxidation to form the inactive metabolites, 3-dechloro-ethylifosfamide or 2-dechloroethylifosfamide with liberation of the toxic metabolite, chloroacetaldehyde. Small quantities (nmol/mL) of ifosfamide mustard and 4-hydroxyifosfamide are detectable in human plasma. Metabolism of ifosfamide is required for the generation of the biologically active species and while metabolism is extensive, it is also quite variable among patients. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ifosfamide is extensively metabolized in humans and the metabolic pathways appear to be saturated at high doses. After administration of doses of 5 g/m2 of 14C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. At doses of 1.6–2.4 g/m2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 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): 7-15 hours. The elimination half-life increase appeared to be related to the increase in ifosfamide volume of distribution with age. •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.4±0.33 L/h/m^2 [pediatric patients] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 (mouse) = 390-1005 mg/kg, LD 50 (rat) = 150-190 mg/kg. Side effects include nausea, vomiting and myelosuppression. Toxic effects include central nervous system toxicity (confusion, hallucinations) and urotoxic effects (cystitis, blood in urine). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ifex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ifosfamida Ifosfamide Ifosfamidum Iphosphamide Isofosfamide Isophosphamide Isosfamide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ifosfamide is an alkylating and immunosuppressive agent used in chemotherapy for the treatment of cancers, including testicular cancer, ovarian cancer, cervical cancer, osteocarcinoma, bladder cancer, small cell lung cancer, and non-Hodgkin's lymphoma.

It is reported that ifosfamide, due to its mechanism of action, can produce a significant reduction in the platelet number generating severe thrombocytopenia. This effect can derive from a high risk of bleeding events. When this agent is combined with anticoagulant agents, there is a high risk of bleeding events that can be very severe. The severity of the interaction is major.

Question: Does Abciximab and Ifosfamide interact? Information: •Drug A: Abciximab •Drug B: Ifosfamide •Severity: MAJOR •Description: The risk or severity of bleeding can be increased when Ifosfamide is combined with Abciximab. •Extended Description: It is reported that ifosfamide, due to its mechanism of action, can produce a significant reduction in the platelet number generating severe thrombocytopenia. This effect can derive from a high risk of bleeding events. When this agent is combined with anticoagulant agents, there is a high risk of bleeding events that can be very severe. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer. Also used as a component of various chemotherapeutic regimens for the treatment of cervical cancer, as well as in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas. Other indications include treatment of osteosarcoma, bladder cancer, ovarian cancer. small cell lung cancer, and non-Hodgkin's 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): Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase 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): The exact mechanism of ifosfamide has not been determined, but appears to be similar to other alkylating agents. Ifosfamide requires biotransformation in the liver by mixed-function oxidases (cytochrome P450 system) before it becomes active. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily through the alkylation of DNA, done by attaching the N-7 position of guanine to its reactive electrophilic groups. The formation of inter and intra strand cross-links in the DNA results in 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): Ifosfamide volume of distribution (Vd) approximates the total body water volume, suggesting that distribution takes place with minimal tissue binding. Following intravenous administration of 1.5 g/m2 over 0.5 hour once daily for 5 days to 15 patients with neoplastic disease, the median Vd of ifosfamide was 0.64 L/kg on Day 1 and 0.72 L/kg on Day 5. When given to pediatric patients, the volume of distribution was 21±1.6 L/m^2. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Ifosfamide shows little 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): Primarily hepatic. Ifosfamide is metabolized through two metabolic pathways: ring oxidation ("activation") to form the active metabolite, 4-hydroxy-ifosfamide and side-chain oxidation to form the inactive metabolites, 3-dechloro-ethylifosfamide or 2-dechloroethylifosfamide with liberation of the toxic metabolite, chloroacetaldehyde. Small quantities (nmol/mL) of ifosfamide mustard and 4-hydroxyifosfamide are detectable in human plasma. Metabolism of ifosfamide is required for the generation of the biologically active species and while metabolism is extensive, it is also quite variable among patients. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ifosfamide is extensively metabolized in humans and the metabolic pathways appear to be saturated at high doses. After administration of doses of 5 g/m2 of 14C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. At doses of 1.6–2.4 g/m2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 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): 7-15 hours. The elimination half-life increase appeared to be related to the increase in ifosfamide volume of distribution with age. •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.4±0.33 L/h/m^2 [pediatric patients] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 (mouse) = 390-1005 mg/kg, LD 50 (rat) = 150-190 mg/kg. Side effects include nausea, vomiting and myelosuppression. Toxic effects include central nervous system toxicity (confusion, hallucinations) and urotoxic effects (cystitis, blood in urine). •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ifex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ifosfamida Ifosfamide Ifosfamidum Iphosphamide Isofosfamide Isophosphamide Isosfamide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ifosfamide is an alkylating and immunosuppressive agent used in chemotherapy for the treatment of cancers, including testicular cancer, ovarian cancer, cervical cancer, osteocarcinoma, bladder cancer, small cell lung cancer, and non-Hodgkin's lymphoma. Output: It is reported that ifosfamide, due to its mechanism of action, can produce a significant reduction in the platelet number generating severe thrombocytopenia. This effect can derive from a high risk of bleeding events. When this agent is combined with anticoagulant agents, there is a high risk of bleeding events that can be very severe. The severity of the interaction is major.

Does Abciximab and Iloprost interact?

•Drug A: Abciximab •Drug B: Iloprost •Severity: MINOR •Description: Iloprost may increase the anticoagulant activities of Abciximab. •Extended Description: Since iloprost inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Inhaled iloprost solution is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue diseases (23%). Intravenous iloprost is indicated for the treatment of severe frostbite in adults to reduce the risk of digit amputations. Effectiveness was established in young, healthy adults who suffered frostbite at high altitudes. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer. In patients with primary pulmonary hypertension, iloprost decreased pulmonary vascular resistance and pulmonary artery pressure. Iloprost was shown to inhibit platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated. Iloprost is reported to attenuate ischemia-induced tissue injury. When administered intravenously in patients with peripheral vascular conditions such as critical leg ischemia and delayed amputation, iloprost was shown to promote cytoprotection. In isolated animal heart preparations and in intact animals with ischemia-reperfusion injury, preserved myocardial function was observed following iloprost administraion. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 pulmonary arterial hypertension, endothelial vasoactive mediators such as nitric oxide and prostacyclin are released to induce vasoconstriction. Iloprost mimics the biological actions of prostacyclin, a short-lived prostanoid and potent vasodilator mainly produced in the vascular endothelium. The exact mechanism of iloprost in cytoprotection has not been fully elucidated; however, it is proposed that iloprost decreases catecholamine outflow from sympathetic nerve terminals, preserves mitochondrial function, and reduces oxidative stress. Decreased neutrophil accumulation and membrane stabilization have also been suggested. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following inhalation of iloprost (5 mcg) patients with pulmonary hypertension have iloprost peak plasma levels of approximately 150 pg/mL. Iloprost was generally not detectable in plasma 30 minutes to one hour after inhalation. The absolute bioavailability of inhaled iloprost has not been determined. When iloprost was administered via intravenous infusion at a rate of 2 ng/kg/min, steady-state plasma concentrations were 85 ng/L. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous infusion, the apparent steady-state volume of distribution was 0.7 to 0.8 L/kg in healthy subjects. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Iloprost is approximately 60% protein-bound, mainly to albumin, and this ratio is concentration-independent in the range of 30 to 3000 pg/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): In vitro studies reveal that cytochrome P450-dependent metabolism plays only a minor role in the biotransformation of iloprost. Iloprost is metabolized principally via β-oxidation of the carboxyl side chain. The main metabolite is tetranor-iloprost, which was shown to be pharmacologically inactive in animal experiments. In rabbits, dinor-iloprost has also been identified as a drug metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Unchanged iloprost and its metabolites are mainly excreted in urine. About 70% of the drug and metabolites undergo renal excretion. Following the administration of intravenous infusion at the rate of 2 ng/kg/min and oral dose at 0.1 ug/kg, fecal excretion was 12% and 17%, 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 half-life of iloprost is 20 to 30 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance in normal subjects was approximately 20 mL/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is >100 mg/kg. Cases of overdose have been reported. Frequently observed symptoms following overdose are dizziness, headache, flushing, nausea, jaw pain or back pain. Hypotension, vomiting, and diarrhea are possible. A specific antidote is not known. Interruption of the inhalation session, monitoring, and symptomatic measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ventavis •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): Iloprost is a synthetic prostacyclin analog used to treat pulmonary arterial hypertension (PAH) and frostbites.

Since iloprost inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors. The severity of the interaction is minor.

Question: Does Abciximab and Iloprost interact? Information: •Drug A: Abciximab •Drug B: Iloprost •Severity: MINOR •Description: Iloprost may increase the anticoagulant activities of Abciximab. •Extended Description: Since iloprost inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Inhaled iloprost solution is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue diseases (23%). Intravenous iloprost is indicated for the treatment of severe frostbite in adults to reduce the risk of digit amputations. Effectiveness was established in young, healthy adults who suffered frostbite at high altitudes. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer. In patients with primary pulmonary hypertension, iloprost decreased pulmonary vascular resistance and pulmonary artery pressure. Iloprost was shown to inhibit platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated. Iloprost is reported to attenuate ischemia-induced tissue injury. When administered intravenously in patients with peripheral vascular conditions such as critical leg ischemia and delayed amputation, iloprost was shown to promote cytoprotection. In isolated animal heart preparations and in intact animals with ischemia-reperfusion injury, preserved myocardial function was observed following iloprost administraion. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 pulmonary arterial hypertension, endothelial vasoactive mediators such as nitric oxide and prostacyclin are released to induce vasoconstriction. Iloprost mimics the biological actions of prostacyclin, a short-lived prostanoid and potent vasodilator mainly produced in the vascular endothelium. The exact mechanism of iloprost in cytoprotection has not been fully elucidated; however, it is proposed that iloprost decreases catecholamine outflow from sympathetic nerve terminals, preserves mitochondrial function, and reduces oxidative stress. Decreased neutrophil accumulation and membrane stabilization have also been suggested. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following inhalation of iloprost (5 mcg) patients with pulmonary hypertension have iloprost peak plasma levels of approximately 150 pg/mL. Iloprost was generally not detectable in plasma 30 minutes to one hour after inhalation. The absolute bioavailability of inhaled iloprost has not been determined. When iloprost was administered via intravenous infusion at a rate of 2 ng/kg/min, steady-state plasma concentrations were 85 ng/L. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous infusion, the apparent steady-state volume of distribution was 0.7 to 0.8 L/kg in healthy subjects. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Iloprost is approximately 60% protein-bound, mainly to albumin, and this ratio is concentration-independent in the range of 30 to 3000 pg/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): In vitro studies reveal that cytochrome P450-dependent metabolism plays only a minor role in the biotransformation of iloprost. Iloprost is metabolized principally via β-oxidation of the carboxyl side chain. The main metabolite is tetranor-iloprost, which was shown to be pharmacologically inactive in animal experiments. In rabbits, dinor-iloprost has also been identified as a drug metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Unchanged iloprost and its metabolites are mainly excreted in urine. About 70% of the drug and metabolites undergo renal excretion. Following the administration of intravenous infusion at the rate of 2 ng/kg/min and oral dose at 0.1 ug/kg, fecal excretion was 12% and 17%, 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 half-life of iloprost is 20 to 30 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance in normal subjects was approximately 20 mL/min/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is >100 mg/kg. Cases of overdose have been reported. Frequently observed symptoms following overdose are dizziness, headache, flushing, nausea, jaw pain or back pain. Hypotension, vomiting, and diarrhea are possible. A specific antidote is not known. Interruption of the inhalation session, monitoring, and symptomatic measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ventavis •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): Iloprost is a synthetic prostacyclin analog used to treat pulmonary arterial hypertension (PAH) and frostbites. Output: Since iloprost inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors. The severity of the interaction is minor.

Does Abciximab and Imatinib interact?

•Drug A: Abciximab •Drug B: Imatinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Imatinib. •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): Imatinib is indicated for the treatment of adult and pediatric chronic myeloid leukemia with Philadelphia chromosome mutation (Ph+) in blast crisis, accelerated phase, or chronic phase after IFN-alpha therapy failure. Additionally, imatinib is also indicated to treat adult and pediatric Ph+ acute lymphoblastic leukemia, adult myelodysplastic/myeloproliferative diseases, adult aggressive systemic mastocytosis, adult hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), adult dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors (GIST). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Imatinib is a 2-phenylaminopyrimidine derivative neoplastic agent that belongs to the class of tyrosine kinase inhibitors. Although imatinib inhibits a number of tyrosine kinases, it is quite selective toward the BCR-ABL fusion protein that is present in various cancers. BCR-ABL pathway controls many downstream pathways that are heavily implicated in neoplastic growth such as the Ras/MapK pathway (cellular proliferation), Src/Pax/Fak/Rac pathway (cellular motility), and PI/PI3K/AKT/BCL-2 pathway (apoptosis pathway). Therefore, the BCR-ABL pathway is an attractive target for cancer treatment. Although normal cells also depend on these pathways for growth, these cells tend to have redundant tyrosine kinases to continually function in spite of ABL inhibition from imatinib. Cancer cells, on the other hand, can have a dependence on BCR-ABL, thus more heavily impacted by imatinib. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutively active tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Although the function of normal BCR is still unclear, ABL activation is overexpressed in various tumors and is heavily implicated in cancer cells growth and survival. Imatinib inhibits the BCR-ABL protein by binding to the ATP pocket in the active site, thus preventing downstream phosphorylation of target protein. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-Kit mutation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Imatinib is well absorbed after oral administration with Cmax achieved within 2-4 hours post-dose. Mean absolute bioavailability is 98%. Mean imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of imatinib on repeated dosing, and accumulation is 1.5- to 2.5-fold at a steady state when Gleevec is dosed once daily. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Population pharmacokinetics in adult CML patients estimated the steady-state volume of distribution of imatinib to be 295.0 ± 62.5 L. At a dose of 340 mg/m, the volume of distribution of imatinib in pediatric patients was calculated to be 167 ± 84 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): At clinically relevant concentrations of imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to 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): CYP3A4 is the major enzyme responsible for the metabolism of imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to the parent imatinib. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being 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): Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-desmethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Typically, clearance of imatinib in a 50-year-old patient weighing 50 kg is expected to be 8 L/h, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/h. The inter-patient variability of 40% in clearance does not warrant initial dose adjustment based on body weight and/or age but indicates the need for close monitoring for treatment-related toxicities. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequently reported adverse reactions (>30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain. In the 2-year rat carcinogenicity study administration of imatinib at 15, 30, and 60 mg/kg/day resulted in a statistically significant reduction in the longevity of males at 60 mg/kg/day and females at greater than or equal to 30 mg/kg/day. Target organs for neoplastic changes were the kidneys (renal tubule and renal pelvis), urinary bladder, urethra, preputial and clitoral gland, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach. Neoplastic lesions were not seen at 30 mg/kg/day for the kidneys, urinary bladder, urethra, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach, and 15 mg/kg/day for the preputial and clitoral gland. The papilloma/carcinoma of the preputial/clitoral gland was noted at 30 and 60 mg/kg/day, representing approximately 0.5 to 4 or 0.3 to 2.4 times the human daily exposure (based on AUC) at 400 mg/day or 800 mg/day, respectively, and 0.4 to 3.0 times the daily exposure in children (based on AUC) at 340 mg/m2. The renal tubule adenoma/carcinoma, renal pelvis transitional cell neoplasms, the urinary bladder and urethra transitional cell papillomas, the small intestine adenocarcinomas, the parathyroid glands adenomas, the benign and malignant medullary tumors of the adrenal glands and the non-glandular stomach papillomas/carcinomas were noted at 60 mg/kg/day. The relevance of these findings in the rat carcinogenicity study for humans is not known. Positive genotoxic effects were obtained for imatinib in an in vitro mammalian cell assay (Chinese hamster ovary) for clastogenicity (chromosome aberrations) in the presence of metabolic activation. Two intermediates of the manufacturing process, which are also present in the final product, are positive for mutagenesis in the Ames assay. One of these intermediates was also positive in the mouse lymphoma assay. Imatinib was not genotoxic when tested in an in vitro bacterial cell assay (Ames test), an in vitro mammalian cell assay (mouse lymphoma) and an in vivo rat micronucleus assay. In a study of fertility, male rats were dosed for 70 days prior to mating and female rats were dosed 14 days prior to mating and through to gestational Day 6. Testicular and epididymal weights and percent motile sperm were decreased at 60 mg/kg, approximately three-fourths the maximum clinical dose of 800 mg/day based on BSA. This was not seen at doses less than or equal to 20 mg/kg (one-fourth of the maximum human dose of 800 mg). The fertility of male and female rats was not affected. Fertility was not affected in the preclinical fertility and early embryonic development study although lower testes and epididymal weights, as well as a reduced number of motile sperm, were observed in the high-dose male rats. In the preclinical pre-and postnatal study in rats, fertility in the first generation offspring was also not affected by imatinib mesylate. It is important to consider potential toxicities suggested by animal studies, specifically, liver, kidney, and cardiac toxicity and immunosuppression. Severe liver toxicity was observed in dogs treated for 2 weeks, with elevated liver enzymes, hepatocellular necrosis, bile duct necrosis, and bile duct hyperplasia. Renal toxicity was observed in monkeys treated for 2 weeks, with focal mineralization and dilation of the renal tubules and tubular nephrosis. Increased blood urea nitrogen (BUN) and creatinine were observed in several of these animals. An increased rate of opportunistic infections was observed with chronic imatinib treatment in laboratory animal studies. In a 39-week monkey study, treatment with imatinib resulted in the worsening of normally suppressed malarial infections in these animals. Lymphopenia was observed in animals (as in humans). Additional long-term toxicities were identified in a 2-year rat study. Histopathological examination of the treated rats that died in the study revealed cardiomyopathy (both sexes), chronic progressive nephropathy (females), and preputial gland papilloma as principal causes of death or reasons for sacrifice. Non-neoplastic lesions seen in this 2-year study that were not identified in earlier preclinical studies were the cardiovascular system, pancreas, endocrine organs, and teeth. The most important changes included cardiac hypertrophy and dilatation, leading to signs of cardiac insufficiency in some animals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gleevec, Glivec •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Imatinib Imatinibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Imatinib is a tyrosine kinase inhibitor used to treat a number of leukemias, myelodysplastic/myeloproliferative disease, systemic mastocytosis, hypereosinophilic syndrome, dermatofibrosarcoma protuberans, and gastrointestinal stromal 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 Imatinib interact? Information: •Drug A: Abciximab •Drug B: Imatinib •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Imatinib. •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): Imatinib is indicated for the treatment of adult and pediatric chronic myeloid leukemia with Philadelphia chromosome mutation (Ph+) in blast crisis, accelerated phase, or chronic phase after IFN-alpha therapy failure. Additionally, imatinib is also indicated to treat adult and pediatric Ph+ acute lymphoblastic leukemia, adult myelodysplastic/myeloproliferative diseases, adult aggressive systemic mastocytosis, adult hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), adult dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors (GIST). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Imatinib is a 2-phenylaminopyrimidine derivative neoplastic agent that belongs to the class of tyrosine kinase inhibitors. Although imatinib inhibits a number of tyrosine kinases, it is quite selective toward the BCR-ABL fusion protein that is present in various cancers. BCR-ABL pathway controls many downstream pathways that are heavily implicated in neoplastic growth such as the Ras/MapK pathway (cellular proliferation), Src/Pax/Fak/Rac pathway (cellular motility), and PI/PI3K/AKT/BCL-2 pathway (apoptosis pathway). Therefore, the BCR-ABL pathway is an attractive target for cancer treatment. Although normal cells also depend on these pathways for growth, these cells tend to have redundant tyrosine kinases to continually function in spite of ABL inhibition from imatinib. Cancer cells, on the other hand, can have a dependence on BCR-ABL, thus more heavily impacted by imatinib. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutively active tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Although the function of normal BCR is still unclear, ABL activation is overexpressed in various tumors and is heavily implicated in cancer cells growth and survival. Imatinib inhibits the BCR-ABL protein by binding to the ATP pocket in the active site, thus preventing downstream phosphorylation of target protein. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-Kit mutation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Imatinib is well absorbed after oral administration with Cmax achieved within 2-4 hours post-dose. Mean absolute bioavailability is 98%. Mean imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of imatinib on repeated dosing, and accumulation is 1.5- to 2.5-fold at a steady state when Gleevec is dosed once daily. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Population pharmacokinetics in adult CML patients estimated the steady-state volume of distribution of imatinib to be 295.0 ± 62.5 L. At a dose of 340 mg/m, the volume of distribution of imatinib in pediatric patients was calculated to be 167 ± 84 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): At clinically relevant concentrations of imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to 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): CYP3A4 is the major enzyme responsible for the metabolism of imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to the parent imatinib. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being 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): Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-desmethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively. •Clearance (Drug A): No clearance available •Clearance (Drug B): Typically, clearance of imatinib in a 50-year-old patient weighing 50 kg is expected to be 8 L/h, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/h. The inter-patient variability of 40% in clearance does not warrant initial dose adjustment based on body weight and/or age but indicates the need for close monitoring for treatment-related toxicities. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most frequently reported adverse reactions (>30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain. In the 2-year rat carcinogenicity study administration of imatinib at 15, 30, and 60 mg/kg/day resulted in a statistically significant reduction in the longevity of males at 60 mg/kg/day and females at greater than or equal to 30 mg/kg/day. Target organs for neoplastic changes were the kidneys (renal tubule and renal pelvis), urinary bladder, urethra, preputial and clitoral gland, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach. Neoplastic lesions were not seen at 30 mg/kg/day for the kidneys, urinary bladder, urethra, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach, and 15 mg/kg/day for the preputial and clitoral gland. The papilloma/carcinoma of the preputial/clitoral gland was noted at 30 and 60 mg/kg/day, representing approximately 0.5 to 4 or 0.3 to 2.4 times the human daily exposure (based on AUC) at 400 mg/day or 800 mg/day, respectively, and 0.4 to 3.0 times the daily exposure in children (based on AUC) at 340 mg/m2. The renal tubule adenoma/carcinoma, renal pelvis transitional cell neoplasms, the urinary bladder and urethra transitional cell papillomas, the small intestine adenocarcinomas, the parathyroid glands adenomas, the benign and malignant medullary tumors of the adrenal glands and the non-glandular stomach papillomas/carcinomas were noted at 60 mg/kg/day. The relevance of these findings in the rat carcinogenicity study for humans is not known. Positive genotoxic effects were obtained for imatinib in an in vitro mammalian cell assay (Chinese hamster ovary) for clastogenicity (chromosome aberrations) in the presence of metabolic activation. Two intermediates of the manufacturing process, which are also present in the final product, are positive for mutagenesis in the Ames assay. One of these intermediates was also positive in the mouse lymphoma assay. Imatinib was not genotoxic when tested in an in vitro bacterial cell assay (Ames test), an in vitro mammalian cell assay (mouse lymphoma) and an in vivo rat micronucleus assay. In a study of fertility, male rats were dosed for 70 days prior to mating and female rats were dosed 14 days prior to mating and through to gestational Day 6. Testicular and epididymal weights and percent motile sperm were decreased at 60 mg/kg, approximately three-fourths the maximum clinical dose of 800 mg/day based on BSA. This was not seen at doses less than or equal to 20 mg/kg (one-fourth of the maximum human dose of 800 mg). The fertility of male and female rats was not affected. Fertility was not affected in the preclinical fertility and early embryonic development study although lower testes and epididymal weights, as well as a reduced number of motile sperm, were observed in the high-dose male rats. In the preclinical pre-and postnatal study in rats, fertility in the first generation offspring was also not affected by imatinib mesylate. It is important to consider potential toxicities suggested by animal studies, specifically, liver, kidney, and cardiac toxicity and immunosuppression. Severe liver toxicity was observed in dogs treated for 2 weeks, with elevated liver enzymes, hepatocellular necrosis, bile duct necrosis, and bile duct hyperplasia. Renal toxicity was observed in monkeys treated for 2 weeks, with focal mineralization and dilation of the renal tubules and tubular nephrosis. Increased blood urea nitrogen (BUN) and creatinine were observed in several of these animals. An increased rate of opportunistic infections was observed with chronic imatinib treatment in laboratory animal studies. In a 39-week monkey study, treatment with imatinib resulted in the worsening of normally suppressed malarial infections in these animals. Lymphopenia was observed in animals (as in humans). Additional long-term toxicities were identified in a 2-year rat study. Histopathological examination of the treated rats that died in the study revealed cardiomyopathy (both sexes), chronic progressive nephropathy (females), and preputial gland papilloma as principal causes of death or reasons for sacrifice. Non-neoplastic lesions seen in this 2-year study that were not identified in earlier preclinical studies were the cardiovascular system, pancreas, endocrine organs, and teeth. The most important changes included cardiac hypertrophy and dilatation, leading to signs of cardiac insufficiency in some animals. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Gleevec, Glivec •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Imatinib Imatinibum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Imatinib is a tyrosine kinase inhibitor used to treat a number of leukemias, myelodysplastic/myeloproliferative disease, systemic mastocytosis, hypereosinophilic syndrome, dermatofibrosarcoma protuberans, and gastrointestinal stromal 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 Imdevimab interact?

•Drug A: Abciximab •Drug B: Imdevimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Imdevimab. •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): According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19. This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required. Limitations of use Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2. In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor. Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Imdevimab is part of an investigational recombinant monoclonal antibody cocktail used to treat mild to moderate COVID-19.

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 Imdevimab interact? Information: •Drug A: Abciximab •Drug B: Imdevimab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Imdevimab. •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): According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19. This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required. Limitations of use Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2. In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor. Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2. •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Imdevimab is part of an investigational recombinant monoclonal antibody cocktail used to treat mild to moderate COVID-19. 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 Imlifidase interact?

•Drug A: Abciximab •Drug B: Imlifidase •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Imlifidase. •Extended Description: Imlifidase cleaves IgG antibodies and may therefore inactivate monoclonal antibodies derived from human or rabbit IgG if given concomitantly.1 However, when given at therapeutic doses, imlifidase does not appear to cleave eculizumab. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Imlifidase is indicated for desensitization of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor. The treatment is reserved for patients unlikely to receive a transplant under the available kidney allocation system including prioritization programs for highly sensitized 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): Imlifidase is highly specific to all four human IgG subclasses and does not cleave any other immunoglobulins (IgM, IgA, IgE, IgD). The inactivation of human IgG antibodies occurs rapidly and efficiently after administration of imlifidase, with the effect lasting for several weeks. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Imlifidase is a cysteine protease derived from Streptococcus pyogenes which degrades immunoglobulin G (IgG) in a multistep process. In the first step, imlifidase cleaves one of the two IgG heavy chains at the lower hinge leaving the other intact, resulting in a single cleaved IgG molecule. In the second step, the second heavy chain is cleaved yielding one homodimeric Fc fragment and one F(ab’) 2 fragment. This process removes the ability of the F(ab’) 2 fragments to participate in Fc-mediated functions including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Ultimately, by degrading the entire IgG pool, imlifidase reduces donor-specific antibodies (DSA) and allows transplantation to occur. •Absorption (Drug A): No absorption available •Absorption (Drug B): Given that imlifidase is administered intravenously, it is fully absorbed and bioavailable; imlifidase exposure is dose-proportional and predictable. After a dose of 0.25 mg/kg, the mean Cmax of imlifidase was 5.8 (4.2-8.9) ug/mL. Tmax occurs once infusion is complete or soon after. Food is not expected to impact the effectiveness or absorption of imlifidase. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of imlifidase is reported to be 0.2 L/kg in the elimination phase. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is currently no evidence to suggest that imlifidase binds to any other protein besides its primary target - immunoglobulin G (IgG). Studies have demonstrated that imlifidase is highly specific for IgG and does not bind to any other human immunoglobulins. •Metabolism (Drug A): 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 currently no imlifidase metabolism data available; however, it is thought to be eliminated via proteolysis. •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 distribution half-life of imlifidase is reported to be 1.8 hours, while the mean elimination half-life is reported to be 89 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance value of imlifidase is reported to be 1.8 mL/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is currently no data for imlifidase administered at supra-therapeutic doses; therefore, toxicity information is not readily available. In cases of overdose, the patient should be carefully monitored and symptomatic treatment should be initiated as needed. Although there is no antidote to imlifidase, administration of intravenous IgG may correct depleted IgG levels. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Idefirix •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): Imlifidase is a cysteine protease that specifically cleaves human IgG antibodies, facilitating kidney transplantation in HLA sensitized patients.

Imlifidase cleaves IgG antibodies and may therefore inactivate monoclonal antibodies derived from human or rabbit IgG if given concomitantly.1 However, when given at therapeutic doses, imlifidase does not appear to cleave eculizumab. The severity of the interaction is moderate.

Question: Does Abciximab and Imlifidase interact? Information: •Drug A: Abciximab •Drug B: Imlifidase •Severity: MODERATE •Description: The therapeutic efficacy of Abciximab can be decreased when used in combination with Imlifidase. •Extended Description: Imlifidase cleaves IgG antibodies and may therefore inactivate monoclonal antibodies derived from human or rabbit IgG if given concomitantly.1 However, when given at therapeutic doses, imlifidase does not appear to cleave eculizumab. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Imlifidase is indicated for desensitization of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor. The treatment is reserved for patients unlikely to receive a transplant under the available kidney allocation system including prioritization programs for highly sensitized 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): Imlifidase is highly specific to all four human IgG subclasses and does not cleave any other immunoglobulins (IgM, IgA, IgE, IgD). The inactivation of human IgG antibodies occurs rapidly and efficiently after administration of imlifidase, with the effect lasting for several weeks. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Imlifidase is a cysteine protease derived from Streptococcus pyogenes which degrades immunoglobulin G (IgG) in a multistep process. In the first step, imlifidase cleaves one of the two IgG heavy chains at the lower hinge leaving the other intact, resulting in a single cleaved IgG molecule. In the second step, the second heavy chain is cleaved yielding one homodimeric Fc fragment and one F(ab’) 2 fragment. This process removes the ability of the F(ab’) 2 fragments to participate in Fc-mediated functions including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Ultimately, by degrading the entire IgG pool, imlifidase reduces donor-specific antibodies (DSA) and allows transplantation to occur. •Absorption (Drug A): No absorption available •Absorption (Drug B): Given that imlifidase is administered intravenously, it is fully absorbed and bioavailable; imlifidase exposure is dose-proportional and predictable. After a dose of 0.25 mg/kg, the mean Cmax of imlifidase was 5.8 (4.2-8.9) ug/mL. Tmax occurs once infusion is complete or soon after. Food is not expected to impact the effectiveness or absorption of imlifidase. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of imlifidase is reported to be 0.2 L/kg in the elimination phase. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is currently no evidence to suggest that imlifidase binds to any other protein besides its primary target - immunoglobulin G (IgG). Studies have demonstrated that imlifidase is highly specific for IgG and does not bind to any other human immunoglobulins. •Metabolism (Drug A): 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 currently no imlifidase metabolism data available; however, it is thought to be eliminated via proteolysis. •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 distribution half-life of imlifidase is reported to be 1.8 hours, while the mean elimination half-life is reported to be 89 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance value of imlifidase is reported to be 1.8 mL/h/kg. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is currently no data for imlifidase administered at supra-therapeutic doses; therefore, toxicity information is not readily available. In cases of overdose, the patient should be carefully monitored and symptomatic treatment should be initiated as needed. Although there is no antidote to imlifidase, administration of intravenous IgG may correct depleted IgG levels. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Idefirix •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): Imlifidase is a cysteine protease that specifically cleaves human IgG antibodies, facilitating kidney transplantation in HLA sensitized patients. Output: Imlifidase cleaves IgG antibodies and may therefore inactivate monoclonal antibodies derived from human or rabbit IgG if given concomitantly.1 However, when given at therapeutic doses, imlifidase does not appear to cleave eculizumab. The severity of the interaction is moderate.

Does Abciximab and Indomethacin interact?

•Drug A: Abciximab •Drug B: Indomethacin •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Indomethacin 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): Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis. Intravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is 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): Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation. Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength. In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines. In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment. The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity. There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation. Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2. COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation. The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis. At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth. Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus. By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus. Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent. Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration and about 90% of the dose is absorbed within 4 hours. The bioavailability is about 80-90% following rectal administration. The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state. Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively. With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals. Indometacin is distributed into the synovial fluid and is extensively bound to tissues. It has been detected in human breast milk and placenta. Although indometacin has been shown to cross the blood-brain barrier (BBB), its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations. Like other NSAIDs, indometacin is bound to plasma albumin but it does not bind to red blood cells. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation. O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity. Unconjugated metabolites are also detected in the plasma. Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis. The extent of involvement in the enterohepatic circulation ranges from 27 to 115%. About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase. Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug. The mean half-life of oral indomethacin is estimated to be about 4.5 hours. The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g. •Clearance (Drug A): No clearance available •Clearance (Drug B): In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice. The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively. Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage. The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage. Antacids may be useful. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Indocin, Tivorbex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Indometacin Indometacina Indometacine Indometacinum Indomethacin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Indomethacin is a nonsteroidal anti-inflammatory (NSAID) used for symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants.

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 Indomethacin interact? Information: •Drug A: Abciximab •Drug B: Indomethacin •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Indomethacin 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): Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis. Intravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is 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): Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation. Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength. In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines. In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment. The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity. There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation. Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2. COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation. The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis. At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth. Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus. By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus. Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent. Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration and about 90% of the dose is absorbed within 4 hours. The bioavailability is about 80-90% following rectal administration. The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state. Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively. With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals. Indometacin is distributed into the synovial fluid and is extensively bound to tissues. It has been detected in human breast milk and placenta. Although indometacin has been shown to cross the blood-brain barrier (BBB), its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations. Like other NSAIDs, indometacin is bound to plasma albumin but it does not bind to red blood cells. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation. O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity. Unconjugated metabolites are also detected in the plasma. Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis. The extent of involvement in the enterohepatic circulation ranges from 27 to 115%. About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase. Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug. The mean half-life of oral indomethacin is estimated to be about 4.5 hours. The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g. •Clearance (Drug A): No clearance available •Clearance (Drug B): In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice. The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively. Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage. The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage. Antacids may be useful. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Indocin, Tivorbex •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Indometacin Indometacina Indometacine Indometacinum Indomethacin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Indomethacin is a nonsteroidal anti-inflammatory (NSAID) used for symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants. 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 Inebilizumab interact?

