Israel - English - Ministry of Health

teva pharmaceutical industries ltd, israel - atorvastatin as calcium - tablets - atorvastatin as calcium 80 mg - atorvastatin - atorvastatin - atorvastatin teva is indicated as an adjunct to diet for reduction of elevated total cholesterol ldl- cholesterol apolipoprotein b and triglycerides and to increase hdl cholesterol in patients with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (corresponding to types iia and iib of the fredrickson classification) when response to diet and other nonpharmacological measures is inadequate. atorvastatin teva is also indicated to reduce total-c and ldl -c in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatment (e.g. ldl apheresis) or if such treatments are unavailable. pediatric patients (10-17 years of age) : atorvastatin is indicated as an adjunct to diet to reduce total -c ldl-c and apo b levels in boys and postmenarchal girls 10 to 17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are prese

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

remedyrepack inc. - rosuvastatin calcium (unii: 83mvu38m7q) (rosuvastatin - unii:413kh5zj73) - rosuvastatin 20 mg - rosuvastatin calcium tablets are indicated as an adjunct to diet to: ●       reduce ldl-c, total-c, non-hdl-c and apo-b in children and adolescents 7 to 17 years of age with homozygous familial hypercholesterolemia, either alone or with other lipid-lowering treatments (e.g., ldl apheresis). pediatric use information for patients ages 8 to less than 10 years is approved for astrazeneca’s crestor (rosuvastatin calcium) tablets. however, due to astrazeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. rosuvastatin calcium tablets are indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (type iii hyperlipoproteinemia). rosuvastatin calcium tablets are indicated as adjunctive therapy to other lipid-lowering treatments (e.g., ldl apheresis) or alone if such treatments are unavaila

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

major pharmaceuticals - rosuvastatin calcium (unii: 83mvu38m7q) (rosuvastatin - unii:413kh5zj73) - rosuvastatin 5 mg - rosuvastatin calcium tablets are indicated as an adjunct to diet to: pediatric use information for patients ages 8 to less than 10 years is approved for astrazeneca’s crestor (rosuvastatin calcium) tablets. however, due to astrazeneca’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. rosuvastatin calcium tablets are indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. rosuvastatin calcium tablets are indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (type iii hyperlipoproteinemia). rosuvastatin calcium tablets are indicated as adjunctive therapy to other lipid-lowering treatments (e.g., ldl apheresis) or alone if such treatments are unavailable to reduce ldl-c, total-c, and apob in adult patients with homozygous familial hypercholesterolemia. rosuvastatin calcium tablets have not been studied in fredrickson type i and v dyslipidemias. rosuvastatin calcium tabl

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)

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

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

aurobindo pharma 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): 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)

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)

