الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

bryant ranch prepack - icosapent ethyl (unii: 6gc8a4payh) (icosapent - unii:aan7qov9ea) - icosapent ethyl is indicated: limitations of use the effect of icosapent ethyl on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. icosapent ethyl is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to icosapent ethyl or any of its components. risk summary the available data from published case reports and the pharmacovigilance database on the use of icosapent ethyl in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies in pregnant rats, non-dose-related imbalances for some minor developmental findings were observed with oral administration of icosapent ethyl during organogenesis at exposures that were equivalent to the clinical exposure at the human dose of 4 g/day, based on body surface area comparisons. in a study in pregnant rabbits orally administered icosapent ethyl during organogenesis, there were no clinically relevant adverse developmental effects at exposures that were 5 times the clinical exposure, based on body surface area comparisons (see data). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data in pregnant rats given oral gavage doses of 0.3, 1 and 2 g/kg/day icosapent ethyl from gestation through organogenesis all drug treated groups had non-dose-related imbalances in visceral and skeletal findings, including 13th reduced ribs, additional liver lobes, testes medially displaced and/or not descended, at human systemic exposures following a maximum oral dose of 4 g/day based on body surface comparisons. in a multigenerational developmental study in pregnant rats given doses of 0.3, 1, 3 g/kg/day icosapent ethyl by oral gavage from gestation day 7-17, icosapent ethyl did not affect viability in fetuses (f1 or f2). non-dose-related imbalances in findings of absent optic nerves and unilateral testes atrophy at human exposures based on the maximum dose of 4 g/day and on body surface area comparisons. additional variations consisting of early incisor eruption and increased percent cervical ribs were observed at the same exposures. pups from high dose treated dams exhibited decreased copulation rates, delayed estrus, decreased implantations and decreased surviving fetuses (f2) suggesting potential multigenerational effects of icosapent ethyl at 7 times human systemic exposure following 4 g/day dose based on body surface area comparisons across species. in pregnant rabbits given oral gavage doses of 0.1, 0.3, and 1 g/kg/day icosapent ethyl from gestation through organogenesis, a decrease in body weight and food consumption was observed at the high dose of 1 g/kg/day (5 times the human exposure at the maximum dose of 4 g/day, based on body surface area comparisons). slight increases in resorbed and dead fetuses were noted in the 1 g/kg/day group, but these were not significantly different from the control group. there were no differences between the icosapent ethyl groups and control group as to the number of corpora lutea, number of implantations, number of surviving fetuses, sex ratio, body weight of female fetuses or placental weight. there were no treatment-related malformations or skeletal anomalies. in pregnant rats given icosapent ethyl from gestation day 17 through lactation day 20 at 0.3, 1, 3 g/kg/day no adverse maternal or developmental effects were observed. however, complete litter loss (not dose-related) was noted in 2/23 litters at the low dose and 1/23 mid-dose dams by post-natal day 4 at human exposures at a maximum dose of 4 g/day, based on body surface area comparisons. risk summary published studies have detected omega-3 fatty acids, including epa, in human milk. lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. there are no data on the effects of omega-3 fatty acid ethyl esters on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for icosapent ethyl and any potential adverse effects on the breastfed child from icosapent ethyl or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. of the total number of patients in well-controlled clinical studies of icosapent ethyl, 45% were 65 years of age and over. no overall differences in safety or effectiveness were observed between these patients and younger groups. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in patients with hepatic impairment, alanine aminotransferase (alt) and aspartate aminotransferase (ast) levels should be monitored periodically during therapy with icosapent ethyl.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

amarin pharma inc. - icosapent ethyl (unii: 6gc8a4payh) (icosapent - unii:aan7qov9ea) - icosapent ethyl 1000 mg - vascepa® (icosapent ethyl) is indicated: - as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (tg) levels (≥ 150 mg/dl) and established cardiovascular disease or diabetes mellitus and 2 or more additional risk factors for cardiovascular disease. - established cardiovascular disease or - diabetes mellitus and 2 or more additional risk factors for cardiovascular disease. - as an adjunct to diet to reduce tg levels in adult patients with severe (≥ 500 mg/dl) hypertriglyceridemia. limitations of use: the effect of vascepa on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. vascepa is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to vascepa or any of its components. risk summary the available data from published case reports and the pharmacovigilanc