•Drug A: Abciximab •Drug B: Inebilizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Inebilizumab. •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): Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult 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): Inebilizumab is a CD19-directed monoclonal antibody that results in immunosuppression through B-cell depletion with sufficient efficacy to allow a six-month dosing schedule. Due to this mechanism of action, patients undergoing inebilizumab treatment may be at higher risk of infections and should be monitored for active infections and immunoglobulin levels while undergoing treatment; vaccination is not recommended during inebilizumab treatment. Also, there is a risk of severe infusion reactions. Animal data suggests the possibility of fetal harm with inebilizumab and therefore, effective contraception during and for six months following inebilizumab treatment is recommended. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Neuromyelitis optica spectrum disorder (NMOSD), formerly referred to as Devic's disease, is an antibody-mediated autoimmune condition resulting in astroglial cell death, demyelination, and central nervous system (CNS) inflammation. The presence of anti-aquaporin 4 immunoglobulin (AQP4-IgG) is the most frequent biomarker, although AQP4-IgG negative, anti-myelin oligodendrocyte glycoprotein (anti-MOG) positive, variants with similar presentation also exist. The theoretical origin of symptoms is through AQP4-IgG-mediated astrocyte cytotoxicity and subsequent infiltration of neutrophils, eosinophils, and macrophages, leading to inflammatory-mediated oligodendrocyte damage and myelin sheath loss. In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere. CD19 is a B-cell surface antigen expressed on most B-cells, including the expanded population of CD27 CD38 CD180 CD19 plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients. Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death. Destruction of the specific AQP4-IgG-producing plasmablasts results in lower amounts of AQP4-IgG in the CNS and therefore slows neuronal damage and improves patient outcomes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Inebilizumab is given intravenously and hence is immediately exposed to the systemic circulation. The mean reported C max following second dose 300 mg administration was 108 μg/mL, and the cumulative AUC following 26 weeks of treatment with two IV administrations was 2980 μg*d/mL. In a clinical trial investigating the use of inebilizumab in relapsing multiple sclerosis, the mean C max corresponding to 30, 100, and 600 mg of inebilizumab was 17.9, 43.1, and 248.0 μg/mL and the AUC 0-∞ was 440, 1150, and 6950 μg*d/mL. In another trial for patients with systemic sclerosis, the mean C max varied between 2.7 and 227.0 μg/mL and the AUC 0-∞ varied between 16.1 and 2890.0 μg*d/mL for doses between 0.1 and 10.0 mg/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Inebilizumab has an estimated central volume of distribution of 2.95L and a peripheral volume of distribution of 2.57L. The steady-state volume of distribution in patients administered with a range of doses between 0.1 and 10.0 mg/kg ranged from 53.7 to 71.7 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): Inebilizumab is a monoclonal antibody and is hence likely degraded through proteolysis. •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): Inebilizumab exhibits biphasic pharmacokinetics with a mean terminal half-life of 18 days. The terminal half-life reported in phase I studies varied by dose but was typically close to 18 days, with a range of 6.8 to 18.7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Inebilizumab has an estimated systemic clearance of 0.19 L/day. In phase I studies, the reported clearance varied between 139-180 mL/day in one study, and 3.5-6.2 mL/kg/day in another, depending on the dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding inebilizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as severe infusion reactions, infections, and arthralgia. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Uplizna 3 Vial Kit •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): Inebilizumab is a humanized anti-CD19 cytolytic monoclonal antibody for B-cell depletion in autoimmune conditions. Currently approved only for neuromyelitis optica spectrum disorder (NMOSD).

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 Inebilizumab interact? Information: •Drug A: Abciximab •Drug B: Inebilizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Inebilizumab. •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): Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult 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): Inebilizumab is a CD19-directed monoclonal antibody that results in immunosuppression through B-cell depletion with sufficient efficacy to allow a six-month dosing schedule. Due to this mechanism of action, patients undergoing inebilizumab treatment may be at higher risk of infections and should be monitored for active infections and immunoglobulin levels while undergoing treatment; vaccination is not recommended during inebilizumab treatment. Also, there is a risk of severe infusion reactions. Animal data suggests the possibility of fetal harm with inebilizumab and therefore, effective contraception during and for six months following inebilizumab treatment is recommended. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Neuromyelitis optica spectrum disorder (NMOSD), formerly referred to as Devic's disease, is an antibody-mediated autoimmune condition resulting in astroglial cell death, demyelination, and central nervous system (CNS) inflammation. The presence of anti-aquaporin 4 immunoglobulin (AQP4-IgG) is the most frequent biomarker, although AQP4-IgG negative, anti-myelin oligodendrocyte glycoprotein (anti-MOG) positive, variants with similar presentation also exist. The theoretical origin of symptoms is through AQP4-IgG-mediated astrocyte cytotoxicity and subsequent infiltration of neutrophils, eosinophils, and macrophages, leading to inflammatory-mediated oligodendrocyte damage and myelin sheath loss. In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere. CD19 is a B-cell surface antigen expressed on most B-cells, including the expanded population of CD27 CD38 CD180 CD19 plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients. Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death. Destruction of the specific AQP4-IgG-producing plasmablasts results in lower amounts of AQP4-IgG in the CNS and therefore slows neuronal damage and improves patient outcomes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Inebilizumab is given intravenously and hence is immediately exposed to the systemic circulation. The mean reported C max following second dose 300 mg administration was 108 μg/mL, and the cumulative AUC following 26 weeks of treatment with two IV administrations was 2980 μg*d/mL. In a clinical trial investigating the use of inebilizumab in relapsing multiple sclerosis, the mean C max corresponding to 30, 100, and 600 mg of inebilizumab was 17.9, 43.1, and 248.0 μg/mL and the AUC 0-∞ was 440, 1150, and 6950 μg*d/mL. In another trial for patients with systemic sclerosis, the mean C max varied between 2.7 and 227.0 μg/mL and the AUC 0-∞ varied between 16.1 and 2890.0 μg*d/mL for doses between 0.1 and 10.0 mg/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Inebilizumab has an estimated central volume of distribution of 2.95L and a peripheral volume of distribution of 2.57L. The steady-state volume of distribution in patients administered with a range of doses between 0.1 and 10.0 mg/kg ranged from 53.7 to 71.7 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): Inebilizumab is a monoclonal antibody and is hence likely degraded through proteolysis. •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): Inebilizumab exhibits biphasic pharmacokinetics with a mean terminal half-life of 18 days. The terminal half-life reported in phase I studies varied by dose but was typically close to 18 days, with a range of 6.8 to 18.7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Inebilizumab has an estimated systemic clearance of 0.19 L/day. In phase I studies, the reported clearance varied between 139-180 mL/day in one study, and 3.5-6.2 mL/kg/day in another, depending on the dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding inebilizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as severe infusion reactions, infections, and arthralgia. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Uplizna 3 Vial Kit •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): Inebilizumab is a humanized anti-CD19 cytolytic monoclonal antibody for B-cell depletion in autoimmune conditions. Currently approved only for neuromyelitis optica spectrum disorder (NMOSD). 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 Infliximab interact?

•Drug A: Abciximab •Drug B: Infliximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Infliximab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult or pediatric (≥ 6 years of age) patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy Indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease. Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult or pediatric (≥ 6 years of age) patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy. Indicated for, in combination with methotrexate, reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. Indicated for reducing signs and symptoms in patients with active ankylosing spondylitis. Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Infliximab disrupts the activation of pro-inflammaory cascade signalling. Infliximab has shown to reduce infiltration of inflammatory cells into sites of inflammation. It also attenautes the expression of molecules mediating cellular adhesion {including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)}, chemoattraction {[IL-8 and monocyte chemotactic protein (MCP-1)} and tissue degradation {matrix metalloproteinase (MMP) 1 and 3}. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNF-α. Blocked actions of TNF-α further leads to downregulation of local and systemic pro-inflammatory cytokines (i.e. IL-1, IL-6), reduction of lymphocyte and leukocyte migration to sites of inflammation, induction of apoptosis of TNF-producing cells (i.e. activated monocytes and T lymphocytes), increased levels of nuclear factor-κB inhibitor, and reduction of reduction of endothelial adhesion molecules and acute phase proteins. Its inhibitory actions on TNF-α was demonstrated in human fibroblasts, endothelial cells, neutrophils, B and Tlymphocytes and epithelial cells. Infliximab also atteunates the production of tissue degrading enzymes synthesized by synoviocytes and/or chondrocytes. According to a transgenic mice study that developed polyarthritis due to consitutive levels of human TNF-α, infliximab decreased synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single intravenous infusion, infliximab absorption displays a linear relationship between the dose administered and the maximum serum concentration. In patients with Crohn's disease, the maximum plasma concentration (Cmax) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 75 µg/mL and 181 µg/mL, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Cmax of 120 µg/mL and 189 µg/mL, respectively. In patients with rheumatoid arthritis, the Cmax of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 192±51 µg/mL, 427±106 µg/mL, and 907±183 µg/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a pharmacokinetic study of adult patients, the distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment. In patients with Crohn's disease, the apparent volume of distribution at steady state (Vss) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 80 mL/kg and 65 mL/kg, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Vss of 70 mL/kg and 81 mL/kg, respectively. In patients with rheumatoid arthritis, the Vss of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 4.3±2.5 L, 3.2±0.7 L, and 3.1±0.6 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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Therapeutic monoclonal antibodies including infliximab are predicted to be nonspecifically metabolized to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or arc excreted by the kidney. The reticuloendothelial system (RES) are phagocytic cells of the immune system such as macrophages and monocytes that play a role in the elimination of endogenous IgG antibodies. Although administered infliximab accounts for a small fraction of total endogenous IgG and this route is not likely saturated by therapeutic mAbs, infliximab may be removed by opsonization via RES following binding of the Fc part of the antibody to Fcy-receptors expressed on the RES. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 terminal half-life of infliximab is 7.7 to 9.5 days. The data is based on a pharmacokinetic study in patients with Crohn's disease, plaque psoriasis and rheumatoid arthritis receiving a single dose of infliximab. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with Crohn's disease, the total body clearance (CL) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 18.4 mL/h and 14.3 mL/h, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in CL of 15.2 mL/h and 15.2 mL/h, respectively. In patients with rheumatoid arthritis, the CL of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 11±7.5 mL/h, 11.4±5 mL/h, and 11±8.9 mL/h, respectively. Development of antibodies to infliximab increased infliximab clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In an acute toxicity animal study, the NOAEL of intravenous infliximab in rats was 50 mg/kg. In a repeated dose animal study, the NOAEL values of intravenous infliximab was 50 mg/kg in rats at 2 weeks following 3 doses and 40 mg/kg/day in mice at 6 months. The toxicological potential of infliximab in humans has not yet been fully established. According to an analogous antibody study, infliximab is not predicted to induce tumorigenic, clastogenic or mutagenic effects. No impairment of fertility was observed in a fertility and general reproduction toxicity study with the analogous mouse antibody used in the 6-month chronic toxicity study. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Avsola, Flixabi, Inflectra, Remicade, Renflexis, Zymfentra •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): Infliximab is a monoclonal anti tumor necrosis factor alpha antibody used in the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis.

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 Infliximab interact? Information: •Drug A: Abciximab •Drug B: Infliximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Infliximab. •Extended Description: Biologic therapies carry a risk of immunogenicity which can produce a wide array of adverse effects the most serious of which include anaphylaxis and serum sickness-type reactions . Use of multiple immunoglobulin-based therapies may increase the risk of these immunological complications. A few studies suggest the use of multiple immunoglobulin agents is relatively safe and may be more effective than monotherapy for certain conditions . •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult or pediatric (≥ 6 years of age) patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy Indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease. Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult or pediatric (≥ 6 years of age) patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy. Indicated for, in combination with methotrexate, reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. Indicated for reducing signs and symptoms in patients with active ankylosing spondylitis. Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Infliximab disrupts the activation of pro-inflammaory cascade signalling. Infliximab has shown to reduce infiltration of inflammatory cells into sites of inflammation. It also attenautes the expression of molecules mediating cellular adhesion {including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)}, chemoattraction {[IL-8 and monocyte chemotactic protein (MCP-1)} and tissue degradation {matrix metalloproteinase (MMP) 1 and 3}. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNF-α. Blocked actions of TNF-α further leads to downregulation of local and systemic pro-inflammatory cytokines (i.e. IL-1, IL-6), reduction of lymphocyte and leukocyte migration to sites of inflammation, induction of apoptosis of TNF-producing cells (i.e. activated monocytes and T lymphocytes), increased levels of nuclear factor-κB inhibitor, and reduction of reduction of endothelial adhesion molecules and acute phase proteins. Its inhibitory actions on TNF-α was demonstrated in human fibroblasts, endothelial cells, neutrophils, B and Tlymphocytes and epithelial cells. Infliximab also atteunates the production of tissue degrading enzymes synthesized by synoviocytes and/or chondrocytes. According to a transgenic mice study that developed polyarthritis due to consitutive levels of human TNF-α, infliximab decreased synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single intravenous infusion, infliximab absorption displays a linear relationship between the dose administered and the maximum serum concentration. In patients with Crohn's disease, the maximum plasma concentration (Cmax) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 75 µg/mL and 181 µg/mL, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Cmax of 120 µg/mL and 189 µg/mL, respectively. In patients with rheumatoid arthritis, the Cmax of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 192±51 µg/mL, 427±106 µg/mL, and 907±183 µg/mL, respectively. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a pharmacokinetic study of adult patients, the distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment. In patients with Crohn's disease, the apparent volume of distribution at steady state (Vss) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 80 mL/kg and 65 mL/kg, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in Vss of 70 mL/kg and 81 mL/kg, respectively. In patients with rheumatoid arthritis, the Vss of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 4.3±2.5 L, 3.2±0.7 L, and 3.1±0.6 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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Therapeutic monoclonal antibodies including infliximab are predicted to be nonspecifically metabolized to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or arc excreted by the kidney. The reticuloendothelial system (RES) are phagocytic cells of the immune system such as macrophages and monocytes that play a role in the elimination of endogenous IgG antibodies. Although administered infliximab accounts for a small fraction of total endogenous IgG and this route is not likely saturated by therapeutic mAbs, infliximab may be removed by opsonization via RES following binding of the Fc part of the antibody to Fcy-receptors expressed on the RES. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 terminal half-life of infliximab is 7.7 to 9.5 days. The data is based on a pharmacokinetic study in patients with Crohn's disease, plaque psoriasis and rheumatoid arthritis receiving a single dose of infliximab. •Clearance (Drug A): No clearance available •Clearance (Drug B): In patients with Crohn's disease, the total body clearance (CL) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 18.4 mL/h and 14.3 mL/h, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in CL of 15.2 mL/h and 15.2 mL/h, respectively. In patients with rheumatoid arthritis, the CL of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 11±7.5 mL/h, 11.4±5 mL/h, and 11±8.9 mL/h, respectively. Development of antibodies to infliximab increased infliximab clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): In an acute toxicity animal study, the NOAEL of intravenous infliximab in rats was 50 mg/kg. In a repeated dose animal study, the NOAEL values of intravenous infliximab was 50 mg/kg in rats at 2 weeks following 3 doses and 40 mg/kg/day in mice at 6 months. The toxicological potential of infliximab in humans has not yet been fully established. According to an analogous antibody study, infliximab is not predicted to induce tumorigenic, clastogenic or mutagenic effects. No impairment of fertility was observed in a fertility and general reproduction toxicity study with the analogous mouse antibody used in the 6-month chronic toxicity study. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Avsola, Flixabi, Inflectra, Remicade, Renflexis, Zymfentra •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): Infliximab is a monoclonal anti tumor necrosis factor alpha antibody used in the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis. 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 Inotersen interact?

•Drug A: Abciximab •Drug B: Inotersen •Severity: MODERATE •Description: The risk or severity of thrombocytopenia can be increased when Inotersen is combined with Abciximab. •Extended Description: Since inotersen can cause a reduction in platelet count, the risk of thrombocytopenia can be increased when used in combination with other antiplatelet agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Absorption (Drug A): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Protein binding (Drug A): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Route of elimination (Drug A): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Clearance (Drug A): No clearance available •Toxicity (Drug A): No toxicity available •Brand Names (Drug A): No brand names available •Synonyms (Drug A): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found

Since inotersen can cause a reduction in platelet count, the risk of thrombocytopenia can be increased when used in combination with other antiplatelet agents. The severity of the interaction is moderate.

Question: Does Abciximab and Inotersen interact? Information: •Drug A: Abciximab •Drug B: Inotersen •Severity: MODERATE •Description: The risk or severity of thrombocytopenia can be increased when Inotersen is combined with Abciximab. •Extended Description: Since inotersen can cause a reduction in platelet count, the risk of thrombocytopenia can be increased when used in combination with other antiplatelet agents. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Absorption (Drug A): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Protein binding (Drug A): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Route of elimination (Drug A): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Clearance (Drug A): No clearance available •Toxicity (Drug A): No toxicity available •Brand Names (Drug A): No brand names available •Synonyms (Drug A): No synonyms listed •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Summary not found Output: Since inotersen can cause a reduction in platelet count, the risk of thrombocytopenia can be increased when used in combination with other antiplatelet agents. The severity of the interaction is moderate.

Does Abciximab and Inotuzumab ozogamicin interact?

•Drug A: Abciximab •Drug B: Inotuzumab ozogamicin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Inotuzumab ozogamicin. •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 as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Inotuzumab ozogamicin is an antineoplastic agent that targets CD22 antigen expressed on immature B-cell lymphocytes and blocks further growth of tumor cells. The drug aims to restore normal blood counts and achieve complete remission from the disease. QT interval prolongation was observed in patients receiving inotuzumab ozogamicin. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Inotuzumab ozogamicin is comprised of cytotoxic antibiotic N-acetyl-gamma-calicheamicin dimethylhydrazide attached to a humanized monoclonal IgG4 antibody via 4-(4 acetylphenoxy) butanoic acid (acetyl butyrate) linker. The drug exerts a potent cytotoxic effect against CD22+ B-cell lymphoma when the antibody binds to the CD22 receptor on the surface of B cells. The drug-CD22 complex is rapidly internalized into the cell, forming an endosome which subsequently fuses with lysosomes. N-acetyl-gamma-calicheamicin dimethylhydrazide is then intracellularly released into the acidic environment. N-acetyl-gamma-calicheamicin dimethylhydrazide is a calicheamicin derivative, which is naturally produced by the bacterium Micromonospora echinospora, and is toxic to the body when not bound to the antibody. It mediates apoptosis of the cell by binding to the minor groove of DNA in a sequence-specific manner and undergoing a structural change to generate diradicals. These changes abstract hydrogen ions from the phosphodiester bonds of double-stranded DNA, resulting in breaks and cell apoptosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks. The steady state exposure of the drug is reached by Cycle 4. The mean (SD) maximum serum concentration (Cmax) of inotuzumab ozogamicin was 308 ng/mL (362) with patients receving the recommended dose of 1.8 mg/m^2/cycle. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The total volume of distribution of inotuzumab ozogamicin is approximately 12L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro studies show the binding of the N-acetyl-gamma-calicheamicin dimethylhydrazide to human plasma proteins to be approximately 97%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): N-acetyl-gamma-calicheamicin dimethylhydrazide primarily undergoes nonenzymatic reduction in vitro. The metabolism of N-acetyl-gamma-calicheamicin dimethylhydrazide in human serum is not clearly understood as the level of the drug is below the limit of quantification of 50 pg/mL. The antibody portion of the drug is thought to undergo proteolytic degradation into amino acids then recycled into other proteins. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The drug is disposited in the body after administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half life at the end of Cycle 4 of administration is approximately 12.3 days in a 2-compartment model. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Inotuzumab ozogamicin was shown to be clastogenic in vivo in the bone marrow of male mice but was not mutagenic in an* in vitro* bacterial reverse mutation (Ames) assay. In rat toxicity studies, rats developed oval cell hyperplasia, altered hepatocellular foci, and hepatocellular adenomas however the carcinogenic potential of inotuzumab ozogamicin on humans is undetermined. Based on reproductive toxicity studies involving female rats and non-clinical studies, inotuzumab ozogamicin has the potential to impair reproductive function and fertility in men and women. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Besponsa •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): Inotuzumab ozogamicin is an antibody-drug conjugate used to treat B-cell precursor acute lymphoblastic leukemia (ALL).

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 Inotuzumab ozogamicin interact? Information: •Drug A: Abciximab •Drug B: Inotuzumab ozogamicin •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Inotuzumab ozogamicin. •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 as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Inotuzumab ozogamicin is an antineoplastic agent that targets CD22 antigen expressed on immature B-cell lymphocytes and blocks further growth of tumor cells. The drug aims to restore normal blood counts and achieve complete remission from the disease. QT interval prolongation was observed in patients receiving inotuzumab ozogamicin. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Inotuzumab ozogamicin is comprised of cytotoxic antibiotic N-acetyl-gamma-calicheamicin dimethylhydrazide attached to a humanized monoclonal IgG4 antibody via 4-(4 acetylphenoxy) butanoic acid (acetyl butyrate) linker. The drug exerts a potent cytotoxic effect against CD22+ B-cell lymphoma when the antibody binds to the CD22 receptor on the surface of B cells. The drug-CD22 complex is rapidly internalized into the cell, forming an endosome which subsequently fuses with lysosomes. N-acetyl-gamma-calicheamicin dimethylhydrazide is then intracellularly released into the acidic environment. N-acetyl-gamma-calicheamicin dimethylhydrazide is a calicheamicin derivative, which is naturally produced by the bacterium Micromonospora echinospora, and is toxic to the body when not bound to the antibody. It mediates apoptosis of the cell by binding to the minor groove of DNA in a sequence-specific manner and undergoing a structural change to generate diradicals. These changes abstract hydrogen ions from the phosphodiester bonds of double-stranded DNA, resulting in breaks and cell apoptosis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks. The steady state exposure of the drug is reached by Cycle 4. The mean (SD) maximum serum concentration (Cmax) of inotuzumab ozogamicin was 308 ng/mL (362) with patients receving the recommended dose of 1.8 mg/m^2/cycle. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The total volume of distribution of inotuzumab ozogamicin is approximately 12L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro studies show the binding of the N-acetyl-gamma-calicheamicin dimethylhydrazide to human plasma proteins to be approximately 97%. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): N-acetyl-gamma-calicheamicin dimethylhydrazide primarily undergoes nonenzymatic reduction in vitro. The metabolism of N-acetyl-gamma-calicheamicin dimethylhydrazide in human serum is not clearly understood as the level of the drug is below the limit of quantification of 50 pg/mL. The antibody portion of the drug is thought to undergo proteolytic degradation into amino acids then recycled into other proteins. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The drug is disposited in the body after administration. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half life at the end of Cycle 4 of administration is approximately 12.3 days in a 2-compartment model. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Inotuzumab ozogamicin was shown to be clastogenic in vivo in the bone marrow of male mice but was not mutagenic in an* in vitro* bacterial reverse mutation (Ames) assay. In rat toxicity studies, rats developed oval cell hyperplasia, altered hepatocellular foci, and hepatocellular adenomas however the carcinogenic potential of inotuzumab ozogamicin on humans is undetermined. Based on reproductive toxicity studies involving female rats and non-clinical studies, inotuzumab ozogamicin has the potential to impair reproductive function and fertility in men and women. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Besponsa •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): Inotuzumab ozogamicin is an antibody-drug conjugate used to treat B-cell precursor acute lymphoblastic leukemia (ALL). 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 Interferon alfa-2a interact?

•Drug A: Abciximab •Drug B: Interferon alfa-2a •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-2a. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.223 to 0.748 L/kg [healthy people] •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): Alpha-interferons are totally filtered through the glomeruli and undergo rapid proteolytic degradation during tubular reabsorption, rendering a negligible reappearance of intact alfa interferon in the systemic circulation. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.14 - 3.62 mL/min/kg [healthy] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. •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): Interferon alfa-2a Interferon alfa-2a (genetical recombination) Interferon alfa-2a (recombinant) Interferon alfa-2a, recombinant Interferon alfa-2a,recombinant Interferon alpha-2a Interferon-alfa-2a Recombinant human interferon alfa-2a Recombinant human interferon-alfa-2a •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Interferon alfa-2a is a form of recombinant human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses.

As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Interferon alfa-2a interact? Information: •Drug A: Abciximab •Drug B: Interferon alfa-2a •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-2a. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 0.223 to 0.748 L/kg [healthy people] •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): Alpha-interferons are totally filtered through the glomeruli and undergo rapid proteolytic degradation during tubular reabsorption, rendering a negligible reappearance of intact alfa interferon in the systemic circulation. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). •Clearance (Drug A): No clearance available •Clearance (Drug B): 2.14 - 3.62 mL/min/kg [healthy] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. •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): Interferon alfa-2a Interferon alfa-2a (genetical recombination) Interferon alfa-2a (recombinant) Interferon alfa-2a, recombinant Interferon alfa-2a,recombinant Interferon alpha-2a Interferon-alfa-2a Recombinant human interferon alfa-2a Recombinant human interferon-alfa-2a •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Interferon alfa-2a is a form of recombinant human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses. Output: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Does Abciximab and Interferon alfa-2b interact?

•Drug A: Abciximab •Drug B: Interferon alfa-2b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-2b. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which upon dimerization activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half-life following both intramuscular and subcutaneous injections was approximately 2 to 3 hours. The elimination half-life was approximately 2 hours following intravenous injection. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Intron A •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): Interferon alfa-2b is a form of recombinant human interferon used to treat hepatitis B and C infection, genital warts, hairy cell leukemia, follicular lymphoma, malignant melanoma, and AIDs-related Kaposi's sarcoma.

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 Interferon alfa-2b interact? Information: •Drug A: Abciximab •Drug B: Interferon alfa-2b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-2b. •Extended Description: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which upon dimerization activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The elimination half-life following both intramuscular and subcutaneous injections was approximately 2 to 3 hours. The elimination half-life was approximately 2 hours following intravenous injection. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Intron A •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): Interferon alfa-2b is a form of recombinant human interferon used to treat hepatitis B and C infection, genital warts, hairy cell leukemia, follicular lymphoma, malignant melanoma, and AIDs-related Kaposi's sarcoma. 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 Interferon alfa-n3 interact?

•Drug A: Abciximab •Drug B: Interferon alfa-n3 •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-n3. •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 intralesional treatment of refractory or recurring external condylomata acuminata. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Interferon alfa-n3 upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. •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): Alferon N •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): Interferon alfa-n3 is a purified form of human interferon used to stimulate the innate antiviral response in the treatment of genital warts due to human papilloma virus.

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 Interferon alfa-n3 interact? Information: •Drug A: Abciximab •Drug B: Interferon alfa-n3 •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-n3. •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 intralesional treatment of refractory or recurring external condylomata acuminata. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Interferon alfa-n3 upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. •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): Alferon N •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): Interferon alfa-n3 is a purified form of human interferon used to stimulate the innate antiviral response in the treatment of genital warts due to human papilloma virus. 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 Interferon beta-1b interact?

•Drug A: Abciximab •Drug B: Interferon beta-1b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon beta-1b. •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): Interferon beta-1b is a drug used for the treatment of relapsing/remitting multiple sclerosis. It has been shown to slow the advance of the disease as well as to decrease the frequency of attacks. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Interferon beta upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Type I interferons also induce the synthesis of several key antiviral mediators including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon beta binds to type I interferon receptors (IFNAR1 and IFNAR2c) which activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon beta binds more stably to type I interferon receptors than interferon alpha. •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): 0.25 to 2,88 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 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): 9.4 – 28.9 mL/min•kg-1 [patients with diseases other than MS receiving single intravenous doses up to 2.0 mg] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Betaferon, Betaseron, Extavia •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): Interferon beta-1b is a form of recombinant human interferon used to slow the progression of relapsing multiple sclerosis and to reduce the frequency of clinical symptoms.

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 Interferon beta-1b interact? Information: •Drug A: Abciximab •Drug B: Interferon beta-1b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon beta-1b. •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): Interferon beta-1b is a drug used for the treatment of relapsing/remitting multiple sclerosis. It has been shown to slow the advance of the disease as well as to decrease the frequency of attacks. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Interferon beta upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Type I interferons also induce the synthesis of several key antiviral mediators including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Interferon beta binds to type I interferon receptors (IFNAR1 and IFNAR2c) which activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon beta binds more stably to type I interferon receptors than interferon alpha. •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): 0.25 to 2,88 L/kg •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 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): 9.4 – 28.9 mL/min•kg-1 [patients with diseases other than MS receiving single intravenous doses up to 2.0 mg] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Betaferon, Betaseron, Extavia •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): Interferon beta-1b is a form of recombinant human interferon used to slow the progression of relapsing multiple sclerosis and to reduce the frequency of clinical symptoms. 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 Interferon gamma-1b interact?

•Drug A: Abciximab •Drug B: Interferon gamma-1b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon gamma-1b. •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): Interferon gamma-1b is used for the treatment of Chronic granulomatous disease and Osteopetrosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): IFN gamma stimulates expression of the immunoglobulin heavy chain C gamma 3 and C gamma 2a germline transcripts in B cells. Many components of the antigen presentation pathways are also up-regulated by interferon gamma. It is also a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of type I interferons. Interferon gamma may also help the body regulate the activity of fibroblasts. By directly blocking the multiplication of fibroblasts and inhibiting the production and action of TGF-b, a potent scar-inducing molecule, Interferon gamma-1b may prevent excessive scarring. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. •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): Actimmune •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): Interferon gamma-1b is a form of recombinant human interferon used to treat infections associated with chronic granulomatous disease and to slow the progression of severe malignant osteopetrosis.

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 Interferon gamma-1b interact? Information: •Drug A: Abciximab •Drug B: Interferon gamma-1b •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Interferon gamma-1b. •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): Interferon gamma-1b is used for the treatment of Chronic granulomatous disease and Osteopetrosis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): IFN gamma stimulates expression of the immunoglobulin heavy chain C gamma 3 and C gamma 2a germline transcripts in B cells. Many components of the antigen presentation pathways are also up-regulated by interferon gamma. It is also a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of type I interferons. Interferon gamma may also help the body regulate the activity of fibroblasts. By directly blocking the multiplication of fibroblasts and inhibiting the production and action of TGF-b, a potent scar-inducing molecule, Interferon gamma-1b may prevent excessive scarring. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. •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): Actimmune •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): Interferon gamma-1b is a form of recombinant human interferon used to treat infections associated with chronic granulomatous disease and to slow the progression of severe malignant osteopetrosis. 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 Ipilimumab interact?

•Drug A: Abciximab •Drug B: Ipilimumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ipilimumab. •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): Ipilimumab is indicated in the following cancerous conditions: Melanoma Treatment of unresectable or metastatic melanoma in patients ≥12 years old Treatment of unresectable or metastatic melanoma, in combination with nivolumab, in adult patients Adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of >1 mm who have undergone complete resection, including total lymphadenectomy Renal Cell Carcinoma (RCC) First-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma in combination with nivolumab Colorectal Cancer In combination with nivolumab, treatment of patients ≥12 years old with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following previous treatment with a fluoropyrimidine, oxaliplatin, and irinotecan Hepatocellular Carcinoma In combination with nivolumab, treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib Non-Small Cell Lung Cancer (NSCLC) Treatment of adult patients with metastatic non-small cell lung cancer expressing PD-L1, with no EFGR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab Treatment of adult patients with metastatic or recurrent non-small cell lung cancer, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy Malignant Pleural Mesothelioma Treatment of adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with nivolumab Esophageal Cancer - Treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, as first line treatment in combination with nivolumab •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ipilimumab is a human IgG1 that binds CTLA-4, preventing 1 T-cell inhibition signal pathway. It has a long duration of action as it is given every 3 to 4 weeks. Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion related reactions, and embryo-fetal toxicity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that competes with the stimulatory CD28 for binding to B7 on antigen presenting cells. CTLA-4 and CD28 are both presented on the surface of T-cells. Ipilimumab is a human IgG1 that binds CTLA-4, preventing the inhibition of T-cell mediated immune responses to tumors. •Absorption (Drug A): No absorption available •Absorption (Drug B): C max was 65.8µg/mL for 2-6 year olds, 70.1µg/mL for 6-<12 year olds, and 73.3µg/mL in patients 12 years and older. Data regarding the AUC and T max of ipilumumab are not readily available. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady-state of ipilimumab is 7.21L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Data regarding the protein binding of ipilimumab 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): The metabolism of ipilimumab does not involve the cytochrome P450 enzyme system. Because ipilimumab is a protein, it is expected to be degraded into small peptides and amino acids by proteolytic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Data regarding the route of elimination of ipilimumab is not readily 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): Ipilimumab has a half life of 14.7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ipilimumab has a clearance of 15.3 mL/hr. Systemic clearance increases proportionally with body weight. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding ipilumumab overdose is not readily available. However, the most common adverse reactions to ipilumumab are fatigue, diarrhea, pruritus, rash, and colitis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Yervoy •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): Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody used to treat metastatic or unresectable melanoma.

