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

remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 10 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see warnings and precautions ( 5.7) and use in specific populations ( 8.1)] . warfarin sodium can cause fetal harm when administered to a pregnant woman. warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. if warfarin sodium is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see use in specific populations ( 8.1)] . warfarin sodium is contraindicated in patients with: - hemorrhagic tendencies or blood dyscrasias - recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see warnings and precautions ( 5.8)] - bleeding tendencies associated with: − active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract − central nervous system hemorrhage − cerebral aneurysms, dissecting aorta − pericarditis and pericardial effusions − bacterial endocarditis - threatened abortion, eclampsia, and preeclampsia - unsupervised patients with conditions associated with potential high level of non-compliance - spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding - hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see adverse reactions ( 6)] - major regional or lumbar block anesthesia - malignant hypertension risk summary warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of warfarin sodium may outweigh the risks [see warnings and precautions ( 5.7)] . warfarin sodium can cause fetal harm. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the u.s. general population and may not reflect the incidences observed in practice. consider the benefits and risks of warfarin sodium and possible risks to the fetus when prescribing warfarin sodium to a pregnant woman. adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 fetal/neonatal adverse reactions in humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, dandy-walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see contraindications ( 4)] . risk summary warfarin was not present in human milk from mothers treated with warfarin from a limited published study. because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for warfarin sodium and any potential adverse effects on the breastfed infant from warfarin sodium or from the underlying maternal condition before prescribing warfarin sodium to a lactating woman. clinical considerations monitor breastfeeding infants for bruising or bleeding. data human data based on published data in 15 nursing mothers, warfarin was not detected in human milk. among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. prothrombin times were not obtained for the other 9 nursing infants. effects in premature infants have not been evaluated. pregnancy testing warfarin sodium can cause fetal harm [see use in specific populations ( 8.1)] . verify the pregnancy status of females of reproductive potential prior to initiating warfarin sodium therapy. contraception females advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of warfarin sodium. adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. pediatric patients administered warfarin sodium should avoid any activity or sport that may result in traumatic injury. the developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target inrs. because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target inr ranges may be difficult to achieve and maintain in pediatric patients, and more frequent inr determinations are recommended. bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. infants and children receiving vitamin k-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy. of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. no overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. patients 60 years or older appear to exhibit greater than expected inr response to the anticoagulant effects of warfarin [see clinical pharmacology ( 12.3)] . warfarin sodium is contraindicated in any unsupervised patient with senility. conduct more frequent monitoring for bleeding with administration of warfarin sodium to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. consider lower initiation and maintenance doses of warfarin sodium in elderly patients [see dosage and administration ( 2.2, 2.3)] . renal clearance is considered to be a minor determinant of anticoagulant response to warfarin. no dosage adjustment is necessary for patients with renal impairment. instruct patients with renal impairment taking warfarin to monitor their inr more frequently [see warnings and precautions ( 5.4)] . hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. conduct more frequent monitoring for bleeding when using warfarin sodium in these patients.

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

remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 4 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see warnings and precautions ( 5.7) and use in specific populations ( 8.1)] . warfarin sodium can cause fetal harm when administered to a pregnant woman. warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. if warfarin sodium is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see use in specific populations ( 8.1)] . warfarin sodium is contraindicated in patients with: - hemorrhagic tendencies or blood dyscrasias - recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see warnings and precautions ( 5.8)] - bleeding tendencies associated with: − active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract − central nervous system hemorrhage − cerebral aneurysms, dissecting aorta − pericarditis and pericardial effusions − bacterial endocarditis - threatened abortion, eclampsia, and preeclampsia - unsupervised patients with conditions associated with potential high level of non-compliance - spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding - hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see adverse reactions ( 6)] - major regional or lumbar block anesthesia - malignant hypertension risk summary warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of warfarin sodium may outweigh the risks [see warnings and precautions ( 5.7)] . warfarin sodium can cause fetal harm. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the u.s. general population and may not reflect the incidences observed in practice. consider the benefits and risks of warfarin sodium and possible risks to the fetus when prescribing warfarin sodium to a pregnant woman. adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 fetal/neonatal adverse reactions in humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, dandy-walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see contraindications ( 4)] . risk summary warfarin was not present in human milk from mothers treated with warfarin from a limited published study. because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for warfarin sodium and any potential adverse effects on the breastfed infant from warfarin sodium or from the underlying maternal condition before prescribing warfarin sodium to a lactating woman. clinical considerations monitor breastfeeding infants for bruising or bleeding. data human data based on published data in 15 nursing mothers, warfarin was not detected in human milk. among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. prothrombin times were not obtained for the other 9 nursing infants. effects in premature infants have not been evaluated. pregnancy testing warfarin sodium can cause fetal harm [see use in specific populations ( 8.1)] . verify the pregnancy status of females of reproductive potential prior to initiating warfarin sodium therapy. contraception females advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of warfarin sodium. adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. pediatric patients administered warfarin sodium should avoid any activity or sport that may result in traumatic injury. the developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target inrs. because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target inr ranges may be difficult to achieve and maintain in pediatric patients, and more frequent inr determinations are recommended. bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. infants and children receiving vitamin k-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy. of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. no overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. patients 60 years or older appear to exhibit greater than expected inr response to the anticoagulant effects of warfarin [see clinical pharmacology ( 12.3)] . warfarin sodium is contraindicated in any unsupervised patient with senility. conduct more frequent monitoring for bleeding with administration of warfarin sodium to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. consider lower initiation and maintenance doses of warfarin sodium in elderly patients [see dosage and administration ( 2.2, 2.3)] . renal clearance is considered to be a minor determinant of anticoagulant response to warfarin. no dosage adjustment is necessary for patients with renal impairment. instruct patients with renal impairment taking warfarin to monitor their inr more frequently [see warnings and precautions ( 5.4)] . hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. conduct more frequent monitoring for bleeding when using warfarin sodium in these patients.