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

apotex corp - icosapent ethyl (unii: 6gc8a4payh) (icosapent - unii:aan7qov9ea) - icosapent ethyl capsules are indicated: - as an adjunct to diet to reduce triglyceride (tg) levels in adult patients with severe (≥500 mg/dl) hypertriglyceridemia. limitations of use: the effect of icosapent ethyl capsules on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. icosapent ethyl capsules are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to icosapent ethyl or any of its components. risk summary the available data from published case reports and the pharmacovigilance database on the use of icosapent ethyl capsules in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies in pregnant rats, non-dose-related imbalances for some minor developmental findings were observed with oral administration of icosapent ethyl during organogenesis at exposures that were equivalent to the clinical exposure at the human dose of 4 g/day, based on body surface area comparisons. in a study in pregnant rabbits orally administered icosapent ethyl during organogenesis, there were no clinically relevant adverse developmental effects at exposures that were 5 times the clinical exposure, based on body surface area comparisons (see data) .   the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data in pregnant rats given oral gavage doses of 0.3, 1 and 2 g/kg/day icosapent ethyl from gestation through organogenesis all drug treated groups had non-dose-related imbalances in visceral and skeletal findings, including 13th  reduced ribs, additional liver lobes, testes medially displaced and/or not descended at human systemic exposures following a maximum oral dose of 4 g/day based on body surface comparisons.   in a multigenerational developmental study in pregnant rats given doses of 0.3, 1, 3 g/kg/day icosapent ethyl by oral gavage from gestation day 7-17, icosapent ethyl did not affect viability in fetuses (f1 or f2). non-dose-related imbalances in findings of absent optic nerves and unilateral testes atrophy at human exposures based on the maximum dose of 4 g/day and on body surface area comparisons.  additional variations consisting of early incisor eruption and increased percent cervical ribs were observed at the same exposures. pups from high dose treated dams exhibited decreased copulation rates, delayed estrus, decreased implantations and decreased surviving fetuses (f2) suggesting potential multigenerational effects of icosapent ethyl at 7 times human systemic exposure following 4 g/day dose based on body surface area comparisons across species.  in pregnant rabbits given oral gavage doses of 0.1, 0.3, and 1 g/kg/day icosapent ethyl from gestation through organogenesis, a decrease in body weight and food consumption was observed at the high dose of 1 g/kg/day (5 times the human exposure at the maximum dose of 4 g/day, based on body surface area comparisons). slight increases in resorbed and dead fetuses were noted in the 1 g/kg/day group, but these were not significantly different from the control group. there were no differences between the icosapent ethyl groups and control group as to the number of corpora lutea, number of implantations, number of surviving fetuses, sex ratio, body weight of female fetuses or placental weight. there were no treatment-related malformations or skeletal anomalies.  in pregnant rats given icosapent ethyl from gestation day 17 through lactation day 20 at 0.3, 1, 3 g/kg/day no adverse maternal or developmental effects were observed. however, complete litter loss (not dose-related) was noted in 2/23 litters at the low dose and 1/23 mid-dose dams by post-natal day 4 at human exposures at a maximum dose of 4 g/day, based on body surface area comparisons. risk summary published studies have detected omega-3 fatty acids, including epa, in human milk. lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. there are no data on the effects of omega-3 fatty acid ethyl esters on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for icosapent ethyl capsules and any potential adverse effects on the breastfed child from icosapent ethyl or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. of the total number of patients in well-controlled clinical studies of icosapent ethyl, 45% were 65 years of age and over. no overall differences in safety or effectiveness were observed between these patients and younger groups. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in patients with hepatic impairment, alanine aminotransferase (alt) and aspartate aminotransferase (ast) levels should be monitored periodically during therapy with icosapent ethyl capsules.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