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 Ipilimumab interact? Information: •Drug A: Abciximab •Drug B: Ipilimumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ipilimumab. •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): Ipilimumab is indicated in the following cancerous conditions: Melanoma Treatment of unresectable or metastatic melanoma in patients ≥12 years old Treatment of unresectable or metastatic melanoma, in combination with nivolumab, in adult patients Adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of >1 mm who have undergone complete resection, including total lymphadenectomy Renal Cell Carcinoma (RCC) First-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma in combination with nivolumab Colorectal Cancer In combination with nivolumab, treatment of patients ≥12 years old with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following previous treatment with a fluoropyrimidine, oxaliplatin, and irinotecan Hepatocellular Carcinoma In combination with nivolumab, treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib Non-Small Cell Lung Cancer (NSCLC) Treatment of adult patients with metastatic non-small cell lung cancer expressing PD-L1, with no EFGR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab Treatment of adult patients with metastatic or recurrent non-small cell lung cancer, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy Malignant Pleural Mesothelioma Treatment of adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with nivolumab Esophageal Cancer - Treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, as first line treatment in combination with nivolumab •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ipilimumab is a human IgG1 that binds CTLA-4, preventing 1 T-cell inhibition signal pathway. It has a long duration of action as it is given every 3 to 4 weeks. Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion related reactions, and embryo-fetal toxicity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that competes with the stimulatory CD28 for binding to B7 on antigen presenting cells. CTLA-4 and CD28 are both presented on the surface of T-cells. Ipilimumab is a human IgG1 that binds CTLA-4, preventing the inhibition of T-cell mediated immune responses to tumors. •Absorption (Drug A): No absorption available •Absorption (Drug B): C max was 65.8µg/mL for 2-6 year olds, 70.1µg/mL for 6-<12 year olds, and 73.3µg/mL in patients 12 years and older. Data regarding the AUC and T max of ipilumumab are not readily available. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution at steady-state of ipilimumab is 7.21L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Data regarding the protein binding of ipilimumab 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): The metabolism of ipilimumab does not involve the cytochrome P450 enzyme system. Because ipilimumab is a protein, it is expected to be degraded into small peptides and amino acids by proteolytic enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Data regarding the route of elimination of ipilimumab is not readily 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): Ipilimumab has a half life of 14.7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Ipilimumab has a clearance of 15.3 mL/hr. Systemic clearance increases proportionally with body weight. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Data regarding ipilumumab overdose is not readily available. However, the most common adverse reactions to ipilumumab are fatigue, diarrhea, pruritus, rash, and colitis. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Yervoy •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): Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody used to treat metastatic or unresectable melanoma. 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 Irinotecan interact?

•Drug A: Abciximab •Drug B: Irinotecan •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Irinotecan. •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): Irinotecan is indicated for the treatment of: - Metastatic carcinoma of the colon or rectum as first-line treatment in combination with fluorouracil and leucovorin. - Metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy, as monotherapy or in combination with fluorouracil and leucovorin. Irinotecan liposome injection is used in adults for the treatment of: - Metastatic pancreatic adenocarcinoma in combination with oxaliplatin, fluorouracil, and leucovorin as first-line treatment. - Metastatic pancreatic adenocarcinoma in combination with fluorouracil and leucovorin after disease progression following gemcitabine-based 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): Irinotecan is an antineoplastic agent. The administration of irinotecan has resulted in antitumor activity in mice bearing cancers of rodent origin and in human carcinoma xenografts of various histological types. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): DNA topoisomerase I is a nuclear enzyme that ensures proper DNA topology during replication and transcription. It relieves torsional strain in the DNA double helix during replication and transcription by creating reversible single-strand breaks. Upon administration, irinotecan is converted into its active metabolite, SN-38, by carboxylesterase in the liver and gastrointestinal tract. Irinotecan and SN-38 both inhibit DNA topoisomerase I, acting on the S and G2 phases of the cell cycle. Irinotecan and SN-38 bind to the topoisomerase I-DNA complex and prevent the religation of single-strand breaks. The ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38 interferes with the moving replication fork, inducing replication arrest and lethal double-stranded breaks in DNA. Because double-stranded breaks cannot be efficiently repaired by mammalian cells, apoptosis of cancer cells occurs. •Absorption (Drug A): No absorption available •Absorption (Drug B): Over the recommended dose range of 50 to 350 mg/m, the AUC of irinotecan increases linearly with dose; the AUC of SN-38 increases less than proportionally with dose. Maximum concentrations of the active metabolite SN-38 are generally seen within 1 hour following the end of a 90-minute infusion of irinotecan. The plasma levels of SN-38 are much lower than that of irinotecan. Following intravenous infusion in patients with solid tumours, the mean (± standard deviation) C max was 1,660 ± 797 ng/mL at a dose of 125 mg/m and 3,392 ± 874 ng/mL at a dose of 340 mg/m. The AUC 0–24 was 10,200 ± 3,270 ng x h/mL at a dose of 125 mg/m and 20,604 ± 6,027 ng x h/mL at a dose of 340 mg/m. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous infusion in patients with solid tumours, the mean (± standard deviation) volume of distribution of terminal elimination phase was 110 ± 48.5 L/m at a dose of 125 mg/m and 234 ± 69.6 L/m at a dose of 340 mg/m. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Irinotecan is about 30% to 68% bound to plasma proteins. SN-38 is approximately 95% bound to plasma proteins. Irinotecan and SN-38 are mainly 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): Upon administration, irinotecan is converted primarily in the liver into its active metabolite, SN-38, by carboxylesterase. SN-38 is formed by cleavage of the carbamate bond between the camptothecin moiety and the dipiperidino side chain. While in vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies, SN-38 is approximately 1000 times as potent as irinotecan as an inhibitor of topoisomerase I. SN-38 can further be glucuronidated by UGT1A1 to form SN-38G. Irinotecan can also undergo CYP3A4-mediated oxidation to form NPC and APC. While some sources state that NPC and APC are weak inhibitors of topoisomerase I, they are unlikely to contribute to the pharmacological activity of irinotecan. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The disposition of irinotecan has not been fully elucidated in humans. The urinary excretion of irinotecan, SN-38, and SN-38 glucuronide are 11% to 20%, <1%, and 3%, respectively. The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours in two patients ranged from approximately 25% (100 mg/m ) to 50% (300 mg/m ). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 intravenous infusion of irinotecan in humans, the mean terminal elimination half-life of irinotecan is about 6 to 12 hours. The mean terminal elimination half-life of the active metabolite SN-38 is about 10 to 20 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (± standard deviation) total systemic clearance of irinotecan in patients with solid tumours was 13.3 ± 6.01 L/h/m at a dose of 125 mg/m and 13.9 ± 4.0 L/h/m at a dose of 340 mg/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 is 1045 mg/kg in mice and 867 mg/kg in rats. In clinical trials involving patients with various cancers, single doses of up to 750 mg/m of irinotecan were associated with similar adverse events reported with the recommended dosage and regimen. There have been reports of overdosage at doses up to approximately twice the recommended therapeutic dose, which may be fatal. The most significant adverse reactions reported were severe neutropenia and severe diarrhea. Because there is no known antidote for overdosage of irinotecan, maximum supportive care should be instituted to prevent dehydration due to diarrhea and to treat any infectious complications. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Camptosar, Onivyde •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl 4-(2-(5-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-hydroxy-4H-1,2,4-triazol-4-yl)-1H-indol-1-yl)ethyl)piperidine-1-carboxylate Irinotecan Irinotecan lactone Irinotecan liposome injection Irinotecanum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Irinotecan is a topoisomerase inhibitor used to treat metastatic carcinoma of the colon or rectum and pancreatic adenocarcinoma.

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 Irinotecan interact? Information: •Drug A: Abciximab •Drug B: Irinotecan •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Irinotecan. •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): Irinotecan is indicated for the treatment of: - Metastatic carcinoma of the colon or rectum as first-line treatment in combination with fluorouracil and leucovorin. - Metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy, as monotherapy or in combination with fluorouracil and leucovorin. Irinotecan liposome injection is used in adults for the treatment of: - Metastatic pancreatic adenocarcinoma in combination with oxaliplatin, fluorouracil, and leucovorin as first-line treatment. - Metastatic pancreatic adenocarcinoma in combination with fluorouracil and leucovorin after disease progression following gemcitabine-based 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): Irinotecan is an antineoplastic agent. The administration of irinotecan has resulted in antitumor activity in mice bearing cancers of rodent origin and in human carcinoma xenografts of various histological types. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): DNA topoisomerase I is a nuclear enzyme that ensures proper DNA topology during replication and transcription. It relieves torsional strain in the DNA double helix during replication and transcription by creating reversible single-strand breaks. Upon administration, irinotecan is converted into its active metabolite, SN-38, by carboxylesterase in the liver and gastrointestinal tract. Irinotecan and SN-38 both inhibit DNA topoisomerase I, acting on the S and G2 phases of the cell cycle. Irinotecan and SN-38 bind to the topoisomerase I-DNA complex and prevent the religation of single-strand breaks. The ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38 interferes with the moving replication fork, inducing replication arrest and lethal double-stranded breaks in DNA. Because double-stranded breaks cannot be efficiently repaired by mammalian cells, apoptosis of cancer cells occurs. •Absorption (Drug A): No absorption available •Absorption (Drug B): Over the recommended dose range of 50 to 350 mg/m, the AUC of irinotecan increases linearly with dose; the AUC of SN-38 increases less than proportionally with dose. Maximum concentrations of the active metabolite SN-38 are generally seen within 1 hour following the end of a 90-minute infusion of irinotecan. The plasma levels of SN-38 are much lower than that of irinotecan. Following intravenous infusion in patients with solid tumours, the mean (± standard deviation) C max was 1,660 ± 797 ng/mL at a dose of 125 mg/m and 3,392 ± 874 ng/mL at a dose of 340 mg/m. The AUC 0–24 was 10,200 ± 3,270 ng x h/mL at a dose of 125 mg/m and 20,604 ± 6,027 ng x h/mL at a dose of 340 mg/m. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Following intravenous infusion in patients with solid tumours, the mean (± standard deviation) volume of distribution of terminal elimination phase was 110 ± 48.5 L/m at a dose of 125 mg/m and 234 ± 69.6 L/m at a dose of 340 mg/m. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Irinotecan is about 30% to 68% bound to plasma proteins. SN-38 is approximately 95% bound to plasma proteins. Irinotecan and SN-38 are mainly 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): Upon administration, irinotecan is converted primarily in the liver into its active metabolite, SN-38, by carboxylesterase. SN-38 is formed by cleavage of the carbamate bond between the camptothecin moiety and the dipiperidino side chain. While in vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies, SN-38 is approximately 1000 times as potent as irinotecan as an inhibitor of topoisomerase I. SN-38 can further be glucuronidated by UGT1A1 to form SN-38G. Irinotecan can also undergo CYP3A4-mediated oxidation to form NPC and APC. While some sources state that NPC and APC are weak inhibitors of topoisomerase I, they are unlikely to contribute to the pharmacological activity of irinotecan. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The disposition of irinotecan has not been fully elucidated in humans. The urinary excretion of irinotecan, SN-38, and SN-38 glucuronide are 11% to 20%, <1%, and 3%, respectively. The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours in two patients ranged from approximately 25% (100 mg/m ) to 50% (300 mg/m ). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 intravenous infusion of irinotecan in humans, the mean terminal elimination half-life of irinotecan is about 6 to 12 hours. The mean terminal elimination half-life of the active metabolite SN-38 is about 10 to 20 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (± standard deviation) total systemic clearance of irinotecan in patients with solid tumours was 13.3 ± 6.01 L/h/m at a dose of 125 mg/m and 13.9 ± 4.0 L/h/m at a dose of 340 mg/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 is 1045 mg/kg in mice and 867 mg/kg in rats. In clinical trials involving patients with various cancers, single doses of up to 750 mg/m of irinotecan were associated with similar adverse events reported with the recommended dosage and regimen. There have been reports of overdosage at doses up to approximately twice the recommended therapeutic dose, which may be fatal. The most significant adverse reactions reported were severe neutropenia and severe diarrhea. Because there is no known antidote for overdosage of irinotecan, maximum supportive care should be instituted to prevent dehydration due to diarrhea and to treat any infectious complications. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Camptosar, Onivyde •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl 4-(2-(5-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-hydroxy-4H-1,2,4-triazol-4-yl)-1H-indol-1-yl)ethyl)piperidine-1-carboxylate Irinotecan Irinotecan lactone Irinotecan liposome injection Irinotecanum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Irinotecan is a topoisomerase inhibitor used to treat metastatic carcinoma of the colon or rectum and pancreatic adenocarcinoma. 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 Isatuximab interact?

•Drug A: Abciximab •Drug B: Isatuximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Isatuximab. •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): Isatuximab is indicated in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma in adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. It is also indicated in combination carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Isatuximab results in the apoptosis of malignant plasma cells via inhibition of a surface protein key to their survival and proliferation. It has a relatively long residence time in the body, taking approximately 2 months to clear following the final dose, and may therefore be infused on a weekly or bimonthly schedule. Isatuximab is given in combination with pomalidomide due to a synergy that exists between the two - isatuximab can induce a depletion in host NK lymphocytes, yet the ADCC effect of anti-CD38 mAbs has been shown to be superior in patient samples with a high ratio of NK to myleoma cells. Pomalidomide, another antineoplastic agent, has the ability to induce and enhance NK lymphocyte activity and thus works synergistically to enhance isatuximab-mediated killing of myeloma cells. Isatuximab is formulated as an intravenous infusion and its administration may result in infusion-related reactions characterized most commonly by dyspnea, cough, chills, and nausea. All noted reactions started during the first infusion and 98% resolved on the same day. Reactions may be mitigated by pre-medication with acetaminophen, H2 antagonists, diphenyhdramine, and/or dexamethasone. Patients with grade 1 or 2 reactions may restart the infusion at a slower rate following resolution of symptoms, but patients experiencing a grade 3 or higher reaction (e.g. hypertension, bronchospasm) should discontinue therapy indefinitely. Isatuximab can generate false positive results for indirect antglobulin tests (indirect Coombs tests), immunofixation tests, and serum protein electrophoresis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Multiple myeloma is a blood cancer characterized by an overproduction of malignant plasma cells in the bone marrow. A unique characteristic of myeloma cells is their dense and uniform expression of CD38 surface glycoproteins - these proteins, also expressed in relatively minor quantities on other lymphoid and myeloid cells, have been identified as performing several critical cellular functions, and this, along with their relative abundance on myeloma cells, has made them an attractive target for multiple myeloma treatment. CD38 was first identified as an activation marker, but has subsequently demonstrated roles in adhesion to endothelial CD31 proteins, as an accessory component of the synapse complex, and as an ectoenzyme involved in the metabolism of extracellular NAD+ and cytoplasmic NADP. The products of CD38’s ectoenzymatic activity include the calcium-mobilizing compound adenosine diphosphate ribose (ADPR), which can be further metabolized by CD203a/PC-1 and CD73 to adenosine, an immunosuppressive molecule that may play a role in tumour cell evasion of the immune system. Isatuximab is an IgG1-derived monoclonal antibody targeted against CD38 proteins. Its activity against CD38 results in a number of downstream effects, including direct apoptosis of the affected cell and activation of immune mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC), all of which result in potent anti-tumour activity. Via allosteric antagonism, isatuximab also inhibits CD38 ectoenzymatic activity, preventing the immunosuppressive effects of its downstream products. Isatuximab may also exert its effects via downstream promotion of lysosome-dependent cell death, upregulation of reactive oxygen species, and restoration of antitumor immune effector cell functions. •Absorption (Drug A): No absorption available •Absorption (Drug B): When administered at the recommended dose and schedule, the steady-state C max and AUC were found to be 351 µg/mL and 72,600 μg∙h/mL, respectively. It takes approximately 8 weeks for isatuximab to reach steady-state. Over a dosage range of 1 mg/kg to 20 mg/kg given every 2 weeks AUC increases in a greater than dose-proportional manner, whereas over a dosage range of 5 mg/kg to 20 mg/kg every 4 weeks (followed by every 2 weeks) AUC was found to increase proportionately with dose. Steady-state AUC is lower in patients with increased body weight, but not to the extent that dose adjustments are required. T max ranges from approximately 2 to 5 hours, increasing with dose and with repeated dosing. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The predicted volume of distribution of isatuximab is 8.13 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): Isatuximab metabolism is likely to involve catabolism to smaller proteins and peptides. •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): Total clearance decreases with increasing dose and with multiple dosing. At steady-state, it takes approximately 2 months to eliminate ≥99% of isatuximab from plasma following the last dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no known antidote for isatuximab, nor does there appear to be any clinical experience with overdose. Symptoms of overdosage are likely to be consistent with isatuximab's adverse effect profile and may therefore include significant infusion-site reactions, gastrointestinal disturbances, and may increase the risk of infection. Treatment of overdose should involve careful monitoring of the patient and symptomatic and supportive measures as clinically indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Sarclisa •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): Isatuximab is a chimeric monoclonal antibody targeted against surface CD38 glycoproteins for the treatment of multiple myeloma in patients who have failed previous therapies.

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 Isatuximab interact? Information: •Drug A: Abciximab •Drug B: Isatuximab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Isatuximab. •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): Isatuximab is indicated in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma in adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. It is also indicated in combination carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Isatuximab results in the apoptosis of malignant plasma cells via inhibition of a surface protein key to their survival and proliferation. It has a relatively long residence time in the body, taking approximately 2 months to clear following the final dose, and may therefore be infused on a weekly or bimonthly schedule. Isatuximab is given in combination with pomalidomide due to a synergy that exists between the two - isatuximab can induce a depletion in host NK lymphocytes, yet the ADCC effect of anti-CD38 mAbs has been shown to be superior in patient samples with a high ratio of NK to myleoma cells. Pomalidomide, another antineoplastic agent, has the ability to induce and enhance NK lymphocyte activity and thus works synergistically to enhance isatuximab-mediated killing of myeloma cells. Isatuximab is formulated as an intravenous infusion and its administration may result in infusion-related reactions characterized most commonly by dyspnea, cough, chills, and nausea. All noted reactions started during the first infusion and 98% resolved on the same day. Reactions may be mitigated by pre-medication with acetaminophen, H2 antagonists, diphenyhdramine, and/or dexamethasone. Patients with grade 1 or 2 reactions may restart the infusion at a slower rate following resolution of symptoms, but patients experiencing a grade 3 or higher reaction (e.g. hypertension, bronchospasm) should discontinue therapy indefinitely. Isatuximab can generate false positive results for indirect antglobulin tests (indirect Coombs tests), immunofixation tests, and serum protein electrophoresis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Multiple myeloma is a blood cancer characterized by an overproduction of malignant plasma cells in the bone marrow. A unique characteristic of myeloma cells is their dense and uniform expression of CD38 surface glycoproteins - these proteins, also expressed in relatively minor quantities on other lymphoid and myeloid cells, have been identified as performing several critical cellular functions, and this, along with their relative abundance on myeloma cells, has made them an attractive target for multiple myeloma treatment. CD38 was first identified as an activation marker, but has subsequently demonstrated roles in adhesion to endothelial CD31 proteins, as an accessory component of the synapse complex, and as an ectoenzyme involved in the metabolism of extracellular NAD+ and cytoplasmic NADP. The products of CD38’s ectoenzymatic activity include the calcium-mobilizing compound adenosine diphosphate ribose (ADPR), which can be further metabolized by CD203a/PC-1 and CD73 to adenosine, an immunosuppressive molecule that may play a role in tumour cell evasion of the immune system. Isatuximab is an IgG1-derived monoclonal antibody targeted against CD38 proteins. Its activity against CD38 results in a number of downstream effects, including direct apoptosis of the affected cell and activation of immune mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC), all of which result in potent anti-tumour activity. Via allosteric antagonism, isatuximab also inhibits CD38 ectoenzymatic activity, preventing the immunosuppressive effects of its downstream products. Isatuximab may also exert its effects via downstream promotion of lysosome-dependent cell death, upregulation of reactive oxygen species, and restoration of antitumor immune effector cell functions. •Absorption (Drug A): No absorption available •Absorption (Drug B): When administered at the recommended dose and schedule, the steady-state C max and AUC were found to be 351 µg/mL and 72,600 μg∙h/mL, respectively. It takes approximately 8 weeks for isatuximab to reach steady-state. Over a dosage range of 1 mg/kg to 20 mg/kg given every 2 weeks AUC increases in a greater than dose-proportional manner, whereas over a dosage range of 5 mg/kg to 20 mg/kg every 4 weeks (followed by every 2 weeks) AUC was found to increase proportionately with dose. Steady-state AUC is lower in patients with increased body weight, but not to the extent that dose adjustments are required. T max ranges from approximately 2 to 5 hours, increasing with dose and with repeated dosing. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The predicted volume of distribution of isatuximab is 8.13 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): Isatuximab metabolism is likely to involve catabolism to smaller proteins and peptides. •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): Total clearance decreases with increasing dose and with multiple dosing. At steady-state, it takes approximately 2 months to eliminate ≥99% of isatuximab from plasma following the last dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no known antidote for isatuximab, nor does there appear to be any clinical experience with overdose. Symptoms of overdosage are likely to be consistent with isatuximab's adverse effect profile and may therefore include significant infusion-site reactions, gastrointestinal disturbances, and may increase the risk of infection. Treatment of overdose should involve careful monitoring of the patient and symptomatic and supportive measures as clinically indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Sarclisa •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): Isatuximab is a chimeric monoclonal antibody targeted against surface CD38 glycoproteins for the treatment of multiple myeloma in patients who have failed previous therapies. 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 Isocarboxazid interact?

•Drug A: Abciximab •Drug B: Isocarboxazid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Isocarboxazid is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Isocarboxazid is indicated for the treatment of the enduring and debilitating symptoms of depression that have not responded to other antidepressant drugs. Depression is a common but serious mood disorder. The patient will present changes in its feelings, thoughts, and ability to handle everyday activities. For a mood disorder to be considered as depression, the symptoms should be present for at least two weeks. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In vivo and in vitro studies demonstrated isocarboxazid-driven inhibition of MAO in the brain, heart, and liver. The reduced MAO activity, caused by isocarboxazid, results in an increased concentration of serotonin, epinephrine, norepinephrine, and dopamine in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The increase of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors like isocarboxazid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Isocarboxazid works by irreversibly blocking the action of monoamine oxidases (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Isocarboxacid, like other monoamine oxidase inhibitors, are unique psychopharmacological agents whose clinical effect is related to the direct action of the monoamine oxidases to transform them into reactive metabolites. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are readily absorbed by the GI tract, present a low bioavailability and reach peak concentrations in 1-2 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs present a very high protein binding percentage. •Metabolism (Drug A): 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 pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are rapidly metabolized by acetylation in the liver. As part of the metabolism, hippuric acid is a major metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Most of the eliminated dose is found in the urine, accounting for the 42.5% of the administered dose after 24 hours. From this amount, 75% of the renally eliminated drug is in the form of hippuric acid. Another section of the eliminated dose is observed through the intestinal tract and it accounts for 22% of the administered dose after 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. The isocarboxazid half-life is of little interest as it is an irreversible monoamine oxidase inhibitor. These drugs present a very short half-life of 1.5-4 hours due to rapid hepatic metabolism. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Long-term toxicity studies to evaluate the carcinogenic, mutagenic and fertility impairment potential have not been conducted. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Marplan •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): Isocarboxazid is a monoamine oxidase inhibitor used to treat enduring and debilitating symptoms of depression following inadequate clinical response to other antidepressant drugs.

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

Question: Does Abciximab and Isocarboxazid interact? Information: •Drug A: Abciximab •Drug B: Isocarboxazid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Isocarboxazid is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Isocarboxazid is indicated for the treatment of the enduring and debilitating symptoms of depression that have not responded to other antidepressant drugs. Depression is a common but serious mood disorder. The patient will present changes in its feelings, thoughts, and ability to handle everyday activities. For a mood disorder to be considered as depression, the symptoms should be present for at least two weeks. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In vivo and in vitro studies demonstrated isocarboxazid-driven inhibition of MAO in the brain, heart, and liver. The reduced MAO activity, caused by isocarboxazid, results in an increased concentration of serotonin, epinephrine, norepinephrine, and dopamine in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The increase of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors like isocarboxazid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Isocarboxazid works by irreversibly blocking the action of monoamine oxidases (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Isocarboxacid, like other monoamine oxidase inhibitors, are unique psychopharmacological agents whose clinical effect is related to the direct action of the monoamine oxidases to transform them into reactive metabolites. •Absorption (Drug A): No absorption available •Absorption (Drug B): The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are readily absorbed by the GI tract, present a low bioavailability and reach peak concentrations in 1-2 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs present a very high protein binding percentage. •Metabolism (Drug A): 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 pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are rapidly metabolized by acetylation in the liver. As part of the metabolism, hippuric acid is a major metabolite. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Most of the eliminated dose is found in the urine, accounting for the 42.5% of the administered dose after 24 hours. From this amount, 75% of the renally eliminated drug is in the form of hippuric acid. Another section of the eliminated dose is observed through the intestinal tract and it accounts for 22% of the administered dose after 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. The isocarboxazid half-life is of little interest as it is an irreversible monoamine oxidase inhibitor. These drugs present a very short half-life of 1.5-4 hours due to rapid hepatic metabolism. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Long-term toxicity studies to evaluate the carcinogenic, mutagenic and fertility impairment potential have not been conducted. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Marplan •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): Isocarboxazid is a monoamine oxidase inhibitor used to treat enduring and debilitating symptoms of depression following inadequate clinical response to other antidepressant drugs. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Ixabepilone interact?

•Drug A: Abciximab •Drug B: Ixabepilone •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ixabepilone. •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): Investigated for use/treatment in breast cancer, head and neck cancer, melanoma, lung cancer, lymphoma (non-hodgkin's), prostate cancer, renal cell carcinoma, and cancer/tumors (unspecified). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Binding of Ixabepilone to beta-tubulins (e.g. beta-III tubulin) stabilizes microtubules. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. Like taxol, Ixabepilone binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules. •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): 67-77% •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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mostly fecal and some 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): 52 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): Ixempra •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): Ixabepilone is a microtubule inhibitor administered in combination with capecitabine or alone in the treatment of metastatic or locally advanced breast cancer that has shown inadequate response to taxanes and anthracyclines.

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 Ixabepilone interact? Information: •Drug A: Abciximab •Drug B: Ixabepilone •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Ixabepilone. •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): Investigated for use/treatment in breast cancer, head and neck cancer, melanoma, lung cancer, lymphoma (non-hodgkin's), prostate cancer, renal cell carcinoma, and cancer/tumors (unspecified). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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): Binding of Ixabepilone to beta-tubulins (e.g. beta-III tubulin) stabilizes microtubules. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. Like taxol, Ixabepilone binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules. •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): 67-77% •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): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Mostly fecal and some 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): 52 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): Ixempra •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): Ixabepilone is a microtubule inhibitor administered in combination with capecitabine or alone in the treatment of metastatic or locally advanced breast cancer that has shown inadequate response to taxanes and anthracyclines. 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 Ixekizumab interact?

•Drug A: Abciximab •Drug B: Ixekizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ixekizumab. •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): Ixekizumab is indicated for the treatment of patients aged six years or older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is also indicated in adult patients with active psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis with objective signs of inflammation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): 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): Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) against interleukin-17A (IL-17A) and prevents it from interacting with the IL-17A receptor. As IL-17A is a pro-inflammatory cytokine involved in inflammation and immune responses, blocking its effect is beneficial for use in inflammatory conditions. In particular, IL-17A has been found to be implicated in a variety of autoimmune diseases including Rheumatoid Arthritis and plaque psoriasis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. •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): 13 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.39 L/day •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common adverse reactions associated with Ixekizumab treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Taltz •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): Ixekizumab is a monoclonal antibody used to treat moderate to severe 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 Ixekizumab interact? Information: •Drug A: Abciximab •Drug B: Ixekizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Ixekizumab. •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): Ixekizumab is indicated for the treatment of patients aged six years or older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is also indicated in adult patients with active psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis with objective signs of inflammation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): 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): Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) against interleukin-17A (IL-17A) and prevents it from interacting with the IL-17A receptor. As IL-17A is a pro-inflammatory cytokine involved in inflammation and immune responses, blocking its effect is beneficial for use in inflammatory conditions. In particular, IL-17A has been found to be implicated in a variety of autoimmune diseases including Rheumatoid Arthritis and plaque psoriasis. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. •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): 13 days •Clearance (Drug A): No clearance available •Clearance (Drug B): 0.39 L/day •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The most common adverse reactions associated with Ixekizumab treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Taltz •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): Ixekizumab is a monoclonal antibody used to treat moderate to severe 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 Ketoprofen interact?

•Drug A: Abciximab •Drug B: Ketoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Ketoprofen 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 acute and chronic rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, primary dysmenorrhea and mild to moderate pain associated with musculotendinous trauma (sprains and strains), postoperative (including dental surgery) or postpartum pain. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties. Ketoprofen has pharmacologic actions similar to those of other prototypical NSAIDs, which inhibit prostaglandin synthesis. Ketoprofen is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and alleviate moderate pain. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The anti-inflammatory effects of ketoprofen are believed to be due to inhibition cylooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis via the arachidonic acid pathway. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation. Ketoprofen is a non-specific cyclooxygenase inhibitor and inhibition of COX-1 is thought to confer some of its side effects, such as GI upset and ulceration. Ketoprofen is thought to have anti-bradykinin activity, as well as lysosomal membrane-stabilizing action. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ketoprofen is rapidly and well-absorbed orally, with peak plasma levels occurring within 0.5 to 2 hours. •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% bound, primarily to albumin •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Rapidly and extensively metabolized in the liver, primarily via conjugation to glucuronic acid. No active metabolites have been identified. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In a 24 hour period, approximately 80% of an administered dose of ketoprofen is excreted in the urine, primarily as the glucuronide metabolite. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Conventional capsules: 1.1-4 hours Extended release capsules: 5.4 hours due to delayed absorption (intrinsic clearance is same as conventional capsules) •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral-dose cl=6.9 +/- 0.8 L/h [Ketoprofen Immediate-release capsules (4 × 50 mg)] Oral-dose cl=6.8 +/- 1.8 L/h [Ketoprofen Extended-release capsules (1 × 200 mg)] 0.08 L/kg/h 0.7 L/kg/h [alcoholic cirrhosis patients] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =62.4 mg/kg (rat, oral). Symptoms of overdose include drowsiness, vomiting and abdominal pain. Side effects are usually mild and mainly involved the GI tract. Most common adverse GI effect is dyspepsia (11% of patients). May cause nausea, diarrhea, abdominal pain, constipation and flatulence in greater than 3% of patients. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kiprofen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ketoprofen Ketoprofeno •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ketoprofen is an NSAID used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, dysmenorrhea, mild to moderate muscle pain, postoperative pain, and postpartum 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 Ketoprofen interact? Information: •Drug A: Abciximab •Drug B: Ketoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Ketoprofen 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 acute and chronic rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, primary dysmenorrhea and mild to moderate pain associated with musculotendinous trauma (sprains and strains), postoperative (including dental surgery) or postpartum pain. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties. Ketoprofen has pharmacologic actions similar to those of other prototypical NSAIDs, which inhibit prostaglandin synthesis. Ketoprofen is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and alleviate moderate pain. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The anti-inflammatory effects of ketoprofen are believed to be due to inhibition cylooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis via the arachidonic acid pathway. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation. Ketoprofen is a non-specific cyclooxygenase inhibitor and inhibition of COX-1 is thought to confer some of its side effects, such as GI upset and ulceration. Ketoprofen is thought to have anti-bradykinin activity, as well as lysosomal membrane-stabilizing action. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ketoprofen is rapidly and well-absorbed orally, with peak plasma levels occurring within 0.5 to 2 hours. •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% bound, primarily to albumin •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Rapidly and extensively metabolized in the liver, primarily via conjugation to glucuronic acid. No active metabolites have been identified. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): In a 24 hour period, approximately 80% of an administered dose of ketoprofen is excreted in the urine, primarily as the glucuronide metabolite. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Conventional capsules: 1.1-4 hours Extended release capsules: 5.4 hours due to delayed absorption (intrinsic clearance is same as conventional capsules) •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral-dose cl=6.9 +/- 0.8 L/h [Ketoprofen Immediate-release capsules (4 × 50 mg)] Oral-dose cl=6.8 +/- 1.8 L/h [Ketoprofen Extended-release capsules (1 × 200 mg)] 0.08 L/kg/h 0.7 L/kg/h [alcoholic cirrhosis patients] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 =62.4 mg/kg (rat, oral). Symptoms of overdose include drowsiness, vomiting and abdominal pain. Side effects are usually mild and mainly involved the GI tract. Most common adverse GI effect is dyspepsia (11% of patients). May cause nausea, diarrhea, abdominal pain, constipation and flatulence in greater than 3% of patients. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Kiprofen •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Ketoprofen Ketoprofeno •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Ketoprofen is an NSAID used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, dysmenorrhea, mild to moderate muscle pain, postoperative pain, and postpartum 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 Ketorolac interact?