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

remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 2.5 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism

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

remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 3 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see warnings and precautions ( 5.7) and use in specific populations ( 8.1)] . warfarin sodium can cause fetal harm when administered to a pregnant woman. warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. if warfarin sodium is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see use in specific populations ( 8.1)] . warfarin sodium is contraindicated in patients with: - hemorrhagic tendencies or blood dyscrasias - recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see warnings and precautions ( 5.8)] - bleeding tendencies associated with: − active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract − central nervous system hemorrhage − cerebral aneurysms, dissecting aorta − pericarditis and pericardial effusions − bacterial endocarditis - threatened abortion, eclampsia, and preeclampsia - unsupervised patients with conditions associated with potential high level of non-compliance - spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding - hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see adverse reactions ( 6)] - major regional or lumbar block anesthesia - malignant hypertension risk summary warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of warfarin sodium may outweigh the risks [see warnings and precautions ( 5.7)] . warfarin sodium can cause fetal harm. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the u.s. general population and may not reflect the incidences observed in practice. consider the benefits and risks of warfarin sodium and possible risks to the fetus when prescribing warfarin sodium to a pregnant woman. adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 fetal/neonatal adverse reactions in humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, dandy-walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see contraindications ( 4)] . risk summary warfarin was not present in human milk from mothers treated with warfarin from a limited published study. because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for warfarin sodium and any potential adverse effects on the breastfed infant from warfarin sodium or from the underlying maternal condition before prescribing warfarin sodium to a lactating woman. clinical considerations monitor breastfeeding infants for bruising or bleeding. data human data based on published data in 15 nursing mothers, warfarin was not detected in human milk. among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. prothrombin times were not obtained for the other 9 nursing infants. effects in premature infants have not been evaluated. pregnancy testing warfarin sodium can cause fetal harm [see use in specific populations ( 8.1)] . verify the pregnancy status of females of reproductive potential prior to initiating warfarin sodium therapy. contraception females advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of warfarin sodium. adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. pediatric patients administered warfarin sodium should avoid any activity or sport that may result in traumatic injury. the developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target inrs. because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target inr ranges may be difficult to achieve and maintain in pediatric patients, and more frequent inr determinations are recommended. bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. infants and children receiving vitamin k-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy. of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. no overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. patients 60 years or older appear to exhibit greater than expected inr response to the anticoagulant effects of warfarin [see clinical pharmacology ( 12.3)] . warfarin sodium is contraindicated in any unsupervised patient with senility. conduct more frequent monitoring for bleeding with administration of warfarin sodium to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. consider lower initiation and maintenance doses of warfarin sodium in elderly patients [see dosage and administration ( 2.2, 2.3)] . renal clearance is considered to be a minor determinant of anticoagulant response to warfarin. no dosage adjustment is necessary for patients with renal impairment. instruct patients with renal impairment taking warfarin to monitor their inr more frequently [see warnings and precautions ( 5.4)] . hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. conduct more frequent monitoring for bleeding when using warfarin sodium in these patients.

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

remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 1 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism

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

remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 1 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see warnings and precautions ( 5.7) and use in specific populations ( 8.1)] . warfarin sodium can cause fetal harm when administered to a pregnant woman. warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. if warfarin sodium is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see use in specific populations ( 8.1)] . warfarin sodium is contraindicated in patients with: - hemorrhagic tendencies or blood dyscrasias - recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see warnings and precautions ( 5.8)] - bleeding tendencies associated with: − active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract − central nervous system hemorrhage − cerebral aneurysms, dissecting aorta − pericarditis and pericardial effusions − bacterial endocarditis - threatened abortion, eclampsia, and preeclampsia - unsupervised patients with conditions associated with potential high level of non-compliance - spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding - hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see adverse reactions ( 6)] - major regional or lumbar block anesthesia - malignant hypertension risk summary warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of warfarin sodium may outweigh the risks [see warnings and precautions ( 5.7)] . warfarin sodium can cause fetal harm. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the u.s. general population and may not reflect the incidences observed in practice. consider the benefits and risks of warfarin sodium and possible risks to the fetus when prescribing warfarin sodium to a pregnant woman. adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 fetal/neonatal adverse reactions in humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, dandy-walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see contraindications ( 4)] . risk summary warfarin was not present in human milk from mothers treated with warfarin from a limited published study. because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for warfarin sodium and any potential adverse effects on the breastfed infant from warfarin sodium or from the underlying maternal condition before prescribing warfarin sodium to a lactating woman. clinical considerations monitor breastfeeding infants for bruising or bleeding. data human data based on published data in 15 nursing mothers, warfarin was not detected in human milk. among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. prothrombin times were not obtained for the other 9 nursing infants. effects in premature infants have not been evaluated. pregnancy testing warfarin sodium can cause fetal harm [see use in specific populations ( 8.1)] . verify the pregnancy status of females of reproductive potential prior to initiating warfarin sodium therapy. contraception females advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of warfarin sodium. adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. pediatric patients administered warfarin sodium should avoid any activity or sport that may result in traumatic injury. the developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target inrs. because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target inr ranges may be difficult to achieve and maintain in pediatric patients, and more frequent inr determinations are recommended. bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. infants and children receiving vitamin k-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy. of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. no overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. patients 60 years or older appear to exhibit greater than expected inr response to the anticoagulant effects of warfarin [see clinical pharmacology ( 12.3)] . warfarin sodium is contraindicated in any unsupervised patient with senility. conduct more frequent monitoring for bleeding with administration of warfarin sodium to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. consider lower initiation and maintenance doses of warfarin sodium in elderly patients [see dosage and administration ( 2.2, 2.3)] . renal clearance is considered to be a minor determinant of anticoagulant response to warfarin. no dosage adjustment is necessary for patients with renal impairment. instruct patients with renal impairment taking warfarin to monitor their inr more frequently [see warnings and precautions ( 5.4)] . hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. conduct more frequent monitoring for bleeding when using warfarin sodium in these patients.

