Israel - English - Ministry of Health

teva israel ltd - simvastatin - tablets - simvastatin 20 mg - simvastatin - simvastatin - coronary heart disease : in patients with coronary heart disease and hypercholesterolemia simvastatin-teva is indicated to: - reduce the risk of total mortality by reducing coronary death - reduce the risk of non-fatal myocardial infarction - reduce the risk for undergoing myocardial revascularization procedures. - reduce the risk of stroke and transient ischemic attacks (tia). hyperlipidemia: simvastatin-teva is indicated as an adjunct to diet to reduce elevated total-c ldl-c apo b and tg and to increase hdl-c in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (frederickson types iia and iib) simvastatin-teva therefore lowers the ldl-c/hdl-c and the total-c/hdl-c ratios. homozygous familial hypercholesterolemia: simvastatin-teva is also indicated as an adjunct to diet and other non-dietary measures in reducing elevated total cholesterol ldl-cholesterol and apolipoprotein b in patients with homozygous familial hypercholesterolemia when response to these measures is inadequate. hypertriglyceridemia (fredrickson type iv hyperlipidemia). simvastatin-teva is indicated for the treatment of patients with primary dysbetalipoproteinemia (fredrickson type iii hyperlipidemia).

Israel - English - Ministry of Health

teva israel ltd - simvastatin - tablets - simvastatin 10 mg - simvastatin - simvastatin - coronary heart disease : in patients with coronary heart disease and hypercholesterolemia simvastatin-teva is indicated to: - reduce the risk of total mortality by reducing coronary death - reduce the risk of non-fatal myocardial infarction - reduce the risk for undergoing myocardial revascularization procedures.- reduce the risk of stroke and transient ischemic attacks (tia). hyperlipidemia: simvastatin-teva is indicated as an adjunct to diet to reduce elevated total-c ldl-c apo b and tg and to increase hdl-c in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (frederickson types iia and iib) simvastatin-teva therefore lowers the ldl-c/hdl-c and the total-c/hdl-c ratios.homozygous familial hypercholesterolemia: simvastatin-teva is also indicated as an adjunct to diet and other non-dietary measures in reducing elevated total cholesterol ldl-cholesterol and apolipoprotein b in patients with homozygous familial hypercholesterolemia when response to these measures is inadequate. hypertriglyceridemia (fredrickson type iv hyperlipidemia). simvastatin-teva is indicated for the treatment of patients with primary dysbetalipoproteinemia (fredrickson type iii hyperlipidemia).

Israel - English - Ministry of Health

teva israel ltd - simvastatin - tablets - simvastatin 80 mg - simvastatin - simvastatin - coronary heart disease : in patients with coronary heart disease and hypercholesterolemia simvastatin-teva is indicated to: reduce the risk of total mortality by reducing coronary death reduce the risk of non-fatal myocardial infarction reduce the risk for undergoing myocardial revascularization procedures.reduce the risk of stroke and transient ischemic attacks (tia). hyperlipidemia: simvastatin-teva is indicated as an adjunct to diet to reduce elevated total-c ldl-c apo b and tg and to increase hdl-c in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (frederickson types iia and iib) simvastatin-teva therefore lowers the ldl-c/hdl-c and the total-c/hdl-c ratios. homozygous familial hypercholesterolemia: simvastatin-teva is also indicated as an adjunct to diet and other non-dietary measures in reducing elevated total cholesterol ldl-cholesterol and apolipoprotein b in patients with homozygous familial hypercholesterolemia when response to these measures is inadequate. hypertriglyceridemia (fredrickson type iv hyperlipidemia). simvastatin-teva is indicated for the treatment of patients with hypertriglyceridemia (fredrickson type iv hyperlipidemia). dysbetalipoproteinemia (fredrickson type iii hyperlipidemia): simvastatin-teva is also indicated for the treatment of patients with primary dysbetalipoproteinemia (fredrickson type iii hyperlipidemia).