northstar rx llc - icosapent ethyl (unii: 6gc8a4payh) (icosapent - unii:aan7qov9ea) - icosapent ethyl is indicated: limitations of use the effect of icosapent ethyl on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. icosapent ethyl is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to icosapent ethyl or any of its components. risk summary the available data from published case reports and the pharmacovigilance database on the use of icosapent ethyl in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies in pregnant rats, non-dose-related imbalances for some minor developmental findings were observed with oral administration of icosapent ethyl during organogenesis at exposures that were equivalent to the clinical exposure at the human dose of 4 g/day, based on body surface area comparisons. in a study in pregnant rabbits orally administered icosapent ethyl during organogenesis, there were no clinically relevant adverse developmental effects at exposures that were 5 times the clinical exposure, based on body surface area comparisons (see data). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data in pregnant rats given oral gavage doses of 0.3, 1 and 2 g/kg/day icosapent ethyl from gestation through organogenesis all drug treated groups had non-dose-related imbalances in visceral and skeletal findings, including 13th reduced ribs, additional liver lobes, testes medially displaced and/or not descended, at human systemic exposures following a maximum oral dose of 4 g/day based on body surface comparisons. in a multigenerational developmental study in pregnant rats given doses of 0.3, 1, 3 g/kg/day icosapent ethyl by oral gavage from gestation day 7-17, icosapent ethyl did not affect viability in fetuses (f1 or f2). non-dose-related imbalances in findings of absent optic nerves and unilateral testes atrophy at human exposures based on the maximum dose of 4 g/day and on body surface area comparisons. additional variations consisting of early incisor eruption and increased percent cervical ribs were observed at the same exposures. pups from high dose treated dams exhibited decreased copulation rates, delayed estrus, decreased implantations and decreased surviving fetuses (f2) suggesting potential multigenerational effects of icosapent ethyl at 7 times human systemic exposure following 4 g/day dose based on body surface area comparisons across species. in pregnant rabbits given oral gavage doses of 0.1, 0.3, and 1 g/kg/day icosapent ethyl from gestation through organogenesis, a decrease in body weight and food consumption was observed at the high dose of 1 g/kg/day (5 times the human exposure at the maximum dose of 4 g/day, based on body surface area comparisons). slight increases in resorbed and dead fetuses were noted in the 1 g/kg/day group, but these were not significantly different from the control group. there were no differences between the icosapent ethyl groups and control group as to the number of corpora lutea, number of implantations, number of surviving fetuses, sex ratio, body weight of female fetuses or placental weight. there were no treatment-related malformations or skeletal anomalies. in pregnant rats given icosapent ethyl from gestation day 17 through lactation day 20 at 0.3, 1, 3 g/kg/day no adverse maternal or developmental effects were observed. however, complete litter loss (not dose-related) was noted in 2/23 litters at the low dose and 1/23 mid-dose dams by post-natal day 4 at human exposures at a maximum dose of 4 g/day, based on body surface area comparisons. risk summary published studies have detected omega-3 fatty acids, including epa, in human milk. lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. there are no data on the effects of omega-3 fatty acid ethyl esters on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for icosapent ethyl and any potential adverse effects on the breastfed child from icosapent ethyl or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. of the total number of patients in well-controlled clinical studies of icosapent ethyl, 45% were 65 years of age and over. no overall differences in safety or effectiveness were observed between these patients and younger groups. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in patients with hepatic impairment, alanine aminotransferase (alt) and aspartate aminotransferase (ast) levels should be monitored periodically during therapy with icosapent ethyl.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

mission pharmacal company - ascorbic acid (unii: pq6ck8pd0r) (ascorbic acid - unii:pq6ck8pd0r), iron (unii: e1uol152h7) (iron - unii:e1uol152h7), .alpha.-tocopherol acetate (unii: 9e8x80d2l0) (.alpha.-tocopherol - unii:h4n855pnz1), thiamine (unii: x66nso3n35) (thiamine ion - unii:4abt0j945j), niacinamide (unii: 25x51i8rd4) (niacinamide - unii:25x51i8rd4), pyridoxine hydrochloride (unii: 68y4cf58bv) (pyridoxine - unii:kv2jz1bi6z), folic acid (unii: 935e97boy8) (folic acid - unii:935e97boy8), zinc oxide (unii: soi2loh54z) (zinc oxide - unii:soi2loh54z), cupric oxide (unii: v1xjq704r4) (cupric cation - unii:8cbv67279l), docusate sodium (unii: f05q2t2ja0) (docusate - unii:m7p27195ag), calcium citrate (unii: mlm29u2x85) (calcium cation - unii:2m83c4r6zb), thiamine mononitrate (unii: 8k0i04919x) (thiamine ion - unii:4abt0j945j), potassium iodide (unii: 1c4qk22f9j) (iodide ion - unii:09g4i6v86q), ferrous gluconate (unii: u1b11i423z) (ferrous cation - unii:gw89581owr), vitamin d (unii: 9vu1ki44gp) (vitamin d - unii:9vu1ki44gp), riboflavin (unii: tlm2976ofr) (riboflavin - unii:tlm2976ofr) - ascorbic acid 120 mg - citranatal ® 90 dha is a multivitamin/mineral prescription drug indicated for use in improving the nutritional status of women prior to conception, throughout pregnancy, and in the postnatal period for both lactating and nonlactating mothers. this product is contraindicated in patients with a known hypersensitivity to any of the ingredients.