•Drug A: Abciximab •Drug B: Ketorolac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Ketorolac 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): Ketorolac is a Non-steroidal anti-inflammatory drug (NSAID) and has antipyretic, analgesic and anti-inflammatory properties. It is indicated for short term management of acute pain that requires the calibre of pain management offered by opioids. Clinicians may choose to initiate ketorolac to manage post-operative pain, spinal and soft tissue pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders and headaches among other ailments. Regardless of the etiology of pain, patients should use the lowest possible dose, and avoid using ketorolac for an extended period of time (ideally ≤ 5 days). A benefit of choosing ketorolac over other analgesics with similar potency is that that there does not appear to be a risk of dependence or tolerance with ketorolac 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): Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever. As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action. Although ketorolac is non-selective and inhibits both COX-1 and COX-2 enzymes, it's clinical efficacy is derived from it's COX-2 inhibition. The COX-2 enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation. Ketorolac is administered as a racemic mixture; however, the "S" enantiomer is largely responsible for it's pharmacological activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ketorolac is rapidly, and completely absorbed after oral administration with a bioavailability of 80% after oral administration. Cmax is attained 20-60 minutes after administration, and after intramuscular administration, the area under the plasma concentration-time curve (AUC) is proportional to the dose administered. After intramuscular administration, ketorolac demonstrates a time to maximal plasma concentration (tmax) of approximately 45-50 minutes, and a tmax of 30-40 minutes after oral administration. The rate of absorption may be reduced by food; however, the extent of absorption remains unaffected. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of ketorolac in healthy human subjects is 0.25 L/kg or less. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): >99% of Ketorolac is plasma protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ketorolac is heavily metabolized via hydroxylation or conjugation in the liver; however, it appears that the key metabolic pathway is glucuronic acid conjugation. Enzymes involved in phase I metabolism include CYP2C8 and CYP2C9, while phase II metabolism is carried out by UDP-glucuronosyltransferase (UGT) 2B7. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ketorolac is primarily renally eliminated and approximately 92% of the dose can be recovered in the urine with 60% of this proportion recovered unchanged, and 40% recovered as metabolites. In addition 6% of a single dose is eliminated in the feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Ketorolac tromethamine is administered as a racemic mixture, therefore the half-life of each enantiomer must be considered. The half life of the S-enantiomer is ~2.5 hours, while the half life of the R-enantiomer is ~5 hours. Based on this data, the S enantiomer is cleared about twice as fast as the R enantiomer. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of ketorolac is 0.021 to 0.037 L/h/kg. Further, studies have illustrated that clearance of oral, IM and IV doses of ketorolac are comparable which suggests linear kinetics. It should also be noted that clearance in children is about double the clearance found in adults. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The rate of adverse effects increases with higher doses of ketorolac. The most frequently observed adverse effects in patients occurring with an incidence of greater than 10% include: abdominal pain, dyspepsia, nausea, and headaches. Most adverse effects associated with short term use are mild in nature, related to the gastrointestinal tract and nervous system, and occur in roughly 39% of patients. Common symptoms of ketorolac overdose include nausea, vomiting, epigastric pain, gastrointestinal bleeding, lethargy and drowsiness. More rare symptoms of overdose include acute renal failure, hypertension, respiratory depression, and coma. Ketorolac is classified as Pregnancy Category C since there is a lack of evidence demonstrating safety in pregnant women. NSAIDs including ketorolac increase the risk of premature closure of the fetal ductus arteriosus in the 3rd trimester; therefore, beginning at 30 weeks gestation, pregnant women should avoid ketorolac. Ketorolac has been shown to be excreted in breast milk, and although available data has not demonstrated any adverse effects in nursing infants, practitioners should proceed with caution when suggesting ketorolac for nursing mothers. The benefits should outweigh the risks and the mother should be counselled to monitor the infant closely and to contact the infant's healthcare provider should any adverse effects arise. Women who are trying to conceive are not advised to take ketorolac since it's effect on prostaglandin synthesis may impair fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Acular, Acuvail, Omidria, Readysharp Anesthetics Plus Ketorolac, Sprix, Toradol, Toronova Suik •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): Ketorolac is an NSAID used to treat moderate to severe pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders, and headaches.

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 Ketorolac interact? Information: •Drug A: Abciximab •Drug B: Ketorolac •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Ketorolac 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): Ketorolac is a Non-steroidal anti-inflammatory drug (NSAID) and has antipyretic, analgesic and anti-inflammatory properties. It is indicated for short term management of acute pain that requires the calibre of pain management offered by opioids. Clinicians may choose to initiate ketorolac to manage post-operative pain, spinal and soft tissue pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders and headaches among other ailments. Regardless of the etiology of pain, patients should use the lowest possible dose, and avoid using ketorolac for an extended period of time (ideally ≤ 5 days). A benefit of choosing ketorolac over other analgesics with similar potency is that that there does not appear to be a risk of dependence or tolerance with ketorolac 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): Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever. As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action. Although ketorolac is non-selective and inhibits both COX-1 and COX-2 enzymes, it's clinical efficacy is derived from it's COX-2 inhibition. The COX-2 enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation. Ketorolac is administered as a racemic mixture; however, the "S" enantiomer is largely responsible for it's pharmacological activity. •Absorption (Drug A): No absorption available •Absorption (Drug B): Ketorolac is rapidly, and completely absorbed after oral administration with a bioavailability of 80% after oral administration. Cmax is attained 20-60 minutes after administration, and after intramuscular administration, the area under the plasma concentration-time curve (AUC) is proportional to the dose administered. After intramuscular administration, ketorolac demonstrates a time to maximal plasma concentration (tmax) of approximately 45-50 minutes, and a tmax of 30-40 minutes after oral administration. The rate of absorption may be reduced by food; however, the extent of absorption remains unaffected. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of ketorolac in healthy human subjects is 0.25 L/kg or less. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): >99% of Ketorolac is plasma protein bound. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Ketorolac is heavily metabolized via hydroxylation or conjugation in the liver; however, it appears that the key metabolic pathway is glucuronic acid conjugation. Enzymes involved in phase I metabolism include CYP2C8 and CYP2C9, while phase II metabolism is carried out by UDP-glucuronosyltransferase (UGT) 2B7. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Ketorolac is primarily renally eliminated and approximately 92% of the dose can be recovered in the urine with 60% of this proportion recovered unchanged, and 40% recovered as metabolites. In addition 6% of a single dose is eliminated in the feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Ketorolac tromethamine is administered as a racemic mixture, therefore the half-life of each enantiomer must be considered. The half life of the S-enantiomer is ~2.5 hours, while the half life of the R-enantiomer is ~5 hours. Based on this data, the S enantiomer is cleared about twice as fast as the R enantiomer. •Clearance (Drug A): No clearance available •Clearance (Drug B): The plasma clearance of ketorolac is 0.021 to 0.037 L/h/kg. Further, studies have illustrated that clearance of oral, IM and IV doses of ketorolac are comparable which suggests linear kinetics. It should also be noted that clearance in children is about double the clearance found in adults. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The rate of adverse effects increases with higher doses of ketorolac. The most frequently observed adverse effects in patients occurring with an incidence of greater than 10% include: abdominal pain, dyspepsia, nausea, and headaches. Most adverse effects associated with short term use are mild in nature, related to the gastrointestinal tract and nervous system, and occur in roughly 39% of patients. Common symptoms of ketorolac overdose include nausea, vomiting, epigastric pain, gastrointestinal bleeding, lethargy and drowsiness. More rare symptoms of overdose include acute renal failure, hypertension, respiratory depression, and coma. Ketorolac is classified as Pregnancy Category C since there is a lack of evidence demonstrating safety in pregnant women. NSAIDs including ketorolac increase the risk of premature closure of the fetal ductus arteriosus in the 3rd trimester; therefore, beginning at 30 weeks gestation, pregnant women should avoid ketorolac. Ketorolac has been shown to be excreted in breast milk, and although available data has not demonstrated any adverse effects in nursing infants, practitioners should proceed with caution when suggesting ketorolac for nursing mothers. The benefits should outweigh the risks and the mother should be counselled to monitor the infant closely and to contact the infant's healthcare provider should any adverse effects arise. Women who are trying to conceive are not advised to take ketorolac since it's effect on prostaglandin synthesis may impair fertility. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Acular, Acuvail, Omidria, Readysharp Anesthetics Plus Ketorolac, Sprix, Toradol, Toronova Suik •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): Ketorolac is an NSAID used to treat moderate to severe pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders, and headaches. 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 Lanadelumab interact?

•Drug A: Abciximab •Drug B: Lanadelumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Lanadelumab. •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): Lanadelumab is indicated for prophylaxis to prevent attacks in adult and pediatric patients aged 2 years and older with hereditary angioedema. In Canada, it is indicated for use only in adults and adolescents. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 1 studies, the level of kininogen, the substrate of kallikrein, was studied as a marker of kallikrein activity. In patients with C1 deficiency, the level of cleaved kininogen is 4-fold higher when compared with C1-normal individuals. When lanadelumab was administered, the levels of cleaved kininogen were significantly reduced with a dose of 300 and 400 mg of lanadelumab with a maximum reduction at day 22 corresponding with time for maximum concentration. This maximum reduction corresponded with the normal levels of cleaved kininogen. Similarly, the decreases of cleaved kininogen corresponded with reductions in the levels of the activated factor XII. Clinically, the attacks of angioedema completely vanished in the patients receiving a dose of 300 mg of lanadelumab. In other doses such as 400 mg and combo 300/400 mg the attack reduction reached 90%. In phase 3 clinical trials, lanadelumab showed an attack rate reduction of over 70% for all studied regimens. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hereditary angioedema (HEA) is an autosomal dominant disorder resulting from the presence of C1 deficiency. This condition manifests as attacks of subcutaneous or submucosal edema in the face, larynx, GI tract, limbs or genitalia, with laryngeal edema being the most serious due to the potential to compromise the airways. Attacks may be accompanied by pain and considerable dysfunction. Lanadelumab is a plasma kallikrein inhibitor. This enzyme works by cleaving high molecular weight kininogen to generate the pro-inflammatory peptide bradykinin, a potent vasodilator. Because the activity of plasma kallikrein is regulated by C1 esterase inhibitor, patients deficient in C1 esterase inhibitor may be at risk of excessive production of bradykinin leading to serious angioedema. Lanadelumab occludes the proteolytic active site of plasma kallikrein, preventing the cleavage of kininogen to bradykinin. It is a selective inhibitor and does not bind to prekallikrein or inhibit other serine proteases. •Absorption (Drug A): No absorption available •Absorption (Drug B): Drug levels of lanadelumab are dose-dependent and the maximum plasma concentration increases correspondingly with increasing dosage. The C max and AUC ranged from 3800 - 45000 ng/ml and 64000 - 762000 ng.day/ml, respectively, across a dosing range of 30 to 400 mg. A sustained quantifiable drug concentration was observed through day 120. The bioavailability of lanadelumab is approximately 66% with a time to reach peak drug concentration of approximately 7 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of lanadelumab is approximately 14 - 16 L depending on the dose administered. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As with other therapeutic proteins, the degradation of lanadelumab likely occurs via catabolism to 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): Lanadelumab has a half-life of approximately 2 weeks after subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of lanadelumab ranges from 0.667 to 0.809 L/day depending on the administered dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No significant toxicities related to the administration of lanadelumab have been reported. Studies regarding the carcinogenic potential or overdosage effect have not been performed. Published literature supports bradykinin, which is elevated in HAE, as a pro-tumorigenic molecule. However, the malignancy risk in humans from an antibody that inhibits plasma kallikrein activity, such as lanadelumab-flyo, which lowers bradykinin levels, is currently unknown. There are no available data on lanadelumab use in pregnant women to inform of any drug-associated risks. Monoclonal antibodies such as lanadelumab-flyo are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. An enhanced pre-and postnatal development (ePPND) study conducted in pregnant monkeys at doses resulting in exposures of up to 33 times the exposure achieved (on an AUC basis) at the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Takhzyro •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): Lanadelumab is a monoclonal antibody targeted against kallikrein which is used to treat attacks of hereditary angioedema.

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 Lanadelumab interact? Information: •Drug A: Abciximab •Drug B: Lanadelumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Lanadelumab. •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): Lanadelumab is indicated for prophylaxis to prevent attacks in adult and pediatric patients aged 2 years and older with hereditary angioedema. In Canada, it is indicated for use only in adults and adolescents. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 1 studies, the level of kininogen, the substrate of kallikrein, was studied as a marker of kallikrein activity. In patients with C1 deficiency, the level of cleaved kininogen is 4-fold higher when compared with C1-normal individuals. When lanadelumab was administered, the levels of cleaved kininogen were significantly reduced with a dose of 300 and 400 mg of lanadelumab with a maximum reduction at day 22 corresponding with time for maximum concentration. This maximum reduction corresponded with the normal levels of cleaved kininogen. Similarly, the decreases of cleaved kininogen corresponded with reductions in the levels of the activated factor XII. Clinically, the attacks of angioedema completely vanished in the patients receiving a dose of 300 mg of lanadelumab. In other doses such as 400 mg and combo 300/400 mg the attack reduction reached 90%. In phase 3 clinical trials, lanadelumab showed an attack rate reduction of over 70% for all studied regimens. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hereditary angioedema (HEA) is an autosomal dominant disorder resulting from the presence of C1 deficiency. This condition manifests as attacks of subcutaneous or submucosal edema in the face, larynx, GI tract, limbs or genitalia, with laryngeal edema being the most serious due to the potential to compromise the airways. Attacks may be accompanied by pain and considerable dysfunction. Lanadelumab is a plasma kallikrein inhibitor. This enzyme works by cleaving high molecular weight kininogen to generate the pro-inflammatory peptide bradykinin, a potent vasodilator. Because the activity of plasma kallikrein is regulated by C1 esterase inhibitor, patients deficient in C1 esterase inhibitor may be at risk of excessive production of bradykinin leading to serious angioedema. Lanadelumab occludes the proteolytic active site of plasma kallikrein, preventing the cleavage of kininogen to bradykinin. It is a selective inhibitor and does not bind to prekallikrein or inhibit other serine proteases. •Absorption (Drug A): No absorption available •Absorption (Drug B): Drug levels of lanadelumab are dose-dependent and the maximum plasma concentration increases correspondingly with increasing dosage. The C max and AUC ranged from 3800 - 45000 ng/ml and 64000 - 762000 ng.day/ml, respectively, across a dosing range of 30 to 400 mg. A sustained quantifiable drug concentration was observed through day 120. The bioavailability of lanadelumab is approximately 66% with a time to reach peak drug concentration of approximately 7 days. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of lanadelumab is approximately 14 - 16 L depending on the dose administered. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As with other therapeutic proteins, the degradation of lanadelumab likely occurs via catabolism to 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): Lanadelumab has a half-life of approximately 2 weeks after subcutaneous administration. •Clearance (Drug A): No clearance available •Clearance (Drug B): The apparent clearance of lanadelumab ranges from 0.667 to 0.809 L/day depending on the administered dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No significant toxicities related to the administration of lanadelumab have been reported. Studies regarding the carcinogenic potential or overdosage effect have not been performed. Published literature supports bradykinin, which is elevated in HAE, as a pro-tumorigenic molecule. However, the malignancy risk in humans from an antibody that inhibits plasma kallikrein activity, such as lanadelumab-flyo, which lowers bradykinin levels, is currently unknown. There are no available data on lanadelumab use in pregnant women to inform of any drug-associated risks. Monoclonal antibodies such as lanadelumab-flyo are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. An enhanced pre-and postnatal development (ePPND) study conducted in pregnant monkeys at doses resulting in exposures of up to 33 times the exposure achieved (on an AUC basis) at the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Takhzyro •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): Lanadelumab is a monoclonal antibody targeted against kallikrein which is used to treat attacks of hereditary angioedema. 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 Lebrikizumab interact?

•Drug A: Abciximab •Drug B: Lebrikizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Lebrikizumab. •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): Lebrikizumab is approved by the EMA for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents 12 years and older with a body weight of at least 40 kg who are candidates for systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In lebrikizumab clinical studies, lebrikizumab reduced the levels of serum periostin, total immunoglobulin E (IgE), CC chemokine ligand (CCL)17 [thymus and activation-regulated chemokine (TARC)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], and CCL13 [monocyte chemotactic protein-4 (MCP-4)]. The decreases in the type 2 inflammation mediators provide indirect evidence of inhibition of the IL-13 pathway by lebrikizumab. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Lebrikizumab is an immunoglobulin (IgG4) monoclonal antibody that binds with high affinity to interleukin (IL)-13 and selectively inhibits IL-13 signaling through the IL-4 receptor alpha (IL-4Rα)/ IL-13 receptor alpha 1 (IL-13Rα1) heterodimer, thereby inhibiting the downstream effects of IL-13. Inhibition of IL-13 signaling is expected to be of benefit in diseases in which IL-13 is a key contributor to the disease pathogenesis. Lebrikizumab does not prevent the binding of IL-13 to the IL-13 receptor alpha 2 (IL-13Rα2 or decoy receptor), which allows the internalization of IL-13 into the cell. •Absorption (Drug A): No absorption available •Absorption (Drug B): After a subcutaneous dose of 250 mg lebrikizumab, peak serum concentrations were achieved approximately 7 to 8 days post-dose. Following the 500 mg loading doses at week 0 and week 2, steady-state serum concentrations were achieved with the first 250 mg Q2W dose at week 4. Based on a population pharmacokinetic (PK) analysis, the predicted steady-state trough concentrations (C trough,ss ) following lebrikizumab 250 mg Q2W and Q4W subcutaneous dosing in patients with atopic dermatitis (median and 5th - 95th percentile) were 87 (46-159) µg/mL and 36 (18-68) µg/mL, respectively. The absolute bioavailability was estimated at 86% based on a population PK analysis. The injection site location did not significantly influence the absorption of lebrikizumab. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a population PK analysis, the total volume of distribution at steady-state was 5.14 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Little information is available on the protein binding of lebrikizumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Specific metabolism studies were not conducted because lebrikizumab is a protein. Lebrikizumab is expected to degrade to small peptides and individual amino acids via catabolic pathways in the same manner as endogenous IgG. •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 elimination half-life was approximately 24.5 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): In the population PK analysis, clearance was 0.154 L/day and was independent of dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are limited amount of data on the use of lebrikizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of lebrikizumab during pregnancy. The mutagenic potential of lebrikizumab has not been evaluated; however monoclonal antibodies are not expected to alter DNA or chromosomes. Carcinogenicity studies have not been conducted with lebrikizumab. Evaluation of the available evidence related to IL-13 inhibition and animal toxicology data with lebrikizumab does not suggest carcinogenic potential for lebrikizumab. Single intravenous doses up to 10 mg/kg and multiple subcutaneous doses up to 500 mg have been administered to humans in clinical trials without dose-limiting toxicity. There is no specific treatment for lebrikizumab overdose. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately. •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): Lebrikizumab is an IgG4 monoclonal antibody against IL-13 used to treat moderate-to-severe atopic dermatitis in adults and adolescents.

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 Lebrikizumab interact? Information: •Drug A: Abciximab •Drug B: Lebrikizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Lebrikizumab. •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): Lebrikizumab is approved by the EMA for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents 12 years and older with a body weight of at least 40 kg who are candidates for systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): In lebrikizumab clinical studies, lebrikizumab reduced the levels of serum periostin, total immunoglobulin E (IgE), CC chemokine ligand (CCL)17 [thymus and activation-regulated chemokine (TARC)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], and CCL13 [monocyte chemotactic protein-4 (MCP-4)]. The decreases in the type 2 inflammation mediators provide indirect evidence of inhibition of the IL-13 pathway by lebrikizumab. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Lebrikizumab is an immunoglobulin (IgG4) monoclonal antibody that binds with high affinity to interleukin (IL)-13 and selectively inhibits IL-13 signaling through the IL-4 receptor alpha (IL-4Rα)/ IL-13 receptor alpha 1 (IL-13Rα1) heterodimer, thereby inhibiting the downstream effects of IL-13. Inhibition of IL-13 signaling is expected to be of benefit in diseases in which IL-13 is a key contributor to the disease pathogenesis. Lebrikizumab does not prevent the binding of IL-13 to the IL-13 receptor alpha 2 (IL-13Rα2 or decoy receptor), which allows the internalization of IL-13 into the cell. •Absorption (Drug A): No absorption available •Absorption (Drug B): After a subcutaneous dose of 250 mg lebrikizumab, peak serum concentrations were achieved approximately 7 to 8 days post-dose. Following the 500 mg loading doses at week 0 and week 2, steady-state serum concentrations were achieved with the first 250 mg Q2W dose at week 4. Based on a population pharmacokinetic (PK) analysis, the predicted steady-state trough concentrations (C trough,ss ) following lebrikizumab 250 mg Q2W and Q4W subcutaneous dosing in patients with atopic dermatitis (median and 5th - 95th percentile) were 87 (46-159) µg/mL and 36 (18-68) µg/mL, respectively. The absolute bioavailability was estimated at 86% based on a population PK analysis. The injection site location did not significantly influence the absorption of lebrikizumab. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Based on a population PK analysis, the total volume of distribution at steady-state was 5.14 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Little information is available on the protein binding of lebrikizumab. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Specific metabolism studies were not conducted because lebrikizumab is a protein. Lebrikizumab is expected to degrade to small peptides and individual amino acids via catabolic pathways in the same manner as endogenous IgG. •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 elimination half-life was approximately 24.5 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): In the population PK analysis, clearance was 0.154 L/day and was independent of dose. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There are limited amount of data on the use of lebrikizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of lebrikizumab during pregnancy. The mutagenic potential of lebrikizumab has not been evaluated; however monoclonal antibodies are not expected to alter DNA or chromosomes. Carcinogenicity studies have not been conducted with lebrikizumab. Evaluation of the available evidence related to IL-13 inhibition and animal toxicology data with lebrikizumab does not suggest carcinogenic potential for lebrikizumab. Single intravenous doses up to 10 mg/kg and multiple subcutaneous doses up to 500 mg have been administered to humans in clinical trials without dose-limiting toxicity. There is no specific treatment for lebrikizumab overdose. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately. •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): Lebrikizumab is an IgG4 monoclonal antibody against IL-13 used to treat moderate-to-severe atopic dermatitis in adults and adolescents. 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 Lecanemab interact?

•Drug A: Abciximab •Drug B: Lecanemab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Lecanemab. •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): Lecanemab is indicated for the treatment of Alzheimer’s disease. Treatment with lecanemab should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Lecanemab reduces amyloid-β (Aβ) plaques in a dose- and time-dependent manner. In clinical trials, lecanemab also reduced plasma P-tau181. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Extracellular amyloid-β (Aβ) plaques are a hallmark pathology of Alzheimer's disease (AD), making them a desirable therapeutic target for potential drugs for treating AD. The production and accumulation of Aβ plaques in the brain are commonly observed in AD, and distinct characteristics of Aβ plaques - such as the solubility, quantity, and composition of Aβ pools - may affect the disease state. Aβ causes synaptic impairment, neuronal death, and progressive neurodegeneration, which leads to dementia and cognitive impairment associated with AD. Aβ peptides exist in various conformational states, including soluble monomers, soluble aggregates of increasing size, and insoluble fibrils and plaque. Soluble Aβ aggregates such as Aβ protofibrils are more neurotoxic than monomers or insoluble fibrils. Lecanemab is an antibody that lowers Aβ plaques in the brain. It preferentially targets soluble aggregated Aβ and works on Aβ oligomers, protofibrils, and insoluble fibrils. •Absorption (Drug A): No absorption available •Absorption (Drug B): Steady-state concentrations of lecanemab were reached after six weeks when 10 mg/kg of lecanemab was administered every two weeks. Systemic accumulation was 1.4-fold. The peak concentration (C max ) and area under the plasma concentration versus time curve (AUC) of lecanemab increased dose proportionally following a single dose ranging from 0.3 to 15 mg/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean value (95% CI) for the central volume of distribution at steady-state is 3.22 (3.15-3.28) L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Lecanemab is degraded by proteolytic enzymes in the same manner as endogenous IgGs. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is no information available. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life is 5 to 7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of lecanemab (95% CI) is 0.434 (0.420-0.451) L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information available regarding the LD 50 and overdose of lecanemab. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Leqembi •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): Lecanemab is an amyloid beta-targeting antibody used to treat Alzheimer’s Disease in patients with mild cognitive impairment or mild dementia with a known amyloid beta pathology.

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 Lecanemab interact? Information: •Drug A: Abciximab •Drug B: Lecanemab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Lecanemab. •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): Lecanemab is indicated for the treatment of Alzheimer’s disease. Treatment with lecanemab should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Lecanemab reduces amyloid-β (Aβ) plaques in a dose- and time-dependent manner. In clinical trials, lecanemab also reduced plasma P-tau181. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Extracellular amyloid-β (Aβ) plaques are a hallmark pathology of Alzheimer's disease (AD), making them a desirable therapeutic target for potential drugs for treating AD. The production and accumulation of Aβ plaques in the brain are commonly observed in AD, and distinct characteristics of Aβ plaques - such as the solubility, quantity, and composition of Aβ pools - may affect the disease state. Aβ causes synaptic impairment, neuronal death, and progressive neurodegeneration, which leads to dementia and cognitive impairment associated with AD. Aβ peptides exist in various conformational states, including soluble monomers, soluble aggregates of increasing size, and insoluble fibrils and plaque. Soluble Aβ aggregates such as Aβ protofibrils are more neurotoxic than monomers or insoluble fibrils. Lecanemab is an antibody that lowers Aβ plaques in the brain. It preferentially targets soluble aggregated Aβ and works on Aβ oligomers, protofibrils, and insoluble fibrils. •Absorption (Drug A): No absorption available •Absorption (Drug B): Steady-state concentrations of lecanemab were reached after six weeks when 10 mg/kg of lecanemab was administered every two weeks. Systemic accumulation was 1.4-fold. The peak concentration (C max ) and area under the plasma concentration versus time curve (AUC) of lecanemab increased dose proportionally following a single dose ranging from 0.3 to 15 mg/kg. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The mean value (95% CI) for the central volume of distribution at steady-state is 3.22 (3.15-3.28) L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): There is no information available. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Lecanemab is degraded by proteolytic enzymes in the same manner as endogenous IgGs. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): There is no information available. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The terminal half-life is 5 to 7 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The clearance of lecanemab (95% CI) is 0.434 (0.420-0.451) L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): There is no information available regarding the LD 50 and overdose of lecanemab. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Leqembi •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): Lecanemab is an amyloid beta-targeting antibody used to treat Alzheimer’s Disease in patients with mild cognitive impairment or mild dementia with a known amyloid beta pathology. 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 Lenalidomide interact?

•Drug A: Abciximab •Drug B: Lenalidomide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Lenalidomide. •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): Lenalidomide is indicated for the treatment of adult patients with multiple myeloma (MM) in combination with dexamethasone. It is also indicated as maintenance therapy in multiple myeloma following autologous hematopoietic stem cell transplantation (auto-HSCT). It is indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Lenalidomide is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In combination with a rituximab product, lenalidomide is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL) or previously treated marginal zone lymphoma (MZL). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity. Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties. Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells. It delays tumour growth in nonclinical hematopoietic tumour models in vivo, including multiple myeloma. Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis. Lenalidomide also mediates indirect antitumour effects via its immunomodulatory actions: it inhibits the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies. Lenalidomide enhances the host immunity by stimulating T cell proliferation and enhancing the activity of natural killer (NK) cells. Lenalidomide is about 100–1000 times more potent in stimulating T cell proliferation than thalidomide. In vitro, it enhances antibody-dependent cell-mediated cytotoxicity (ADCC), which is even more pronounced when used in combination with rituximab. Due to its anti-inflammatory properties, lenalidomide has been investigated in the context of inflammatory and autoimmune diseases, such as amyotrophic lateral sclerosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Lenalidomide is a drug with multiple mechanisms of action. Lenalidomide exerts immunomodulating effects by altering cytokine production, regulating T cell co-stimulation, and enhancing the NK cell-mediated cytotoxicity. Lenalidomide directly inhibits the cullin ring E3 ubiquitin ligase complex: upon binding to cereblon, a substrate adaptor of the complex, lenalidomide modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros (IKZF1), Aiolos (IKZF3), and CK1α. These substrates are then tagged for ubiquitination and subsequent proteasomal degradation. IKZF1 and IKZF3 are B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells. IKZF3 also regulates the expression of interferon regulatory factor 4 (IRF4), which is a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of lenalidomide can be partly explained by the degradation of IKZF3, since it is a repressor of the interleukin 2 gene (IL2): as lenalidomide decreases the level of IKZF3, the production of IL-2 increases, thereby increasing the proliferation of natural killer (NK), NKT cells, and CD4+ T cells. Lenalidomide inhibits the production of pro-inflammatory cytokines TNF-α, IL-1, IL-6, and IL-12, while elevating the production of anti-inflammatory cytokine IL-10. Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD3 T-cell proliferation and increases the production of IL-2 and IFN-γ in T lymphocytes, which enhances NK cell cytotoxicity and ADCC. It inhibits the expression and function of T-regulatory cells, which are often overabundant in some hematological malignancies. Lenalidomide directly exerts antitumour effects by inhibiting the proliferation and inducing apoptosis of tumour cells. Lenalidomide triggers the activation of pro-apoptotic caspase-8, enhances tumour cell sensitivity to FAS-induced apoptosis, and downregulates NF-κB, an anti-apoptotic protein. Independent of its immunomodulatory effects, lenalidomide mediates anti-angiogenic effects by inhibiting angiogenic growth factors released by tumour cells, such as vascular endothelial growth factor (VEGF), basic fibroblastic-growth factor (BFGF), and hepatocyte-growth factor. In vitro, lenalidomide inhibits cell adhesion molecules such as ICAM-1, LFA-1, β2 and β3 integrins, as well as gap-junction function, thereby preventing metastasis of malignant cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, lenalidomide is rapidly absorbed with high bioavailability. It has a T max ranging from 0.5 to six hours. Lenalidomide exhibits a linear pharmacokinetic profile, with its AUC and C max increasing proportionally with dose. Multiple dosing does not result in drug accumulation. In healthy male subjects, the C max was 413 ± 77 ng/ml and the AUC infinity was 1319 ± 162 h x ng/ml. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In healthy male subjects, the apparent volume of distribution was 75.8 ± 7.3 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, about 30% of lenalidomide was 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): Lenalidomide is not subject to extensive hepatic metabolism involving CYP enzymes and metabolism contributes to a very minor extent to the clearance of lenalidomide in humans. Lenalidomide undergoes hydrolysis in human plasma to form 5-hydroxy-lenalidomide and N-acetyl-lenalidomide. Unchanged lenalidomide is the predominant circulating drug form, with metabolites accounting for less than five percent of the parent drug levels in the circulation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Lenalidomide is eliminated predominantly via urinary excretion in the unchanged form. Following oral administration of 25 mg of radiolabeled lenalidomide in healthy subjects, about 90% of the dose (4.59% as metabolites) was eliminated in urine and 4% of the dose (1.83% as metabolites) was eliminated in feces within ten days post-dose. Approximately 85% of the dose was excreted as lenalidomide in the urine within 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In healthy subjects, the mean half-life of lenalidomide is three hours in the clinically relevant dose range (5–50 mg). Half-life can range from three to five hours in patients with multiple myeloma, myelodysplastic syndromes, or mantle cell lymphoma. •Clearance (Drug A): No clearance available •Clearance (Drug B): The renal clearance of lenalidomide exceeds the glomerular filtration rate. In healthy male subjects, the oral clearance was 318 ± 41 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The lowest lethal dose (LDLo) in rats is >2000 mg/kg following oral administration and >40 mg/kg following intravenous administration. The oral Lowest published toxic dose (TDLo) in humans is 9 mg/kg/4W (intermittent). There is limited clinical experience in managing lenalidomide overdose. In single-dose studies, healthy subjects have been exposed to doses up to 400 mg. In clinical trials, the dose-limiting toxicity was neutropenia and thrombocytopenia. Toxicities associated with lenalidomide, some leading to fatality, include embryo-fetal toxicity, neutropenia, thrombocytopenia, venous (deep vein thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke), serious adverse cardiovascular reactions, second primary malignancies, hepatotoxicity, severe cutaneous reactions, tumour lysis syndrome, tumour flare reaction, hypothyroidism, and hyperthyroidism. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Revlimid •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Lenalidomida Lenalidomide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Lenalidomide is a thalidomide derivative used to treat multiple myeloma and anemia in low to intermediate risk myelodysplastic syndrome.

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 Lenalidomide interact? Information: •Drug A: Abciximab •Drug B: Lenalidomide •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Lenalidomide. •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): Lenalidomide is indicated for the treatment of adult patients with multiple myeloma (MM) in combination with dexamethasone. It is also indicated as maintenance therapy in multiple myeloma following autologous hematopoietic stem cell transplantation (auto-HSCT). It is indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Lenalidomide is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In combination with a rituximab product, lenalidomide is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL) or previously treated marginal zone lymphoma (MZL). •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway 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 hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity. Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties. Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells. It delays tumour growth in nonclinical hematopoietic tumour models in vivo, including multiple myeloma. Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis. Lenalidomide also mediates indirect antitumour effects via its immunomodulatory actions: it inhibits the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies. Lenalidomide enhances the host immunity by stimulating T cell proliferation and enhancing the activity of natural killer (NK) cells. Lenalidomide is about 100–1000 times more potent in stimulating T cell proliferation than thalidomide. In vitro, it enhances antibody-dependent cell-mediated cytotoxicity (ADCC), which is even more pronounced when used in combination with rituximab. Due to its anti-inflammatory properties, lenalidomide has been investigated in the context of inflammatory and autoimmune diseases, such as amyotrophic lateral sclerosis. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Lenalidomide is a drug with multiple mechanisms of action. Lenalidomide exerts immunomodulating effects by altering cytokine production, regulating T cell co-stimulation, and enhancing the NK cell-mediated cytotoxicity. Lenalidomide directly inhibits the cullin ring E3 ubiquitin ligase complex: upon binding to cereblon, a substrate adaptor of the complex, lenalidomide modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros (IKZF1), Aiolos (IKZF3), and CK1α. These substrates are then tagged for ubiquitination and subsequent proteasomal degradation. IKZF1 and IKZF3 are B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells. IKZF3 also regulates the expression of interferon regulatory factor 4 (IRF4), which is a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of lenalidomide can be partly explained by the degradation of IKZF3, since it is a repressor of the interleukin 2 gene (IL2): as lenalidomide decreases the level of IKZF3, the production of IL-2 increases, thereby increasing the proliferation of natural killer (NK), NKT cells, and CD4+ T cells. Lenalidomide inhibits the production of pro-inflammatory cytokines TNF-α, IL-1, IL-6, and IL-12, while elevating the production of anti-inflammatory cytokine IL-10. Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD3 T-cell proliferation and increases the production of IL-2 and IFN-γ in T lymphocytes, which enhances NK cell cytotoxicity and ADCC. It inhibits the expression and function of T-regulatory cells, which are often overabundant in some hematological malignancies. Lenalidomide directly exerts antitumour effects by inhibiting the proliferation and inducing apoptosis of tumour cells. Lenalidomide triggers the activation of pro-apoptotic caspase-8, enhances tumour cell sensitivity to FAS-induced apoptosis, and downregulates NF-κB, an anti-apoptotic protein. Independent of its immunomodulatory effects, lenalidomide mediates anti-angiogenic effects by inhibiting angiogenic growth factors released by tumour cells, such as vascular endothelial growth factor (VEGF), basic fibroblastic-growth factor (BFGF), and hepatocyte-growth factor. In vitro, lenalidomide inhibits cell adhesion molecules such as ICAM-1, LFA-1, β2 and β3 integrins, as well as gap-junction function, thereby preventing metastasis of malignant cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): Following oral administration, lenalidomide is rapidly absorbed with high bioavailability. It has a T max ranging from 0.5 to six hours. Lenalidomide exhibits a linear pharmacokinetic profile, with its AUC and C max increasing proportionally with dose. Multiple dosing does not result in drug accumulation. In healthy male subjects, the C max was 413 ± 77 ng/ml and the AUC infinity was 1319 ± 162 h x ng/ml. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In healthy male subjects, the apparent volume of distribution was 75.8 ± 7.3 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In vitro, about 30% of lenalidomide was 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): Lenalidomide is not subject to extensive hepatic metabolism involving CYP enzymes and metabolism contributes to a very minor extent to the clearance of lenalidomide in humans. Lenalidomide undergoes hydrolysis in human plasma to form 5-hydroxy-lenalidomide and N-acetyl-lenalidomide. Unchanged lenalidomide is the predominant circulating drug form, with metabolites accounting for less than five percent of the parent drug levels in the circulation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Lenalidomide is eliminated predominantly via urinary excretion in the unchanged form. Following oral administration of 25 mg of radiolabeled lenalidomide in healthy subjects, about 90% of the dose (4.59% as metabolites) was eliminated in urine and 4% of the dose (1.83% as metabolites) was eliminated in feces within ten days post-dose. Approximately 85% of the dose was excreted as lenalidomide in the urine within 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In healthy subjects, the mean half-life of lenalidomide is three hours in the clinically relevant dose range (5–50 mg). Half-life can range from three to five hours in patients with multiple myeloma, myelodysplastic syndromes, or mantle cell lymphoma. •Clearance (Drug A): No clearance available •Clearance (Drug B): The renal clearance of lenalidomide exceeds the glomerular filtration rate. In healthy male subjects, the oral clearance was 318 ± 41 mL/min. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The lowest lethal dose (LDLo) in rats is >2000 mg/kg following oral administration and >40 mg/kg following intravenous administration. The oral Lowest published toxic dose (TDLo) in humans is 9 mg/kg/4W (intermittent). There is limited clinical experience in managing lenalidomide overdose. In single-dose studies, healthy subjects have been exposed to doses up to 400 mg. In clinical trials, the dose-limiting toxicity was neutropenia and thrombocytopenia. Toxicities associated with lenalidomide, some leading to fatality, include embryo-fetal toxicity, neutropenia, thrombocytopenia, venous (deep vein thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke), serious adverse cardiovascular reactions, second primary malignancies, hepatotoxicity, severe cutaneous reactions, tumour lysis syndrome, tumour flare reaction, hypothyroidism, and hyperthyroidism. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Revlimid •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Lenalidomida Lenalidomide •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Lenalidomide is a thalidomide derivative used to treat multiple myeloma and anemia in low to intermediate risk myelodysplastic syndrome. 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 Levocarnitine interact?