rising pharma holdings, inc. - rosuvastatin calcium (unii: 83mvu38m7q) (rosuvastatin - unii:413kh5zj73) - rosuvastatin 5 mg - rosuvastatin tablets are indicated: - to reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures in adults without established coronary heart disease who are at increased risk of cardiovascular (cv) disease based on age, hscrp ≥2 mg/l, and at least one additional cv risk factor. - as an adjunct to diet to: reduce ldl-c in adults with primary hyperlipidemia. reduce low-density lipoprotein cholesterol (ldl-c) and slow the progression of atherosclerosis in adults. reduce ldl-c in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (hefh). - reduce ldl-c in adults with primary hyperlipidemia. - reduce low-density lipoprotein cholesterol (ldl-c) and slow the progression of atherosclerosis in adults. - reduce ldl-c in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (hefh). -  as an adjunct to other ldl-c-lowering therapies, or alone if such treatments are unavailable, to reduce ldl-c in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia. hypertriglyceridemia. - primary dysbetalipoproteinemia. - hypertriglyceridemia. rosuvastatin tablets are contraindicated in the following conditions: - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)]. - hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin [see adverse reactions (6.1)] . risk summary discontinue rosuvastatin when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. rosuvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, rosuvastatin 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 rosuvastatin 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 rosuvastatin during the period of organogenesis at doses that resulted in systemic exposures equivalent to human exposures at the maximum recommended human dose (mrhd) of 40 mg/day, based on auc and body surface area (mg/m2 ), respectively (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 in female rats given 5, 15 and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the mrhd dose of 40 mg/day based on auc). in pregnant rats given 2, 10 and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the mrhd of 40 mg/day based body surface area). in pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the mrhd of 40 mg/day based on body surface area). rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. in rabbits, fetal tissue distribution was 25% of maternal plasma concentration after a single oral gavage dose of 1 mg/kg on gestation day 18.   risk summary limited data from case reports in published literature indicate that rosuvastatin is present in human milk. there is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. statins, including rosuvastatin, 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 rosuvastatin [ see use in specific populations (8.1) and clinical pharmacology (12.1)] . the safety and effectiveness of rosuvastatin as an adjunct to diet to reduce ldl-c have been established in pediatric patients 8 years of age and older with hefh. use of rosuvastatin for this indication is based on one 12-week controlled trial with a 40-week open-label extension period in 176 pediatric patients 10 years of age and older with hefh and one 2-year open-label, uncontrolled trial in 175 pediatric patients 8 years of age and older with hefh [ see clinical studies (14)] . in the 1-year trial with a 12-week controlled phase, there was no detectable effect of rosuvastatin on growth, weight, bmi (body mass index), or sexual maturation in patients aged 10 to 17 years. the safety and effectiveness of rosuvastatin as an adjunct to other ldl-c-lowering therapies to reduce ldl-c have been established pediatric patients 7 years of age and older with hofh. use of rosuvastatin for this indication is based on a randomized, placebo-controlled, cross-over study in 14 pediatric patients 7 years of age and older with hofh [ see clinical studies (14)] . the safety and effectiveness of rosuvastatin have not been established in pediatric patients younger than 8 years of age with hefh, younger than 7 years of age with hofh, or in pediatric patients with other types of hyperlipidemia (other than hefh or hofh). of the total number of rosuvastatin-treated patients in clinical studies, 3159 (31%) were 65 years and older, and 698 (6.8%) were 75 years and older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects. advanced age (≥65 years) is a risk factor for rosuvastatin-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 rosuvastatin for the increased risk of myopathy [see warnings and precautions (5.1)]. rosuvastatin exposure is not influenced by mild to moderate renal impairment (clcr ≥30 ml/min/1.73 m2 ). exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (clcr <30 ml/min/1.73 m2 ) who are not receiving hemodialysis [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 not on hemodialysis, the recommended starting dosage is 5 mg daily and should not exceed 10 mg daily [see  dosage and administration (2.5) and warnings and precautions (5.1)]. rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis. chronic alcohol liver disease is known to increase rosuvastatin exposure. patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see contraindications (4), warning and precautions (5.3) and clinical pharmacology (12.3)]. pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in asian subjects when compared with white controls. adjust the rosuvastatin dosage in asian patients [see dosage and administration (2.4) and clinical pharmacology (12.3)] .