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

remedyrepack inc. - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin anhydrous 500 mg - levofloxacin tablets are indicated in adult patients for the treatment of nosocomial pneumonia due to methicillin-susceptible staphylococcus aureus, pseudomonas aeruginosa, serratia marcescens, escherichia coli,  klebsiella pneumoniae, haemophilus influenzae, or streptococcus pneumoniae. adjunctive therapy should be used as clinically indicated. where pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see clinical studies ( 14.1)]. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae (including  multi-drug-resistant streptococcus pneumoniae [mdrsp]), haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae, moraxella catarrhalis, chlamydophila pneumoniae, legionella pneumophila, or mycoplasma pneumoniae [see dosage and administration ( 2.1) and clinical studies ( 14.2)]. mdrsp isolates are isolates resistant to two or more of the following antibacterials: penicillin (mic ≥2 mcg/ml), 2 nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to streptococcus pneumoniae (excluding multi-drug-resistant isolates [mdrsp]),  haemophilus influenzae, haemophilus parainfluenzae, mycoplasma pneumoniae, or chlamydophila pneumoniae [see dosage and administration ( 2.1) and clinical studies ( 14.3)].  levofloxacin tablets are indicated in adult patients for the treatment of complicated skin and skin structure infections due to methicillin-susceptible staphylococcus aureus, enterococcus faecalis, streptococcus pyogenes, or proteus mirabilis [see clinical studies ( 14.5)]. levofloxacin tablets are indicated in adult patients for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible staphylococcus aureus, or streptococcus pyogenes. levofloxacin tablets are indicated in adult patients for the treatment of chronic bacterial prostatitis due to escherichia coli, enterococcus faecalis, or methicillin-susceptible staphylococcus epidermidis [see clinical studies ( 14.6)]. levofloxacin tablets are indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized bacillus anthracis in adults and pediatric patients, 6 months of age and older [see dosage and administration ( 2.2)].  the effectiveness of levofloxacin tablets is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. levofloxacin tablets have not been tested in humans for the post-exposure prevention of inhalation anthrax. the safety of levofloxacin tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. prolonged levofloxacin tablets therapy should only be used when the benefit outweighs the risk [see clinical studies ( 14.9 )]. levofloxacin tablets are indicated for treatment of plague, including pneumonic and septicemic plague, due to yersinia pestis ( y. pestis ) and prophylaxis for plague in adults and pediatric patients, 6 months of age and older [see dosage and administration ( 2.2)]. efficacy studies of levofloxacin tablets could not be conducted in humans with plague for ethical and feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals [see clinical studies ( 14.10)]. levofloxacin tablets are indicated in adult patients for the treatment of complicated urinary tract infections due to escherichia coli, klebsiella pneumoniae, or proteus mirabilis [see clinical studies ( 14.7)].  levofloxacin tablets are indicated in adult patients for the treatment of complicated urinary tract infections (mild to moderate) due to enterococcus faecalis, enterobacter cloacae, escherichia coli, klebsiella pneumoniae, proteus mirabilis, or pseudomonas aeruginosa [see clinical studies (14.8) ]. levofloxacin tablets are indicated in adult patients for the treatment of acute pyelonephritis caused by escherichia coli, including cases with concurrent bacteremia [see clinical studies (14.7, 14.8)]. levofloxacin tablets are indicated in adult patients  for the treatment of uncomplicated urinary tract infections (mild to moderate) due to escherichia coli, klebsiella pneumoniae, or staphylococcus saprophyticus. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1 to  5.15 )] and for some patients uncomplicated urinary tract infection is self-limiting, reserve levofloxacin tablets for treatment of uncomplicated urinary tract infections in patients who have no alternative treatment options. levofloxacin tablets are indicated in adult patients for the treatment of acute bacterial exacerbation of chronic bronchitis (abecb) due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae, haemophilus influenzae, haemophilus parainfluenzae, or moraxella catarrhalis. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1to  5.15 )] and for some patients abecb is self-limiting, reserve levofloxacin tablets for treatment of abecb in patients who have no alternative treatment options. levofloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (abs) due to streptococcus pneumoniae, haemophilus influenzae, or moraxella catarrhalis [see clinical studies ( 14.4)]. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1to  5.15)] and for some patients abs is self-limiting, reserve levofloxacin tablets for treatment of abs in patients who have no alternative treatment options. to reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin tablets and other antibacterial drugs, levofloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. culture and susceptibility testing appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see microbiology ( 12.4)] . therapy with levofloxacin tablets may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected. as with other drugs in this class, some isolates of pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin tablets. culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance. levofloxacin tablets are contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see warnings and precautions ( 5.3)]. risk summary published information from case reports, case control studies and observational studies on levofloxacin administered during pregnancy have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies, oral administration of levofloxacin to pregnant rats and rabbits during organogenesis at doses up to 9.4 times and 1.1 times the maximum recommended human dose (mrhd), respectively, did not result in teratogenicity. fetal toxicity was seen in the rat study, but was absent at doses up to 1.2 times the maximum recommended human dose (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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.  data animal data levofloxacin was not teratogenic in an embryofetal development study in rats treated during organogenesis with oral doses as high as 810 mg/kg/day which corresponds to 9.4 times the mrhd (based upon doses normalized for total body surface area). the oral dose of 810 mg/kg/day (high dose) to rats caused decreased fetal body weight and increased fetal mortality that was not seen at the next lower dose (mid-dose, 90 mg/kg/day, equivalent to 1.2 times the mrhd (based upon doses normalized for total body surface area). maternal toxicity was limited to lower weight gain in the mid and high dose groups. no teratogenicity was observed in an embryofetal development study in rabbits dosed orally during organogenesis with doses as high as 50 mg/kg/day, which corresponds to 1.1 times the mrhd (based upon doses normalized for total body surface area). maternal toxicity at that dose consisted of lower weight gain and decreased food consumption relative to controls and abortion in four of sixteen dams. risk summary published literature reports that levofloxacin is present in human milk following intravenous and oral administration ( see data ). there is no information regarding effects of levofloxacin on milk production or the breastfed infant. because of the potential risks of serious adverse reactions, in breastfed infants, for most indications, a lactating woman may consider pumping and discarding breast milk during treatment with levofloxacin and an additional two days (five half-lives) after the last dose. alternatively, advise a lactating woman that breastfeeding is not recommended during treatment with levofloxacin and for an additional two days (five half-lives) after the last dose [see use in specific