•Drug A: Abciximab •Drug B: Levocarnitine •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Levocarnitine. •Extended Description: It is reported that L-carnitine can decrease different blood coagulation factors such as fibrinogen, Factor VII, fibrin degradation products, and plasminogen activator inhibitor-1 as well as the platelet aggregation. This effect can produce an increase in the anticoagulation functions of other anticoagulants like warfarin. This interaction can actually be used to decrease hypercoagulation states in diabetes patients and to decrease inflammation factors while helping regulate the coagulation state •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism such as glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency. Used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal 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): Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady state volume of distribution (Vss) of an intravenously administered dose, above endogenous baseline levels, was calculated to be 29.0 +/- 7.1L. However this value is predicted to be an underestimate of the true Vss. •Protein binding (Drug A): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): After oral administration L-carnitine which is unabsorbed is metabolized in the gastrointestinal tract by bacterial microflora. Major metabolites include trimethylamine N-oxide and [3H]-gamma-butyrobetaine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following a single intravenous dose, 73.1 +/- 16% of the dose was excreted in the urine during the 0-24 hour interval. Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 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): 17.4 hours (elimination) following a single intravenous dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance was found to be a mean of 4L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 > 8g/kg (mouse, oral). Adverse effects include hypertension, fever, tachycardia and seizures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Carnitor •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (R)-Carnitine Carnitina Carnitine L-Carnitine Levocarnitin Levocarnitina Lévocarnitine Levocarnitine Levocarnitinum Vitamin BT •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Levocarnitine is a quaternary ammonium compound used to treat carnitine deficiency or to stimulate gastric and pancreatic secretions in hyperlipoproteinemia.

It is reported that L-carnitine can decrease different blood coagulation factors such as fibrinogen, Factor VII, fibrin degradation products, and plasminogen activator inhibitor-1 as well as the platelet aggregation. This effect can produce an increase in the anticoagulation functions of other anticoagulants like warfarin. This interaction can actually be used to decrease hypercoagulation states in diabetes patients and to decrease inflammation factors while helping regulate the coagulation state The severity of the interaction is minor.

Question: Does Abciximab and Levocarnitine interact? Information: •Drug A: Abciximab •Drug B: Levocarnitine •Severity: MINOR •Description: The therapeutic efficacy of Abciximab can be increased when used in combination with Levocarnitine. •Extended Description: It is reported that L-carnitine can decrease different blood coagulation factors such as fibrinogen, Factor VII, fibrin degradation products, and plasminogen activator inhibitor-1 as well as the platelet aggregation. This effect can produce an increase in the anticoagulation functions of other anticoagulants like warfarin. This interaction can actually be used to decrease hypercoagulation states in diabetes patients and to decrease inflammation factors while helping regulate the coagulation state •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is 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 primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism such as glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency. Used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal 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): Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The steady state volume of distribution (Vss) of an intravenously administered dose, above endogenous baseline levels, was calculated to be 29.0 +/- 7.1L. However this value is predicted to be an underestimate of the true Vss. •Protein binding (Drug A): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): After oral administration L-carnitine which is unabsorbed is metabolized in the gastrointestinal tract by bacterial microflora. Major metabolites include trimethylamine N-oxide and [3H]-gamma-butyrobetaine. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following a single intravenous dose, 73.1 +/- 16% of the dose was excreted in the urine during the 0-24 hour interval. Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 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): 17.4 hours (elimination) following a single intravenous dose. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total body clearance was found to be a mean of 4L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD 50 > 8g/kg (mouse, oral). Adverse effects include hypertension, fever, tachycardia and seizures. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Carnitor •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): (R)-Carnitine Carnitina Carnitine L-Carnitine Levocarnitin Levocarnitina Lévocarnitine Levocarnitine Levocarnitinum Vitamin BT •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Levocarnitine is a quaternary ammonium compound used to treat carnitine deficiency or to stimulate gastric and pancreatic secretions in hyperlipoproteinemia. Output: It is reported that L-carnitine can decrease different blood coagulation factors such as fibrinogen, Factor VII, fibrin degradation products, and plasminogen activator inhibitor-1 as well as the platelet aggregation. This effect can produce an increase in the anticoagulation functions of other anticoagulants like warfarin. This interaction can actually be used to decrease hypercoagulation states in diabetes patients and to decrease inflammation factors while helping regulate the coagulation state The severity of the interaction is minor.

Does Abciximab and Levomilnacipran interact?

•Drug A: Abciximab •Drug B: Levomilnacipran •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Levomilnacipran. •Extended Description: Drugs that inhibit serotonin reuptake, such as levomilnacipran, interfere with platelet function by affecting the release of serotonin by platelets and may result in an increased risk of bleeding. Concomitant use of levomilnacipran with the subject drug, an antiplatelet agent, may potentiate 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): Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) 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): Levomilnacipran is an antidepressant that binds with high affinity to human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively). It potently inhibits 5-HT and NE reuptake (IC50 = 16 - 19 and 11 nM, respectively). Levomilnacipran does not bind to any other receptors, ion channels, or transporters, including serotonergic (5HT1-7), α- and β adrenergic, muscarinic, or histaminergic receptors and Ca, Na, K or Cl channels to a significant degree. Levomilnacipran did not inhibit monoamine oxidase (MAO). Furthermore, levomilnacipran does not prolong the QTc interval to a clinically relevant extent. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Levomilnacipran is a potent and selective selective serotonin and norepinephrine reuptake inhibitor (SNRI). The exact mechanism of the antidepressant action of levomilnacipran is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system through inhibition of reuptake at serotonin and norepinephrine transporters. Like milnacipran, levomilnacipran is a more potent inhibitor of the norepinephrine transporter than the serotonin transporter: it exhibits over a 15-fold higher selectivity for norepinephrine versus serotonin reuptake inhibition. •Absorption (Drug A): No absorption available •Absorption (Drug B): The steady-state concentration of levomilnacipran was dose-proportional when administered at a dose ranging from 25 mg to 300 mg (2.5 times the maximum recommended dosage of levomilnacipran) once daily. After daily dosing of 120 mg levomilnacipran, the mean C max value was 341 ng/mL, and the mean steady-state AUC value was 5196 ng x h/mL. The relative bioavailability of oral levomilnacipran extended-release capsules was 92% when compared to oral solution. The median time to peak concentration (T max ) of levomilnacipran ranges from six to eight hours after oral administration. Levomilnacipran concentration was not significantly affected when it was administered with food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Levomilnacipran is widely distributed, with an apparent volume of distribution ranging from 387 to 473 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Levomilnacipran is 22% bound to plasma proteins over the concentration range of 10 to 1000 ng/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Levomilnacipran undergoes desethylation to form desethyl levomilnacipran (or N-desethyl levomilnacipran) and hydroxylation to form p-hydroxy-levomilnacipran, which are pharmacologically inactive. Both oxidative metabolites can undergo further glucuronidation. Desethylation is primarily catalyzed by CYP3A4 with minor contributions by CYP2C8, 2C19, 2D6, and 2J2. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Levomilnacipran and its metabolites are eliminated primarily by renal excretion. Following oral administration of C-levomilnacipran solution, approximately 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran was the major metabolite excreted in the urine, accounting for approximately 18% of the dose. Other identifiable metabolites excreted in the urine were levomilnacipran glucuronide (4%), desethyl levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxy levomilnacipran (1%). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The apparent terminal elimination half-life of extended-release levomilnacipran is approximately 12 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following oral administration, the mean apparent total clearance of levomilnacipran is 21-29 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats was 238 mg/kg. There is limited clinical experience with levomilnacipran overdose in humans. In clinical studies, cases of ingestions up to 360 mg daily were reported with none being fatal. As there is no known specific antidote, levomilnacipran overdose should be managed with supportive measures, including close medical supervision and monitoring, with the consideration of possible multiple drug involvement. The high volume of distribution of levomilnacipran suggests that dialysis will not be effective in reducing levomilnacipran plasma concentrations. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fetzima •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): Levomilnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used to treat major depressive disorder (MDD) in adults.

Drugs that inhibit serotonin reuptake, such as levomilnacipran, interfere with platelet function by affecting the release of serotonin by platelets and may result in an increased risk of bleeding. Concomitant use of levomilnacipran with the subject drug, an antiplatelet agent, may potentiate the risk of bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Levomilnacipran interact? Information: •Drug A: Abciximab •Drug B: Levomilnacipran •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Levomilnacipran. •Extended Description: Drugs that inhibit serotonin reuptake, such as levomilnacipran, interfere with platelet function by affecting the release of serotonin by platelets and may result in an increased risk of bleeding. Concomitant use of levomilnacipran with the subject drug, an antiplatelet agent, may potentiate 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): Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) 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): Levomilnacipran is an antidepressant that binds with high affinity to human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively). It potently inhibits 5-HT and NE reuptake (IC50 = 16 - 19 and 11 nM, respectively). Levomilnacipran does not bind to any other receptors, ion channels, or transporters, including serotonergic (5HT1-7), α- and β adrenergic, muscarinic, or histaminergic receptors and Ca, Na, K or Cl channels to a significant degree. Levomilnacipran did not inhibit monoamine oxidase (MAO). Furthermore, levomilnacipran does not prolong the QTc interval to a clinically relevant extent. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Levomilnacipran is a potent and selective selective serotonin and norepinephrine reuptake inhibitor (SNRI). The exact mechanism of the antidepressant action of levomilnacipran is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system through inhibition of reuptake at serotonin and norepinephrine transporters. Like milnacipran, levomilnacipran is a more potent inhibitor of the norepinephrine transporter than the serotonin transporter: it exhibits over a 15-fold higher selectivity for norepinephrine versus serotonin reuptake inhibition. •Absorption (Drug A): No absorption available •Absorption (Drug B): The steady-state concentration of levomilnacipran was dose-proportional when administered at a dose ranging from 25 mg to 300 mg (2.5 times the maximum recommended dosage of levomilnacipran) once daily. After daily dosing of 120 mg levomilnacipran, the mean C max value was 341 ng/mL, and the mean steady-state AUC value was 5196 ng x h/mL. The relative bioavailability of oral levomilnacipran extended-release capsules was 92% when compared to oral solution. The median time to peak concentration (T max ) of levomilnacipran ranges from six to eight hours after oral administration. Levomilnacipran concentration was not significantly affected when it was administered with food. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Levomilnacipran is widely distributed, with an apparent volume of distribution ranging from 387 to 473 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Levomilnacipran is 22% bound to plasma proteins over the concentration range of 10 to 1000 ng/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Levomilnacipran undergoes desethylation to form desethyl levomilnacipran (or N-desethyl levomilnacipran) and hydroxylation to form p-hydroxy-levomilnacipran, which are pharmacologically inactive. Both oxidative metabolites can undergo further glucuronidation. Desethylation is primarily catalyzed by CYP3A4 with minor contributions by CYP2C8, 2C19, 2D6, and 2J2. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Levomilnacipran and its metabolites are eliminated primarily by renal excretion. Following oral administration of C-levomilnacipran solution, approximately 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran was the major metabolite excreted in the urine, accounting for approximately 18% of the dose. Other identifiable metabolites excreted in the urine were levomilnacipran glucuronide (4%), desethyl levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxy levomilnacipran (1%). •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The apparent terminal elimination half-life of extended-release levomilnacipran is approximately 12 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Following oral administration, the mean apparent total clearance of levomilnacipran is 21-29 L/h. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats was 238 mg/kg. There is limited clinical experience with levomilnacipran overdose in humans. In clinical studies, cases of ingestions up to 360 mg daily were reported with none being fatal. As there is no known specific antidote, levomilnacipran overdose should be managed with supportive measures, including close medical supervision and monitoring, with the consideration of possible multiple drug involvement. The high volume of distribution of levomilnacipran suggests that dialysis will not be effective in reducing levomilnacipran plasma concentrations. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Fetzima •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): Levomilnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used to treat major depressive disorder (MDD) in adults. Output: Drugs that inhibit serotonin reuptake, such as levomilnacipran, interfere with platelet function by affecting the release of serotonin by platelets and may result in an increased risk of bleeding. Concomitant use of levomilnacipran with the subject drug, an antiplatelet agent, may potentiate the risk of bleeding. The severity of the interaction is minor.

Does Abciximab and Levonorgestrel interact?

•Drug A: Abciximab •Drug B: Levonorgestrel •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Levonorgestrel 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): Emergency contraception Levonorgestrel, in the single-agent emergency contraceptive form, is indicated for the prevention of pregnancy after the confirmed or suspected failure of contraception methods or following unprotected intercourse. It is distributed by prescription for patients under 17, and over the counter for those above this age. This levonorgestrel-only form of contraception is not indicated for regular contraception and must be taken as soon as possible within 72 hours after intercourse. It has shown a lower efficacy when it is used off label within 96 hours. Long-term contraception or nonemergency contraception In addition to the above indication in emergency contraception, levonorgestrel is combined with other contraceptives in contraceptive formulations designed for regular use, for example with ethinyl estradiol. It is used in various hormone-releasing intrauterine devices for long-term contraception ranging for a duration of 3-5 years. Product labeling for Mirena specifically mentions that it is recommended in women who have had at least 1 child and can be indicated for the prevention of pregnancy for up to 8 years. A subdermal implant is also available for the prevention of pregnancy for up to 5 years. Hormone therapy and off-label uses Levonorgestrel is prescribed in combination with estradiol as hormone therapy during menopause to manage vasomotor symptoms and to prevent osteoporosis. Off-label, levonorgestrel may be used to treat menorrhagia, endometrial hyperplasia, 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): Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Mechanism of action on ovulation Oral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation. Mechanism of action in cervical mucus changes Similar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted. Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred. Interestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus. The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation. Effects on implantation * The effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious. Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity. Mechanism of action in hormone therapy When combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use. •Absorption (Drug A): No absorption available •Absorption (Drug B): Orally administered levonorgestrel is absorbed in the gastrointestinal tract while levonorgestrel administered through an IUD device is absorbed in the endometrium. Levonorgestrel is absorbed immediately in the interstitial fluids when it is inserted as a subdermal implant. After insertion of the subdermal implant, the Cmax of levonorgestrel is attained within 2-3 days. The Cmax following one dose of 0.75 mg of oral levonorgestrel is reached within the hour after administration, according to one reference. In a pharmacokinetic study of 1.5 mg of levonorgestrel in women with a normal BMI and those considered to be obese (BMI>30), mean Cmax was found to be 16.2 ng/mL and 10.5 ng/mL respectively. Tmax was found to be 2 hours for those with normal BMI and 2.5 hours for patients with increased BMI. The bioavailability of levonorgestrel approaches 100%. Mean AUC has been shown to be higher in patients with a normal BMI, measuring at 360.1 h × ng/mL versus a range of 197.28 to 208.1 h × ng/mL in an obese group of patients. Obesity may contribute to decreased efficacy of levonorgestrel in contraception. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): One pharmacokinetic study determined a mean steady-state volume of distribution of 1.5 mg of levonorgestrel to be 162.2 L in those with normal BMI and in the range of 404.7 L to 466.4 L in obese patients with a body mass index of at least 30. Mean volume of distribution in 16 patients receiving 0.75 mg of levonorgestrel in another pharmacokinetic study was 260 L. The Plan B one-step FDA label reports an apparent volume of distribution of 1.8 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding of levonorgestrel ranges from 97.5-99%, and it is mainly bound to sex hormone-binding globulin (SHBG). Levonorgestrel is also bound to albumin. The prescribing information for the implanted levonorgestrel indicates that the concentration of sex hormone-binding globulin (SHBG) is reduced in the span of a few days after levonorgestrel administration, decreasing the levels of the drug. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): After absorption of the oral emergency contraceptive preparation, levonorgestrel is conjugated and forms a large number of sulfate conjugates. In addition, glucuronide conjugates have been identified in the plasma. High levels of conjugated and unconjugated 3α, 5β-tetrahydrolevonorgestrel are found in the plasma. The entire metabolic pathway for levonorgestrel has not been studied, however, 16β-hydroxylation is one pathway that has been identified. Small quantities of 3α, 5α­ tetrahydrolevonorgestrel and 16βhydroxylevonorgestrel are also formed. No active metabolites have been identified. The rate of metabolism may be considerably different according to the patient and may explain a wide variation in levonorgestrel clearance. Liver CYP3A4 and CYP3A5 hepatic enzymes are reported to be involved in the metabolism of levonorgestrel. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 45% of an oral levonorgestrel dose and its conjugated or sulfate metabolites are found to be excreted in the urine. Approximately 32% of an orally ingested dose is found excreted in feces, primarily in the form of glucuronide conjugates of levonorgestrel. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 a 0.75 mg dose of 1.5 mg of levonorgestrel ranges between 20-60 hours post-administration. A pharmacokinetic study of women with a normal BMI and BMI over revealed an elimination half-life of 29.7 h and 41.0-46.4 hours, respectively. Another pharmacokinetic study revealed a mean elimination half-life of 24.4 hours after a 0.75 mg dose of levonorgestrel was administered to 16 patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance was found to 4.8 L/h in healthy female volunteers with a normal BMI, and 7.70-8.51 L/h in obese patients after a single 1.5 mg dose. After a 0.75 mg dose of levonorgestrel in 16 patients in another pharmacokinetic study, mean clearance was calculated at 7.06 L/h. Following levonorgestrel implant removal, the serum concentration falls below 100 pg/mL within the first 96 hours and further falls below the sensitivity of detection within the range of 5 days to 2 weeks. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 in rats is greater than 5000 mg/kg. An overdose of this drug, like other contraceptives, may cause nausea and withdrawal bleeding. Provide symptomatic treatment in the case of a levonorgestrel overdose and contact the local poison control center. There is no specific antidote for a levonorgestrel overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Afirmelle 28 Day, Aftera, Alesse, Altavera 28 Day, Amethia 91 Day, Amethyst, Ashlyna 91 Day, Aubra 28 Day, Aviane 28, Ayuna 28 Day Pack, Balcoltra 28 Day, Bionafem, Camrese 91 Day, Camreselo 91 Day, Chateal 28 Day, Climara Pro, Curae, Daysee 91 Day, Delyla 28 Day, Dolishale 28 Day, Econtra, Enpresse 28 Day, Fallback Solo, Falmina 28 Day, Fayosim 91 Day, Her Style, Iclevia 91 Day, Indayo, Introvale 91 Day, Jaimiess 91 Day, Jolessa 91 Day, Joyeaux 28 Day, Kurvelo, Kyleena, Levonest 28 Day, Levora 0.15/30 28 Day, Liletta, Lo Simpesse, LoJaimiess, Loseasonique, Lutera 28 Day, Marlissa 28 Day, Min-ovral, Mirena, Morning After, My Choice, My Way, Myzilra 28 Day, New Day, Next Choice, Next Choice One Dose, Opcicon One-step, Option 2, Orsythia 28 Day, Plan B, Plan B One-step, Portia 28 Day, Preventeza, Quartette 91 Day Pack, React, Rivelsa 91 Day, Seasonale, Seasonique, Setlakin 91 Day, Simpesse, Skyla, Sronyx 28 Day, Take Action, Triquilar, Trivora 28 Day, Twirla 3 Count Weekly Patch, Tyblume 28 Day, Vienva 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 18-Methylnorethisterone Levonorgestrel Lèvonorgestrel Levonorgestrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Levonorgestrel is a progestin found in oral and IUD contraceptives and at higher doses in emergency contraceptives.

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 Levonorgestrel interact? Information: •Drug A: Abciximab •Drug B: Levonorgestrel •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Levonorgestrel 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): Emergency contraception Levonorgestrel, in the single-agent emergency contraceptive form, is indicated for the prevention of pregnancy after the confirmed or suspected failure of contraception methods or following unprotected intercourse. It is distributed by prescription for patients under 17, and over the counter for those above this age. This levonorgestrel-only form of contraception is not indicated for regular contraception and must be taken as soon as possible within 72 hours after intercourse. It has shown a lower efficacy when it is used off label within 96 hours. Long-term contraception or nonemergency contraception In addition to the above indication in emergency contraception, levonorgestrel is combined with other contraceptives in contraceptive formulations designed for regular use, for example with ethinyl estradiol. It is used in various hormone-releasing intrauterine devices for long-term contraception ranging for a duration of 3-5 years. Product labeling for Mirena specifically mentions that it is recommended in women who have had at least 1 child and can be indicated for the prevention of pregnancy for up to 8 years. A subdermal implant is also available for the prevention of pregnancy for up to 5 years. Hormone therapy and off-label uses Levonorgestrel is prescribed in combination with estradiol as hormone therapy during menopause to manage vasomotor symptoms and to prevent osteoporosis. Off-label, levonorgestrel may be used to treat menorrhagia, endometrial hyperplasia, 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): Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Mechanism of action on ovulation Oral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation. Mechanism of action in cervical mucus changes Similar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted. Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred. Interestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus. The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation. Effects on implantation * The effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious. Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity. Mechanism of action in hormone therapy When combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use. •Absorption (Drug A): No absorption available •Absorption (Drug B): Orally administered levonorgestrel is absorbed in the gastrointestinal tract while levonorgestrel administered through an IUD device is absorbed in the endometrium. Levonorgestrel is absorbed immediately in the interstitial fluids when it is inserted as a subdermal implant. After insertion of the subdermal implant, the Cmax of levonorgestrel is attained within 2-3 days. The Cmax following one dose of 0.75 mg of oral levonorgestrel is reached within the hour after administration, according to one reference. In a pharmacokinetic study of 1.5 mg of levonorgestrel in women with a normal BMI and those considered to be obese (BMI>30), mean Cmax was found to be 16.2 ng/mL and 10.5 ng/mL respectively. Tmax was found to be 2 hours for those with normal BMI and 2.5 hours for patients with increased BMI. The bioavailability of levonorgestrel approaches 100%. Mean AUC has been shown to be higher in patients with a normal BMI, measuring at 360.1 h × ng/mL versus a range of 197.28 to 208.1 h × ng/mL in an obese group of patients. Obesity may contribute to decreased efficacy of levonorgestrel in contraception. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): One pharmacokinetic study determined a mean steady-state volume of distribution of 1.5 mg of levonorgestrel to be 162.2 L in those with normal BMI and in the range of 404.7 L to 466.4 L in obese patients with a body mass index of at least 30. Mean volume of distribution in 16 patients receiving 0.75 mg of levonorgestrel in another pharmacokinetic study was 260 L. The Plan B one-step FDA label reports an apparent volume of distribution of 1.8 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): The protein binding of levonorgestrel ranges from 97.5-99%, and it is mainly bound to sex hormone-binding globulin (SHBG). Levonorgestrel is also bound to albumin. The prescribing information for the implanted levonorgestrel indicates that the concentration of sex hormone-binding globulin (SHBG) is reduced in the span of a few days after levonorgestrel administration, decreasing the levels of the drug. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): After absorption of the oral emergency contraceptive preparation, levonorgestrel is conjugated and forms a large number of sulfate conjugates. In addition, glucuronide conjugates have been identified in the plasma. High levels of conjugated and unconjugated 3α, 5β-tetrahydrolevonorgestrel are found in the plasma. The entire metabolic pathway for levonorgestrel has not been studied, however, 16β-hydroxylation is one pathway that has been identified. Small quantities of 3α, 5α­ tetrahydrolevonorgestrel and 16βhydroxylevonorgestrel are also formed. No active metabolites have been identified. The rate of metabolism may be considerably different according to the patient and may explain a wide variation in levonorgestrel clearance. Liver CYP3A4 and CYP3A5 hepatic enzymes are reported to be involved in the metabolism of levonorgestrel. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Approximately 45% of an oral levonorgestrel dose and its conjugated or sulfate metabolites are found to be excreted in the urine. Approximately 32% of an orally ingested dose is found excreted in feces, primarily in the form of glucuronide conjugates of levonorgestrel. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 a 0.75 mg dose of 1.5 mg of levonorgestrel ranges between 20-60 hours post-administration. A pharmacokinetic study of women with a normal BMI and BMI over revealed an elimination half-life of 29.7 h and 41.0-46.4 hours, respectively. Another pharmacokinetic study revealed a mean elimination half-life of 24.4 hours after a 0.75 mg dose of levonorgestrel was administered to 16 patients. •Clearance (Drug A): No clearance available •Clearance (Drug B): Clearance was found to 4.8 L/h in healthy female volunteers with a normal BMI, and 7.70-8.51 L/h in obese patients after a single 1.5 mg dose. After a 0.75 mg dose of levonorgestrel in 16 patients in another pharmacokinetic study, mean clearance was calculated at 7.06 L/h. Following levonorgestrel implant removal, the serum concentration falls below 100 pg/mL within the first 96 hours and further falls below the sensitivity of detection within the range of 5 days to 2 weeks. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 in rats is greater than 5000 mg/kg. An overdose of this drug, like other contraceptives, may cause nausea and withdrawal bleeding. Provide symptomatic treatment in the case of a levonorgestrel overdose and contact the local poison control center. There is no specific antidote for a levonorgestrel overdose. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Afirmelle 28 Day, Aftera, Alesse, Altavera 28 Day, Amethia 91 Day, Amethyst, Ashlyna 91 Day, Aubra 28 Day, Aviane 28, Ayuna 28 Day Pack, Balcoltra 28 Day, Bionafem, Camrese 91 Day, Camreselo 91 Day, Chateal 28 Day, Climara Pro, Curae, Daysee 91 Day, Delyla 28 Day, Dolishale 28 Day, Econtra, Enpresse 28 Day, Fallback Solo, Falmina 28 Day, Fayosim 91 Day, Her Style, Iclevia 91 Day, Indayo, Introvale 91 Day, Jaimiess 91 Day, Jolessa 91 Day, Joyeaux 28 Day, Kurvelo, Kyleena, Levonest 28 Day, Levora 0.15/30 28 Day, Liletta, Lo Simpesse, LoJaimiess, Loseasonique, Lutera 28 Day, Marlissa 28 Day, Min-ovral, Mirena, Morning After, My Choice, My Way, Myzilra 28 Day, New Day, Next Choice, Next Choice One Dose, Opcicon One-step, Option 2, Orsythia 28 Day, Plan B, Plan B One-step, Portia 28 Day, Preventeza, Quartette 91 Day Pack, React, Rivelsa 91 Day, Seasonale, Seasonique, Setlakin 91 Day, Simpesse, Skyla, Sronyx 28 Day, Take Action, Triquilar, Trivora 28 Day, Twirla 3 Count Weekly Patch, Tyblume 28 Day, Vienva 28 Day •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 18-Methylnorethisterone Levonorgestrel Lèvonorgestrel Levonorgestrelum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Levonorgestrel is a progestin found in oral and IUD contraceptives and at higher doses in emergency contraceptives. 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 Linezolid interact?

•Drug A: Abciximab •Drug B: Linezolid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Linezolid is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Linezolid is indicated in adults and children for the treatment of infections caused by susceptible Gram-positive bacteria, including nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and vancomycin-resistant Enterococcus faecium infections. Examples of susceptible bacteria include Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae. Linezolid is not indicated for the treatment of Gram-negative infections, nor has it been evaluated for use longer than 28 days. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Linezolid is an oxazolidinone antibacterial agent effective against most strains of aerobic Gram-positive bacteria and mycobacteria. It appears to be bacteriostatic against both staphylococci and enterococci and bactericidal against most isolates of streptococci. Linezolid has shown some in vitro activity against Gram-negative and anaerobic bacteria but is not considered efficacious against these organisms. Linezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO) enzymes and can therefore contribute to the development of serotonin syndrome when administered alongside serotonergic agents such as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Linezolid should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections, as the risk of therapy appears to outweigh its benefits under these circumstances. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Linezolid exerts its antibacterial effects by interfering with bacterial protein translation. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is essential for bacterial reproduction, thereby preventing bacteria from dividing. Point mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant Enterococcus faecium and Staphylococcus aureus have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use. •Absorption (Drug A): No absorption available •Absorption (Drug B): Linezolid is extensively absorbed following oral administration and has an absolute bioavailability of approximately 100%. Maximum plasma concentrations are reached within approximately 1 to 2 hours after dosing (T max ) and range from 8.1-12.9 mcg/mL after single doses and 11.0-21.2 mcg/mL after multiple dosing. The absorption of orally administered linezolid is not significantly affected by co-administration with food and it may therefore be given without regard to the timing of meals. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): At steady-state, the volume of distribution of linezolid in healthy adults is approximately 40-50 liters. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding of linezolid is approximately 31% - primarily to serum albumin - and is concentration-dependent. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Linezolid is primarily metabolized to two inactive metabolites: an aminoethoxyacetic acid metabolite (PNU-142300) and a hydroxyethyl glycine metabolite (PNU-142586), both of which are the result of morpholine ring oxidation. The hydroxyethyl glycine metabolite - the most abundant of the two metabolites - is likely generated via non-enzymatic processes, though further detail has not been elucidated. While the specific enzymes responsible for the biotransformation of linezolid are unclear, it does not appear to be subject to metabolism via the CYP450 enzyme system, nor does it meaningfully inhibit or induce these enzymes. Linezolid is, however, a reversible and non-selective inhibitor of monoamine oxidase enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary excretion is the primary means by which linezolid and its metabolic products are excreted. Following the administration of a radiolabeled dose of linezolid under steady-state conditions, approximately 84% of radioactivity was recovered in the urine, of which approximately 30% is unchanged parent drug, 40% is the hydroxyethyl glycine metabolite, and 10% is the aminoethoxyacetic acid metabolite. Fecal elimination is comparatively minor, with no parent drug observed in feces and only 6% and 3% of an administered dose found in the feces as the hydroxyethyl glycine metabolite and the aminoethoxyacetic acid metabolite, 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 elimination half-life is estimated to be between 5 and 7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total clearance of linezolid is estimated to be 100-200 mL/min, the majority of which appears to be non-renal. Mean renal clearance is approximately 40 mL/min, which suggests net tubular reabsorption, while non-renal clearance is estimated to account for roughly 65% of total clearance, or 70-150 mL/min on average. Variability in linezolid clearance is high, particularly for non-renal clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Clinical signs of overdosage observed in rats were decreased activity and ataxia (2000 mg/kg/day) and in dogs were vomiting and tremors (3000 mg/kg/day). Treatment of overdose should involve symptomatic and supportive measures and may include hemodialysis if clinically necessary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Zyvox, Zyvoxam •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Linezolid Linezolide Linezolidum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Linezolid is an oxazolidinone antibiotic used to treat infections by susceptible strains of aerobic Gram-positive bacteria.

