United States - English - NLM (National Library of Medicine)

sandoz inc - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 125 mg in 125 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in: risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulants (see clinical considerations ). in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3 and 0.2-times, respectively, the maximum recommended human dose (mhrd) (see data ). the estimated background risk of major birth defects and miscarri

United States - English - NLM (National Library of Medicine)

amneal pharmaceuticals llc - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban 100 mg in 1 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in - patients with major bleeding [see warnings and precautions (5.1)]. - patients with history of hypersensitivity to argatroban. airway, skin, and generalized hypersensitivity reactions have been reported [see adverse reactions (6.1)]. risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see clinical considerations) . in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3- and 0.2-times, respectively, the maximum recommended human dose (mhrd) (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high risk pregnancy conditions. published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. fetal/neonatal adverse reactions use of anticoagulants, including argatroban, may increase the risk of bleeding in the fetus and neonate. monitor neonates for bleeding [see warnings and precautions (5.1, 5.3)] . labor or delivery all patients receiving anticoagulants, including pregnant women, are at risk for bleeding. pregnant women receiving argatroban should be carefully monitored for evidence of excessive bleeding or unexpected changes in coagulation parameters [see warnings and precautions (5.1, 5.3)] . data animal data developmental studies performed in rats with argatroban at intravenous doses up to 27 mg/kg/day (0.3 times the maximum recommended human dose, based on body surface area) and in rabbits at intravenous doses up to 10.8 mg/kg/day (0.2 times the maximum recommended human dose, based on body surface area) have revealed no evidence of harm to the fetus. risk summary there are no data on the presence of argatroban in human milk, or its effects on milk production. argatroban is present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for argatroban and any potential adverse effects on the breastfed infant from argatroban or from the underlying maternal condition. safety and effectiveness have not been established in pediatric patients. argatroban was studied among 18 seriously ill pediatric patients who required an alternative to heparin anticoagulation. most patients were diagnosed with hit or suspected hit. age ranges of patients were < 6 months, n = 8; six months to < 8 years, n = 6; 8 to 16 years, n = 4. all patients had serious underlying conditions and were receiving multiple concomitant medications. thirteen patients received argatroban solely as a continuous infusion (no bolus dose). dosing was initiated in the majority of these 13 patients at 1 mcg/kg/min. dosing was titrated as needed to achieve and maintain an aptt of 1.5 to 3 times the baseline value. most patients required multiple dose adjustments to maintain anticoagulation parameters within the desired range. during the 30-day study period, thrombotic events occurred during argatroban administration to two patients: and following argatroban discontinuation in three other patients. major bleeding occurred among two patients: one patient experienced an intracranial hemorrhage after 4 days of argatroban therapy in the setting of sepsis and thrombocytopenia and  another patient experienced an intracranial hemorrhage  after receiving argatroban for greater than 14 days. the study findings did not establish the safe and effective use of argatroban in pediatric patients and the dosing of 1 mcg/kg/in was not supported by the pharmacokinetic data described below. pediatric pharmacokinetics (pk) and pharmacodynamics (pd) pk parameters of argatroban were characterized in population pk/pd analysis model with sparse data from 15 seriously ill pediatric patients. argatroban clearance in these seriously ill pediatric patients (0.16 l/hr/kg) was 50% lower compared to argatroban clearance in healthy adults (0.31 l/hr/kg). four pediatric patients with elevated bilirubin (secondary to cardiac complications or hepatic impairment) had, on average, 80% lower clearance (0.03 l/hr/kg) when compared to pediatric patients with normal bilirubin levels. these pk/pd analysis models based on a goal of aptt prolongation of 1.5 to 3 times the baseline value and avoidance of an aptt > 100 seconds for seriously ill pediatric patients with hit/hitts who require an alternative to heparin suggested the following: - for patients with normal hepatic function , a starting infusion rate of 0.75 mcg/kg/min may have comparable aptt responses as a starting dose of 2 mcg/kg/min in healthy adults. additionally, based on an evaluation of aptt every two hours, increasing the dosage by 0.1 to 0.25 mcg/kg/min could achieve additional aptt responses. - for patients with hepatic impairment a starting infusion rate of 0.2 mcg/kg/min with increasing dosing by increments of 0.05 mcg/kg/min may have comparable argatroban exposure as expected with adult doses. the safety and effectiveness of argatroban with the above dosing have not been adequately assessed in pediatric patients and the safety and effectiveness of argatroban is not established in pediatric patients. in addition, the described dosage did not take into account multiple factors that could affect the dosage such as current aptt, target aptt, and the clinical status of the patient. of the total number of subjects (1340) in clinical studies of argatroban, 35% were 65 and over. in the clinical studies of adult patients with hit (with or without thrombosis), the effectiveness of argatroban was not affected by age. no trends were observed across age groups for both aptt and the act. the safety analysis did suggest that older patients had increased underlying conditions, which may predispose them to events. the studies were not sized appropriately to detect differences in safety between age groups. dose reduction and careful titration are required when administering argatroban to patients with hepatic impairment. reversal of anticoagulant effect may be prolonged in this population [see dosage and administration (2.3), warning and precautions (5.2), clinical pharmacology (12.3)].

