Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

contract pharmacy services-pa - clopidogrel bisulfate (unii: 08i79htp27) (clopidogrel - unii:a74586sno7) - clopidogrel 75 mg - - clopidogrel tablets are indicated to reduce the rate of myocardial infarction and stroke (mi) in patients with non-st-segment elevation acs [unstable angina (ua)/non-st-elevation myocardial infarction (nstemi)], including patients who are to be managed medically and those who are to be managed with coronary revascularization. clopidogrel tablets should be administered in conjunction with aspirin. - clopidogrel tablets are indicated to reduce the rate of myocardial infarction and stroke in patients with acute st-elevation myocardial infarction (stemi) who are to be managed medically. clopidogrel tablets should be administered in conjunction with aspirin. in patients with established peripheral arterial disease or with a history of recent myocardial infarction (mi) or recent stroke clopidogrel tablets are indicated to reduce the rate of mi and stroke. clopidogrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. clopidogrel tablets are c

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

pd-rx pharmaceuticals, inc. - clopidogrel bisulfate (unii: 08i79htp27) (clopidogrel - unii:a74586sno7) - clopidogrel 75 mg - - plavix is indicated to reduce the rate of myocardial infarction (mi) and stroke in patients with non–st-segment elevation acs (unstable angina [ua]/non–st-elevation myocardial infarction [nstemi]), including patients who are to be managed medically and those who are to be managed with coronary revascularization. plavix should be administered in conjunction with aspirin. - plavix is indicated to reduce the rate of myocardial infarction and stroke in patients with acute st-elevation myocardial infarction (stemi) who are to be managed medically. plavix should be administered in conjunction with aspirin. in patients with established peripheral arterial disease or with a history of recent myocardial infarction (mi) or recent stroke plavix is indicated to reduce the rate of mi and stroke. plavix is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. plavix is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any comp

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride 50 mg - trazodone hydrochloride tablets usp are indicated for the treatment of major depressive disorder (mdd) in adults. the efficacy of trazodone hydrochloride tablets usp has been established in trials with the immediate release formulation of trazodone [see clinical studies (14)]. none. teratogenic effects pregnancy category c trazodone hydrochloride has been shown to cause increased fetal resorption and other adverse effects on the fetus in two studies using the rat when given at dose levels approximately 30 to 50 times the proposed maximum human dose. there was also an increase in congenital anomalies in one of three rabbit studies at approximately 15 to 50 times the maximum human dose. there are no adequate and well-controlled studies in pregnant women. trazodone hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. trazodone and/or its metabolites have been found in the milk of lactating rats, suggesting that the drug may be secreted in human mi

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride 50 mg - trazodone hydrochloride tablets usp are indicated for the treatment of major depressive disorder (mdd) in adults. the efficacy of trazodone hydrochloride tablets has been established in trials with the immediate release formulation of trazodone [see clinical studies (14) ]. none. pregnancy category c trazodone hydrochloride has been shown to cause increased fetal resorption and other adverse effects on the fetus in two studies using the rat when given at dose levels approximately 30 to 50 times the proposed maximum human dose. there was also an increase in congenital anomalies in one of three rabbit studies at approximately 15 to 50 times the maximum human dose. there are no adequate and well-controlled studies in pregnant women. trazodone hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. trazodone and/or its metabolites have been found in the milk of lactating rats, suggesting that the drug may be secreted in human milk. caution should b

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

proficient rx lp - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride 50 mg - trazodone hydrochloride tablets usp are indicated for the treatment of major depressive disorder (mdd) in adults. the efficacy of trazodone hydrochloride tablets has been established in trials with the immediate release formulation of trazodone [see clinical studies (14) ]. none. pregnancy category c trazodone hydrochloride has been shown to cause increased fetal resorption and other adverse effects on the fetus in two studies using the rat when given at dose levels approximately 30 to 50 times the proposed maximum human dose. there was also an increase in congenital anomalies in one of three rabbit studies at approximately 15 to 50 times the maximum human dose. there are no adequate and well-controlled studies in pregnant women. trazodone hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. trazodone and/or its metabolites have been found in the milk of lactating rats, suggesting that the drug may be secreted in human milk. caution should b