populations (8.4) and clinical pharmacology (12.3)] . however, for inhalation anthrax (post exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breastfeeding while the mother (and potentially the infant) is (are) on levofloxacin may be acceptable [see dosage and administration (2.2), pediatric use (8.4), and clinical studies (14.2)]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for levofloxacin and any potential adverse effects on the breastfed child from levofloxacin or from the underlying maternal condition. data a published literature reports that peak levofloxacin human milk concentration was 8.2 mg/l at 5 hours after dosing in a woman who received 500 mg of intravenous, followed by oral, levofloxacin daily. for an infant fed exclusively with human milk (approximately 900 ml/day), an estimated maximum daily dose of levofloxacin through breastfeeding is 5 mg (i.e., approximately 1% of maternal daily dose). the above data come from a single case and may not be generalizable to the general population of lactating women. quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. [see warnings and precautions ( 5.12) and animal toxicology and/or pharmacology ( 13.2)]. inhalational anthrax (post-exposure) levofloxacin is indicated in pediatric patients 6 months of age and older, for inhalational anthrax (post-exposure). the risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate. the safety of levofloxacin in pediatric patients treated for more than 14 days has not been studied [see indications and usage (1.7),   dosage and administration ( 2.2 ) and clinical studies ( 14.9)]. plague levofloxacin is indicated in pediatric patients, 6 months of age and older, for treatment of plague, including pneumonic and septicemic plague due to yersinia pestis (y. pestis) and prophylaxis for plague. efficacy studies of levofloxacin could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals. the risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate [see indications and usage ( 1.8),  dosage and administration ( 2.2)  and clinical studies ( 14.10 )]. safety and effectiveness of levofloxacin in pediatric patients below the age of six months have not been established. pharmacokinetics following intravenous administration the pharmacokinetics of levofloxacin following a single intravenous dose were investigated in pediatric patients ranging in age from six months to 16 years. pediatric patients cleared levofloxacin faster than adult patients resulting in lower plasma exposures than adults for a given mg/kg dose [see clinical pharmacology ( 12.3) and clinical studies ( 14.9) ]. dosage in pediatric patients with inhalational anthrax or plague for the recommended levofloxacin tablet dosage in pediatric patients with inhalational anthrax or plague, see dosage and administration ( 2.2 ). levofloxacin tablets cannot be administered to pediatric patients who weigh less than 30 kg because of the limitations of the available strengths. alternative formulations of levofloxacin may be considered for pediatric patients who weigh less than 30 kg. adverse reactions in clinical trials, 1,534 pediatric patients (6 months to 16 years of age) were treated with oral and intravenous levofloxacin. pediatric patients 6 months to 5 years of age received levofloxacin 10 mg/kg twice a day and pediatric patients greater than 5 years of age received 10 mg/kg once a day (maximum 500 mg per day) for approximately 10 days. levofloxacin tablets can only be administered to pediatric patients with inhalational anthrax (post-exposure) or plague who are 30 kg or greater due to the limitations of the available strengths [see dosage and administration ( 2.2)]. a subset of pediatric patients in the clinical trials (1,340 levofloxacin-treated and 893 non-fluoroquinolone-treated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocol-defined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) during 60 days and 1 year following the first dose of the study drug. pediatric patients treated with levofloxacin had a significantly higher incidence of musculoskeletal disorders when compared to the non-fluoroquinolone-treated children as illustrated in table 7. levofloxacin tablets can only be administered to pediatric patients with inhalational anthrax (post-exposure) or plague who are 30 kg or greater due to the limitations of the available strengths [see dosage and administration ( 2.2 )]. table 7:  incidence of musculoskeletal disorders in pediatric clinical trial * non-fluoroquinolone: ceftriaxone, amoxicillin/clavulanate, clarithromycin † 2-sided fisher's exact test  ‡  there were 1,199 levofloxacin-treated and 804 non-fluoroquinolone-treated pediatric patients who had a one-year evaluation visit. however, the incidence of musculoskeletal disorders was calculated using all reported events during the specified period for all pediatric patients enrolled regardless of whether they completed the 1-year evaluation visit. arthralgia was the most frequently occurring musculoskeletal disorder in both treatment groups. most of the musculoskeletal disorders in both groups involved multiple weight-bearing joints. disorders were moderate in 8/46 (17%) children and mild in 35/46 (76%) levofloxacin-treated pediatric patients and most were treated with analgesics. the median time to resolution was 7 days for levofloxacin-treated pediatric patients and 9 for non-fluoroquinolone-treated children (approximately 80% resolved within 2 months in both groups). no pediatric patient had a severe or serious disorder and all musculoskeletal disorders resolved without sequelae. vomiting and diarrhea were the most frequently reported adverse reactions, occurring in similar frequency in the levofloxacin-treated and non-fluoroquinolone-treated pediatric patients. in addition to the adverse reactions reported in pediatric patients in clinical trials, adverse reactions reported in adults during clinical trials or post-marketing experience [see adverse reactions ( 6)] may also be expected to occur in pediatric patients. geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as levofloxacin. this risk is further increased in patients receiving concomitant corticosteroid therapy. tendinitis or tendon rupture can involve the achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. caution should be used when prescribing levofloxacin to elderly patients especially those on corticosteroids. patients should be informed of this potential side effect and advised to discontinue  levofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see boxed warning; warnings and precautions ( 5.2); and adverse reactions ( 6.3)]. in phase 3 clinical trials, 1,945 levofloxacin-treated patients (26%) were ≥ 65 years of age. of these, 1,081 patients (14%) were between the ages of 65 and 74 and 864 patients (12%) were 75 years or older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. severe, and sometimes fatal, cases of hepatotoxicity have been reported post-marketing in association with levofloxacin. the majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see warnings and precautions ( 5.8)]. epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see warnings and precautions ( 5.9)]. elderly patients may be more susceptible to drug-associated effects on the qt interval. therefore, precaution should be taken when using levofloxacin with concomitant drugs that can result in prolongation of the qt interval (e.g., class ia or class iii antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known qt prolongation, uncorrected hypokalemia) [see warnings and precautions ( 5.11)]. the pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. however, since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [ see clinical pharmacology ( 12.3)]. clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with renal impairment (creatinine clearance < 50 ml/min), requiring dosage adjustment in such patients to avoid accumulation. neither hemodialysis nor continuous ambulatory peritoneal dialysis (capd) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or capd [see dosage and administration ( 2.3)]. pharmacokinetic studies in patients with hepatic impairment have not been conducted. due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