Israel - English - Ministry of Health

teva israel ltd - simvastatin - tablets - simvastatin 40 mg - simvastatin - simvastatin - coronary heart disease : in patients with coronary heart disease and hypercholesterolemia simvastatin-teva is indicated to: reduce the risk of total mortality by reducing coronary death ;reduce the risk of non-fatal myocardial infarction ;reduce the risk for undergoing myocardial revascularization procedures. reduce the risk of stroke and transient ischemic attacks (tia). hyperlipidemia: simvastatin-teva is indicated as an adjunct to diet to reduce elevated total-c ldl-c apo b and tg and to increase hdl-c in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (frederickson types iia and iib) simvastatin-teva therefore lowers the ldl-c/hdl-c and the total-c/hdl-c ratios. homozygous familial hypercholesterolemia: simvastatin-teva is also indicated as an adjunct to diet and other non-dietary measures in reducing elevated total cholesterol ldl-cholesterol and apolipoprotein b in patients with homozygous familial hypercholesterolemia when response to these measures is inadequate. hypertriglyceridemia (fredrickson type iv hyperlipidemia). simvastatin-teva is indicated for the treatment of patients with hypertriglyceridemia ( fredrickson type iv hyperlipidemia). dysbetalipoproteinemia (fredrickson type iii hyperlipidemia): simvastatin-teva is also indicated for the treatment of patients with primary dysbetalipoproteinemia (fredrickson type iii hyperlipidemia).

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

northstar rx llc - simvastatin (unii: agg2fn16ev) (simvastatin - unii:agg2fn16ev) - simvastatin 5 mg - simvastatin tablets are indicated: - to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. - as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c): in adults with primary hyperlipidemia. in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - in adults with primary hyperlipidemia. - in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - as an adjunct to other ldl-c-lowering therapies to reduce ldl-c in adults with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia. hypertriglyceridemia. - primary dysbetalipoproteinemia. - hypertriglyceridemia. simvastatin tablets are contraindicated in the following conditions: - concomitant use of strong cyp3a4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see drug interactions (7.1)]. - concomitant use of cyclosporine, danazol or gemfibrozil [see drug interactions (7.1)]. - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)] . - hypersensitivity to simvastatin or any excipients in simvastatin tablets. hypersensitivity reactions, including anaphylaxis, angioedema and stevens-johnson syndrome, have been reported [see adverse reactions (6.2)]. risk summary discontinue simvastatin when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, simvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see clinical pharmacology (12.1)]. in addition, treatment of hyperlipidemia is not generally necessary during pregnancy. atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. published data from prospective and retrospective observational cohort studies with simvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data) . in animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m2 ) (see data). 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. data human data a medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. the relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. there were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. in the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. animal data simvastatin was given to pregnant rats at doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) from gestation days 6 to 17 and to pregnant rabbits from gestation days 6 to 18 at doses of 2.5, 5, and 10 mg/kg/day (0.5 times, 1 times, and 2 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area). for both species, there was no evidence of maternal toxicity or embryolethality. in rats, mean fetal body weights in the 25 mg/kg/day group were decreased 5.4%. similar fetal body weight effects were not observed in rabbits. simvastatin doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) were given to pregnant rats from gestation day 15 to lactation day 21. slight decreases in maternal body weight gain and pup postnatal day 0 weight were observed in the 25 mg/kg/day dose group. mean body weight gain of pups during lactation was slightly decreased at doses ≥12.5 mg/kg/day. post weaning weight, behavior, reproductive performance and fertility of the offspring were not affected at any dose tested. placental transfer of simvastatin was not evaluated in rats or rabbits. however, it has been shown that other drugs in this class cross the placenta. risk summary there is no information about the presence of simvastatin in human or animal milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. however, it has been shown that another drug in this class passes into human milk. statins, including simvastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with simvastatin [see use in specific populations (8.1), clinical pharmacology (12.1)]. the safety and effectiveness of simvastatin as an adjunct to diet to reduce ldl-c have been established in pediatric patients 10 years of age and older with hefh. use of simvastatin for this indication is based on a double-blind, placebo-controlled clinical study in 175 pediatric patients (99 boys and 76 girls at least 1 year post-menarche) 10 years of age and older with hefh. in this limited controlled study, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls. the safety and effectiveness of simvastatin have not been established in pediatric patients younger than 10 years of age with hefh or in pediatric patients with other types of hyperlipidemia (other than hefh). of the total number of simvastatin-treated patients in clinical studies 1,021 (23%) patients, 5,366 (52%) patients, and 363 (15%) patients were ≥65 years old, respectively. in study hps, 615 (6%) patients were ≥75 years old [see clinical studies (14)]. in a clinical study of patients treated with simvastatin 80 mg daily, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age. a pharmacokinetic study with simvastatin use showed the mean plasma level of total inhibitors to be approximately 45% higher in geriatric patients between 70 to 78 years of age compared with patients between 18 to 30 years of age [see clinical pharmacology (12.3)] . advanced age (≥65 years) is a risk factor for simvastatin-associated myopathy and rhabdomyolysis. dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. monitor geriatric patients receiving simvastatin for the increased risk of myopathy [see warnings and precautions (5.1)]. renal impairment is a risk factor for myopathy and rhabdomyolysis. monitor all patients with renal impairment for development of myopathy. in patients with severe renal impairment (clcr 15 to 29 ml/min), the recommended starting dosage is simvastatin 5 mg once daily [see dosage and administration (2.4), warnings and precautions (5.1)]. simvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see contraindications (4), warnings and precautions (5.3)]. in a clinical study in which patients at high risk of cvd were treated with simvastatin 40 mg/day (median follow-up 3.9 years), the incidence of myopathy was approximately 0.05% for non-chinese patients (n=7367) compared with 0.24% for chinese patients (n=5468). in this study, the incidence of myopathy for chinese patients on simvastatin 40 mg/day or ezetimibe/simvastatin 10/40 mg/day coadministered with extended-release niacin 2 g/day was 1.24%. chinese patients may be at higher risk for myopathy, monitor these patients appropriately. coadministration of simvastatin with lipid-modifying doses of niacin-containing products (≥1 g/day niacin) is not recommended in chinese patients [see warnings and precautions (5.1), drug interactions (7.1)].