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

aurobindo pharma limited - rosuvastatin calcium (unii: 83mvu38m7q) (rosuvastatin - unii:413kh5zj73) - rosuvastatin 5 mg - rosuvastatin tablets are indicated: - to reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures in adults without established coronary heart disease who are at increased risk of cardiovascular (cv) disease based on age, hscrp ≥2 mg/l, and at least one additional cv risk factor. - as an adjunct to diet to: reduce ldl-c in adults with primary hyperlipidemia. reduce low-density lipoprotein cholesterol (ldl-c) and slow the progression of atherosclerosis in adults. reduce ldl-c in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (hefh). - reduce ldl-c in adults with primary hyperlipidemia. - reduce low-density lipoprotein cholesterol (ldl-c) and slow the progression of atherosclerosis in adults. - reduce ldl-c in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (hefh). -  as an adjunct to other ldl-c-lowering therapies, or alone if such treatments are unavailable, to reduce ldl-c in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia. hypertriglyceridemia. - primary dysbetalipoproteinemia. - hypertriglyceridemia. rosuvastatin tablets are contraindicated in the following conditions: - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)]. - hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin [see adverse reactions (6.1)] . risk summary discontinue rosuvastatin when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. rosuvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, rosuvastatin 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 rosuvastatin 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 rosuvastatin during the period of organogenesis at doses that resulted in systemic exposures equivalent to human exposures at the maximum recommended human dose (mrhd) of 40 mg/day, based on auc and body surface area (mg/m2 ), respectively (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 in female rats given 5, 15 and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the mrhd dose of 40 mg/day based on auc). in pregnant rats given 2, 10 and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the mrhd of 40 mg/day based body surface area). in pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the mrhd of 40 mg/day based on body surface area). rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. in rabbits, fetal tissue distribution was 25% of maternal plasma concentration after a single oral gavage dose of 1 mg/kg on gestation day 18.   risk summary limited data from case reports in published literature indicate that rosuvastatin is present in human milk. there is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. statins, including rosuvastatin, 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 rosuvastatin [ see use in specific populations (8.1) and clinical pharmacology (12.1)] . the safety and effectiveness of rosuvastatin as an adjunct to diet to reduce ldl-c have been established in pediatric patients 8 years of age and older with hefh. use of rosuvastatin for this indication is based on one 12-week controlled trial with a 40-week open-label extension period in 176 pediatric patients 10 years of age and older with hefh and one 2-year open-label, uncontrolled trial in 175 pediatric patients 8 years of age and older with hefh [ see clinical studies (14)] . in the 1-year trial with a 12-week controlled phase, there was no detectable effect of rosuvastatin on growth, weight, bmi (body mass index), or sexual maturation in patients aged 10 to 17 years. the safety and effectiveness of rosuvastatin as an adjunct to other ldl-c-lowering therapies to reduce ldl-c have been established pediatric patients 7 years of age and older with hofh. use of rosuvastatin for this indication is based on a randomized, placebo-controlled, cross-over study in 14 pediatric patients 7 years of age and older with hofh [ see clinical studies (14)] . the safety and effectiveness of rosuvastatin have not been established in pediatric patients younger than 8 years of age with hefh, younger than 7 years of age with hofh, or in pediatric patients with other types of hyperlipidemia (other than hefh or hofh). of the total number of rosuvastatin-treated patients in clinical studies, 3159 (31%) were 65 years and older, and 698 (6.8%) were 75 years and older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects. advanced age (≥65 years) is a risk factor for rosuvastatin-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 rosuvastatin for the increased risk of myopathy [see warnings and precautions (5.1)]. rosuvastatin exposure is not influenced by mild to moderate renal impairment (clcr ≥30 ml/min/1.73 m2 ). exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (clcr <30 ml/min/1.73 m2 ) who are not receiving hemodialysis [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 not on hemodialysis, the recommended starting dosage is 5 mg daily and should not exceed 10 mg daily [see  dosage and administration (2.5) and warnings and precautions (5.1)]. rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis. chronic alcohol liver disease is known to increase rosuvastatin exposure. patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see contraindications (4), warning and precautions (5.3)  and clinical pharmacology (12.3)]. pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in asian subjects when compared with white controls. adjust the rosuvastatin dosage in asian patients [see dosage and administration (2.4) and clinical pharmacology (12.3)] .