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

accord healthcare, inc. - letrozole (unii: 7lkk855w8i) (letrozole - unii:7lkk855w8i) - letrozole 2.5 mg - letrozole tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.  letrozole tablets are indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy. the effectiveness of letrozole tablets in extended adjuvant treatment of early breast cancer is based on an analysis of disease-free survival in patients treated with letrozole tablets for a median of 60 months [see clinical studies ( 14.2, 14.3)] . letrozole tablets are indicated for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer. letrozole tablets are also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy  [see clinical studies ( 14.4, 14.5)]. - pregnancy: letrozole can cause fetal harm [see use in specific populations ( 8.1)] . pregnancy: letrozole can cause fetal harm [see use in specific populations ( 8.1)] . - known hypersensitivity to the active substance, or to any of the excipients [see adverse reactions ( 6)] . known hypersensitivity to the active substance, or to any of the excipients [see adverse reactions ( 6)] . risk summary  based on postmarketing reports, findings from animal studies and the mechanism of action, letrozole can cause fetal harm and is contraindicated for use in pregnant women. in post-marketing reports, use of letrozole during pregnancy resulted in cases of spontaneous abortions and congenital birth defects; however, the data are insufficient to inform a drug-associated risk [see contraindications ( 4), warnings and precautions ( 5.6), adverse reactions ( 6.2) and clinical pharmacology ( 12.1)]. in animal reproduction studies, administration of letrozole to pregnant animals during organogenesis resulted in increased post-implantation pregnancy loss and resorption, fewer live fetuses, and fetal malformation affecting the renal and skeletal systems in rats and rabbits at doses approximately 0.1 times the daily maximum recommended human dose (mrhd) on a mg/m 2 basis (see data). the background risk of major birth defects and miscarriage for the indicated population is unknown. however, the background risk in the u.s. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. data animal data in a fertility and early embryonic development toxicity study in female rats, oral administration of letrozole starting 2 weeks before mating until pregnancy day 6 resulted in an increase in pre-implantation loss at doses ≥ 0.003 mg/kg/day (approximately 0.01 times the maximum recommended human dose on a mg/m 2 basis). in an embryo-fetal developmental toxicity study in rats, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.003 mg/kg (approximately 0.01 time the maximum recommended human dose on a mg/m 2 basis) resulted in embryo-fetal toxicity including intrauterine mortality, increased resorptions and postimplantation loss, decreased numbers of live fetuses and fetal anomalies including absence and shortening of renal papilla, dilation of ureter, edema and incomplete ossification of frontal skull and metatarsals. letrozole was teratogenic to rats at a dose of 0.03 mg/kg (approximately 0.01 times the maximum recommended human dose on a mg/m 2 basis) and caused fetal domed head and cervical/centrum vertebral fusion. in the embryo-fetal development toxicity study in rabbits, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.002 mg/kg (approximately 0.01 times the maximum recommended human dose on a mg/m 2 basis) resulted in embryo-fetal toxicity including intrauterine mortality, increased resorption, increased postimplantation loss and decreased numbers of live fetuses. fetal anomalies included incomplete ossification of the skull, sternebrae, and fore- and hind legs. risk summary it is not known if letrozole is present in human milk. there are no data on the effects of letrozole on the breastfed infant or milk production. exposure of lactating rats to letrozole was associated with impaired reproductive performance of the male offspring (see data). because of the potential for serious adverse reactions in breastfed infants from letrozole tablets, advise lactating women not to breastfeed while taking letrozole tablets and for at least 3 weeks after the last dose. data animal data in a postnatal developmental toxicity study in lactating rats, letrozole was administered orally at doses of 1, 0.003, 0.03 or 0.3 mg/kg/day on day 0 through day 20 of lactation. the reproductive performance of the male offspring was impaired at letrozole dose as low as 0.003 mg/kg/day (approximately 0.01 times the maximum recommended human dose on a mg/m 2 basis), as reflected by decreased mating and pregnancy ratios. there were no effects on the reproductive performance of female offspring. pregnancy testing based on animal studies, letrozole can cause fetal harm when administered to a pregnant woman [see use in specific populations ( 8.1)]. females of reproductive potential should have a pregnancy test prior to starting treatment with letrozole. contraception females based on animal studies, letrozole tablets can cause fetal harm when administered to a pregnant woman [see use in specific populations ( 8.1)]. . advise females of reproductive potential to use effective contraception during treatment with letrozole tablets and for at least 3 weeks after the last dose. infertility females based on studies in female animals, letrozole tablets may impair fertility in females of reproductive potential [see nonclinical toxicology ( 13.1)]. males based on studies in male animals, letrozole tablets may impair fertility in males of reproductive potential [see nonclinical toxicology ( 13.1)]. the safety and effectiveness in pediatric patients have not been established. letrozole administration to young (postnatal day 7) rats for 12 weeks duration at 0.003, 0.03, 0.3 mg/kg/day by oral gavage resulted in adverse skeletal/growth effects (bone maturation, bone mineral density) and neuroendocrine and reproductive developmental perturbations of the hypothalamic-pituitary axis. administration of 0.3 mg/kg/day resulted in auc values that were similar to the auc in adult patients receiving the recommended dose of 2.5 mg/day. decreased fertility was accompanied by hypertrophy of the hypophysis and testicular changes that included degeneration of the seminiferous tubular epithelium and atrophy of the female reproductive tract. young rats in this study were allowed to recover following discontinuation of letrozole treatment for 42 days. histopathological changes were not reversible at clinically relevant exposures. the median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64 to 65 years. about 1/3 of the patients were greater than or equal to 70 years old. in the first-line study, patients greater than or equal to 70 years of age experienced longer time to tumor progression and higher response rates than patients less than 70. for the extended adjuvant setting (ma-17), more than 5,100 postmenopausal women were enrolled in the clinical study. in total, 41% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. in the extended adjuvant setting, no overall differences in safety or efficacy were observed between these older patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. in the adjuvant setting (big 1-98), more than 8,000 postmenopausal women were enrolled in the clinical study. in total, 36 % of patients were aged 65 years or older at enrollment, while 12% were 75 or older. more adverse reactions were generally reported in elderly patients irrespective of study treatment allocation. however, in comparison to tamoxifen, no overall differences with regards to the safety and efficacy profiles were observed between elderly patients and younger patients.