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

zydus pharmaceuticals usa inc. - simvastatin (unii: agg2fn16ev) (simvastatin - unii:agg2fn16ev) - simvastatin 5 mg - simvastatin  is indicated: - to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. - as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c): - in adults with primary hyperlipidemia. - in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - as an adjunct to other ldl-c-lowering therapies to reduce ldl-c in adults with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: - primary dysbetalipoproteinemia. - hypertriglyceridemia. simvastatin is contraindicated in the following conditions: - concomitant use of strong cyp3a

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

lupin pharmaceuticals, inc. - simvastatin (unii: agg2fn16ev) (simvastatin - unii:agg2fn16ev) - simvastatin 5 mg - simvastatin tablets usp are indicated: - to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. - as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c): in adults with primary hyperlipidemia. in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - in adults with primary hyperlipidemia. - in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - as an adjunct to other ldl-c-lowering therapies to reduce ldl-c in adults with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia. hypertriglyceridemia. - primary dysbetalipoproteinemia. - hypertriglyceridemia. simvastatin is contraindicated in the following conditions: - concomitant use of strong cyp3a4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see drug interactions (7.1)]. - concomitant use of cyclosporine, danazol or gemfibrozil [see drug interactions (7.1)]. - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)] - hypersensitivity to simvastatin or any excipients in simvastatin tablets usp. hypersensitivity reactions, including anaphylaxis, angioedema and stevens-johnson syndrome, have been reported [see adverse reactions (6.2)] risk summary discontinue simvastatin when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, simvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see clinical pharmacology (12.1)] . in addition, treatment of hyperlipidemia is not generally necessary during pregnancy. atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. published data from prospective and retrospective observational cohort studies with simvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data). in animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m2 ) (see data) . 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. data human data: a medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. the relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. there were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. in the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. animal data: simvastatin was given to pregnant rats at doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) from gestation days 6-17 and to pregnant rabbits from gestation days 6-18 at doses of 2.5, 5, and 10 mg/kg/day (0.5 times, 1 times, and 2 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area). for both species, there was no evidence of maternal toxicity or embryolethality. in rats, mean fetal body weights in the 25 mg/kg/day group were decreased 5.4%. similar fetal body weight effects were not observed in rabbits. simvastatin doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) were given to pregnant rats from gestation day 15 to lactation day 21. slight decreases in maternal body weight gain and pup postnatal day 0 weight were observed in the 25 mg/kg/day dose group. mean body weight gain of pups during lactation was slightly decreased at doses ≥12.5 mg/kg/day. post weaning weight, behavior, reproductive performance and fertility of the offspring were not affected at any dose tested. placental transfer of simvastatin was not evaluated in rats or rabbits. however, it has been shown that other drugs in this class cross the placenta. risk summary there is no information about the presence of simvastatin in human or animal milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. however, it has been shown that another drug in this class passes into human milk. statins, including simvastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with simvastatin [see use in specific populations (8.1), clinical pharmacology (12.1)]. the safety and effectiveness of simvastatin as an adjunct to diet to reduce ldl-c have been established in pediatric patients 10 years of age and older with hefh. use of simvastatin for this indication is based on a double-blind, placebo-controlled clinical study in 175 pediatric patients (99 boys and 76 girls at least 1 year post-menarche) 10 years of age and older with hefh. in this limited controlled study, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls. the safety and effectiveness of simvastatin have not been established in pediatric patients younger than 10 years of age with hefh or in pediatric patients with other types of hyperlipidemia (other than hefh). of the total number of simvastatin-treated patients in clinical studies 1,021 (23%) patients, 5,366 (52%) patients, and 363 (15%) patients were ≥65 years old, respectively. in study hps, 615 (6%) patients were ≥75 years old [see clinical studies (14)] . in a clinical study of patients treated with simvastatin 80 mg daily, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age. a pharmacokinetic study with simvastatin use showed the mean plasma level of total inhibitors to be approximately 45% higher in geriatric patients between 70-78 years of age compared with patients between 18-30 years of age [see clinical pharmacology (12.3)] . renal impairment is a risk factor for myopathy and rhabdomyolysis. monitor all patients with renal impairment for development of myopathy. in patients with severe renal impairment (clcr 15 – 29 ml/min), the recommended starting dosage is simvastatin 5 mg once daily [see dosage and administration (2.4), warnings and precautions (5.1)] . simvastatin is not available in a 5 mg strength. use another simvastatin product to initiate dosing in such patients. simvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see contraindications (4), warnings and precautions (5.3)] . in a clinical study in which patients at high risk of cvd were treated with simvastatin 40 mg/day (median follow-up 3.9 years), the incidence of myopathy was approximately 0.05% for non-chinese patients (n=7367) compared with 0.24% for chinese patients (n=5468). in this study, the incidence of myopathy for chinese patients on simvastatin 40 mg/day or ezetimibe/simvastatin 10/40 mg/day coadministered with extended-release niacin 2 g/day was 1.24%. chinese patients may be at higher risk for myopathy, monitor these patients appropriately. coadministration of simvastatin with lipid-modifying doses of niacin-containing products (≥1 g/day niacin) is not recommended in chinese patients [see warnings and precautions (5.1), drug interactions (7.1)].