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

remedyrepack inc. - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin anhydrous 250 mg - levofloxacin tablets are indicated in adult patients for the treatment of nosocomial pneumonia due to methicillin-susceptible staphylococcus aureus, pseudomonas aeruginosa, serratia marcescens, escherichia coli,  klebsiella pneumoniae, haemophilus influenzae, or streptococcus pneumoniae. adjunctive therapy should be used as clinically indicated. where pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see clinical studies ( 14.1)]. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae (including  multi-drug-resistant streptococcus pneumoniae [mdrsp]), haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae, moraxella catarrhalis, chlamydophila pneumoniae, legionella pneumophila, or mycoplasma pneumoniae [see dosage and administration ( 2.1) and clinical studies ( 14.2)]. mdrsp isolates are isolates resistant to two or more of the following antibacterials: penicillin (mic ≥2 mcg/ml), 2 nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to streptococcus pneumoniae (excluding multi-drug-resistant isolates [mdrsp]),  haemophilus influenzae, haemophilus parainfluenzae, mycoplasma pneumoniae, or chlamydophila pneumoniae [see dosage and administration ( 2.1) and clinical studies ( 14.3)].  levofloxacin tablets are indicated in adult patients for the treatment of complicated skin and skin structure infections due to methicillin-susceptible staphylococcus aureus, enterococcus faecalis, streptococcus pyogenes, or proteus mirabilis [see clinical studies ( 14.5)]. levofloxacin tablets are indicated in adult patients for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible staphylococcus aureus, or streptococcus pyogenes. levofloxacin tablets are indicated in adult patients for the treatment of chronic bacterial prostatitis due to escherichia coli, enterococcus faecalis, or methicillin-susceptible staphylococcus epidermidis [see clinical studies ( 14.6)]. levofloxacin tablets are indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized bacillus anthracis in adults and pediatric patients, 6 months of age and older [see dosage and administration ( 2.2)].  the effectiveness of levofloxacin tablets is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. levofloxacin tablets have not been tested in humans for the post-exposure prevention of inhalation anthrax. the safety of levofloxacin tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. prolonged levofloxacin tablets therapy should only be used when the benefit outweighs the risk [see clinical studies ( 14.9 )]. levofloxacin tablets are indicated for treatment of plague, including pneumonic and septicemic plague, due to yersinia pestis ( y. pestis ) and prophylaxis for plague in adults and pediatric patients, 6 months of age and older [see dosage and administration ( 2.2)]. efficacy studies of levofloxacin tablets could not be conducted in humans with plague for ethical and feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals [see clinical studies ( 14.10)]. levofloxacin tablets are indicated in adult patients for the treatment of complicated urinary tract infections due to escherichia coli, klebsiella pneumoniae, or proteus mirabilis [see clinical studies ( 14.7)].  levofloxacin tablets are indicated in adult patients for the treatment of complicated urinary tract infections (mild to moderate) due to enterococcus faecalis, enterobacter cloacae, escherichia coli, klebsiella pneumoniae, proteus mirabilis, or pseudomonas aeruginosa [see clinical studies (14.8) ]. levofloxacin tablets are indicated in adult patients for the treatment of acute pyelonephritis caused by escherichia coli, including cases with concurrent bacteremia [see clinical studies (14.7, 14.8)]. levofloxacin tablets are indicated in adult patients  for the treatment of uncomplicated urinary tract infections (mild to moderate) due to escherichia coli, klebsiella pneumoniae, or staphylococcus saprophyticus. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1 to  5.15 )] and for some patients uncomplicated urinary tract infection is self-limiting, reserve levofloxacin tablets for treatment of uncomplicated urinary tract infections in patients who have no alternative treatment options. levofloxacin tablets are indicated in adult patients for the treatment of acute bacterial exacerbation of chronic bronchitis (abecb) due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae, haemophilus influenzae, haemophilus parainfluenzae, or moraxella catarrhalis. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1to  5.15 )] and for some patients abecb is self-limiting, reserve levofloxacin tablets for treatment of abecb in patients who have no alternative treatment options. levofloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (abs) due to streptococcus pneumoniae, haemophilus influenzae, or moraxella catarrhalis [see clinical studies ( 14.4)]. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1to  5.15)] and for some patients abs is self-limiting, reserve levofloxacin tablets for treatment of abs in patients who have no alternative treatment options. to reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin tablets and other antibacterial drugs, levofloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. culture and susceptibility testing appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see microbiology ( 12.4)] . therapy with levofloxacin tablets may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected. as with other drugs in this class, some isolates of pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin tablets. culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance. levofloxacin tablets are contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see warnings and precautions ( 5.3)]. risk summary published information from case reports, case control studies and observational studies on levofloxacin administered during pregnancy have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies, oral administration of levofloxacin to pregnant rats and rabbits during organogenesis at doses up to 9.4 times and 1.1 times the maximum recommended human dose (mrhd), respectively, did not result in teratogenicity. fetal toxicity was seen in the rat study, but was absent at doses up to 1.2 times the maximum recommended human dose (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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.  data animal data levofloxacin was not teratogenic in an embryofetal development study in rats treated during organogenesis with oral doses as high as 810 mg/kg/day which corresponds to 9.4 times the mrhd (based upon doses normalized for total body surface area). the oral dose of 810 mg/kg/day (high dose) to rats caused decreased fetal body weight and increased fetal mortality that was not seen at the next lower dose (mid-dose, 90 mg/kg/day, equivalent to 1.2 times the mrhd (based upon doses normalized for total body surface area). maternal toxicity was limited to lower weight gain in the mid and high dose groups. no teratogenicity was observed in an embryofetal development study in rabbits dosed orally during organogenesis with doses as high as 50 mg/kg/day, which corresponds to 1.1 times the mrhd (based upon doses normalized for total body surface area). maternal toxicity at that dose consisted of lower weight gain and decreased food consumption relative to controls and abortion in four of sixteen dams. risk summary published literature reports that levofloxacin is present in human milk following intravenous and oral administration ( see data ). there is no information regarding effects of levofloxacin on milk production or the breastfed infant. because of the potential risks of serious adverse reactions, in breastfed infants, for most indications, a lactating woman may consider pumping and discarding breast milk during treatment with levofloxacin and an additional two days (five half-lives) after the last dose. alternatively, advise a lactating woman that breastfeeding is not recommended during treatment with levofloxacin and for an additional two days (five half-lives) after the last dose [see use in specific