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

novartis pharmaceuticals corporation - letrozole (unii: 7lkk855w8i) (letrozole - unii:7lkk855w8i) - letrozole 2.5 mg - femara (letrozole) is indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.  femara is indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy. the effectiveness of femara in extended adjuvant treatment of early breast cancer is based on an analysis of disease-free survival (dfs) in patients treated with femara for a median of 60 months [see clinical studies (14.2, 14.3)] .  femara is indicated for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer. femara is also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy [see clinical studies (14.4, 14.5)].   - pregnancy: letrozole can cause fetal harm [see use in specific populations (8.1)] . - known hypersensitivity to the active substance, or to any of the excipients [see adverse reactions (6)] . risk summary based on postmarketing reports, findings from animal studies and the mechanism of action, femara can cause fetal harm and is contraindicated for use in pregnant women. in post-marketing reports, use of letrozole during pregnancy resulted in cases of spontaneous abortions and congenital birth defects; however, the data are insufficient to inform a drug-associated risk [see contraindications (4), warnings and precautions (5.6), adverse reactions (6.2), and clinical pharmacology (12.1)] . in animal reproduction studies, administration of letrozole to pregnant animals during organogenesis resulted in increased post-implantation pregnancy loss and resorption, fewer live fetuses, and fetal malformation affecting the renal and skeletal systems in rats and rabbits at doses approximately 0.1 times the daily maximum recommended human dose (mrhd) on a mg/m2 basis (see data) . the background risk of major birth defects and miscarriage for the indicated population is unknown. however, the background risk in the u.s. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies. data animal data in a fertility and early embryonic development toxicity study in female rats, oral administration of letrozole starting 2 weeks before mating until pregnancy day 6 resulted in an increase in pre-implantation loss at doses ≥ 0.003 mg/kg/day (approximately 0.01 times the maximum recommended human dose on a mg/m2 basis). in an embryo-fetal developmental toxicity study in rats, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.003 mg/kg (approximately 0.01 time the maximum recommended human dose on a mg/m2 basis) resulted in embryo-fetal toxicity including intrauterine mortality, increased resorptions and postimplantation loss, decreased numbers of live fetuses and fetal anomalies, including absence and shortening of renal papilla, dilation of ureter, edema, and incomplete ossification of frontal skull and metatarsals. letrozole was teratogenic to rats at a dose of 0.03 mg/kg (approximately 0.01 times the maximum recommended human dose on a mg/m2 basis) and caused fetal domed head and cervical/centrum vertebral fusion. in the embryo-fetal development toxicity study in rabbits, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.002 mg/kg (approximately 0.01 times the maximum recommended human dose on a mg/m2 basis) resulted in embryo-fetal toxicity, including intrauterine mortality, increased resorption, increased postimplantation loss and decreased numbers of live fetuses. fetal anomalies included incomplete ossification of the skull, sternebrae, and fore- and hind legs. risk summary it is not known if letrozole is present in human milk. there are no data on the effects of letrozole on the breastfed infant or milk production. exposure of lactating rats to letrozole was associated with impaired reproductive performance of the male offspring (see data) . because of the potential for serious adverse reactions in breastfed infants from femara, advise lactating women not to breastfeed while taking femara and for at least 3 weeks after the last dose. data animal data in a postnatal developmental toxicity study in lactating rats, letrozole was administered orally at doses of 1, 0.003, 0.03, or 0.3 mg/kg/day on day 0 through day 20 of lactation. the reproductive performance of the male offspring was impaired at letrozole dose as low as 0.003 mg/kg/day (approximately 0.01 times the maximum recommended human dose on a mg/m2 basis), as reflected by decreased mating and pregnancy ratios. there were no effects on the reproductive performance of female offspring. pregnancy testing based on animal studies, femara can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . females of reproductive potential should have a pregnancy test prior to starting treatment with femara. contraception females based on animal studies, femara can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment with femara and for at least 3 weeks after the last dose. infertility females based on studies in female animals, femara may impair fertility in females of reproductive potential [see nonclinical toxicology (13.1)] . males based on studies in male animals, femara may impair fertility in males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and effectiveness in pediatric patients have not been established. letrozole administration to young (postnatal day 7) rats for 12 weeks duration at 0.003, 0.03, 0.3 mg/kg/day by oral gavage resulted in adverse skeletal/growth effects (bone maturation, bone mineral density) and neuroendocrine and reproductive developmental perturbations of the hypothalamic-pituitary axis. administration of 0.3 mg/kg/day resulted in auc values that were similar to the auc in adult patients receiving the recommended dose of 2.5 mg/day. decreased fertility was accompanied by hypertrophy of the hypophysis and testicular changes that included degeneration of the seminiferous tubular epithelium and atrophy of the female reproductive tract. young rats in this study were allowed to recover following discontinuation of letrozole treatment for 42 days. histopathological changes were not reversible at clinically relevant exposures. the median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64-65 years. about 1/3 of the patients were greater than or equal to 70 years old. in the first-line study, patients greater than or equal to 70 years of age experienced longer time to tumor progression and higher response rates than patients less than 70. for the extended adjuvant setting (ma-17), more than 5,100 postmenopausal women were enrolled in the clinical study. in total, 41% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. in the extended adjuvant setting, no overall differences in safety or efficacy were observed between these older patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. in the adjuvant setting (big 1-98), more than 8,000 postmenopausal women were enrolled in the clinical study. in total, 36% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. more adverse reactions were generally reported in elderly patients irrespective of study treatment allocation. however, in comparison to tamoxifen, no overall differences with regards to the safety and efficacy profiles were observed between elderly patients and younger patients.