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

pd-rx pharmaceuticals, inc. - simvastatin (unii: agg2fn16ev) (simvastatin - unii:agg2fn16ev) - simvastatin 10 mg - simvastatin tablet is indicated: • to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. • as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c):       o in adults with primary hyperlipidemia.       o in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). • as an adjunct to other ldl-c-lowering therapies to reduce ldl-c in adults with homozygous familial hypercholesterolemia (hofh). • as an adjunct to diet for the treatment of adults with:       o primary dysbetalipoproteinemia.       o hypertriglyceridemia. simvastatin tablets are contraindicated in the

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

remedyrepack inc. - simvastatin (unii: agg2fn16ev) (simvastatin - unii:agg2fn16ev) - simvastatin 20 mg - simvastatin tablet is indicated: • to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. • as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c):       o in adults with primary hyperlipidemia.       o in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). • as an adjunct to other ldl-c-lowering therapies to reduce ldl-c in adults with homozygous familial hypercholesterolemia (hofh). • as an adjunct to diet for the treatment of adults with:       o primary dysbetalipoproteinemia.       o hypertriglyceridemia. simvastatin tablets are contraindicated in the following conditions: - concomitant use of strong cyp3a4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see drug interactions (7.1)]. - concomitant use of cyclosporine, danazol or gemfibrozil [see drug interactions (7.1)]. - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)]. - hypersensitivity to simvastatin or any excipients in simvastatin tablets. hypersensitivity reactions, including anaphylaxis, angioedema and stevens-johnson syndrome, have been reported [see adverse reactions (6.2)]. risk summary discontinue simvastatin tablets when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. simvastatin tablets decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, simvastatin tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action [ see clinical pharmacology ( 12.1) ]. in addition, treatment of hyperlipidemia is not generally necessary during pregnancy. atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. published data from prospective and retrospective observational cohort studies with simvastatin tablets use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data) . in animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m 2 ) (see data) . 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. data human data a medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. the relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. there were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. in the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. animal data simvastatin was given to pregnant rats at doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) from gestation days 6 to 17 and to pregnant rabbits from gestation days 6 to 18 at doses of 2.5, 5, and 10 mg/kg/day (0.5 times, 1 times, and 2 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area). for both species, there was no evidence of maternal toxicity or embryolethality. in rats, mean fetal body weights in the 25 mg/kg/day group were decreased 5.4%. similar fetal body weight effects were not observed in rabbits. simvastatin doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) were given to pregnant rats from gestation day 15 to lactation day 21. slight decreases in maternal body weight gain and pup postnatal day 0 weight were observed in the 25 mg/kg/day dose group. mean body weight gain of pups during lactation was slightly decreased at doses ≥12.5 mg/kg/day. post weaning weight, behavior, reproductive performance and fertility of the offspring were not affected at any dose tested. placental transfer of simvastatin was not evaluated in rats or rabbits. however, it has been shown that other drugs in this