Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - triazolam (unii: 1hm943223r) (triazolam - unii:1hm943223r) - triazolam is indicated for the short-term treatment of insomnia (generally 7 to 10 days) in adults. triazolam is contraindicated in: pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to triazolam during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for other psychiatric medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/. risk summary infants born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and neonatal withdrawal (see clinical considerations) [see warnings and precautions ( 5.10 )]. at this time, there is no clear evidence that triazolam exposure in early pregnancy can cause major birth defects (see data). the estimated background risk of major birth defects and miscarriage for the indicated population

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - finasteride tablets are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to:      -     improve symptoms      -    reduce the risk of acute urinary retention      -    reduce the risk of the need for surgery including transurethral resection of the prostate (turp) and prostatectomy. finasteride tablets administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of bph (a confirmed ≥ 4 point increase in american urological association (aua) symptom score). finasteride tablets are not approved for the prevention of prostate cancer.   finasteride tablets are contraindicated in the following: - hypersensitivity to any component of this medication. - pregnancy. finasteride use is contraindicated in females when they are or may potentially be pregnant. because of the ability of type ii 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (dht), finasteride

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - chantix is indicated for use as an aid to smoking cessation treatment. chantix is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to chantix. risk summary available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke [see data]. smoking during pregnancy is associated with maternal, fetal, and neonatal risks (see clinical considerations) . in animal studies, varenicline did not result in major malformations but caused decreased fetal weights in rabbits when dosed during organogenesis at exposures equivalent to 50 times the exposure at the maximum recommended human dose (mrhd). additionally, administration of varenicline to pregnant rats during organogenesis through lactation produced developmental toxicity in offspring at maternal exposures equivalent to 36 times human exposure at the mrhd [see data] . the estimated background risk of oral clefts is increased by

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - desvenlafaxine succinate (unii: zb22enf0xr) (desvenlafaxine - unii:ng99554anw) - desvenlafaxine is indicated for the treatment of adults with major depressive disorder (mdd) [see clinical studies (14)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185. risk summary based on data from published observational studies, exposure to snris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.4) and clinical considerations]. there are no published studies on desvenlafaxine in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes (see data ). there are risks associated with untreated depression in pregnancy and with exposure to snris and ssris, including desvenlafaxine, during pregnancy (see clinical considerations ). in reproductive developmental studies in rats and rabbits treated with desvenlafaxine succinate, there was no evidence of teratogenicity at a plasma exposure (auc) that is up to 19-times (rats) and 0.5-times (rabbits) the exposure at an adult human dose of 100 mg per day. however, fetotoxicity and pup deaths were observed in rats at 4.5-times the auc exposure observed with an adult human dose of 100 mg per day. 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. clinical considerations disease-associated maternal and/or embryo/fetal risk a prospective longitudinal study of 201 women with history of major depression who were euthymic at the beginning of pregnancy, showed that women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication. maternal adverse reactions exposure to desvenlafaxine in mid to late pregnancy may increase the risk for preeclampsia, and exposure to desvenlafaxine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.4)]. fetal/neonatal adverse reactions exposure to snris or ssris in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. monitor neonates who were exposed to desvenlafaxine in the third trimester of pregnancy for drug discontinuation syndrome (see data). data human data published epidemiological studies of pregnant women exposed to the parent compound venlafaxine have not reported a clear association with major birth defects or miscarriage. methodological limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders, and confirmatory studies; therefore, these studies cannot establish or exclude any drug-associated risk during pregnancy. retrospective cohort studies based on claims data have shown an association between venlafaxine use and preeclampsia, compared to depressed women who did not take an antidepressant during pregnancy. one study that assessed venlafaxine exposure in the second trimester or first half of the third trimester and preeclampsia showed an increased risk compared to unexposed depressed women [adjusted (adj) rr 1.57, 95% ci 1.29-1.91]. preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg/day and a duration of treatment >30 days. another study that assessed venlafaxine exposure in gestational weeks 10-20 and preeclampsia showed an increased risk at doses equal to or greater than 150 mg/day. available data are limited by possible outcome misclassification and possible confounding due to depression severity and other confounders. retrospective cohort studies based on claims data have suggested an association between venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. one study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred through delivery, compared to unexposed depressed women [adj rr 2.24 (95% ci 1.69-2.97)]. there was no increased risk in women who were exposed to venlafaxine earlier in pregnancy. limitations