United States - English - NLM (National Library of Medicine)

sandoz inc - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 1 mg in 1 ml - argatroban in sodium chloride injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban in sodium chloride injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban in sodium chloride injection is contraindicated in: - patients with major bleeding [see warnings and precautions (5.1)] . - patients with a history of hypersensitivity to argatroban. airway, skin, and generalized hypersensitivity reactions have been reported [see adverse reactions (6.1)] . risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulations (see clinical considerations) . in animal reproductiv

United States - English - NLM (National Library of Medicine)

eagle pharmaceuticals, inc. - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 1 mg in 1 ml - argatroban in sodium chloride injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban in sodium chloride injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban in sodium chloride injection is contraindicated in: - patients with major bleeding [see warnings and precautions (5.1)]. - patients with a history of hypersensitivity to argatroban. airway, skin, and generalized hypersensitivity reactions have been reported [see adverse reactions (6.1)] . risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulations (see clinical considerations) . in animal reproductive

United States - English - NLM (National Library of Medicine)

gland pharma limited - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 125 mg in 125 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in: • patients with major bleeding, • patients with a history of hypersensitivity to argatroban. airway, skin, and generalized hypersensitivity reactions have been reported [see adverse reactions ( 6.4)] . pregnancy category b there are no adequate and well-controlled studies of argatroban use in pregnant women. developmental studies performed in rats with argatroban at intravenous doses up to 27 mg/kg/day (0.3 times the maximum recommended human dose, based on body surface area) and in rabbits at intravenous doses up to 10.8 mg/kg/day (0.2 times the maximum recommended human dose, based on body surface area) have revealed no evidence of impaired fertility or harm to the fetus. because animal