class cross the placenta. risk summary there is no information about the presence of simvastatin in human or animal milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. however, it has been shown that another drug in this class passes into human milk. statins, including simvastatin tablets, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with simvastatin tablets[ see use in specific populations ( 8.1), clinical pharmacology ( 12.1) ]. the safety and effectiveness of simvastatin tablets as an adjunct to diet to reduce ldl-c have been established in pediatric patients 10 years of age and older with hefh. use of simvastatin tablets for this indication is based on a double-blind, placebo-controlled clinical study in 175 pediatric patients (99 boys and 76 girls at least 1 year post-menarche) 10 years of age and older with hefh. in this limited controlled study, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls. the safety and effectiveness of simvastatin tablets have not been established in pediatric patients younger than 10 years of age with hefh or in pediatric patients with other types of hyperlipidemia (other than hefh). of the total number of  simvastatin tablets-treated patients in clinical studies 1,021 (23%) patients, 5,366 (52%) patients, and 363 (15%) patients were ≥65 years old, respectively. in study hps, 615 (6%) patients were ≥75 years old [ see clinical studies ( 14)]. in a clinical study of patients treated with simvastatin tablets 80 mg daily, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age. a pharmacokinetic study with simvastatin tablets use showed the mean plasma level of total inhibitors to be approximately 45% higher in geriatric patients between 70 to 78 years of age compared with patients between 18 to 30 years of age [ see clinical pharmacology ( 12.3) ]. advanced age (≥65 years) is a risk factor for  simvastatin tablets-associated myopathy and rhabdomyolysis. dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. monitor geriatric patients receiving simvastatin tablets for the increased risk of myopathy [ see warnings and precautions ( 5.1) ]. renal impairment is a risk factor for myopathy and rhabdomyolysis. monitor all patients with renal impairment for development of myopathy. in patients with severe renal impairment (clcr 15 to  29 ml/min), the recommended starting dosage is simvastatin 5 mg once daily [ see dosage and administration ( 2.4), warnings and precautions ( 5.1) ]. simvastatin tablet is contraindicated in patients with acute liver failure or decompensated cirrhosis [ see contraindications ( 4), warnings and precautions ( 5.3) ]. in a clinical study in which patients at high risk of cvd were treated with simvastatin 40 mg/day (median follow-up 3.9 years), the incidence of myopathy was approximately 0.05% for non-chinese patients (n=7367) compared with 0.24% for chinese patients (n=5468). in this study, the incidence of myopathy for chinese patients on simvastatin 40 mg/day or ezetimibe/simvastatin 10/40 mg/day coadministered with extended-release niacin 2 g/day was 1.24%. chinese patients may be at higher risk for myopathy, monitor these patients appropriately. coadministration of simvastatin with lipid-modifying doses of niacin-containing products (≥1 g/day niacin) is not recommended in chinese patients [ see warnings and precautions ( 5.1), drug interactions ( 7.1) ].

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

micro labs limited - simvastatin (unii: agg2fn16ev) (simvastatin - unii:agg2fn16ev) - simvastatin 5 mg - simvastatin tablets are indicated: • to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. • as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c):       o in adults with primary hyperlipidemia.       o in adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). • as an adjunct to other ldl-c-lowering therapies to reduce ldl-c in adults with homozygous familial hypercholesterolemia (hofh). • as an adjunct to diet for the treatment of adults with:       o primary dysbetalipoproteinemia.       o hypertriglyceridemia. simvastatin tablets are contraindicated in th