populations (8.4) and clinical pharmacology (12.3)] . however, for inhalation anthrax (post exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breastfeeding while the mother (and potentially the infant) is (are) on levofloxacin may be acceptable [see dosage and administration (2.2), pediatric use (8.4), and clinical studies (14.2)]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for levofloxacin and any potential adverse effects on the breastfed child from levofloxacin or from the underlying maternal condition. data a published literature reports that peak levofloxacin human milk concentration was 8.2 mg/l at 5 hours after dosing in a woman who received 500 mg of intravenous, followed by oral, levofloxacin daily. for an infant fed exclusively with human milk (approximately 900 ml/day), an estimated maximum daily dose of levofloxacin through breastfeeding is 5 mg (i.e., approximately 1% of maternal daily dose). the above data come from a single case and may not be generalizable to the general population of lactating women. quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. [see warnings and precautions ( 5.12) and animal toxicology and/or pharmacology ( 13.2)]. inhalational anthrax (post-exposure) levofloxacin is indicated in pediatric patients 6 months of age and older, for inhalational anthrax (post-exposure). the risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate. the safety of levofloxacin in pediatric patients treated for more than 14 days has not been studied [see indications and usage (1.7),   dosage and administration ( 2.2 ) and clinical studies ( 14.9)]. plague levofloxacin is indicated in pediatric patients, 6 months of age and older, for treatment of plague, including pneumonic and septicemic plague due to yersinia pestis (y. pestis) and prophylaxis for plague. efficacy studies of levofloxacin could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals. the risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate [see indications and usage ( 1.8),  dosage and administration ( 2.2)  and clinical studies ( 14.10 )]. safety and effectiveness of levofloxacin in pediatric patients below the age of six months have not been established. pharmacokinetics following intravenous administration the pharmacokinetics of levofloxacin following a single intravenous dose were investigated in pediatric patients ranging in age from six months to 16 years. pediatric patients cleared levofloxacin faster than adult patients resulting in lower plasma exposures than adults for a given mg/kg dose [see clinical pharmacology ( 12.3) and clinical studies ( 14.9) ]. dosage in pediatric patients with inhalational anthrax or plague for the recommended levofloxacin tablet dosage in pediatric patients with inhalational anthrax or plague, see dosage and administration ( 2.2 ). levofloxacin tablets cannot be administered to pediatric patients who weigh less than 30 kg because of the limitations of the available strengths. alternative formulations of levofloxacin may be considered for pediatric patients who weigh less than 30 kg. adverse reactions in clinical trials, 1,534 pediatric patients (6 months to 16 years of age) were treated with oral and intravenous levofloxacin. pediatric patients 6 months to 5 years of age received levofloxacin 10 mg/kg twice a day and pediatric patients greater than 5 years of age received 10 mg/kg once a day (maximum 500 mg per day) for approximately 10 days. levofloxacin tablets can only be administered to pediatric patients with inhalational anthrax (post-exposure) or plague who are 30 kg or greater due to the limitations of the available strengths [see dosage and administration ( 2.2)]. a subset of pediatric patients in the clinical trials (1,340 levofloxacin-treated and 893 non-fluoroquinolone-treated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocol-defined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) during 60 days and 1 year following the first dose of the study drug. pediatric patients treated with levofloxacin had a significantly higher incidence of musculoskeletal disorders when compared to the non-fluoroquinolone-treated children as illustrated in table 7. levofloxacin tablets can only be administered to pediatric patients with inhalational anthrax (post-exposure) or plague who are 30 kg or greater due to the limitations of the available strengths [see dosage and administration ( 2.2 )]. table 7:  incidence of musculoskeletal disorders in pediatric clinical trial * non-fluoroquinolone: ceftriaxone, amoxicillin/clavulanate, clarithromycin † 2-sided fisher's exact test  ‡  there were 1,199 levofloxacin-treated and 804 non-fluoroquinolone-treated pediatric patients who had a one-year evaluation visit. however, the incidence of musculoskeletal disorders was calculated using all reported events during the specified period for all pediatric patients enrolled regardless of whether they completed the 1-year evaluation visit. arthralgia was the most frequently occurring musculoskeletal disorder in both treatment groups. most of the musculoskeletal disorders in both groups involved multiple weight-bearing joints. disorders were moderate in 8/46 (17%) children and mild in 35/46 (76%) levofloxacin-treated pediatric patients and most were treated with analgesics. the median time to resolution was 7 days for levofloxacin-treated pediatric patients and 9 for non-fluoroquinolone-treated children (approximately 80% resolved within 2 months in both groups). no pediatric patient had a severe or serious disorder and all musculoskeletal disorders resolved without sequelae. vomiting and diarrhea were the most frequently reported adverse reactions, occurring in similar frequency in the levofloxacin-treated and non-fluoroquinolone-treated pediatric patients. in addition to the adverse reactions reported in pediatric patients in clinical trials, adverse reactions reported in adults during clinical trials or post-marketing experience [see adverse reactions ( 6)] may also be expected to occur in pediatric patients. geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as levofloxacin. this risk is further increased in patients receiving concomitant corticosteroid therapy. tendinitis or tendon rupture can involve the achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. caution should be used when prescribing levofloxacin to elderly patients especially those on corticosteroids. patients should be informed of this potential side effect and advised to discontinue  levofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see boxed warning; warnings and precautions ( 5.2); and adverse reactions ( 6.3)]. in phase 3 clinical trials, 1,945 levofloxacin-treated patients (26%) were ≥ 65 years of age. of these, 1,081 patients (14%) were between the ages of 65 and 74 and 864 patients (12%) were 75 years or older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. severe, and sometimes fatal, cases of hepatotoxicity have been reported post-marketing in association with levofloxacin. the majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see warnings and precautions ( 5.8)]. epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see warnings and precautions ( 5.9)]. elderly patients may be more susceptible to drug-associated effects on the qt interval. therefore, precaution should be taken when using levofloxacin with concomitant drugs that can result in prolongation of the qt interval (e.g., class ia or class iii antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known qt prolongation, uncorrected hypokalemia) [see warnings and precautions ( 5.11)]. the pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. however, since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [ see clinical pharmacology ( 12.3)]. clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with renal impairment (creatinine clearance < 50 ml/min), requiring dosage adjustment in such patients to avoid accumulation. neither hemodialysis nor continuous ambulatory peritoneal dialysis (capd) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or capd [see dosage and administration ( 2.3)]. pharmacokinetic studies in patients with hepatic impairment have not been conducted. due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