United States - English - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 50 mg in 50 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in: - patients with major bleeding, [see warnings and precautions (5.1)] - patients with a history of hypersensitivity to argatroban. airway, skin, and generalized hypersensitivity reactions have been reported [see adverse reactions (6.1)] risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see clinical considerations) . in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3- and 0.2-times, respectively, the maximum recommended human dose (mhrd) (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. disease-associated maternal and/or embryo/fetal risk pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high risk pregnancy conditions. published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. fetal/neonatal adverse reactions use of anticoagulants, including argatroban, may increase the risk of bleeding in the fetus and neonate. monitor neonates for bleeding [see warnings and precautions (5.1, 5.3)] . l abor or delivery all patients receiving anticoagulants, including pregnant women, are at risk for bleeding. pregnant women receiving argatroban should be carefully monitored for evidence of excessive bleeding or unexpected changes in coagulation parameters [see warnings and precautions (5.1, 5.3)] . animal data developmental studies performed in rats with argatroban at intravenous doses up to 27 mg/kg/day (0.3 times the maximum recommended human dose, based on body surface area) and in rabbits at intravenous doses up to 10.8 mg/kg/day (0.2 times the maximum recommended human dose, based on body surface area) have revealed no evidence of harm to the fetus. r isk summary there are no data on the presence of argatroban in human milk, or its effects on milk production. argatroban is present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for argatroban and any potential adverse effects on the breastfed infant from argatroban or from the underlying maternal condition. safety and effectiveness have not been established in pediatric patients. argatroban was studied among 18 seriously ill pediatric patients who required an alternative to heparin anticoagulation. most patients were diagnosed with hit or suspected hit. age ranges of patients were <6 months, n = 8; six months to <8 years, n = 6; 8 to 16 years, n = 4. all patients had serious underlying conditions and were receiving multiple concomitant medications. thirteen patients received argatroban solely as a continuous infusion (no bolus dose). dosing was initiated in the majority of these 13 patients at 1 mcg/kg/min. dosing was titrated as needed to achieve and maintain an aptt of 1.5 to 3 times the baseline value. most patients required multiple dose adjustments to maintain anticoagulation parameters within the desired range. during the 30-day study period, thrombotic events occurred during argatroban administration to two patients and following argatroban discontinuation in three other patients. major bleeding occurred among two patients: one patient experienced an intracranial hemorrhage after 4 days of argatroban therapy in the setting of sepsis and thrombocytopenia and another patient experienced an intracranial hemorrhage after receiving argatroban for greater than 14 days. the study findings did not establish the safe and effective use of argatroban in pediatric patients and the dosing of 1 mcg/kg/min was not supported by the pharmacokinetic data described below. pediatric pharmacokinetics (pk) and pharmacodynamics (pd) pk parameters of argatroban were characterized in population pk/pd analysis model with sparse data from 15 seriously ill pediatric patients. argatroban clearance in these seriously ill pediatric patients (0.16 l/hr/kg) was 50% lower compared to argatroban clearance in healthy adults (0.31 l/hr/kg). four pediatric patients with elevated bilirubin (secondary to cardiac complications or hepatic impairment) had, on average, 80% lower clearance (0.03 l/hr/kg) when compared to pediatric patients with normal bilirubin levels. these pk/pd analysis models based on a goal of aptt prolongation of 1.5 to 3 times the baseline value and avoidance of an aptt >100 seconds for seriously ill pediatric patients with hit/hitts who require an alternative to heparin suggested the following: - for patients with normal hepatic function , a starting infusion rate of 0.75 mcg/kg/min may have comparable aptt responses as a starting dose of 2 mcg/kg/min in healthy adults.additionally, based on an evaluation of aptt every two hours, increasing the dosage by 0.1 to 0.25 mcg/kg/min could achieve additional aptt responses. - for patients with hepatic impairment a starting infusion rate of 0.2 mcg/kg/min with increasing dosing by increments of 0.05 mcg/kg/min may have comparable argatroban exposure as expected with adult doses. the safety and effectiveness of argatroban with the above dosing have not been adequately assessed in pediatric patients and the safety and effectiveness of argatroban is not established in pediatric patients. in addition, the described dosage did not take into account multiple factors that could affect the dosage such as current aptt, target aptt, and the clinical status of the patient. of the total number of subjects (1340) in clinical studies of argatroban, 35% were 65 and over. in the clinical studies of adult patients with hit (with or without thrombosis), the effectiveness of argatroban was not affected by age. no trends were observed across age groups for both aptt and the act. the safety analysis did suggest that older patients had increased underlying conditions, which may predispose them to adverse reactions. the studies were not sized appropriately to detect differences in safety between age groups. dose reduction and careful titration are required when administering argatroban to patients with hepatic impairment.  reversal of anticoagulant effect may be prolonged in this population [see dosage and administration (2.4), warning and precautions (5.2), clinical pharmacology (12.3)].

United States - English - NLM (National Library of Medicine)

par pharmaceutical, inc. - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 250 mg in 2.5 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in - patients with major bleeding [see warnings and precautions (5.1) ]. - patients with history of hypersensitivity to argatroban. airway, skin, and generalized hypersensitivity reactions have been reported [see adverse reactions (6.1) ]. limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see clinical considerations ). in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous

United States - English - NLM (National Library of Medicine)

hospira, inc. - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban 100 mg in 1 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see clinical considerations) . in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3-and 0.2-times, respectively, the maximum recommended human dose (mhrd) (see data) . the estimated background risk of major birth defects and

United States - English - NLM (National Library of Medicine)

novartis pharmaceuticals corporation - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban 100 mg in 1 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary interventions (pci). argatroban is contraindicated in risk summary limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see clinical considerations) . in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3- and 0.2-times, respectively, the maximum recommended human dose (mhrd) (see data) . the estimated background risk of major birth defects a

United States - English - NLM (National Library of Medicine)

mylan institutional llc - argatroban (unii: iy90u61z3s) (argatroban anhydrous - unii:ocy3u280y3) - argatroban anhydrous 250 mg in 2.5 ml - argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (hit). argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention (pci). argatroban is contraindicated in limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. there are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see clinical considerations) . in animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3- and 0.2-times, respectively, the maximum recommended human dose (mhrd) (see data) . the estimated background risk of major birth defects and miscarriage