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

Question: Does Abciximab and Linezolid interact? Information: •Drug A: Abciximab •Drug B: Linezolid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Linezolid is combined with Abciximab. •Extended Description: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): Linezolid is indicated in adults and children for the treatment of infections caused by susceptible Gram-positive bacteria, including nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and vancomycin-resistant Enterococcus faecium infections. Examples of susceptible bacteria include Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae. Linezolid is not indicated for the treatment of Gram-negative infections, nor has it been evaluated for use longer than 28 days. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Linezolid is an oxazolidinone antibacterial agent effective against most strains of aerobic Gram-positive bacteria and mycobacteria. It appears to be bacteriostatic against both staphylococci and enterococci and bactericidal against most isolates of streptococci. Linezolid has shown some in vitro activity against Gram-negative and anaerobic bacteria but is not considered efficacious against these organisms. Linezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO) enzymes and can therefore contribute to the development of serotonin syndrome when administered alongside serotonergic agents such as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Linezolid should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections, as the risk of therapy appears to outweigh its benefits under these circumstances. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Linezolid exerts its antibacterial effects by interfering with bacterial protein translation. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is essential for bacterial reproduction, thereby preventing bacteria from dividing. Point mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant Enterococcus faecium and Staphylococcus aureus have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use. •Absorption (Drug A): No absorption available •Absorption (Drug B): Linezolid is extensively absorbed following oral administration and has an absolute bioavailability of approximately 100%. Maximum plasma concentrations are reached within approximately 1 to 2 hours after dosing (T max ) and range from 8.1-12.9 mcg/mL after single doses and 11.0-21.2 mcg/mL after multiple dosing. The absorption of orally administered linezolid is not significantly affected by co-administration with food and it may therefore be given without regard to the timing of meals. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): At steady-state, the volume of distribution of linezolid in healthy adults is approximately 40-50 liters. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding of linezolid is approximately 31% - primarily to serum albumin - and is concentration-dependent. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Linezolid is primarily metabolized to two inactive metabolites: an aminoethoxyacetic acid metabolite (PNU-142300) and a hydroxyethyl glycine metabolite (PNU-142586), both of which are the result of morpholine ring oxidation. The hydroxyethyl glycine metabolite - the most abundant of the two metabolites - is likely generated via non-enzymatic processes, though further detail has not been elucidated. While the specific enzymes responsible for the biotransformation of linezolid are unclear, it does not appear to be subject to metabolism via the CYP450 enzyme system, nor does it meaningfully inhibit or induce these enzymes. Linezolid is, however, a reversible and non-selective inhibitor of monoamine oxidase enzymes. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary excretion is the primary means by which linezolid and its metabolic products are excreted. Following the administration of a radiolabeled dose of linezolid under steady-state conditions, approximately 84% of radioactivity was recovered in the urine, of which approximately 30% is unchanged parent drug, 40% is the hydroxyethyl glycine metabolite, and 10% is the aminoethoxyacetic acid metabolite. Fecal elimination is comparatively minor, with no parent drug observed in feces and only 6% and 3% of an administered dose found in the feces as the hydroxyethyl glycine metabolite and the aminoethoxyacetic acid metabolite, 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 elimination half-life is estimated to be between 5 and 7 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Total clearance of linezolid is estimated to be 100-200 mL/min, the majority of which appears to be non-renal. Mean renal clearance is approximately 40 mL/min, which suggests net tubular reabsorption, while non-renal clearance is estimated to account for roughly 65% of total clearance, or 70-150 mL/min on average. Variability in linezolid clearance is high, particularly for non-renal clearance. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Clinical signs of overdosage observed in rats were decreased activity and ataxia (2000 mg/kg/day) and in dogs were vomiting and tremors (3000 mg/kg/day). Treatment of overdose should involve symptomatic and supportive measures and may include hemodialysis if clinically necessary. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Zyvox, Zyvoxam •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Linezolid Linezolide Linezolidum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Linezolid is an oxazolidinone antibiotic used to treat infections by susceptible strains of aerobic Gram-positive bacteria. Output: It has been reported that concomitant administration of antiplatelet agents and monoamine oxidase inhibitor antidepressants that increase the levels of serotonin are associated with an increase in hemorrhage. This interaction is due to the inhibition of serotonin reuptake in platelets which produces a reduction of serotonin to even 1% of the normal quantity. Serotonin is very important for the aggregation of platelets and the lack of serotonin does not allow the normal aggregation process of the platelets. The severity of the interaction is moderate.

Does Abciximab and Lomustine interact?

•Drug A: Abciximab •Drug B: Lomustine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Lomustine. •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 primary and metastatic brain tumors as a component of combination chemotherapy in addition to appropriate surgical and/or radiotherapeutic procedures. Also used in combination with other agents as secondary therapy for the treatment of refractory or relapsed Hodgkin's disease. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Lomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle–phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well and rapidly 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): 50% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hepatic. Rapid and complete, with active metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat: LD 50 = 70 mg/kg. Pulmonary toxicity has been reported at cumulative doses usually greater than 1,100 mg/m2. There is one report of pulmonary toxicity at a cumulative dose of only 600 mg. The onset of toxicity has varied from 6 months after initiation of therapy, to as late as 15 years after. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ceenu, Gleostine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chloroethylcyclohexylnitrosourea CINU Cyclohexyl chloroethyl nitrosourea Lomustina Lomustine Lomustinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Lomustine is an alkylating agent used as a part of chemotherapeutic regimens for the treatment of primary and metastatic brain tumors as well as refractory or relapsed Hodgkin's disease in addition to surgical and/or radiotherapeutic treatments.

As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Lomustine interact? Information: •Drug A: Abciximab •Drug B: Lomustine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Lomustine. •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 primary and metastatic brain tumors as a component of combination chemotherapy in addition to appropriate surgical and/or radiotherapeutic procedures. Also used in combination with other agents as secondary therapy for the treatment of refractory or relapsed Hodgkin's disease. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Lomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle–phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins. •Absorption (Drug A): No absorption available •Absorption (Drug B): Well and rapidly 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): 50% •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Hepatic. Rapid and complete, with active metabolites. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat: LD 50 = 70 mg/kg. Pulmonary toxicity has been reported at cumulative doses usually greater than 1,100 mg/m2. There is one report of pulmonary toxicity at a cumulative dose of only 600 mg. The onset of toxicity has varied from 6 months after initiation of therapy, to as late as 15 years after. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Ceenu, Gleostine •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chloroethylcyclohexylnitrosourea CINU Cyclohexyl chloroethyl nitrosourea Lomustina Lomustine Lomustinum •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Lomustine is an alkylating agent used as a part of chemotherapeutic regimens for the treatment of primary and metastatic brain tumors as well as refractory or relapsed Hodgkin's disease in addition to surgical and/or radiotherapeutic treatments. Output: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Does Abciximab and Loncastuximab tesirine interact?

•Drug A: Abciximab •Drug B: Loncastuximab tesirine •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Loncastuximab tesirine. •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): Loncastuximab tesirine is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma who have undergone two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. The above indication is approved under accelerated FDA approval following the results of clinical studies. Continued approval is dependant upon the results of confirmatory clinical trials. In Europe, Loncastuximab tesirine is approved for treatment of both adult and pediatric patients aged 12 years old or older for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Loncastuximab tesirine exhibits antitumour activity against malignant B-cells, treating lymphomas. Higher exposure in Cycle 1 of therapy in clinical trials was associated with an increased incidence of Grade ≥2 adverse reactions, including liver function test abnormalities, skin and nail reactions, and liver function test abnormalities. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Human CD19 antigen is a membrane glycoprotein in the immunoglobulin superfamily expressed in the various stages of B-cell development; it is detected in most malignancies of B-cell origin. Additionally, CD19 has rapid internalization kinetics and does not shed into the general circulation, rendering it a useful therapeutic target for antibody-drug conjugates (ADCs) in the treatment of B-cell malignancies. Loncastuximab tesirine is an antibody-drug conjugate designed to target human CD19. It is a humanized monoclonal antibody and conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin by a protease enzyme cleavable valine-alanine linker. The monoclonal IgG1 kappa antibody component binds to CD19, a transmembrane protein located on B-cell surfaces. The small molecule component, SG3199, functions as a PBD dimer and alkylating agent. Following binding to CD19, loncastuximab tesirine becomes internalized into the cell and subsequently proteolytic cleavage releases the SG3199 component. SG3199 binds to the DNA minor groove, forming cytotoxic DNA interstrand crosslinks, leading to B-cell cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Due to its intravenous route of administration, loncastuximab tesirine is readily absorbed into the circulation. Cmax during Cycle 1 of therapy was 2995 μg/L and 3155 μg/L in Cycle 2. AUC was 15,245 - 22,823 μg*day/L during pharmacokinetic studies. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In clinical studies, the average loncastuximab tesirine-lpyl volume of distribution was 7.11 liters, with a range between 7.19-8.43 liters. •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 monoclonal antibody portion of loncastuximab tesirine-lpyl is catabolized into small peptides. In vitro studies show that the small molecule cytotoxin portion, SG3199, is metabolized by CYP3A4/5. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main excretion pathways of SG3199 have not been formally studied in humans. SG3199 is thought to be minimally excreted 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): The half-life of loncastuximab tesirine-lpyl was 7.06-12.5 days at steady-state. •Clearance (Drug A): No clearance available •Clearance (Drug B): In pharmacokinetic studies, the mean clearance of loncastuximab tesirine-lpyl decreased with time from 0.499 L/day after a single dose to 0.275 L/day at steady-state. One pharmacokinetic study measured a clearance ranging from 0.5-0.64 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for loncastuximab tesirine is not readily available in the literature. Toxicity is increased at higher doses, and may lead to discontinuation. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Zynlonta •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): Loncastuximab tesirine is an antibody-drug conjugate used for the treatment of relapsed and refractory B-cell lymphomas.

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 Loncastuximab tesirine interact? Information: •Drug A: Abciximab •Drug B: Loncastuximab tesirine •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Loncastuximab tesirine. •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): Loncastuximab tesirine is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma who have undergone two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. The above indication is approved under accelerated FDA approval following the results of clinical studies. Continued approval is dependant upon the results of confirmatory clinical trials. In Europe, Loncastuximab tesirine is approved for treatment of both adult and pediatric patients aged 12 years old or older for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Loncastuximab tesirine exhibits antitumour activity against malignant B-cells, treating lymphomas. Higher exposure in Cycle 1 of therapy in clinical trials was associated with an increased incidence of Grade ≥2 adverse reactions, including liver function test abnormalities, skin and nail reactions, and liver function test abnormalities. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Human CD19 antigen is a membrane glycoprotein in the immunoglobulin superfamily expressed in the various stages of B-cell development; it is detected in most malignancies of B-cell origin. Additionally, CD19 has rapid internalization kinetics and does not shed into the general circulation, rendering it a useful therapeutic target for antibody-drug conjugates (ADCs) in the treatment of B-cell malignancies. Loncastuximab tesirine is an antibody-drug conjugate designed to target human CD19. It is a humanized monoclonal antibody and conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin by a protease enzyme cleavable valine-alanine linker. The monoclonal IgG1 kappa antibody component binds to CD19, a transmembrane protein located on B-cell surfaces. The small molecule component, SG3199, functions as a PBD dimer and alkylating agent. Following binding to CD19, loncastuximab tesirine becomes internalized into the cell and subsequently proteolytic cleavage releases the SG3199 component. SG3199 binds to the DNA minor groove, forming cytotoxic DNA interstrand crosslinks, leading to B-cell cell death. •Absorption (Drug A): No absorption available •Absorption (Drug B): Due to its intravenous route of administration, loncastuximab tesirine is readily absorbed into the circulation. Cmax during Cycle 1 of therapy was 2995 μg/L and 3155 μg/L in Cycle 2. AUC was 15,245 - 22,823 μg*day/L during pharmacokinetic studies. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): In clinical studies, the average loncastuximab tesirine-lpyl volume of distribution was 7.11 liters, with a range between 7.19-8.43 liters. •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 monoclonal antibody portion of loncastuximab tesirine-lpyl is catabolized into small peptides. In vitro studies show that the small molecule cytotoxin portion, SG3199, is metabolized by CYP3A4/5. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The main excretion pathways of SG3199 have not been formally studied in humans. SG3199 is thought to be minimally excreted 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): The half-life of loncastuximab tesirine-lpyl was 7.06-12.5 days at steady-state. •Clearance (Drug A): No clearance available •Clearance (Drug B): In pharmacokinetic studies, the mean clearance of loncastuximab tesirine-lpyl decreased with time from 0.499 L/day after a single dose to 0.275 L/day at steady-state. One pharmacokinetic study measured a clearance ranging from 0.5-0.64 L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): LD50 information for loncastuximab tesirine is not readily available in the literature. Toxicity is increased at higher doses, and may lead to discontinuation. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Zynlonta •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): Loncastuximab tesirine is an antibody-drug conjugate used for the treatment of relapsed and refractory B-cell lymphomas. 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 Lornoxicam interact?

•Drug A: Abciximab •Drug B: Lornoxicam •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Lornoxicam is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of acute mild to moderate pain, as well as pain and inflammation of the joints caused by certain types of rheumatic diseases. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 other NSAIDS, lornoxicam's anti-inflammatory and analgesic activity is related to its inhibitory action on prostaglandin and thromboxane synthesis through the inhibition of both COX-1 and COX-2. This leads to the reduction of inflammation, pain, fever, and swelling, which are mediated by prostaglandins. However, the exact mechanism of lornoxicam, like that of the other NSAIDs, has not been fully determined. •Absorption (Drug A): No absorption available •Absorption (Drug B): Lornoxicam is absorbed rapidly and almost completely from the GI tract (90-100%). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Lornoxicam is 99% bound to plasma proteins (almost exlusively 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): Lornoxicam is metabolized completely by cyp 2C9 with the principal metabolite being 5'-hydroxy-lornoxicam and only negligible amounts of intact lornoxicam are excreted unchanged in the urine. Approximately 2/3 of the drug is eliminated via the liver and 1/3 via the kidneys in the active form. •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): 3-5 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): 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): Lornoxicam is an NSAID indicated in the treatment of mild to moderate pain, as well as rheumatoid arthritis and osteoarthritis.

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 Lornoxicam interact? Information: •Drug A: Abciximab •Drug B: Lornoxicam •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Lornoxicam is combined with Abciximab. •Extended Description: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): For the treatment of acute mild to moderate pain, as well as pain and inflammation of the joints caused by certain types of rheumatic diseases. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this 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 other NSAIDS, lornoxicam's anti-inflammatory and analgesic activity is related to its inhibitory action on prostaglandin and thromboxane synthesis through the inhibition of both COX-1 and COX-2. This leads to the reduction of inflammation, pain, fever, and swelling, which are mediated by prostaglandins. However, the exact mechanism of lornoxicam, like that of the other NSAIDs, has not been fully determined. •Absorption (Drug A): No absorption available •Absorption (Drug B): Lornoxicam is absorbed rapidly and almost completely from the GI tract (90-100%). •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Lornoxicam is 99% bound to plasma proteins (almost exlusively 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): Lornoxicam is metabolized completely by cyp 2C9 with the principal metabolite being 5'-hydroxy-lornoxicam and only negligible amounts of intact lornoxicam are excreted unchanged in the urine. Approximately 2/3 of the drug is eliminated via the liver and 1/3 via the kidneys in the active form. •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): 3-5 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): 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): Lornoxicam is an NSAID indicated in the treatment of mild to moderate pain, as well as rheumatoid arthritis and osteoarthritis. 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 Loxoprofen interact?

•Drug A: Abciximab •Drug B: Loxoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Loxoprofen 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): Loxoprofen is non-steroidal anti-inflammatory medication (NSAID) indicated for pain and inflammation related to musculoskeletal and joint disorders. In addition to its effects on pain, it is an antipyretic and anti-inflammatory medication. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase. Cyclooxygenase (COX) is present in 2 forms, COX-1 and COX-2, with each serving different functions. COX-1 is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation. COX-2 is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain. Loxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc). •Absorption (Drug A): No absorption available •Absorption (Drug B): Loxoprofen is rapidly and completely absorbed from the GI tract with a bioavailability of 95%. The absorption phase of the medication occurs in the first 4-6 hours after ingestion. Food ingestion with the medication causes a slight decrease in the rate of loxoprofen absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Loxoprofen has a volume of distribution of 0.16 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 99% albumin-bound. At doses of loxoprofen greater than 500 mg/day, clearance of the drug increases as saturation of plasma protein binding occurs at higher doses. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Loxoprofen is a prodrug that is rapidly converted to its active trans-alcohol metabolite by carbonyl reductase in the liver. This same process also results in a cis-alcohol metabolite, though this isomer carries little pharmacological activity. The parent drug has also been observed to undergo oxidation via CYP3A4/5 to two hydroxylated metabolites (M3 and M4) and glucuronidation by UGT2B7 to two glucuronide metabolites (M5 and M6). The alcohol metabolites of loxoprofen also undergo glucuronide conjugation via UGT2B7 to two glucuronide metabolites (M7 and M8) prior to excretion. When applied in topical formulations, loxoprofen is metabolized to its active trans-alcohol form by carbonyl reductase in the skin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 50% renal excretion. This drug is 20% - 30% excreted in the stool. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 Loxoprofen is approximately 15 hours. Steady concentration is achieved after 2-3 doses. •Clearance (Drug A): No clearance available •Clearance (Drug B): Most of the drug as unchanged loxoprofen, 6-0-desmethyl loxoprofen (less than 1%) and glucuronide or other conjugates (66-92%). In patients with renal failure, metabolites may accumulate. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adverse effects include anorexia, nausea, vomiting, bleeding, anemia, diarrhea, and constipation. Loxoprofen toxicity may lead to gastrointestinal disturbance (including flatulence, dyspepsia and gastritis) and renal failure. •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): Loxoprofen is an NSAID used to treat pain and inflammation in musculoskeletal conditions.

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 Loxoprofen interact? Information: •Drug A: Abciximab •Drug B: Loxoprofen •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Loxoprofen 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): Loxoprofen is non-steroidal anti-inflammatory medication (NSAID) indicated for pain and inflammation related to musculoskeletal and joint disorders. In addition to its effects on pain, it is an antipyretic and anti-inflammatory medication. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase. Cyclooxygenase (COX) is present in 2 forms, COX-1 and COX-2, with each serving different functions. COX-1 is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation. COX-2 is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain. Loxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc). •Absorption (Drug A): No absorption available •Absorption (Drug B): Loxoprofen is rapidly and completely absorbed from the GI tract with a bioavailability of 95%. The absorption phase of the medication occurs in the first 4-6 hours after ingestion. Food ingestion with the medication causes a slight decrease in the rate of loxoprofen absorption. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Loxoprofen has a volume of distribution of 0.16 L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 99% albumin-bound. At doses of loxoprofen greater than 500 mg/day, clearance of the drug increases as saturation of plasma protein binding occurs at higher doses. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Loxoprofen is a prodrug that is rapidly converted to its active trans-alcohol metabolite by carbonyl reductase in the liver. This same process also results in a cis-alcohol metabolite, though this isomer carries little pharmacological activity. The parent drug has also been observed to undergo oxidation via CYP3A4/5 to two hydroxylated metabolites (M3 and M4) and glucuronidation by UGT2B7 to two glucuronide metabolites (M5 and M6). The alcohol metabolites of loxoprofen also undergo glucuronide conjugation via UGT2B7 to two glucuronide metabolites (M7 and M8) prior to excretion. When applied in topical formulations, loxoprofen is metabolized to its active trans-alcohol form by carbonyl reductase in the skin. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): 50% renal excretion. This drug is 20% - 30% excreted in the stool. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and 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 Loxoprofen is approximately 15 hours. Steady concentration is achieved after 2-3 doses. •Clearance (Drug A): No clearance available •Clearance (Drug B): Most of the drug as unchanged loxoprofen, 6-0-desmethyl loxoprofen (less than 1%) and glucuronide or other conjugates (66-92%). In patients with renal failure, metabolites may accumulate. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Adverse effects include anorexia, nausea, vomiting, bleeding, anemia, diarrhea, and constipation. Loxoprofen toxicity may lead to gastrointestinal disturbance (including flatulence, dyspepsia and gastritis) and renal failure. •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): Loxoprofen is an NSAID used to treat pain and inflammation in musculoskeletal conditions. 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 Lynestrenol interact?

•Drug A: Abciximab •Drug B: Lynestrenol •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Lynestrenol is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): No indication available •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 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): Lynestrenol is a progestin used for contraception and in the treatment of menstrual disorders.

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 Lynestrenol interact? Information: •Drug A: Abciximab •Drug B: Lynestrenol •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Lynestrenol is combined with Abciximab. •Extended Description: Oral contraceptives may increase blood clotting factors and decrease the effectiveness of anticoagulants due to their prothrombotic effects.1,2,4 In contrast, in some patients anticoagulant effects may actually be potentiated by the use of oral contraceptives, although this risk appears to be relatively low. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): No indication available •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): No pharmacodynamics available •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): No mechanism of action available •Absorption (Drug A): No absorption available •Absorption (Drug B): No absorption available •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): No volume of distribution available •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): No metabolism available •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): No half-life available •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No toxicity available •Brand Names (Drug A): No brand names available •Brand Names (Drug B): No brand names available •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 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): Lynestrenol is a progestin used for contraception and in the treatment of menstrual disorders. 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 Margetuximab interact?

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

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

•Drug A: Abciximab •Drug B: Mechlorethamine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mechlorethamine. •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 palliative treatment of Hodgkin's disease (Stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides, and bronchogenic carcinoma. Also for the palliative treatment of metastatic carcinoma resulting in effusion. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mechlorethamine also known as mustine, nitrogen mustard, and HN2, is the prototype anticancer chemotherapeutic drug. Successful clinical use of mechlorethamine gave birth to the field of anticancer chemotherapy. The drug is an analogue of mustard gas and was derived from toxic gas warfare research. Mechlorethamine is a nitrogen mustard alkylating agent. 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. Mechlorethamine is cell cycle phase-nonspecific. •Absorption (Drug A): No absorption available •Absorption (Drug B): Partially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids. When it is topically administered, systemic exposure was undetectable. •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): Undergoes rapid chemical transformation and combines with water or reactive compounds of cells, so that the drug is no longer present in active form a few minutes after administration. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 15 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overexposure include severe leukopenia, anemia, thrombocytopenia, and a hemorrhagic diathesis with subsequent delayed bleeding may develop. Death may follow. The most common adverse reactions (≥5%) of the topical formulation are dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, and hyperpigmentation. The oral LD50 for a rat is 10 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Valchlor •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chlormethine Chlormethinum Clormetina Mechlorethamine Mustine Nitrogen mustard •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mechlorethamine is an antineoplastic agent used to treat Hodgkin's disease, lymphosarcoma, and chronic myelocytic or 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 Mechlorethamine interact? Information: •Drug A: Abciximab •Drug B: Mechlorethamine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mechlorethamine. •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 palliative treatment of Hodgkin's disease (Stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides, and bronchogenic carcinoma. Also for the palliative treatment of metastatic carcinoma resulting in effusion. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mechlorethamine also known as mustine, nitrogen mustard, and HN2, is the prototype anticancer chemotherapeutic drug. Successful clinical use of mechlorethamine gave birth to the field of anticancer chemotherapy. The drug is an analogue of mustard gas and was derived from toxic gas warfare research. Mechlorethamine is a nitrogen mustard alkylating agent. 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. Mechlorethamine is cell cycle phase-nonspecific. •Absorption (Drug A): No absorption available •Absorption (Drug B): Partially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids. When it is topically administered, systemic exposure was undetectable. •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): Undergoes rapid chemical transformation and combines with water or reactive compounds of cells, so that the drug is no longer present in active form a few minutes after administration. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 15 minutes •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Symptoms of overexposure include severe leukopenia, anemia, thrombocytopenia, and a hemorrhagic diathesis with subsequent delayed bleeding may develop. Death may follow. The most common adverse reactions (≥5%) of the topical formulation are dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, and hyperpigmentation. The oral LD50 for a rat is 10 mg/kg. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Valchlor •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Chlormethine Chlormethinum Clormetina Mechlorethamine Mustine Nitrogen mustard •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mechlorethamine is an antineoplastic agent used to treat Hodgkin's disease, lymphosarcoma, and chronic myelocytic or 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 Meclofenamic acid interact?

•Drug A: Abciximab •Drug B: Meclofenamic acid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Meclofenamic 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): For the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss. Also for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The mode of action, like that of other nonsteroidal anti-inflammatory agents, is not known. Therapeutic action does not result from pituitary-adrenal stimulation. In animal studies, meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro meclofenamic acid was found to be an inhibitor of human leukocyte 5-lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamic acid. There is no evidence that meclofenamic acid alters the course of the underlying disease. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed in man following single and multiple oral doses with peak plasma concentrations occurring in 0.5 to 2 hours. The concomitant administration of antacids (aluminum and magnesium hydroxides) does not interfere with absorption of meclofenamic acid. Unlike most NSAIDs, which when administered with food have a decrease in rate but not in extent of absorption, meclofenamic acid is decreased in both. It has been reported that following the administration of meclofenamic acid capsules one-half hour after a meal, the average extent of bioavailability decreased by 26%, the average peak concentration (C max ) decreased fourfold and the time to C max was delayed by 3 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 9.1 to 43.2 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Greater than 99% bound to plasma proteins over a wide drug 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): Hepatic. Meclofenamic acid is extensively metabolized to an active metabolite (Metabolite I; 3-hydroxymethyl metabolite of meclofenamic acid) and at least six other less well characterized minor metabolites. Only Metabolite I has been shown in vitro to inhibit cyclooxygenase activity with approximately one fifth the activity of meclofenamic acid. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Other metabolites, whose excretion rates are unknown, account for the remaining 35% to 62% of the dose excreted in the urine. The remainder of the administered dose (approximately 30%) is eliminated in the feces (apparently through biliary excretion). Trace amounts of meclofenamate sodium are excreted in human 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): In a study in 10 healthy subjects following a single oral dose the apparent elimination half-life ranged from 0.8 to 5.3 hours. Metabolite I (3-hydroxymethyl metabolite of meclofenamic acid) has a mean half-life of approximately 15 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral cl=206 mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): After a massive overdose, CNS stimulation may be manifested by irrational behavior, marked agitation and generalized seizures. Following this phase, renal toxicity (falling urine output, rising creatinine, abnormal urinary cellular elements) may be noted with possible oliguria or anuria and azotemia. A 24 year-old male was anuric for approximately one week after ingesting an overdose of 6 to 7 grams of meclofenamate sodium. Spontaneous diuresis and recovery subsequently occurred. •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 méclofénamique ácido meclofenámico Acidum meclofenamicum Meclofenamate Meclofenamic 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): Meclofenamic acid is an NSAID used to treat mild to moderate pain, primary dysmenorrhea, heavy menstrual blood loss, rheumatoid arthritis, and osteoarthritis.

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 Meclofenamic acid interact? Information: •Drug A: Abciximab •Drug B: Meclofenamic acid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Meclofenamic 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): For the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss. Also for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The mode of action, like that of other nonsteroidal anti-inflammatory agents, is not known. Therapeutic action does not result from pituitary-adrenal stimulation. In animal studies, meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro meclofenamic acid was found to be an inhibitor of human leukocyte 5-lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamic acid. There is no evidence that meclofenamic acid alters the course of the underlying disease. •Absorption (Drug A): No absorption available •Absorption (Drug B): Rapidly absorbed in man following single and multiple oral doses with peak plasma concentrations occurring in 0.5 to 2 hours. The concomitant administration of antacids (aluminum and magnesium hydroxides) does not interfere with absorption of meclofenamic acid. Unlike most NSAIDs, which when administered with food have a decrease in rate but not in extent of absorption, meclofenamic acid is decreased in both. It has been reported that following the administration of meclofenamic acid capsules one-half hour after a meal, the average extent of bioavailability decreased by 26%, the average peak concentration (C max ) decreased fourfold and the time to C max was delayed by 3 hours. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 9.1 to 43.2 L •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Greater than 99% bound to plasma proteins over a wide drug 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): Hepatic. Meclofenamic acid is extensively metabolized to an active metabolite (Metabolite I; 3-hydroxymethyl metabolite of meclofenamic acid) and at least six other less well characterized minor metabolites. Only Metabolite I has been shown in vitro to inhibit cyclooxygenase activity with approximately one fifth the activity of meclofenamic acid. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Other metabolites, whose excretion rates are unknown, account for the remaining 35% to 62% of the dose excreted in the urine. The remainder of the administered dose (approximately 30%) is eliminated in the feces (apparently through biliary excretion). Trace amounts of meclofenamate sodium are excreted in human 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): In a study in 10 healthy subjects following a single oral dose the apparent elimination half-life ranged from 0.8 to 5.3 hours. Metabolite I (3-hydroxymethyl metabolite of meclofenamic acid) has a mean half-life of approximately 15 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral cl=206 mL/min •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): After a massive overdose, CNS stimulation may be manifested by irrational behavior, marked agitation and generalized seizures. Following this phase, renal toxicity (falling urine output, rising creatinine, abnormal urinary cellular elements) may be noted with possible oliguria or anuria and azotemia. A 24 year-old male was anuric for approximately one week after ingesting an overdose of 6 to 7 grams of meclofenamate sodium. Spontaneous diuresis and recovery subsequently occurred. •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 méclofénamique ácido meclofenámico Acidum meclofenamicum Meclofenamate Meclofenamic 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): Meclofenamic acid is an NSAID used to treat mild to moderate pain, primary dysmenorrhea, heavy menstrual blood loss, rheumatoid arthritis, and osteoarthritis. 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 Medroxyprogesterone acetate interact?

•Drug A: Abciximab •Drug B: Medroxyprogesterone acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Medroxyprogesterone 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): Medroxyprogesterone acetate (MPA) oral tablets are indicated to treat secondary amenorrhea, reduce the incidence of endometrial hyperplasia in postmenopausal women, and to treat abnormal uterine bleeding due to hormonal imbalance, not organic pathology. Oral tablets containing MPA and conjugated estrogens are indicated to prevent postmenopausal osteoporosis and to treat moderate to severe menopausal symptoms such as vasomotor symptoms, vulvar atrophy, and vaginal atrophy. Subcutaneous MPA is indicated to prevent pregnancy and manage pain associated with endometriosis. Intramuscular MPA is indicated to prevent pregnancy, and at higher concentrations for palliative treatment of endometrial or renal 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): Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines. MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long. The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly. Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy. This action also thins the endometrium. MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium. MPA can also induce p53 dependant apoptosis in certain cancer cell lines, and inhibit GABA-A receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of oral medroxyprogesterone acetate (MPA) varies considerably between formulations. A 1000mg oral dose reaches an average C max of 145-315nmol/L while a 500mg oral dose reaches an average C max of 33-178nmol/L with a T max of 1-3 hours and a lag time of half an hour. The AUC of a 500mg oral dose of MPA was 543.4-1981.1nmol*L/h depending on formulation. Intramuscular MPA reaches a C max of 4.69±1.52nmol/L with a T max of 4.75±2.09 days and an AUC of 81.58±27.64days*nmol/L. Subcutaneous MPA reaches a C max of 3.83±1.56nmol/L with a T±max of 6.52±2.07 days and an AUC of 72.26±38.73days*nmol/L. However, the pharmacokinetics of MPA may also vary depending on injection site. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of medroxyprogesterone acetate is 20±3L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Medroxyprogesterone acetate is 86% protein bound in serum, mainly to albumin. No binding occurs with 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): Medroxyprogesterone acetate undergoes beta hydroxylation to form the metabolites 6-beta (M-2), 2-beta (M-4), and 1-beta-hydroxymedroxyprogesterone acetate (M-3). M-2 and M-4 are further metabolized to 2-beta,6-beta-dihydroxymedroxyprogesterone (M-1). M-3 is further metabolized to 1,2-dehydromedroxyprogesterone acetate (M-5). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The majority of medroxyprogesterone acetate (MPA) is eliminated in the urine as glucuronide conjugates and a minority of sulphate conjugates. Glucuronide conjugates are also detected in the feces. Determining the exact ratio of metabolites and parent compound eliminated in the urine and feces is difficult as the metabolite profile in the urine is not significantly different and radio labelling studies are not readily 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): Oral medroxyprogesterone acetate (MPA) has an absorption half life of 15-30min and a biological half life of 40-60 hours. Intramuscular MPA has an absorption half life of 0.86±0.30 days and an elimination half life of 24.03±21.74 days. Subcutaneous MPA has an absorption half life of 1.05±0.56 days and an elimination half life of 30.90±15.11 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance of medroxyprogesterone acetate (MPA) is 1668±146L/day or 21.9±4.3L/kg/day. Due to the high inter patient variability in MPA pharmacokinetics, clearance has been reported to be 1600-4000L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is >6400mg/kg and in mice is >16g/kg. The intraperitoneal LD 50 in rats is >900mg/kg and in mice is >1500mg/kg. The subcutaneous LD 50 in rats is >900mg/kg and in mice is>1500mg/kg. Patients experiencing and overdose or oral medroxyprogesterone acetate (MPA) may present with nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. Treat patients by stopping MPA and beginning symptomatic treatment. Patients who have been given too much of a MPA depo injection should contact a healthcare professional, hospital emergency department, or local poison control immediately. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Depo-provera, Depo-subq Provera, Premphase 28 Day, Prempro 0.625/2.5 28 Day, Provera •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Medroxyacetate progesterone Medroxyprogesterone acetate Methylacetoxyprogesterone Metigestrona •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Medroxyprogesterone acetate is a progestin used as a contraceptive and in the treatment of secondary amenorrhea, abnormal uterine bleeding, pain from endometriosis, endometrial and renal carcinomas, paraphilia in males, and GnRH-dependent precocious puberty.