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

avpak - fluoxetine hydrochloride (unii: i9w7n6b1kj) (fluoxetine - unii:01k63sup8d) - fluoxetine 10 mg - fluoxetine capsules are indicated for the treatment of: - acute and maintenance treatment of major depressive disorder [see clinical studies (14.1)] . -  acute and maintenance treatment of obsessions and compulsions in patients with obsessive compulsive disorder (ocd) [see clinical studies (14.2)] . -  acute and maintenance treatment of binge-eating and vomiting behaviors in patients with moderate to severe bulimia nervosa [see clinical studies (14.3)] . - acute treatment of panic disorder, with or without agoraphobia [see clinical studies (14.4)] . fluoxetine capsules and olanzapine in combination are indicated for the treatment of: - acute treatment of depressive episodes associated with bipolar i disorder. - treatment resistant depression (major depressive disorder in patients, who do not respond to 2 sep

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

contract pharmacy services-pa - fluoxetine hydrochloride (unii: i9w7n6b1kj) (fluoxetine - unii:01k63sup8d) - fluoxetine 20 mg - fluoxetine capsules are indicated for the treatment of: - acute and maintenance treatment of major depressive disorder [see clinical studies (14.1)] . -  acute and maintenance treatment of obsessions and compulsions in patients with obsessive compulsive disorder (ocd) [see clinical studies (14.2)] . -  acute and maintenance treatment of binge-eating and vomiting behaviors in patients with moderate to severe bulimia nervosa [see clinical studies (14.3)] . - acute treatment of panic disorder, with or without agoraphobia [see clinical studies (14.4)] . fluoxetine capsules and olanzapine in combination are indicated for the treatment of: - acute treatment of depressive episodes associated with bipolar i disorder. fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associate