of this study include possible confounding due to depression severity and other confounders. another study showed an increased risk for postpartum hemorrhage when snri exposure occurred for at least 15 days in in the last month of pregnancy or through delivery, compared to unexposed women (adj rr 1.64-1.76). the results of this study may be confounded by the effects of depression. neonates exposed to snris or ssris, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.2)]. animal data when desvenlafaxine succinate was administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 300 mg/kg/day and 75 mg/kg/day, respectively, no teratogenic effects were observed. these doses were associated with a plasma exposure (auc) 19 times (rats) and 0.5 times (rabbits) the auc exposure at an adult human dose of 100 mg per day. however, fetal weights were decreased and skeletal ossification was delayed in rats in association with maternal toxicity at the highest dose, with an auc exposure at the no-effect dose that is 4.5-times the auc exposure at an adult human dose of 100 mg per day. when desvenlafaxine succinate was administered orally to pregnant rats throughout gestation and lactation, there was a decrease in pup weights and an increase in pup deaths during the first four days of lactation at the highest dose of 300 mg/kg/day. the cause of these deaths is not known. the auc exposure at the no-effect dose for rat pup mortality was 4.5-times the auc exposure at an adult human dose of 100 mg per day. post-weaning growth and reproductive performance of the progeny were not affected by maternal treatment with desvenlafaxine succinate at exposures 19 times the auc exposure at an adult human dose of 100 mg per day. risk summary available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants (see data). there are no data on the effects of desvenlafaxine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for desvenlafaxine and any potential adverse effects on the breastfed child from desvenlafaxine or from the underlying maternal condition. data a lactation study was conducted in 10 breastfeeding women (at a mean of 4.3 months post‑partum) who were being treated with a 50-150 mg daily dose of desvenlafaxine for postpartum depression. sampling was performed at steady state (up to 8 samples) over a 24 hour dosing period, and included foremilk and hindmilk. the mean relative infant dose was calculated to be 6.8% (range of 5.5-8.1%). no adverse reactions were seen in the infants. the safety and effectiveness of desvenlafaxine have not been established in pediatric patients for the treatment of mdd. efficacy was not demonstrated in two adequate and well controlled, 8-week, randomized, double-blind, placebo-controlled, parallel group studies conducted in 587 patients (7 to 17 years of age) for the treatment of mdd. antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patients [see the boxed warning and warnings and precautions (5.1)]. desvenlafaxine was associated with a decrease in body weight in placebo-controlled trials in pediatric patients with mdd. the incidence of weight loss (≥3.5% of baseline weight) was 22%, 14%, and 7% for patients treated with low dose desvenlafaxine, high dose desvenlafaxine, and placebo, respectively. the risks associated with longer term desvenlafaxine use were assessed in 6-month, open-label extension studies in pediatric patients (7 to 17 years of age) with mdd. pediatric patients (7 to 17 years of age) had mean changes in weight that approximated expected changes, based on data from age- and sex-matched peers. in clinical trials, when compared to adult patients receiving the same dose of desvenlafaxine, exposure to desvenlafaxine was similar in adolescent patients 12 to 17 years of age, and was about 30% higher in pediatric patients 7 to 11 years of age. juvenile animal studies in a juvenile animal study, male and female rats were treated with desvenlafaxine (75, 225 and 675 mg/kg/day) starting on postnatal day (pnd) 22 through 112. behavioral deficits (longer time immobile in a motor activity test, longer time swimming in a straight channel test, and lack of habituation in an acoustic startle test) were observed in males and females but were reversed after a recovery period. a no adverse effect level (noael) was not identified for these deficits. the low adverse effect level (loael) was 75 mg/kg/day which was associated with plasma exposure (auc) twice the levels measured with a pediatric dose of 100 mg/day. in a second juvenile animal study, male and female rats were administered desvenlafaxine (75, 225 or 675 mg/kg/day) for 8-9 weeks starting on pnd 22 and were mated with naïve counterparts. delays in sexual maturation and decreased fertility, number of implantation sites and total live embryos were observed in treated females at all doses. the loael for these findings is 75 mg/kg/day which was associated with an auc twice the levels measured with a pediatric dose of 100 mg/day. these findings were reversed at the end of a 4-week recovery period. the relevance of these findings to humans is not known. of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older. no overall differences in safety or efficacy were observed between these patients and younger patients; however, in the short-term placebo-controlled studies, there was a higher incidence of systolic orthostatic hypotension in patients ≥ 65 years of age compared to patients < 65 years of age treated with desvenlafaxine [see adverse reactions ( 6.1 )] . for elderly patients, possible reduced renal clearance of desvenlafaxine should be considered when determining dose [see dosage and administration (2.2) and clinical pharmacology (12.3)] . ssris and snris, including desvenlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see warnings and precautions (5.9)] . adjust the maximum recommended dosage in patients with moderate or severe renal impairment (clcr 15 to 50 ml/min, c-g), or end-stage renal disease (clcr < 15 ml/min, c-g) [see dosage and administration (2.2) and clinical pharmacology (12.3)]. adjust the maximum recommended dosage in patients with moderate to severe hepatic impairment (child-pugh score 7 to 15) [see dosage and administration (2.3) and clinical pharmacology (12.3 )] . desvenlafaxine is not a controlled substance.