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 Medroxyprogesterone acetate interact? Information: •Drug A: Abciximab •Drug B: Medroxyprogesterone acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Medroxyprogesterone 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): Medroxyprogesterone acetate (MPA) oral tablets are indicated to treat secondary amenorrhea, reduce the incidence of endometrial hyperplasia in postmenopausal women, and to treat abnormal uterine bleeding due to hormonal imbalance, not organic pathology. Oral tablets containing MPA and conjugated estrogens are indicated to prevent postmenopausal osteoporosis and to treat moderate to severe menopausal symptoms such as vasomotor symptoms, vulvar atrophy, and vaginal atrophy. Subcutaneous MPA is indicated to prevent pregnancy and manage pain associated with endometriosis. Intramuscular MPA is indicated to prevent pregnancy, and at higher concentrations for palliative treatment of endometrial or renal 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): Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines. MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long. The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly. Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy. This action also thins the endometrium. MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium. MPA can also induce p53 dependant apoptosis in certain cancer cell lines, and inhibit GABA-A receptors. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of oral medroxyprogesterone acetate (MPA) varies considerably between formulations. A 1000mg oral dose reaches an average C max of 145-315nmol/L while a 500mg oral dose reaches an average C max of 33-178nmol/L with a T max of 1-3 hours and a lag time of half an hour. The AUC of a 500mg oral dose of MPA was 543.4-1981.1nmol*L/h depending on formulation. Intramuscular MPA reaches a C max of 4.69±1.52nmol/L with a T max of 4.75±2.09 days and an AUC of 81.58±27.64days*nmol/L. Subcutaneous MPA reaches a C max of 3.83±1.56nmol/L with a T±max of 6.52±2.07 days and an AUC of 72.26±38.73days*nmol/L. However, the pharmacokinetics of MPA may also vary depending on injection site. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of medroxyprogesterone acetate is 20±3L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Medroxyprogesterone acetate is 86% protein bound in serum, mainly to albumin. No binding occurs with 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): Medroxyprogesterone acetate undergoes beta hydroxylation to form the metabolites 6-beta (M-2), 2-beta (M-4), and 1-beta-hydroxymedroxyprogesterone acetate (M-3). M-2 and M-4 are further metabolized to 2-beta,6-beta-dihydroxymedroxyprogesterone (M-1). M-3 is further metabolized to 1,2-dehydromedroxyprogesterone acetate (M-5). •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The majority of medroxyprogesterone acetate (MPA) is eliminated in the urine as glucuronide conjugates and a minority of sulphate conjugates. Glucuronide conjugates are also detected in the feces. Determining the exact ratio of metabolites and parent compound eliminated in the urine and feces is difficult as the metabolite profile in the urine is not significantly different and radio labelling studies are not readily 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): Oral medroxyprogesterone acetate (MPA) has an absorption half life of 15-30min and a biological half life of 40-60 hours. Intramuscular MPA has an absorption half life of 0.86±0.30 days and an elimination half life of 24.03±21.74 days. Subcutaneous MPA has an absorption half life of 1.05±0.56 days and an elimination half life of 30.90±15.11 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean clearance of medroxyprogesterone acetate (MPA) is 1668±146L/day or 21.9±4.3L/kg/day. Due to the high inter patient variability in MPA pharmacokinetics, clearance has been reported to be 1600-4000L/day. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is >6400mg/kg and in mice is >16g/kg. The intraperitoneal LD 50 in rats is >900mg/kg and in mice is >1500mg/kg. The subcutaneous LD 50 in rats is >900mg/kg and in mice is>1500mg/kg. Patients experiencing and overdose or oral medroxyprogesterone acetate (MPA) may present with nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. Treat patients by stopping MPA and beginning symptomatic treatment. Patients who have been given too much of a MPA depo injection should contact a healthcare professional, hospital emergency department, or local poison control immediately. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Depo-provera, Depo-subq Provera, Premphase 28 Day, Prempro 0.625/2.5 28 Day, Provera •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Medroxyacetate progesterone Medroxyprogesterone acetate Methylacetoxyprogesterone Metigestrona •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Medroxyprogesterone acetate is a progestin used as a contraceptive and in the treatment of secondary amenorrhea, abnormal uterine bleeding, pain from endometriosis, endometrial and renal carcinomas, paraphilia in males, and GnRH-dependent precocious puberty. 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 Mefenamic acid interact?

•Drug A: Abciximab •Drug B: Mefenamic acid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Mefenamic 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): For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced. •Absorption (Drug A): No absorption available •Absorption (Drug B): Mefenamic acid is rapidly absorbed after oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1.06 L/kg [Normal Healthy Adults (18-45 yr)] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 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): Mefenamic acid undergoes metabolism by CYP2C9 to 3-hydroxymethyl mefenamic acid, and further oxidation to a 3-carboxymefenamic acid may occur. The activity of these metabolites has not been studied. Mefenamic acid is also glucuronidated directly. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat LD 50: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Mefenamic, Ponstel •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Acide méfénamique ácido mefenámico Acidum mefenamicum Mefenamic acid Mefenaminsäure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mefenamic acid is an NSAID used to treat mild to moderate pain for no more than a week, and primary dysmenorrhea.

Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. The severity of the interaction is moderate.

Question: Does Abciximab and Mefenamic acid interact? Information: •Drug A: Abciximab •Drug B: Mefenamic acid •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Mefenamic 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): For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced. •Absorption (Drug A): No absorption available •Absorption (Drug B): Mefenamic acid is rapidly absorbed after oral administration. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): 1.06 L/kg [Normal Healthy Adults (18-45 yr)] •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): 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): Mefenamic acid undergoes metabolism by CYP2C9 to 3-hydroxymethyl mefenamic acid, and further oxidation to a 3-carboxymefenamic acid may occur. The activity of these metabolites has not been studied. Mefenamic acid is also glucuronidated directly. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 2 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)] •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Oral, rat LD 50: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Mefenamic, Ponstel •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Acide méfénamique ácido mefenámico Acidum mefenamicum Mefenamic acid Mefenaminsäure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mefenamic acid is an NSAID used to treat mild to moderate pain for no more than a week, and primary dysmenorrhea. Output: Both anticoagulants and non-steroidal anti-inflammatory agents are associated with a risk for bleeding events. Concomitant use of anticoagulants with over-the-counter NSAIDs may significantly increase the risk for gastrointestinal hemorrhage while concomitant use of anticoagulants with acetaminophen may lead to increased risk for general all-site bleeding events. NSAIDs such as ibuprofen are substrates of CYP2C9, which may also interfere with the metabolism of S-warfarin and further increase the risk for warfarin-associated bleeding. The severity of the interaction is moderate.

Does Abciximab and Megestrol acetate interact?

•Drug A: Abciximab •Drug B: Megestrol acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Megestrol 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 treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Variable, but well absorbed orally. •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. Megestrol metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. No active metabolites have been identified. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The major route of drug elimination in humans is urine. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 34 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362]. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Megace •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Megestrol 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): Megestrol acetate is a progestin that is administered orally to treat anorexia and cachexia or serious unexplained weight loss and is also used as an antineoplastic agent to treat certain types of malignancy.

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 Megestrol acetate interact? Information: •Drug A: Abciximab •Drug B: Megestrol acetate •Severity: MODERATE •Description: The risk or severity of adverse effects can be increased when Megestrol 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 treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes. •Absorption (Drug A): No absorption available •Absorption (Drug B): Variable, but well absorbed orally. •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. Megestrol metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. No active metabolites have been identified. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): The major route of drug elimination in humans is urine. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): 34 hours •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362]. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Megace •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Megestrol 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): Megestrol acetate is a progestin that is administered orally to treat anorexia and cachexia or serious unexplained weight loss and is also used as an antineoplastic agent to treat certain types of malignancy. 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 Meloxicam interact?

•Drug A: Abciximab •Drug B: Meloxicam •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Meloxicam 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): Meloxicam is indicated for the symptomatic treatment of arthritis and osteoarthritis. In addition, it is indicated for the pauciarticular and polyarticular course of Juvenile Rheumatoid Arthritis (JRA) in patients aged 2 years old or above. Off-label uses include the treatment of dental or post-surgical pain. In addition to the above, meloxicam has also been studied in the treatment of neuropathic pain. Meloxicam, in combination with bupivacaine, is indicated for postsurgical analgesia in adult patients for up to 72 hours following soft tissue surgical procedures, foot and ankle procedures, and other orthopedic procedures in which direct exposure to articular cartilage is avoided. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever. Prostaglandins are substances that contribute to inflammation. This drug also exerts preferential actions against COX-2, which may reduce the possible gastrointestinal effects of this drug. In humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate(ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as aquaporin-1 expression. As with other NSAIDS, prolonged use of meloxicum can result in renal or cardiovascular impairment or thrombotic cardiovascular events. A note on gastrointestinal effects As meloxicam preferentially inhibits COX-2, it is thought to cause less gastrointestinal irritation compared to other NSAIDS. Despite this, it still carries a risk of gastric inflammation, bleeding and ulceration. In one study, patients on meloxicam suffered from gastrointestinal symptoms at a rate of 13% compared to 19% of those on diclofenac. GI events were found to be less severe in the meloxicam-treated 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): Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms. As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-2, but also exerts some activity against COX-1, causing gastrointestinal irritation. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability oral capsules after a dose was 89% in one pharmacokinetic study. Cmax was reached 5–6 hours after administration of a single dose given after the first meal of the day. The Cmax doubled when the drug was administered in the fasting state. Despite this, meloxicam can be taken without regard to food, unlike many other NSAIDS. Meloxicam formulated for instillation with bupivacaine produced varied systemic measures following a single dose of varying strength. In patients undergoing bunionectomy, 1.8 mg of meloxicam produced a C max of 26 ± 14 ng/mL, a median T max of 18 h, and an AUC ∞ of 2079 ± 1631 ng*h/mL. For a 9 mg dose used in herniorrhaphy, the corresponding values were 225 ± 96 ng/mL, 54 h, and the AUC ∞ was not reported. Lastly, a 12 mg dose used in total knee arthroplasty produced values of 275 ± 134 ng/mL, 36 h, and 25,673 ± 17,666 ng*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of meloxicam is 10-15L. Because of its high binding to albumin, it is likely to be distributed in highly perfused tissues, such as the liver and kidney. Meloxicam concentrations in synovial fluid, measured after an oral dose, is estimated at 40% to 50% of the concentrations measured in the plasma. This drug is known to cross the placenta in humans. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Meloxicam is about 99.4% protein bound, primarily to albumin. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Meloxicam is almost completely metabolized. CYP2C9 is the main enzyme responsible for the metabolism of meloxicam with minor contributions from CYP3A4. Meloxicam has 4 major metabolites with no activity determined. About 60% of the ingested dose is metabolized to 5'-carboxy meloxicam from hepatic cytochrome enzyme oxidation of an intermediate metabolite, 5’-hydroxymethylmeloxicam. Two other metabolites are likely produced via peroxidation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Meloxicam is mainly eliminated through metabolism. Its metabolites are cleared through renal and fecal elimination. Less than <0.25% of a dose is eliminated in the urine as unchanged drug. About 1.6% of the parent drug is excreted in the feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of meloxicam is approximately 20 hours, which is considerably longer than most other NSAIDS. It can therefore be dosed without the need for slow-release formulations. Meloxicam applied together with bupivacaine for postsurgical analgesia had a median half-life of 33-42 hours, depending on dose and application site. •Clearance (Drug A): No clearance available •Clearance (Drug B): After an oral dose, the total clearance of meloxicam is 0.42–0.48 L/h. The FDA label indicates a plasma clearance from 7 to 9 mL/min. No dose changes are required in mild to moderate renal or hepatic impairment. The use of meloxicam in patients with severe renal or hepatic impairment has not been studied. FDA prescribing information advises against it. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 in rats is 98 mg/kg. Signs and symptoms of overdose with meloxicam may include shallow breathing, seizure, decreased urine output, gastrointestinal irritation, nausea, vomiting, gastrointestinal bleeding, and black tarry stools. In the case of an overdose, offer supportive treatment and attempt to remove gastrointestinal contents. Cholestyramine has been shown to enhance the elimination of meloxicam. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Anjeso, Mobic, Qmiiz, Vivlodex, Zynrelef •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): Meloxicam is an NSAID used to treat osteoarthritis in adults, rheumatoid arthritis in adults, and juvenile rheumatoid arthritis in pediatrics.

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 Meloxicam interact? Information: •Drug A: Abciximab •Drug B: Meloxicam •Severity: MODERATE •Description: The risk or severity of bleeding and hemorrhage can be increased when Meloxicam 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): Meloxicam is indicated for the symptomatic treatment of arthritis and osteoarthritis. In addition, it is indicated for the pauciarticular and polyarticular course of Juvenile Rheumatoid Arthritis (JRA) in patients aged 2 years old or above. Off-label uses include the treatment of dental or post-surgical pain. In addition to the above, meloxicam has also been studied in the treatment of neuropathic pain. Meloxicam, in combination with bupivacaine, is indicated for postsurgical analgesia in adult patients for up to 72 hours following soft tissue surgical procedures, foot and ankle procedures, and other orthopedic procedures in which direct exposure to articular cartilage is avoided. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever. Prostaglandins are substances that contribute to inflammation. This drug also exerts preferential actions against COX-2, which may reduce the possible gastrointestinal effects of this drug. In humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate(ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as aquaporin-1 expression. As with other NSAIDS, prolonged use of meloxicum can result in renal or cardiovascular impairment or thrombotic cardiovascular events. A note on gastrointestinal effects As meloxicam preferentially inhibits COX-2, it is thought to cause less gastrointestinal irritation compared to other NSAIDS. Despite this, it still carries a risk of gastric inflammation, bleeding and ulceration. In one study, patients on meloxicam suffered from gastrointestinal symptoms at a rate of 13% compared to 19% of those on diclofenac. GI events were found to be less severe in the meloxicam-treated 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): Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms. As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-2, but also exerts some activity against COX-1, causing gastrointestinal irritation. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absolute bioavailability oral capsules after a dose was 89% in one pharmacokinetic study. Cmax was reached 5–6 hours after administration of a single dose given after the first meal of the day. The Cmax doubled when the drug was administered in the fasting state. Despite this, meloxicam can be taken without regard to food, unlike many other NSAIDS. Meloxicam formulated for instillation with bupivacaine produced varied systemic measures following a single dose of varying strength. In patients undergoing bunionectomy, 1.8 mg of meloxicam produced a C max of 26 ± 14 ng/mL, a median T max of 18 h, and an AUC ∞ of 2079 ± 1631 ng*h/mL. For a 9 mg dose used in herniorrhaphy, the corresponding values were 225 ± 96 ng/mL, 54 h, and the AUC ∞ was not reported. Lastly, a 12 mg dose used in total knee arthroplasty produced values of 275 ± 134 ng/mL, 36 h, and 25,673 ± 17,666 ng*h/mL. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of meloxicam is 10-15L. Because of its high binding to albumin, it is likely to be distributed in highly perfused tissues, such as the liver and kidney. Meloxicam concentrations in synovial fluid, measured after an oral dose, is estimated at 40% to 50% of the concentrations measured in the plasma. This drug is known to cross the placenta in humans. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Meloxicam is about 99.4% protein bound, primarily to albumin. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Meloxicam is almost completely metabolized. CYP2C9 is the main enzyme responsible for the metabolism of meloxicam with minor contributions from CYP3A4. Meloxicam has 4 major metabolites with no activity determined. About 60% of the ingested dose is metabolized to 5'-carboxy meloxicam from hepatic cytochrome enzyme oxidation of an intermediate metabolite, 5’-hydroxymethylmeloxicam. Two other metabolites are likely produced via peroxidation. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Meloxicam is mainly eliminated through metabolism. Its metabolites are cleared through renal and fecal elimination. Less than <0.25% of a dose is eliminated in the urine as unchanged drug. About 1.6% of the parent drug is excreted in the feces. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half-life of meloxicam is approximately 20 hours, which is considerably longer than most other NSAIDS. It can therefore be dosed without the need for slow-release formulations. Meloxicam applied together with bupivacaine for postsurgical analgesia had a median half-life of 33-42 hours, depending on dose and application site. •Clearance (Drug A): No clearance available •Clearance (Drug B): After an oral dose, the total clearance of meloxicam is 0.42–0.48 L/h. The FDA label indicates a plasma clearance from 7 to 9 mL/min. No dose changes are required in mild to moderate renal or hepatic impairment. The use of meloxicam in patients with severe renal or hepatic impairment has not been studied. FDA prescribing information advises against it. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD50 in rats is 98 mg/kg. Signs and symptoms of overdose with meloxicam may include shallow breathing, seizure, decreased urine output, gastrointestinal irritation, nausea, vomiting, gastrointestinal bleeding, and black tarry stools. In the case of an overdose, offer supportive treatment and attempt to remove gastrointestinal contents. Cholestyramine has been shown to enhance the elimination of meloxicam. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Anjeso, Mobic, Qmiiz, Vivlodex, Zynrelef •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): Meloxicam is an NSAID used to treat osteoarthritis in adults, rheumatoid arthritis in adults, and juvenile rheumatoid arthritis in pediatrics. 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 Melphalan interact?

•Drug A: Abciximab •Drug B: Melphalan •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Melphalan. •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): Melphalan is indicated for use as a high-dose conditioning treatment prior to hematopoietic stem cell transplantation in patients with multiple myeloma. It is also indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Melphalan is a component of HEPZATO KIT, a liver-directed therapy indicated for the treatment of adults with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Melphalan possesses cytotoxic, immunosuppressive, and myeloablative activities. Melphalan produces chromosomal aberrations in vitro and in vivo; thus, it is considered to be potentially leukemogenic in humans. It also causes dose-limiting bone marrow suppression. The peak mean heart rate increased by 20 bpm from baseline following melphalan 100 mg/m for two consecutive days in multiple myeloma patients undergoing autologous stem cell transplantation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Melphalan is an alkylating agent of the bischloroethylamine type. It is believed to be taken up by tumour cells via a neutral amino acid active pathway shared by leucine. Melphalan binds at the N7 position of guanine and induces inter-strand cross-links in DNA, disrupting DNA synthesis or transcription. It can also cause DNA-protein cross-linking and induce lesions in RNA, proteins, and lipids. Melphalan is cytotoxic in resting and rapidly dividing tumour cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absorption of oral melphalan is highly variable concerning both the time to the first appearance of the drug in plasma (range: 0 to 6 hours) and peak plasma concentration (C max ). The average absolute bioavailability of melphalan ranges from 56% to 93%. High variability in bioavailability may be due to incomplete intestinal absorption, variable first-pass hepatic metabolism, or rapid hydrolysis. T max was one hour in patients who received single oral doses of 0.2 mg/kg to 0.25 mg/kg of melphalan. Oral administration of melphalan with a high-fat meal may reduce melphalan exposure (AUC) by 36% to 54%. Mean (± SD) C max and AUC 0-inf were 5.8 ± 1.5 mcg/mL and 451 ± 109 mcg x min/mL, respectively, following intravenous administration of 100 mg/m in multiple myeloma patients. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of melphalan ranges from approximately 35.5 to 185.7 L/m. Penetration into cerebrospinal fluid is low. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Protein binding of melphalan ranges from 50% to 90%. Serum albumin is the major binding protein, accounting for approximately 40% to 60% of the plasma protein binding, while α1-acid glycoprotein accounts for about 20% of the plasma protein binding. Approximately 30% of melphalan is covalently and irreversibly bound to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Melphalan primarily undergoes chemical hydrolysis to inactive metabolites, monohydroxymelphalan and dihydroxymelphalan. No other melphalan metabolites have been observed in humans. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 5.8% to 21.3% of melphalan is excreted in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In patients given a single oral dose of 0.6 mg/kg of melphalan, the terminal elimination plasma half-life (± SD) was 1.5 ± 0.83 hours. Following intravenous administration, the terminal elimination half-life is approximately 75 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): Average total body clearance (CL) ranges from approximately 250 to 325 mL/min/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral and intraperitoneal LD 50 in rats is 4484 µg/kg and 11200 µg/kg, respectively. The subcutaneous LD 50 in mice is 32 mg/kg. Overdoses resulting in death have been reported with melphalan. Overdoses, including intravenous doses up to 290 mg/m and oral doses up to 50 mg/day for 16 days, have been reported. Symptoms of overdose include severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, cholinomimetic effects, mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract. Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia, caused by an associated inappropriate secretion of ADH syndrome, has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely. The principal toxic effect is bone marrow suppression. Melphalan is not removed from plasma via hemodialysis, and overdose is typically managed by general supportive measures, with appropriate blood transfusions and antibiotics. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alkeran, Evomela, Hepzato •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): L-PAM L-Phenylalanine mustard L-Sarcolysine Melfalano Melphalan Melphalanum p-L-Sarcolysin Phenylalanine mustard Phenylalanine nitrogen mustard •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Melphalan is an alkylating agent used to treat multiple myeloma, ovarian carcinoma, uveal melanoma with unresectable hepatic metastases, and for high-dose conditioning before hematopoietic stem cell transplant in patients.

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 Melphalan interact? Information: •Drug A: Abciximab •Drug B: Melphalan •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Melphalan. •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): Melphalan is indicated for use as a high-dose conditioning treatment prior to hematopoietic stem cell transplantation in patients with multiple myeloma. It is also indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Melphalan is a component of HEPZATO KIT, a liver-directed therapy indicated for the treatment of adults with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Melphalan possesses cytotoxic, immunosuppressive, and myeloablative activities. Melphalan produces chromosomal aberrations in vitro and in vivo; thus, it is considered to be potentially leukemogenic in humans. It also causes dose-limiting bone marrow suppression. The peak mean heart rate increased by 20 bpm from baseline following melphalan 100 mg/m for two consecutive days in multiple myeloma patients undergoing autologous stem cell transplantation. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Melphalan is an alkylating agent of the bischloroethylamine type. It is believed to be taken up by tumour cells via a neutral amino acid active pathway shared by leucine. Melphalan binds at the N7 position of guanine and induces inter-strand cross-links in DNA, disrupting DNA synthesis or transcription. It can also cause DNA-protein cross-linking and induce lesions in RNA, proteins, and lipids. Melphalan is cytotoxic in resting and rapidly dividing tumour cells. •Absorption (Drug A): No absorption available •Absorption (Drug B): The absorption of oral melphalan is highly variable concerning both the time to the first appearance of the drug in plasma (range: 0 to 6 hours) and peak plasma concentration (C max ). The average absolute bioavailability of melphalan ranges from 56% to 93%. High variability in bioavailability may be due to incomplete intestinal absorption, variable first-pass hepatic metabolism, or rapid hydrolysis. T max was one hour in patients who received single oral doses of 0.2 mg/kg to 0.25 mg/kg of melphalan. Oral administration of melphalan with a high-fat meal may reduce melphalan exposure (AUC) by 36% to 54%. Mean (± SD) C max and AUC 0-inf were 5.8 ± 1.5 mcg/mL and 451 ± 109 mcg x min/mL, respectively, following intravenous administration of 100 mg/m in multiple myeloma patients. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of melphalan ranges from approximately 35.5 to 185.7 L/m. Penetration into cerebrospinal fluid is low. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Protein binding of melphalan ranges from 50% to 90%. Serum albumin is the major binding protein, accounting for approximately 40% to 60% of the plasma protein binding, while α1-acid glycoprotein accounts for about 20% of the plasma protein binding. Approximately 30% of melphalan is covalently and irreversibly bound to plasma proteins. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Melphalan primarily undergoes chemical hydrolysis to inactive metabolites, monohydroxymelphalan and dihydroxymelphalan. No other melphalan metabolites have been observed in humans. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): About 5.8% to 21.3% of melphalan is excreted in urine. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): In patients given a single oral dose of 0.6 mg/kg of melphalan, the terminal elimination plasma half-life (± SD) was 1.5 ± 0.83 hours. Following intravenous administration, the terminal elimination half-life is approximately 75 minutes. •Clearance (Drug A): No clearance available •Clearance (Drug B): Average total body clearance (CL) ranges from approximately 250 to 325 mL/min/m. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral and intraperitoneal LD 50 in rats is 4484 µg/kg and 11200 µg/kg, respectively. The subcutaneous LD 50 in mice is 32 mg/kg. Overdoses resulting in death have been reported with melphalan. Overdoses, including intravenous doses up to 290 mg/m and oral doses up to 50 mg/day for 16 days, have been reported. Symptoms of overdose include severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, cholinomimetic effects, mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract. Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia, caused by an associated inappropriate secretion of ADH syndrome, has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely. The principal toxic effect is bone marrow suppression. Melphalan is not removed from plasma via hemodialysis, and overdose is typically managed by general supportive measures, with appropriate blood transfusions and antibiotics. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Alkeran, Evomela, Hepzato •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): L-PAM L-Phenylalanine mustard L-Sarcolysine Melfalano Melphalan Melphalanum p-L-Sarcolysin Phenylalanine mustard Phenylalanine nitrogen mustard •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Melphalan is an alkylating agent used to treat multiple myeloma, ovarian carcinoma, uveal melanoma with unresectable hepatic metastases, and for high-dose conditioning before hematopoietic stem cell transplant in patients. 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 Mepolizumab interact?

•Drug A: Abciximab •Drug B: Mepolizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Mepolizumab. •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): Mepolizumab is an anti-IL-5 IgG1 kappa monoclonal antibody indicated as an add-on maintenance treatment in patients aged six years and older with severe eosinophilic asthma and as a treatment in adult patients for eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab is also indicated for the treatment of hypereosinophilic syndrome (HES) in patients aged 12 and older in whom eosinophilia is present for at least six months without an identifiable non-hematologic secondary cause. Mepolizumab is additionally indicated as an add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in patients ≥18 years old with inadequate response to nasal corticosteroids. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels, generally in the range of 60-90% of baseline depending on dose, which in turn offers therapeutic benefit in the specific conditions for which mepolizumab is indicated. Mepolizumab has a relatively long half-life of between 16 and 22 days, which allows for long-lasting therapeutic benefit and a four-week dosing schedule. Despite a good demonstrated safety profile, mepolizumab use does act to depress part of the immune system and may be associated with increased infections, such as with herpes zoster virus; pre-existing helminth infections should be treated before starting mepolizumab therapy. Inhaled and oral corticosteroids should not be discontinued after starting mepolizumab but may be tapered as appropriate. Mepolizumab should not be used to treat acute bronchospasms or status asthmatics. Finally, hypersensitivity reactions, including anaphylaxis, have been reported in patients; mepolizumab should be discontinued in patients with suspected or confirmed hypersensitivity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hypereosinophilia is typically considered as an absolute eosinophil count of 1500/mm or higher and is associated with aberrant immune responses in several conditions, including severe asthma, eosinophilic granulomatosis with polyangiitis, and the variable spectrum of hypereosinophilic syndrome (HES). Eosinophils are involved in the inflammatory response by secretion of molecules such as MBP, leukotrienes, matrix metalloproteinases, transforming growth factor-β, nitric oxide, and other reactive oxygen species. Interleukin-5 (IL-5) is the primary cytokine associated with the differentiation of bone marrow progenitor cells into mature inflammatory neutrophils and the subsequent migration, activation, and prolonged survival of activated neutrophils. In concert with other cells, including lymphocytes, neutrophils, mast cells, and macrophages, which themselves can secrete additional pro-inflammatory molecules, high concentrations of neutrophils are associated with tissue damage and fibrosis, leading to the symptoms of eosinophilic diseases. Typically, eosinophils arise from both CD34 and dual CD34, IL-5 receptor-positive (IL-5R ) progenitor cells, which is in part mediated by the cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Although there exists a population of eosinophils that are insensitive to IL-5 levels, the main population of inflammatory eosinophils proliferates and migrates into the tissue in response to IL-5. Mepolizumab is a fully-humanized monoclonal IgG1 kappa antibody that binds IL-5 with a dissociation constant of 100 pM, preventing IL-5 from binding to and subsequently activating IL-5R cells. This reduction lowers circulating blood eosinophil levels and therefore exerts a beneficial effect in eosinophilic disease; the exact mechanistic nature of mepolizumab action has not been definitively determined. Not all patients will benefit from mepolizumab treatment, such as those with milder asthma or those with a sub-type of HES that is independent of IL-5 signalling. •Absorption (Drug A): No absorption available •Absorption (Drug B): Mepolizumab is administered subcutaneously and has a bioavailability of approximately 80% based on a 100 mg dose given to both adult and adolescent subjects with asthma. With the recommended four-week dosing schedule, there is an approximately two-fold accumulation of mepolizumab at steady-state. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mepolizumab has a population central volume of distribution of 3.6 L (for a 70 kg individual) in adult asthma patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As a monoclonal antibody, mepolizumab is subject to proteolytic degradation at sites distributed throughout the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Mepolizumab has a mean terminal half-life of between 16 and 22 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Mepolizumab has an estimated apparent population systemic clearance of 0.28 L/day (for a 70-kg individual) in adult and adolescent subjects. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding mepolizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as newly established or worsening chronic infections, including those caused by helminths, and generalized immune depression. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nucala •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): Mepolizumab is a fully-humanized monoclonal IgG1 kappa anti-IL-5 antibody used in conjunction with other therapies to treat severe asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome.

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 Mepolizumab interact? Information: •Drug A: Abciximab •Drug B: Mepolizumab •Severity: MINOR •Description: The risk or severity of adverse effects can be increased when Abciximab is combined with Mepolizumab. •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): Mepolizumab is an anti-IL-5 IgG1 kappa monoclonal antibody indicated as an add-on maintenance treatment in patients aged six years and older with severe eosinophilic asthma and as a treatment in adult patients for eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab is also indicated for the treatment of hypereosinophilic syndrome (HES) in patients aged 12 and older in whom eosinophilia is present for at least six months without an identifiable non-hematologic secondary cause. Mepolizumab is additionally indicated as an add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in patients ≥18 years old with inadequate response to nasal corticosteroids. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels, generally in the range of 60-90% of baseline depending on dose, which in turn offers therapeutic benefit in the specific conditions for which mepolizumab is indicated. Mepolizumab has a relatively long half-life of between 16 and 22 days, which allows for long-lasting therapeutic benefit and a four-week dosing schedule. Despite a good demonstrated safety profile, mepolizumab use does act to depress part of the immune system and may be associated with increased infections, such as with herpes zoster virus; pre-existing helminth infections should be treated before starting mepolizumab therapy. Inhaled and oral corticosteroids should not be discontinued after starting mepolizumab but may be tapered as appropriate. Mepolizumab should not be used to treat acute bronchospasms or status asthmatics. Finally, hypersensitivity reactions, including anaphylaxis, have been reported in patients; mepolizumab should be discontinued in patients with suspected or confirmed hypersensitivity. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Hypereosinophilia is typically considered as an absolute eosinophil count of 1500/mm or higher and is associated with aberrant immune responses in several conditions, including severe asthma, eosinophilic granulomatosis with polyangiitis, and the variable spectrum of hypereosinophilic syndrome (HES). Eosinophils are involved in the inflammatory response by secretion of molecules such as MBP, leukotrienes, matrix metalloproteinases, transforming growth factor-β, nitric oxide, and other reactive oxygen species. Interleukin-5 (IL-5) is the primary cytokine associated with the differentiation of bone marrow progenitor cells into mature inflammatory neutrophils and the subsequent migration, activation, and prolonged survival of activated neutrophils. In concert with other cells, including lymphocytes, neutrophils, mast cells, and macrophages, which themselves can secrete additional pro-inflammatory molecules, high concentrations of neutrophils are associated with tissue damage and fibrosis, leading to the symptoms of eosinophilic diseases. Typically, eosinophils arise from both CD34 and dual CD34, IL-5 receptor-positive (IL-5R ) progenitor cells, which is in part mediated by the cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Although there exists a population of eosinophils that are insensitive to IL-5 levels, the main population of inflammatory eosinophils proliferates and migrates into the tissue in response to IL-5. Mepolizumab is a fully-humanized monoclonal IgG1 kappa antibody that binds IL-5 with a dissociation constant of 100 pM, preventing IL-5 from binding to and subsequently activating IL-5R cells. This reduction lowers circulating blood eosinophil levels and therefore exerts a beneficial effect in eosinophilic disease; the exact mechanistic nature of mepolizumab action has not been definitively determined. Not all patients will benefit from mepolizumab treatment, such as those with milder asthma or those with a sub-type of HES that is independent of IL-5 signalling. •Absorption (Drug A): No absorption available •Absorption (Drug B): Mepolizumab is administered subcutaneously and has a bioavailability of approximately 80% based on a 100 mg dose given to both adult and adolescent subjects with asthma. With the recommended four-week dosing schedule, there is an approximately two-fold accumulation of mepolizumab at steady-state. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): Mepolizumab has a population central volume of distribution of 3.6 L (for a 70 kg individual) in adult asthma patients. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): No protein binding available •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): As a monoclonal antibody, mepolizumab is subject to proteolytic degradation at sites distributed throughout the body. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): No route of elimination available •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): Mepolizumab has a mean terminal half-life of between 16 and 22 days. •Clearance (Drug A): No clearance available •Clearance (Drug B): Mepolizumab has an estimated apparent population systemic clearance of 0.28 L/day (for a 70-kg individual) in adult and adolescent subjects. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Toxicity information regarding mepolizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as newly established or worsening chronic infections, including those caused by helminths, and generalized immune depression. Symptomatic and supportive measures are recommended. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Nucala •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): Mepolizumab is a fully-humanized monoclonal IgG1 kappa anti-IL-5 antibody used in conjunction with other therapies to treat severe asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome. 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 Mercaptopurine interact?

•Drug A: Abciximab •Drug B: Mercaptopurine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mercaptopurine. •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 and maintenance therapy of acute lymphatic leukemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for 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): Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). TIMP inhibits several reactions that involve inosinic acid (IMP), such as the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). Upon methylation, TIMP forms 6-methylthioinosinate (MTIMP) which inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase in addition to TIMP. Glutamine-5-phosphoribosylpyrophosphate amidotransferase is the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. According to experimental findings using radiolabeled mercaptopurine, mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. In comparison, some mercaptopurine may be converted to nucleotide derivatives of 6-thioguanine (6-TG) via actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase that convert TIMP to thioguanylic acid (TGMP). •Absorption (Drug A): No absorption available •Absorption (Drug B): Clinical studies have shown that the absorption of an oral dose of mercaptopurine in humans is incomplete and variable, averaging approximately 50% of the administered dose. The factors influencing absorption are unknown. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution exceeded that of the total body water. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding averages 19% over the concentration range 10 to 50 µg/mL (a concentration only achieved by intravenous administration of mercaptopurine at doses exceeding 5 to 10 mg/kg). •Metabolism (Drug A): 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. Degradation primarily by xanthine oxidase. The catabolism of mercaptopurine and its metabolites is complex. In humans, after oral administration of S-6-mercaptopurine, urine contains intact mercaptopurine, thiouric acid (formed by direct oxidation by xanthine oxidase, probably via 6-mercapto-8-hydroxypurine), and a number of 6-methylated thiopurines. The methylthiopurines yield appreciable amounts of inorganic sulfate. •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): Triphasic: 45 minutes, 2.5 hours, and 10 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Signs and symptoms of overdosage may be immediate such as anorexia, nausea, vomiting, and diarrhea; or delayed such as myelosuppression, liver dysfunction, and gastroenteritis. The oral LD 50 of mercaptopurine was determined to be 480 mg/kg in the mouse and 425 mg/kg in the rat. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Purixan •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,9-DIHYDRO-6H-PURINE-6-THIONE Mercaptopurina Mercaptopurine Mercaptopurinum Mercapurin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mercaptopurine is an antineoplastic agent used to treat 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 Mercaptopurine interact? Information: •Drug A: Abciximab •Drug B: Mercaptopurine •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Mercaptopurine. •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 and maintenance therapy of acute lymphatic leukemia. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for 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): Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). TIMP inhibits several reactions that involve inosinic acid (IMP), such as the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). Upon methylation, TIMP forms 6-methylthioinosinate (MTIMP) which inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase in addition to TIMP. Glutamine-5-phosphoribosylpyrophosphate amidotransferase is the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. According to experimental findings using radiolabeled mercaptopurine, mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. In comparison, some mercaptopurine may be converted to nucleotide derivatives of 6-thioguanine (6-TG) via actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase that convert TIMP to thioguanylic acid (TGMP). •Absorption (Drug A): No absorption available •Absorption (Drug B): Clinical studies have shown that the absorption of an oral dose of mercaptopurine in humans is incomplete and variable, averaging approximately 50% of the administered dose. The factors influencing absorption are unknown. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution exceeded that of the total body water. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Plasma protein binding averages 19% over the concentration range 10 to 50 µg/mL (a concentration only achieved by intravenous administration of mercaptopurine at doses exceeding 5 to 10 mg/kg). •Metabolism (Drug A): 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. Degradation primarily by xanthine oxidase. The catabolism of mercaptopurine and its metabolites is complex. In humans, after oral administration of S-6-mercaptopurine, urine contains intact mercaptopurine, thiouric acid (formed by direct oxidation by xanthine oxidase, probably via 6-mercapto-8-hydroxypurine), and a number of 6-methylated thiopurines. The methylthiopurines yield appreciable amounts of inorganic sulfate. •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): Triphasic: 45 minutes, 2.5 hours, and 10 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): No clearance available •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Signs and symptoms of overdosage may be immediate such as anorexia, nausea, vomiting, and diarrhea; or delayed such as myelosuppression, liver dysfunction, and gastroenteritis. The oral LD 50 of mercaptopurine was determined to be 480 mg/kg in the mouse and 425 mg/kg in the rat. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Purixan •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 1,9-DIHYDRO-6H-PURINE-6-THIONE Mercaptopurina Mercaptopurine Mercaptopurinum Mercapurin •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mercaptopurine is an antineoplastic agent used to treat 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 Mesalazine interact?