بلجيكا - الإنجليزية - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

basf a.s. - omega-3-acid ethyl esters 1000 mg - capsule, soft - 1000 mg - eicosapentaenoic acid; docosahexaenoic acid; omega-3 fatty acids ethyl esters 1000 mg - omega-3-triglycerides incl. other esters and acids

سنغافورة - الإنجليزية - HSA (Health Sciences Authority)

dch auriga singapore - omega-3-acid ethyl esters 90 (containing: eicosapent (epa) 460mg and doconexent (dha) 380mg ethyl esters and α-tocopherol 4 mg) - capsule - 1000mg - omega-3-acid ethyl esters 90 (containing: eicosapent (epa) 460mg and doconexent (dha) 380mg ethyl esters and α-tocopherol 4 mg) 1000mg

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

bryant ranch prepack - omega-3-acid ethyl esters (unii: d87ygh4z0q) (omega-3 fatty acids - unii:71m78end5s) - omega-3-acid ethyl esters capsules are indicated as an adjunct to diet to reduce triglyceride (tg) levels in adult patients with severe (greater than or equal to 500 mg/dl) hypertriglyceridemia. usage considerations: patients should be placed on an appropriate lipid-lowering diet before receiving omega-3-acid ethyl esters capsules and should continue this diet during treatment with omega-3-acid ethyl esters capsules. laboratory studies should be done to ascertain that the lipid levels are consistently abnormal before instituting therapy with omega-3-acid ethyl esters capsules. every attempt should be made to control serum lipids with appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that are contributing to the lipid abnormalities. medications known to exacerbate hypertriglyceridemia (such as beta blockers, thiazides, estrogens) should be discontinued or changed, if possible, prior to consideration of tg-lowering drug therapy. limitations of use: the effect of omega-3-acid ethyl esters capsules on the risk for pancreatitis has not been determined. the effect of omega-3-acid ethyl esters capsules on cardiovascular mortality and morbidity has not been determined. omega-3-acid ethyl esters are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters or any of its components. risk summary the available data from published case reports and the pharmacovigilance database on the use of omega-3-acid ethyl esters in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, omega-3-acid ethyl esters given orally to female rats prior to mating through lactation did not have adverse effects on reproduction or development when given at doses 5 times the maximum recommended human dose (mrhd) of 4 grams/day, based on a body surface area comparison. omega-3-acid ethyl esters given orally to rats and rabbits during organogenesis was not teratogenic at clinically relevant exposures, based on body surface area comparison (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 animal data : in female rats given oral doses of omega-3-acid ethyl esters (100 mg/kg/day, 600 mg/kg/day, or 2,000 mg/kg/day) beginning 2 weeks prior to mating through lactation, no adverse effects were observed at 2,000 mg/kg/day (5 times the mrhd based on body surface area [mg/m 2 ]). in a dose-ranging study, female rats given oral doses of omega-3-acid ethyl esters (1,000 mg/kg/day, 3,000 mg/kg/day, or 6,000 mg/kg/day) beginning 2 weeks prior to mating through postpartum day 7 had decreased live births (20% reduction) and pup survival to postnatal day 4 (40% reduction) at or greater than 3,000 mg/kg/day in the absence of maternal toxicity at 3,000 mg/kg/day (7 times the mrhd based on body surface area [mg/m 2 ]). in pregnant rats given oral doses of omega-3-acid ethyl esters (1,000 mg/kg/day, 3,000 mg/kg/day, or 6,000 mg/kg/day) during organogenesis, no adverse effects were observed in fetuses at a maternally toxic dose (increased food consumption) of 6,000 mg/kg/day (14 times the mrhd based on body surface area [mg/m 2 ]). in pregnant rats given oral doses of omega-3-acid ethyl esters (100 mg/kg/day, 600 mg/kg/day, or 2,000 mg/kg/day) from gestation day 14 through lactation day 21, no adverse effects were observed at 2,000 mg/kg/day (5 times the mrhd based on body surface area [mg/m 2 ]). in pregnant rabbits given oral doses of omega-3-acid ethyl esters (375 mg/kg/day, 750 mg/kg/day, or 1,500 mg/kg/day) during organogenesis, no adverse effects were observed in fetuses given 375 mg/kg/day (2 times the mrhd based on body surface area [mg/m 2 ]). however, at higher doses, increases in fetal skeletal variations and reduced fetal growth were evident at maternally toxic doses (reduced food consumption and body weight gain) greater than or equal to 750 mg/kg/day (4 times the mrhd), and embryolethality was evident at 1,500 mg/kg/day (7 times the mrhd). risk summary published studies have detected omega-3 fatty acids, including epa and dha, in human milk. lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. there are no data available on the effects of omega3 fatty acid ethyl esters on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for omega-3-acid ethyl esters and any potential adverse effects on the breastfed child from omega-3-acid ethyl esters or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. a limited number of subjects older than 65 years were enrolled in the clinical trials of omega‑3‑acid ethyl esters. safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