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

remedyrepack inc. - clopidogrel bisulfate (unii: 08i79htp27) (clopidogrel - unii:a74586sno7) - clopidogrel 75 mg - - clopidogrel tablets are indicated to reduce the rate of myocardial infarction (mi) and stroke in patients with non-st-segment elevation acs (unstable angina [ua]/non-st-elevation myocardial infarction [nstemi]), including patients who are to be managed medically and those who are to be managed with coronary revascularization. clopidogrel tablets should be administered in conjunction with aspirin. - clopidogrel tablets are indicated to reduce the rate of myocardial infarction and stroke in patients with acute st-elevation myocardial infarction (stemi) who are to be managed medically. clopidogrel tablets should be administered in conjunction with aspirin. in patients with established peripheral arterial disease or with a history of recent myocardial infarction (mi) or recent stroke clopidogrel tablets are indicated to reduce the rate of mi and stroke. clopidogrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. clopidogrel tablets are contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the product [see adverse reactions (6.2)] . risk summary available data from cases reported in published literature and postmarketing surveillance with clopidogrel use in pregnant women have not identified any drug-associated risks for major birth defects or miscarriage [see data] .there are risks to the pregnant woman and fetus associated with myocardial infarction and stroke [see clinical considerations] . no evidence of fetotoxicity was observed when clopidogrel was administered to pregnant rats and rabbits during organogenesis at doses corresponding to 65 and 78 times the recommended daily human dose [see data] . the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. all pregnancies have a background risk of birth defects, 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 myocardial infarction and stroke are medical emergencies. therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of clopidogrel on the fetus. labor or delivery clopidogrel use during labor or delivery will increase the risk of maternal bleeding and hemorrhage. avoid neuraxial blockade during clopidogrel use because of the risk of spinal hematoma. when possible, discontinue clopidogrel 5 to 7 days prior to labor, delivery, or neuraxial blockade. data human data the available data from published case reports over two decades of postmarketing use have not identified an association with clopidogrel use in pregnancy and major birth defects, miscarriage, or adverse fetal outcomes. animal data embryo-fetal developmental toxicology studies were performed in pregnant rats and rabbits with doses up to 500 and 300 mg/kg/day, respectively, administered during organogenesis. these doses, corresponding to 65 and 78 times the recommended daily human dose, respectively, on a mg/m2 basis, revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. risk summary there are no data on the presence of clopidogrel in human milk or the effects on milk production. no adverse effects on breastfed infants have been observed with maternal clopidogrel use during lactation in a small number of postmarketing cases. studies in rats have shown that clopidogrel and/or its metabolites are present in the milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for clopidogrel and any potential adverse effects on the breastfed infant from clopidogrel or from underlying maternal condition. safety and effectiveness in pediatric populations have not been established. a randomized, placebo-controlled trial (clarinet) did not demonstrate a clinical benefit of clopidogrel in neonates and infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary arterial shunt. possible factors contributing to this outcome were the dose of clopidogrel, the concomitant administration of aspirin, and the late initiation of therapy following shunt palliation. it cannot be ruled out that a trial with a different design would demonstrate a clinical benefit in this patient population. of the total number of subjects in the caprie and cure controlled clinical studies, approximately 50% of patients treated with clopidogrel bisulfate were 65 years of age and older, and 15% were 75 years and older. in commit, approximately 58% of the patients treated with clopidogrel bisulfate were 60 years and older, 26% of whom were 70 years and older. the observed risk of bleeding events with clopidogrel bisulfate plus aspirin versus placebo plus aspirin by age category is provided in table 1 and table 2 for the cure and commit trials, respectively [see adverse reactions (6.1)] . no dosage adjustment is necessary in elderly patients. experience is limited in patients with severe and moderate renal impairment [see clinical pharmacology (12.2)]. no dosage adjustment is necessary in patients with hepatic impairment [see clinical pharmacology (12.2)] .