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

bayer healthcare pharmaceuticals inc. - gadoxetate disodium (unii: hoy74vze0m) (gadolinium cation (3+) - unii:azv954tz9n) - gadoxetate disodium 181.43 mg in 1 ml - eovist is indicated for intravenous use in magnetic resonance imaging (mri) of the liver to detect and characterize lesions in patients with known or suspected focal liver disease. eovist is contraindicated in patients with history of severe hypersensitivity reactions to eovist [see warnings and precautions ( 5.3 )] . gbcas have been shown to cross the human placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data). in animal reproduction studies, no teratogenicity was observed with repeated daily intravenous administration of gadoxetate disodium to rats during organogenesis at doses up to 32 times the recommended single human dose; however, an increase in preimplantation loss was noted at doses 3.2 times the single human dose. post implantation loss was observed with repeated daily intravenous administration of gadoxetate disodium to rabbits on gestation days 6 through 18 at doses 26 times the recommended single human dose (see data) . because of the potential risks of gadolinium to the fetus, use eovist only if imaging is essential during pregnancy and cannot be delayed. the background risk in the u.s. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. contrast enhancement is visualized in the placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the maternal indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. animal data gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. animal reproductive and developmental toxicity studies were done in rats and rabbits. gadoxetate disodium was not teratogenic when given intravenously during organogenesis to pregnant rats at doses up to 32 times the recommended single human dose (mmol/m2 basis). however, an increase in preimplantation loss was noted at 3.2 times the human dose (mmol/m2 basis). compared to untreated controls, rates of postimplantation loss and absorption increased and litter size decreased when pregnant rabbits received gadoxetate disodium at doses 26 times the recommended human single dose (mmol/m2 basis). this occurred without evidence of maternal toxicity. because pregnant animals received repeated daily doses of gadoxetate disodium, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans. risk summary there is no information regarding the presence of gadoxetate disodium in human milk, the effects of the drug in a breastfed infant, or the effects of the drug on milk production. however, published lactation data on other gbcas report that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited gbca gastrointestinal absorption in the breastfed infant. in rat lactation studies with [153 gd] gadoxetate disodium, less than 0.5% of the total administered radioactivity was transferred to the nursing pup. clinical considerations a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for up to 10 hours after eovist administration in order to minimize exposure to a breastfed infant. data animal data in lactating rats given 0.1 mmol/kg [153 gd] gadoxetate disodium, less than 0.5% of the total administered radioactivity was transferred to the neonates via maternal milk, mostly within 2 hours. adequate and well-controlled studies of eovist in pediatric patients have not been conducted. an observational study with eovist was performed in 52 patients (aged > 2 months and < 18 years) referred for evaluation of suspected or known focal liver lesions. eovist improved border delineation and increased contrast of the primary lesion in the majority of patients when compared to non-contrast images. no safety issues were identified. no dose adjustment according to age is necessary in pediatric patients. the safety and effectiveness of eovist have not been established in premature infants. nsf risk no case of nsf associated with eovist or any other gbca has been identified in pediatric patients ages 6 years and younger. juvenile animal data single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants. in clinical studies of eovist, 674 (34%) patients were 65 years of age and over, while 20 (1%) were 80 years of age and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, use of eovist in an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. in a clinical pharmacology study, slight to moderate differences in pharmacokinetic parameters of gadoxetate disodium (increased auc and terminal half-life, decreased total clearance) were found in a group of geriatric volunteers in comparison to non-geriatric volunteers. no clinically relevant differences in liver contrast enhancement were found. in a clinical pharmacology study in a group of patients with moderate renal impairment, a moderate increase in auc and terminal half-life was observed in comparison to healthy volunteers with normal renal function. hepatic contrast did not differ among the groups. end-stage renal failure may impair eovist imaging performance [see warnings and precautions (5.6)]. in a study of patients with end-stage renal failure, the terminal half-life was prolonged about 12-fold and the auc was increased about 6-fold. hepatic contrast was markedly reduced in these patients, which was attributed to significantly elevated serum ferritin levels [see warnings and precautions ( 5.2 )] . approximately 30% of the injected dose was removed by dialysis in a single 3-hour dialysis session, which started one hour after an eovist dose. eovist was almost completely eliminated via dialysis and biliary excretion within the observation period of 6 days, predominantly within the first 3 days. in a clinical pharmacology study in groups of patients with mild or moderate hepatic impairment, a slight to moderate increase in plasma auc, half-life and urinary excretion, as well as decrease in hepatobiliary excretion was observed in comparison to healthy subjects with normal liver function. hepatic contrast signal did not differ among the groups. severe hepatic impairment may impair eovist imaging performance [see warnings and precautions (5.6)] . in patients with severe hepatic impairment, especially in patients with abnormally high (> 3 mg/dl) serum bilirubin levels, the auc was increased up to 60% and the elimination half-life was increased up to 49%. the hepatobiliary excretion substantially decreased to about 5% of the administered dose and reduced hepatic contrast signal was observed. a dose adjustment is not necessary for patients with hepatic impairment. in clinical studies, 489 patients had a diagnosis of liver cirrhosis (child-pugh category a, n = 270; category b, n = 98; category c, n = 24; unknown category, n = 97). no difference in diagnostic performance and safety was observed among these patients.