international brand management, llc - omega-3-acid ethyl esters (unii: d87ygh4z0q) (omega-3 fatty acids - unii:71m78end5s) - omega-3-acid ethyl esters 1 g in 1 g - each capsule contains 1 gram of omega-3-acid ethyl esters liquid concentrate consisting of at least 900 mg of omega-3-acid ethyl esters.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

chartwell rx, llc - omega-3-acid ethyl esters (unii: d87ygh4z0q) (omega-3 fatty acids - unii:71m78end5s) - omega-3-acid ethyl esters capsules are indicated as an adjunct to diet to reduce triglyceride (tg) levels in adult patients with severe (greater than or equal to 500 mg/dl) hypertriglyceridemia. usage considerations: patients should be placed on an appropriate lipid-lowering diet before receiving omega-3-acid ethyl esters capsules and should continue this diet during treatment with omega-3-acid ethyl esters capsules. laboratory studies should be done to ascertain that the lipid levels are consistently abnormal before instituting therapy with omega-3-acid ethyl esters capsules. every attempt should be made to control serum lipids with appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that are contributing to the lipid abnormalities. medications known to exacerbate hypertriglyceridemia (such as beta blockers, thiazides, estrogens) should be discontinued or changed, if possible, prior to consideration of tg-lowering drug therapy. limitations of use: the effect of omega-3-acid ethyl esters capsules on the risk for pancreatitis has not been determined. the effect of omega-3-acid ethyl esters capsules on cardiovascular mortality and morbidity has not been determined. omega-3-acid ethyl esters capsules are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters capsules or any of its components. risk summary the available data from published case reports and the pharmacovigilance database on the use of omega-3-acid ethyl esters in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, omega-3-acid ethyl esters given orally to female rats prior to mating through lactation did not have adverse effects on reproduction or development when given at doses 5 times the maximum recommended human dose (mrhd) of 4 grams/day, based on a body surface area comparison. omega-3-acid ethyl esters given orally to rats and rabbits during organogenesis was not teratogenic at clinically relevant exposures, based on body surface area comparison (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 animal data: in female rats given oral doses of omega-3-acid ethyl esters (100, 600, or 2,000 mg/kg/day) beginning 2 weeks prior to mating through lactation, no adverse effects were observed at 2,000 mg/kg/day (5 times the mrhd based on body surface area [mg/m 2 ]). in a dose-ranging study, female rats given oral doses of omega-3-acid ethyl esters (1,000, 3,000, or 6,000 mg/kg/day) beginning 2 weeks prior to mating through postpartum day 7 had decreased live births (20% reduction) and pup survival to postnatal day 4 (40% reduction) at or greater than 3,000 mg/kg/day in the absence of maternal toxicity at 3,000 mg/kg/day (7 times the mrhd based on body surface area [mg/m 2 ]). in pregnant rats given oral doses of omega-3-acid ethyl esters (1,000, 3,000, or 6,000 mg/kg/day) during organogenesis, no adverse effects were observed in fetuses at a maternally toxic dose (increased food consumption) of 6,000 mg/kg/day (14 times the mrhd based on body surface area [mg/m 2 ]). in pregnant rats given oral doses of omega-3-acid ethyl esters (100, 600, or 2,000 mg/kg/day) from gestation day 14 through lactation day 21, no adverse effects were observed at 2,000 mg/kg/day (5 times the mrhd based on body surface area [mg/m 2 ]). in pregnant rabbits given oral doses of omega-3-acid ethyl esters (375, 750, or 1,500 mg/kg/day) during organogenesis, no adverse effects were observed in fetuses given 375 mg/kg/day (2 times the mrhd based on body surface area [mg/m 2 ]). however, at higher doses, increases in fetal skeletal variations and reduced fetal growth were evident at maternally toxic doses (reduced food consumption and body weight gain) greater than or equal to 750 mg/kg/day (4 times the mrhd), and embryolethality was evident at 1,500 mg/kg/day (7 times the mrhd). risk summary published studies have detected omega-3 fatty acids, including epa and dha, in human milk. lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. there are no data available on the effects of omega­3 fatty acid ethyl esters on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for omega-3-acid ethyl esters and any potential adverse effects on the breastfed child from omega-3-acid ethyl esters or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. a limited number of subjects older than 65 years were enrolled in the clinical trials of omega-3-acid ethyl esters. safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.