•Drug A: Abciximab •Drug B: Mesalazine •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Mesalazine 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): Mesalazine is indicated for the treatment of mildly to moderately active ulcerative colitis in adults and patients 5 years or older.. Mesalazine is also indicated for the maintenance of remission of ulcerative colitis in adults and maintenance of remission of Crohn's ileocolitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter responsible for most of the side effects associated with sulphasalazine therapy, while mesalazine is known to be the active moiety in the treatment of ulcerative colitis. Mesalazine is thought to dampen the inflammatory process through its ability to inhibit prostaglandin synthesis, interfere with leukotriene synthesis, and consequent leukocyte migration as well as act as a potent scavenger of free radicals. Regardless of the mode of action, mesalazine appears to be active mainly topically rather than systemically. Intraperitoneally administered mesalazine at 30 and 340 mg/kg daily had similar efficacy in attenuating colitis as prednisolone 4 to 550 mg/kg daily given intraperitoneally or sulphasalazine 0.34 to 5 mg/kg given orally in immune complex-induced colitis mice. Mesalazine at 5 mmol/L and sulphasalazine 1.5 mmol/L also reversed the increase in water and chloride secretion and decrease the sodium in dinitrochlorbenzene-induced colitis guinea pig. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Although the mechanism of action of mesalazine is not fully understood, it is believed to possess a topical anti-inflammatory effect on colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon. Furthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NFkB) and consequently the production of key pro-inflammatory cytokines. It has been proposed that reduced expression of PPAR gamma nuclear receptors (gamma form of peroxisome proliferator-activated receptors) may be implicated in ulcerative colitis, and that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium. Other research also showed the potential involvement of inducible NO synthase (iNOS) and that mesalazine can inhibit this enzyme to amiliorate the enteropathy in inflammatory bowel diseases. Moreover, since increased leukocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4, and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease it is also believed that mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leukocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals. •Absorption (Drug A): No absorption available •Absorption (Drug B): Depending on the formulation administered, prescribing information for orally administered delayed-released tablets of 2.4g or 4.8g of mesalazine given once daily for 14 days to healthy volunteers was to found to be about 21% to 22% of the administered dose while prescribing information for an orally administered controlled-release capsule formulation suggests 20% to 30% of the mesalazine in the formulation is absorbed. In contrast, when mesalamine is administered orally as an unformulated 1-g aqueous suspension, mesalazine is approximately 80% absorbed. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): For the extended-release formulation, mesalazine has a Vd of 18 L, confirming minimal extravascular penetration of systemically available drug. For the delayed-release formulation, the apparent volume of distribution was estimated to be 4.8 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In an in vitro study, at 2.5 mcg/mL, mesalamine and N-Ac-5-ASA are 43±6% and 78±1% bound, respectively, to plasma proteins. Protein binding of N-Ac-5-ASA does not appear to be concentration dependent at concentrations ranging from 1 to 10 mcg/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Mesalazine is metabolized both pre-systemically by the intestinal mucosa and systemically in the liver to N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) principally by NAT-1. Some acetylation also occurs through the action of colonic bacteria. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Elimination of mesalazine is mainly via the renal route following metabolism to N-acetyl-5-aminosalicylic acid (acetylation). However, there is also limited excretion of the parent mesalazine drug in the urine. After the oral administration of the extended-release formulation of mesalazine, of the approximately 21% to 22% of the drug absorbed, less than 8% of the dose was excreted unchanged in the urine after 24 hours, compared with greater than 13% for N-acetyl-5-aminosalicylic acid. When given the controlled-release formulation, about 130 mg free mesalazine was recovered in the feces following a single 1-g dose, which was comparable to the 140 mg of mesalazine recovered from the molar equivalent sulfasalazine tablet dose of 2.5 g F3001]. Elimination of free mesalazine and salicylates in feces increased proportionately with the dose given. N-acetylmesalazine was the primary compound excreted in the urine (19% to 30%) following the controlled-release dosing. In patients with ulcerative proctitis treated with mesalamine 500 mg as a rectal suppository every 8 hours for 6 days, 12% or less of the dose was eliminated in urine as unchanged 5-ASA and 8% to 77% was eliminated as N-acetyl-5-ASA following the initial dose. At steady state, 11% or less of the dose was eliminated in the urine as unchanged 5-ASA and 3% to 35% was eliminated as N-acetyl-5-ASA. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): For the delayed-release formulation, after intravenous administration, the elimination half-life of mesalamine is reported to be approximately 40 minutes. After oral dosing, the median terminal half life values for mesalamine are usually about 25 hours, but are variable, ranging from 1.5 to 296 hours. There is a large inter-subject and intra-subject variability in the plasma concentrations of mesalamine and N-acetyl-5-aminosalicylic acid and in their terminal half-lives following the administration of mesalazine. For the extended-release formulation, following single and multiple doses of mesalazine, the mean half-lives were 9 to 10 hours for 5-ASA, and 12 to 14 hours for N-Ac-5-ASA. The mean elimination half-life was 5 hours (CV=73%) for 5-ASA and 5 hours (CV=63%) for N-acetyl-5-ASA in patients taking 500 mg mesalazine as a rectal suppository every 8 hours for 6 days. For the rectal enema suspension formulation, the elimination half-life was 0.5 to 1.5 hours for 5-ASA and 5 to 10 hours for N-acetyl-5-ASA. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (SD) renal clearance in L/h for mesalazine following the single dose administration of mesalazine delayed-release tablets 4.8g under fasting conditions to young and elderly subjects were documented as 2.05 ± 1.33 in young subjects aged 18 to 35 years old, 2.04 ± 1.16 in elderly subjects aged 65 to 75 years old and 2.13 ± 1.20 in elderly subjects older than 75 years. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Mesalazine caused no increase in the incidence of neoplastic lesions over controls in a two-year study of Wistar rats fed up to 320 mg/kg/day of mesalazine admixed with diet (about 1.7 times the recommended human intra-rectal dose of CANASA, based on body surface area). Mesalazine was not mutagenic in the Ames test, the mouse lymphoma cell (TK+/-) forward mutation test, or the mouse micronucleus test. No effects on fertility or reproductive performance of the male and female rats were observed at oral mesalamine doses up to 320 mg/kg/day (about 1.7 times the recommended human intra-rectal dose of mesalazine, based on body surface area). Mesalazine is an aminosalicylate, and symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ involvement (e.g., renal and liver). There is no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent further absorption. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function. Mesalazine is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Evaluate renal function in all patients prior to initiation and periodically while on Asacol HD therapy. Monitor patients with known renal impairment or a history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Apriso, Asacol, Canasa, Delzicol, Lialda, Mezavant, Pentasa, Rowasa, Salofalk, Zaldyon •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-aminosalicylic acid 5-ASA m-Aminosalicylic acid Mesalamine Mesalazina Mésalazine Mesalazine Mesalazinum p-Aminosalicylsaeure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mesalazine is an aminosalicylate drug used to treat mild to moderate active ulcerative colitis and also to maintain remission once achieved.

.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 Mesalazine interact? Information: •Drug A: Abciximab •Drug B: Mesalazine •Severity: MODERATE •Description: The risk or severity of bleeding can be increased when Mesalazine 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): Mesalazine is indicated for the treatment of mildly to moderately active ulcerative colitis in adults and patients 5 years or older.. Mesalazine is also indicated for the maintenance of remission of ulcerative colitis in adults and maintenance of remission of Crohn's ileocolitis. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter responsible for most of the side effects associated with sulphasalazine therapy, while mesalazine is known to be the active moiety in the treatment of ulcerative colitis. Mesalazine is thought to dampen the inflammatory process through its ability to inhibit prostaglandin synthesis, interfere with leukotriene synthesis, and consequent leukocyte migration as well as act as a potent scavenger of free radicals. Regardless of the mode of action, mesalazine appears to be active mainly topically rather than systemically. Intraperitoneally administered mesalazine at 30 and 340 mg/kg daily had similar efficacy in attenuating colitis as prednisolone 4 to 550 mg/kg daily given intraperitoneally or sulphasalazine 0.34 to 5 mg/kg given orally in immune complex-induced colitis mice. Mesalazine at 5 mmol/L and sulphasalazine 1.5 mmol/L also reversed the increase in water and chloride secretion and decrease the sodium in dinitrochlorbenzene-induced colitis guinea pig. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Although the mechanism of action of mesalazine is not fully understood, it is believed to possess a topical anti-inflammatory effect on colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon. Furthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NFkB) and consequently the production of key pro-inflammatory cytokines. It has been proposed that reduced expression of PPAR gamma nuclear receptors (gamma form of peroxisome proliferator-activated receptors) may be implicated in ulcerative colitis, and that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium. Other research also showed the potential involvement of inducible NO synthase (iNOS) and that mesalazine can inhibit this enzyme to amiliorate the enteropathy in inflammatory bowel diseases. Moreover, since increased leukocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4, and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease it is also believed that mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leukocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals. •Absorption (Drug A): No absorption available •Absorption (Drug B): Depending on the formulation administered, prescribing information for orally administered delayed-released tablets of 2.4g or 4.8g of mesalazine given once daily for 14 days to healthy volunteers was to found to be about 21% to 22% of the administered dose while prescribing information for an orally administered controlled-release capsule formulation suggests 20% to 30% of the mesalazine in the formulation is absorbed. In contrast, when mesalamine is administered orally as an unformulated 1-g aqueous suspension, mesalazine is approximately 80% absorbed. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): For the extended-release formulation, mesalazine has a Vd of 18 L, confirming minimal extravascular penetration of systemically available drug. For the delayed-release formulation, the apparent volume of distribution was estimated to be 4.8 L. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): In an in vitro study, at 2.5 mcg/mL, mesalamine and N-Ac-5-ASA are 43±6% and 78±1% bound, respectively, to plasma proteins. Protein binding of N-Ac-5-ASA does not appear to be concentration dependent at concentrations ranging from 1 to 10 mcg/mL. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Mesalazine is metabolized both pre-systemically by the intestinal mucosa and systemically in the liver to N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) principally by NAT-1. Some acetylation also occurs through the action of colonic bacteria. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Elimination of mesalazine is mainly via the renal route following metabolism to N-acetyl-5-aminosalicylic acid (acetylation). However, there is also limited excretion of the parent mesalazine drug in the urine. After the oral administration of the extended-release formulation of mesalazine, of the approximately 21% to 22% of the drug absorbed, less than 8% of the dose was excreted unchanged in the urine after 24 hours, compared with greater than 13% for N-acetyl-5-aminosalicylic acid. When given the controlled-release formulation, about 130 mg free mesalazine was recovered in the feces following a single 1-g dose, which was comparable to the 140 mg of mesalazine recovered from the molar equivalent sulfasalazine tablet dose of 2.5 g F3001]. Elimination of free mesalazine and salicylates in feces increased proportionately with the dose given. N-acetylmesalazine was the primary compound excreted in the urine (19% to 30%) following the controlled-release dosing. In patients with ulcerative proctitis treated with mesalamine 500 mg as a rectal suppository every 8 hours for 6 days, 12% or less of the dose was eliminated in urine as unchanged 5-ASA and 8% to 77% was eliminated as N-acetyl-5-ASA following the initial dose. At steady state, 11% or less of the dose was eliminated in the urine as unchanged 5-ASA and 3% to 35% was eliminated as N-acetyl-5-ASA. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): For the delayed-release formulation, after intravenous administration, the elimination half-life of mesalamine is reported to be approximately 40 minutes. After oral dosing, the median terminal half life values for mesalamine are usually about 25 hours, but are variable, ranging from 1.5 to 296 hours. There is a large inter-subject and intra-subject variability in the plasma concentrations of mesalamine and N-acetyl-5-aminosalicylic acid and in their terminal half-lives following the administration of mesalazine. For the extended-release formulation, following single and multiple doses of mesalazine, the mean half-lives were 9 to 10 hours for 5-ASA, and 12 to 14 hours for N-Ac-5-ASA. The mean elimination half-life was 5 hours (CV=73%) for 5-ASA and 5 hours (CV=63%) for N-acetyl-5-ASA in patients taking 500 mg mesalazine as a rectal suppository every 8 hours for 6 days. For the rectal enema suspension formulation, the elimination half-life was 0.5 to 1.5 hours for 5-ASA and 5 to 10 hours for N-acetyl-5-ASA. •Clearance (Drug A): No clearance available •Clearance (Drug B): The mean (SD) renal clearance in L/h for mesalazine following the single dose administration of mesalazine delayed-release tablets 4.8g under fasting conditions to young and elderly subjects were documented as 2.05 ± 1.33 in young subjects aged 18 to 35 years old, 2.04 ± 1.16 in elderly subjects aged 65 to 75 years old and 2.13 ± 1.20 in elderly subjects older than 75 years. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): Mesalazine caused no increase in the incidence of neoplastic lesions over controls in a two-year study of Wistar rats fed up to 320 mg/kg/day of mesalazine admixed with diet (about 1.7 times the recommended human intra-rectal dose of CANASA, based on body surface area). Mesalazine was not mutagenic in the Ames test, the mouse lymphoma cell (TK+/-) forward mutation test, or the mouse micronucleus test. No effects on fertility or reproductive performance of the male and female rats were observed at oral mesalamine doses up to 320 mg/kg/day (about 1.7 times the recommended human intra-rectal dose of mesalazine, based on body surface area). Mesalazine is an aminosalicylate, and symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ involvement (e.g., renal and liver). There is no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent further absorption. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function. Mesalazine is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Evaluate renal function in all patients prior to initiation and periodically while on Asacol HD therapy. Monitor patients with known renal impairment or a history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Apriso, Asacol, Canasa, Delzicol, Lialda, Mezavant, Pentasa, Rowasa, Salofalk, Zaldyon •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): 5-aminosalicylic acid 5-ASA m-Aminosalicylic acid Mesalamine Mesalazina Mésalazine Mesalazine Mesalazinum p-Aminosalicylsaeure •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Mesalazine is an aminosalicylate drug used to treat mild to moderate active ulcerative colitis and also to maintain remission once achieved. 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 Methimazole interact?

•Drug A: Abciximab •Drug B: Methimazole •Severity: MODERATE •Description: Methimazole may increase the anticoagulant activities of Abciximab. •Extended Description: Due to potential inhibition of vitamin K activity by methimazole and other antithyroid agents, the activity of anticoagulants (for example, warfarin) may be increased. The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole and other antithyroid medications. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): In the United States, methimazole is indicated for the treatment of hyperthyroidism in patients with Graves' disease or toxic multinodular goiter for whom thyroidectomy or radioactive iodine therapy are not appropriate treatment options. Methimazole is also indicated for the amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy. In Canada, methimazole carries the above indications and is also indicated for the medical treatment of hyperthyroidism regardless of other available treatment options. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism. Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration. The most serious potential side effect of methimazole therapy is agranulocytosis, and patients should be instructed to monitor for, and report, any signs or symptoms of agranulocytosis such as fever or sore throat. Other cytopenias may also occur during methimazole therapy. There also exists the potential for severe hepatic toxicity with the use of methimazole, and monitoring for signs and symptoms of hepatic dysfunction, such as jaundice, anorexia, pruritus, and elevation in liver transaminases, is prudent in patients using this therapy. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Methimazole's primary mechanism of action appears to be interference in an early step in thyroid hormone synthesis involving thyroid peroxidase (TPO), however the exact method through which methimazole inhibits this step is unclear. TPO, along with hydrogen peroxide, normally catalyzes the conversion of iodide to iodine and then further catalyzes the incorporation of this iodine onto the 3 and/or 5 positions of the phenol rings of tyrosine residues in thyroglobulin. These thyroglobulin molecules then degrade within thyroid follicular cells to form either thyroxine (T 4 ) or tri-iodothyronine (T 3 ), which are the main hormones produced by the thyroid gland. Methimazole may directly inhibit TPO, but has been shown in vivo to instead act as a competitive substrate for TPO, thus becoming iodinated itself and interfering with the iodination of thyroglobulin. Another proposed theory is that methimazole’s sulfur moiety may interact directly with the iron atom at the centre of TPO’s heme molecule, thus inhibiting its ability to iodinate tyrosine residues. Other proposed mechanisms with weaker evidence include methimazole binding directly to thyroglobulin or direct inhibition of thyroglobulin itself. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of methimazole after oral administration is rapid and extensive, with an absolute bioavailability of approximately 0.93 and a T max ranging from 0.25 to 4.0 hours. C max is slightly, but not significantly, higher in hyperthyroid patients, and both C max and AUC are significantly affected by the oral dose administered. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of methimazole has been reported as roughly 20 L. Following oral administration, methimazole is highly concentrated in the thyroid gland - intrathyroidal methimazole levels are approximately 2 to 5 times higher than peak plasma levels, and remain high for 20 hours after ingestion. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Methimazole exhibits little-to-no protein binding, existing primarily as free drug in the serum. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Methimazole is rapidly and extensively metabolized by the liver, mainly via the CYP450 and FMO enzyme systems. Several metabolites have been identified, though the specific enzyme isoforms responsible for their formation are not entirely clear. One of the first methimazole metabolites identified, 3-methyl-2-thiohydantoin, may contribute to antithyroid activity - its antithyroid activity has been demonstrated in rats and may explain the prolonged duration of iodination inhibition following administration despite methimazole's relatively short half-life. A number of metabolites have been investigated as being the culprits behind methimazole-induced hepatotoxicity. Both glyoxal and N-methylthiourea have established cytotoxicity and are known metabolic products of methimazole's dihydrodiol intermediate. Sulfenic and sulfinic acid derivatives of methimazole are thought to be the ultimate toxicants responsible for hepatotoxicity, though their origin is unclear - they may arise from direct oxidation of methimazole via FMO, or from oxidation of N-methylthiourea further downstream in the metabolic process. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary excretion of unchanged methimazole has been reported to be between 7% and 12%. Elimination via feces appears to be limited, with a cumulative fecal excretion of 3% after administration of methimazole. Enterohepatic circulation also appears to play a role in the elimination of methimazole and its metabolites, as significant amounts of these substances are found in the bile 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): Following a single intravenous bolus injection of 10mg of methimazole, the t 1/2 of the distribution phase was 0.17 hours and the t 1/2 of the elimination phase was 5.3 hours. Methimazole's primary active metabolite, 3-methyl-2-thiohydantoin, has a half-life approximately 3 times longer than its parent drug. Renal impairment does not appear to alter the half-life of methimazole, but patients with hepatic impairment showed an increase in half-life roughly proportional to the severity of their impairment - moderate insufficiency resulted in a elimination t 1/2 of 7.1 hours, while severe insufficiency resulted in an elimination t 1/2 of 22.1 hours. There does not appear to be any significant differences in half-life based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients). •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a single intravenous bolus injection of 10mg of methimazole, clearance was found to be 5.70 L/h. Renal impairment does not appear to alter clearance of methimazole, but patients with hepatic impairment showed a reduction in clearance roughly proportional to the severity of their impairment - moderate insufficiency resulted in a clearance of 3.49 L/h, while severe insufficiency resulted in a clearance of 0.83 L/h. There does not appear to be any significant differences in clearance based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 of methimazole in rats is 2250 mg/kg. Signs and symptoms of methimazole overdose may include gastrointestinal distress, headache, fever, joint pain, pruritus, and edema. More serious adverse effects, such as aplastic anemia or agranulocytosis, may manifest within hours to days. Hepatitis, nephrotic syndrome, exfoliative dermatitis, and CNS effects such as neuropathy or CNS depression/stimulation are also potential, albeit less frequent, results of overdose. Management of overdose involves supportive treatment as dictated by the patient's status. This may involve monitoring of the patient's vital signs, blood gases, serum electrolytes, or bone marrow function as indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tapazole •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Methimazole Thiamazol Thiamazole Thiamazolum Tiamazol •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methimazole is a thionamide antithyroid agent that inhibits the actions of thyroid peroxidase, leading to a reduction in thyroid hormone synthesis and amelioration of hyperthyroidism.

Due to potential inhibition of vitamin K activity by methimazole and other antithyroid agents, the activity of anticoagulants (for example, warfarin) may be increased. The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole and other antithyroid medications. The severity of the interaction is moderate.

Question: Does Abciximab and Methimazole interact? Information: •Drug A: Abciximab •Drug B: Methimazole •Severity: MODERATE •Description: Methimazole may increase the anticoagulant activities of Abciximab. •Extended Description: Due to potential inhibition of vitamin K activity by methimazole and other antithyroid agents, the activity of anticoagulants (for example, warfarin) may be increased. The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole and other antithyroid medications. •Indication (Drug A): Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting. •Indication (Drug B): In the United States, methimazole is indicated for the treatment of hyperthyroidism in patients with Graves' disease or toxic multinodular goiter for whom thyroidectomy or radioactive iodine therapy are not appropriate treatment options. Methimazole is also indicated for the amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy. In Canada, methimazole carries the above indications and is also indicated for the medical treatment of hyperthyroidism regardless of other available treatment options. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism. Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration. The most serious potential side effect of methimazole therapy is agranulocytosis, and patients should be instructed to monitor for, and report, any signs or symptoms of agranulocytosis such as fever or sore throat. Other cytopenias may also occur during methimazole therapy. There also exists the potential for severe hepatic toxicity with the use of methimazole, and monitoring for signs and symptoms of hepatic dysfunction, such as jaundice, anorexia, pruritus, and elevation in liver transaminases, is prudent in patients using this therapy. •Mechanism of action (Drug A): Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/or conformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion. •Mechanism of action (Drug B): Methimazole's primary mechanism of action appears to be interference in an early step in thyroid hormone synthesis involving thyroid peroxidase (TPO), however the exact method through which methimazole inhibits this step is unclear. TPO, along with hydrogen peroxide, normally catalyzes the conversion of iodide to iodine and then further catalyzes the incorporation of this iodine onto the 3 and/or 5 positions of the phenol rings of tyrosine residues in thyroglobulin. These thyroglobulin molecules then degrade within thyroid follicular cells to form either thyroxine (T 4 ) or tri-iodothyronine (T 3 ), which are the main hormones produced by the thyroid gland. Methimazole may directly inhibit TPO, but has been shown in vivo to instead act as a competitive substrate for TPO, thus becoming iodinated itself and interfering with the iodination of thyroglobulin. Another proposed theory is that methimazole’s sulfur moiety may interact directly with the iron atom at the centre of TPO’s heme molecule, thus inhibiting its ability to iodinate tyrosine residues. Other proposed mechanisms with weaker evidence include methimazole binding directly to thyroglobulin or direct inhibition of thyroglobulin itself. •Absorption (Drug A): No absorption available •Absorption (Drug B): Absorption of methimazole after oral administration is rapid and extensive, with an absolute bioavailability of approximately 0.93 and a T max ranging from 0.25 to 4.0 hours. C max is slightly, but not significantly, higher in hyperthyroid patients, and both C max and AUC are significantly affected by the oral dose administered. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The apparent volume of distribution of methimazole has been reported as roughly 20 L. Following oral administration, methimazole is highly concentrated in the thyroid gland - intrathyroidal methimazole levels are approximately 2 to 5 times higher than peak plasma levels, and remain high for 20 hours after ingestion. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Methimazole exhibits little-to-no protein binding, existing primarily as free drug in the serum. •Metabolism (Drug A): Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally. •Metabolism (Drug B): Methimazole is rapidly and extensively metabolized by the liver, mainly via the CYP450 and FMO enzyme systems. Several metabolites have been identified, though the specific enzyme isoforms responsible for their formation are not entirely clear. One of the first methimazole metabolites identified, 3-methyl-2-thiohydantoin, may contribute to antithyroid activity - its antithyroid activity has been demonstrated in rats and may explain the prolonged duration of iodination inhibition following administration despite methimazole's relatively short half-life. A number of metabolites have been investigated as being the culprits behind methimazole-induced hepatotoxicity. Both glyoxal and N-methylthiourea have established cytotoxicity and are known metabolic products of methimazole's dihydrodiol intermediate. Sulfenic and sulfinic acid derivatives of methimazole are thought to be the ultimate toxicants responsible for hepatotoxicity, though their origin is unclear - they may arise from direct oxidation of methimazole via FMO, or from oxidation of N-methylthiourea further downstream in the metabolic process. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Urinary excretion of unchanged methimazole has been reported to be between 7% and 12%. Elimination via feces appears to be limited, with a cumulative fecal excretion of 3% after administration of methimazole. Enterohepatic circulation also appears to play a role in the elimination of methimazole and its metabolites, as significant amounts of these substances are found in the bile 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): Following a single intravenous bolus injection of 10mg of methimazole, the t 1/2 of the distribution phase was 0.17 hours and the t 1/2 of the elimination phase was 5.3 hours. Methimazole's primary active metabolite, 3-methyl-2-thiohydantoin, has a half-life approximately 3 times longer than its parent drug. Renal impairment does not appear to alter the half-life of methimazole, but patients with hepatic impairment showed an increase in half-life roughly proportional to the severity of their impairment - moderate insufficiency resulted in a elimination t 1/2 of 7.1 hours, while severe insufficiency resulted in an elimination t 1/2 of 22.1 hours. There does not appear to be any significant differences in half-life based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients). •Clearance (Drug A): No clearance available •Clearance (Drug B): Following a single intravenous bolus injection of 10mg of methimazole, clearance was found to be 5.70 L/h. Renal impairment does not appear to alter clearance of methimazole, but patients with hepatic impairment showed a reduction in clearance roughly proportional to the severity of their impairment - moderate insufficiency resulted in a clearance of 3.49 L/h, while severe insufficiency resulted in a clearance of 0.83 L/h. There does not appear to be any significant differences in clearance based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients). •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 of methimazole in rats is 2250 mg/kg. Signs and symptoms of methimazole overdose may include gastrointestinal distress, headache, fever, joint pain, pruritus, and edema. More serious adverse effects, such as aplastic anemia or agranulocytosis, may manifest within hours to days. Hepatitis, nephrotic syndrome, exfoliative dermatitis, and CNS effects such as neuropathy or CNS depression/stimulation are also potential, albeit less frequent, results of overdose. Management of overdose involves supportive treatment as dictated by the patient's status. This may involve monitoring of the patient's vital signs, blood gases, serum electrolytes, or bone marrow function as indicated. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Tapazole •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Methimazole Thiamazol Thiamazole Thiamazolum Tiamazol •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methimazole is a thionamide antithyroid agent that inhibits the actions of thyroid peroxidase, leading to a reduction in thyroid hormone synthesis and amelioration of hyperthyroidism. Output: Due to potential inhibition of vitamin K activity by methimazole and other antithyroid agents, the activity of anticoagulants (for example, warfarin) may be increased. The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole and other antithyroid medications. The severity of the interaction is moderate.

Does Abciximab and Methotrexate interact?

•Drug A: Abciximab •Drug B: Methotrexate •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Methotrexate. •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): Methotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis. Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis. It has also been approved by the EMA for the treatment of adult patients requiring systemic therapy for moderate-to-severe plaque psoriasis. Other formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma. It is also used in the maintenance of acute lymphocytic leukemia. Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions. It has a long duration of action and is generally given to patients once weekly. Methotrexate has a narrow therapeutic index. Do not take methotrexate 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): Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate. Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase. Inhibtion of nucleotide synthesis prevents cell division. In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate. This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action. •Absorption (Drug A): No absorption available •Absorption (Drug B): Methotrexate has a bioavailability of 64-90%, though this decreases at oral doses above 25mg due to saturation of the carrier mediated transport of methotrexate.. Methotrexate has a T max of 1 to 2 hours. oral doses of 10-15µg reach serum levels of 0.01-0.1µM. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of methotrexate at steady state is approximately 1L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Methotrexate is 46.5-54% 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): Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues. Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate. A small amount of methotrexate is also converted to 7-hydroxymethotrexate. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite. Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half life of low dose methotrexate is 3 to 10 hours in adults. The half life for high dose methotrexate is 8 to 15 hours. Pediatric patients taking methotrexate for acute lymphoblastic anemia experience a terminal half life of 0.7 to 5.8 hours. Pediatric patients taking methotrexate for juvenile idiopathic arthritis experience a half life of 0.9 to 2.3 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Methotrexate clearance varies widely between patients and decreases with increasing doses. Currently, predicting clearance of methotrexate is difficult and exceedingly high serum levels of methotrexate can still occur when all precautions are taken. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is 135mg/kg and in mice is 146mg/kg. Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding. In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Metoject, Nordimet, Otrexup, Rasuvo, Reditrex, Trexall, Xatmep •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Amethopterin Methotrexat Méthotrexate Methotrexate Methotrexatum Metotrexato •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methotrexate is an antineoplastic agent used the treatment of a wide variety of cancers as well as severe psoriasis, severe rheumatoid arthritis, and juvenile rheumatoid arthritis.

As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.

Question: Does Abciximab and Methotrexate interact? Information: •Drug A: Abciximab •Drug B: Methotrexate •Severity: MINOR •Description: The risk or severity of bleeding can be increased when Abciximab is combined with Methotrexate. •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): Methotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis. Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis. It has also been approved by the EMA for the treatment of adult patients requiring systemic therapy for moderate-to-severe plaque psoriasis. Other formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma. It is also used in the maintenance of acute lymphocytic leukemia. Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma. •Pharmacodynamics (Drug A): Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes. •Pharmacodynamics (Drug B): Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions. It has a long duration of action and is generally given to patients once weekly. Methotrexate has a narrow therapeutic index. Do not take methotrexate 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): Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate. Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase. Inhibtion of nucleotide synthesis prevents cell division. In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate. This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action. •Absorption (Drug A): No absorption available •Absorption (Drug B): Methotrexate has a bioavailability of 64-90%, though this decreases at oral doses above 25mg due to saturation of the carrier mediated transport of methotrexate.. Methotrexate has a T max of 1 to 2 hours. oral doses of 10-15µg reach serum levels of 0.01-0.1µM. •Volume of distribution (Drug A): No volume of distribution available •Volume of distribution (Drug B): The volume of distribution of methotrexate at steady state is approximately 1L/kg. •Protein binding (Drug A): No protein binding available •Protein binding (Drug B): Methotrexate is 46.5-54% 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): Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues. Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate. A small amount of methotrexate is also converted to 7-hydroxymethotrexate. •Route of elimination (Drug A): No route of elimination available •Route of elimination (Drug B): Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite. Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile. •Half-life (Drug A): Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. •Half-life (Drug B): The half life of low dose methotrexate is 3 to 10 hours in adults. The half life for high dose methotrexate is 8 to 15 hours. Pediatric patients taking methotrexate for acute lymphoblastic anemia experience a terminal half life of 0.7 to 5.8 hours. Pediatric patients taking methotrexate for juvenile idiopathic arthritis experience a half life of 0.9 to 2.3 hours. •Clearance (Drug A): No clearance available •Clearance (Drug B): Methotrexate clearance varies widely between patients and decreases with increasing doses. Currently, predicting clearance of methotrexate is difficult and exceedingly high serum levels of methotrexate can still occur when all precautions are taken. •Toxicity (Drug A): No toxicity available •Toxicity (Drug B): The oral LD 50 in rats is 135mg/kg and in mice is 146mg/kg. Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding. In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase. •Brand Names (Drug A): No brand names available •Brand Names (Drug B): Metoject, Nordimet, Otrexup, Rasuvo, Reditrex, Trexall, Xatmep •Synonyms (Drug A): No synonyms listed •Synonyms (Drug B): Amethopterin Methotrexat Méthotrexate Methotrexate Methotrexatum Metotrexato •Summary (Drug A): Abciximab is a monoclonal anti-glycoprotein IIb/IIIa receptor antibody used to prevent thrombosis during percutaneous coronary intervention. •Summary (Drug B): Methotrexate is an antineoplastic agent used the treatment of a wide variety of cancers as well as severe psoriasis, severe rheumatoid arthritis, and juvenile rheumatoid arthritis. Output: As their name suggested, myelosuppressive agents can decrease the production of cells found in the bone marrow, including thrombocytes.5,1 Low levels of thrombocytes, or thrombocytopenia, can increase the risk of bleeding due to the inability to form blood clots. Therefore, concomitant administration of agents that prevent thrombotic events such as antiplatelet agents can further exacerbate this risk into abnormal bleeding. The severity of the interaction is minor.