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

teva pharmaceuticals usa, inc. - pravastatin sodium (unii: 3m8608uq61) (pravastatin - unii:kxo2kt9n0g) - pravastatin sodium 10 mg - pravastatin sodium tablets are indicated: - to reduce the risk of myocardial infarction, myocardial revascularization procedures, and cardiovascular mortality in adults with elevated low-density lipoprotein cholesterol (ldl-c) without clinically evident coronary heart disease (chd). - to reduce the risk of coronary death, myocardial infarction, myocardial revascularization procedures, stroke or transient ischemic attack, and slow the progression of coronary atherosclerosis in adults with clinically evident chd. - as an adjunct to diet to reduce ldl-c in adults with primary hyperlipidemia. - as an adjunct to diet to reduce ldl-c in pediatric patients ages 8 years and older with heterozygous familial hypercholesterolemia (hefh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia. hypertriglyceridemia. - primary dysbetalipoproteinemia. - hypertriglyceridemia. - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)]. - hypersensitivity to any pravastatin or any excipients in pravastatin sodium tablets. risk summary discontinue pravastatin when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. pravastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, pravastatin 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 pravastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data) . in animal reproduction studies, no evidence of fetal malformations was seen in pregnant rats or rabbits orally administered pravastatin during the period of organogenesis at doses that resulted in 10 times and 120 times, respectively, the human exposure at the maximum recommended human dose (mrhd) of 80 mg/day, based on body surface area (mg/m2 ). an imbalance in some fetal skeletal variations, increased offspring mortality, and developmental delays occurred when pregnant rats were exposed to 10 times to 12 times the mrhd during organogenesis to parturition (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 1,152 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 cofounders – 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 cofounders. 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 embryofetal and neonatal mortality was observed in rats given pravastatin during the period of organogenesis or during organogenesis continuing through weaning. in pregnant rats given oral gavage doses of 4, 20, 100, 500, and 1,000 mg/kg/day from gestation days 7 through 17 (organogenesis) increased mortality of offspring and increased cervical rib skeletal anomalies were observed at ≥100 mg/kg/day systemic exposure, 10 times the human exposure at 80 mg/day mrhd based on body surface area (mg/m2 ). in other studies, no teratogenic effects were observed when pravastatin was dosed orally during organogenesis in rabbits (gestation days 6 through 18) up to 50 mg/kg/day or in rats (gestation days 7 through 17) up to 1,000 mg/kg/day. exposures were 10 times (rabbit) or 120 times (rat) the human exposure at 80 mg/day mrhd based on body surface area (mg/m2 ). in pregnant rats given oral gavage doses of 10, 100, and 1,000 mg/kg/day from gestation day 17 through lactation day 21 (weaning), developmental delays were observed at ≥100 mg/kg/day systemic exposure, corresponding to 12 times the human exposure at 80 mg/day mrhd, based on body surface area (mg/m2 ). in pregnant rats, pravastatin crosses the placenta and is found in fetal tissue at 30% of the maternal plasma levels following administration of a single dose of 20 mg/day orally on gestation day 18, which corresponds to exposure 2 times the mrhd of 80 mg daily based on body surface area (mg/m2 ). risk summary based on one lactation study in published literature, pravastatin is present in human milk. there is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. statins, including pravastatin, 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 pravastatin [see use in specific populations (8.1), clinical pharmacology (12.1)] . the safety and effectiveness of pravastatin as an adjunct to diet to reduce ldl-c have been established in pediatric patients 8 years of age and older with hefh. use of pravastatin for this indication is based on a double-blind, placebo-controlled clinical study in 214 pediatric patients (100 males and 114 females) 8 years of age and older with hefh. doses greater than 40 mg daily have not been studied in this population. the safety and effectiveness of pravastatin 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). in clinical studies, 4,797 (36.4%) pravastatin-treated patients were aged 65 and older and 110 (0.8%) were aged 75 and older. no significant differences in efficacy or safety were observed between geriatric patients and younger patients. mean pravastatin aucs are 25% to 50% higher in elderly subjects than in healthy young subjects, but mean maximum plasma concentration (cmax ), time to maximum plasma concentration (tmax ), and half-life (t½ ) values are similar in both age groups and substantial accumulation of pravastatin would not be expected in the elderly [see clinical pharmacology (12.3)]. advanced age (≥65 years) is a risk factor for pravastatin-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 pravastatin 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, the recommended starting dose is pravastatin sodium 10 mg once daily. the maximum recommended dosage in patients with severe renal impairment is pravastatin 40 mg once daily. the recommended dosage for patients with mild or moderate renal impairment is the same as patients with normal renal function [see dosage and administration (2.4), warnings and precautions (5.1), clinical pharmacology (12.3)] . pravastatin shows a large inter-subject variability in pharmacokinetics in patients with liver cirrhosis [clinical pharmacology (12.3)] . pravastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see contraindications (4), warnings and precautions (5.3)] .