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

remedyrepack inc. - clopidogrel bisulfate (unii: 08i79htp27) (clopidogrel - unii:a74586sno7) - clopidogrel 75 mg - • clopidogrel is indicated to reduce the rate of myocardial infarction (mi) and stroke in patients with non-st-segment elevation acs (unstable angina [ua]/non-st-elevation myocardial infarction [nstemi]), including patients who are to be managed medically and those who are to be managed with coronary revascularization. clopidogrel should be administered in conjunction with aspirin. • clopidogrel is indicated to reduce the rate of myocardial infarction and stroke in patients with acute st-elevation myocardial infarction (stemi) who are to be managed medically. clopidogrel should be administered in conjunction with aspirin. in patients with established peripheral arterial disease or with a history of recent myocardial infarction (mi) or recent stroke clopidogrel is indicated to reduce the rate of mi and stroke. clopidogrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. clopidogrel tablets are contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the product [see adverse reactions ( 6.2)] . risk summary available data from cases reported in published literature and postmarketing surveillance with clopidogrel use in pregnant women have not identified any drug-associated risks for major birth defects or miscarriage [see data]. there are risks to the pregnant woman and fetus associated with myocardial infarction and stroke [ see clinical considerations ]. no evidence of fetotoxicity was observed when clopidogrel was administered to pregnant rats and rabbits during organogenesis at doses corresponding to 65 and 78 times the recommended daily human dose [ see data ]. the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. all pregnancies have a background risk of birth defects, 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 myocardial infarction and stroke are medical emergencies. therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of clopidogrel on the fetus. labor or delivery clopidogrel use during labor or delivery will increase the risk of maternal bleeding and hemorrhage. avoid neuraxial blockade during clopidogrel use because of the risk of spinal hematoma. when possible, discontinue clopidogrel 5 to 7 days prior to labor, delivery, or neuraxial blockade. data human data the available data from published case reports over two decades of postmarketing use have not identified an association with clopidogrel use in pregnancy and major birth defects, miscarriage, or adverse fetal outcomes. animal data embryo-fetal developmental toxicology studies were performed in pregnant rats and rabbits with doses up to 500 and 300 mg/kg/day, respectively, administered during organogenesis. these doses, corresponding to 65 and 78 times the recommended daily human dose, respectively, on a mg/m2 basis, revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. risk summary there are no data on the presence of clopidogrel in human milk or the effects on milk production. no adverse effects on breastfed infants have been observed with maternal clopidogrel use during lactation in a small number of postmarketing cases. studies in rats have shown that clopidogrel and/or its metabolites are present in the milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for clopidogrel and any potential adverse effects on the breastfed infant from clopidogrel or from underlying maternal condition. safety and effectiveness in pediatric populations have not been established. a randomized, placebo-controlled trial (clarinet) did not demonstrate a clinical benefit of clopidogrel in neonates and infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary arterial shunt. possible factors contributing to this outcome were the dose of clopidogrel, the concomitant administration of aspirin, and the late initiation of therapy following shunt palliation. it cannot be ruled out that a trial with a different design would demonstrate a clinical benefit in this patient population. of the total number of subjects in the caprie and cure controlled clinical studies, approximately 50% of patients treated with clopidogrel  were 65 years of age and older, and 15% were 75 years and older. in commit, approximately 58% of the patients treated with clopidogrel were 60 years and older, 26% of whom were 70 years and older. the observed risk of bleeding events with clopidogrel plus aspirin versus placebo plus aspirin by age category is provided in table 1 and table 2 for the cure and commit trials, respectively [see adverse reactions ( 6.1)] . no dosage adjustment is necessary in elderly patients. experience is limited in patients with severe and moderate renal impairment [see clinical pharmacology ( 12.2)]. no dosage adjustment is necessary in patients with hepatic impairment [see clinical pharmacology ( 12.2)] .