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - canagliflozin (unii: 0sac974z85) (canagliflozin anhydrous - unii:6s49dgr869) - invokana (canagliflozin) is indicated: - as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (cvd). - to reduce the risk of end-stage kidney disease (eskd), doubling of serum creatinine, cardiovascular (cv) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. limitations of use invokana is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see warnings and precautions (5.1)] . invokana is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m 2 . invokana is likely to be ineffective in this setting based upon its mechanism of action. invokana is contraindicated in patients with a serious hypersensitivity reaction to invokana, such as anaphylaxis or angioedema [see warnings and precautions (5.8)and adverse reactions (6.1, 6.2)] . risk summary based on animal data showing adverse renal effects, invokana is not recommended during the second and third trimesters of pregnancy. limited data with invokana in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations]. in animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on auc. the estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a hba 1c >7 and has been reported to be as high as 20–25% in women with a hba 1c >10. the estimated background risk of 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 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. animal data canagliflozin dosed directly to juvenile rats from postnatal day (pnd) 21 until pnd 90 at doses of 4, 20, 65, or 100 mg/kg increased kidney weights and dose dependently increased the incidence and severity of renal pelvic and tubular dilatation at all doses tested. exposure at the lowest dose was greater than or equal to 0.5-times the 300 mg clinical dose, based on auc. these outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development. the renal pelvic dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. in embryo-fetal development studies in rats and rabbits, canagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. no developmental toxicities independent of maternal toxicity were observed when canagliflozin was administered at doses up to 100 mg/kg in pregnant rats and 160 mg/kg in pregnant rabbits during embryonic organogenesis or during a study in which maternal rats were dosed from gestation day (gd) 6 through pnd 21, yielding exposures up to approximately 19-times the 300 mg clinical dose, based on auc. risk summary there is no information regarding the presence of invokana in human milk, the effects on the breastfed infant, or the effects on milk production. canagliflozin is present in the milk of lactating rats [see data] . since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. because of the potential for serious adverse reactions in a breastfed infant, advise women that use of invokana is not recommended while breastfeeding. data animal data radiolabeled canagliflozin administered to lactating rats on day 13 post-partum was present at a milk/plasma ratio of 1.40, indicating that canagliflozin and its metabolites are transferred into milk at a concentration comparable to that in plasma. juvenile rats directly exposed to canagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. safety and effectiveness of invokana in pediatric patients under 18 years of age have not been established. in 13 clinical trials of invokana, 2,294 patients 65 years and older, and 351 patients 75 years and older were exposed to invokana [see clinical studies (14.1)] . patients 65 years and older had a higher incidence of adverse reactions related to reduced intravascular volume with invokana (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300 mg daily dose, compared to younger patients; a more prominent increase in the incidence was seen in patients who were 75 years and older [see dosage and administration (2.1)and adverse reactions (6.1)]. smaller reductions in hba 1c with invokana relative to placebo were seen in older (65 years and older; -0.61% with invokana 100 mg and -0.74% with invokana 300 mg relative to placebo) compared to younger patients (-0.72% with invokana 100 mg and -0.87% with invokana 300 mg relative to placebo). the efficacy and safety of invokana for glycemic control were evaluated in a trial that included patients with moderate renal impairment (egfr 30 to less than 50 ml/min/1.73 m 2 ) [see clinical studies (14.1)] . these patients had less overall glycemic efficacy, and patients treated with 300 mg per day had increases in serum potassium, which were transient and similar by the end of study. patients with renal impairment using invokana for glycemic control may also be more likely to experience hypotension and may be at higher risk for acute kidney injury [see warnings and precautions (5.3)] . efficacy and safety studies with invokana did not enroll patients with eskd on dialysis or patients with an egfr less than 30 ml/min/1.73 m 2 [see clinical pharmacology (12.3)] . no dosage adjustment is necessary in patients with mild or moderate hepatic impairment. the use of invokana has not been studied in patients with severe hepatic impairment and is therefore not recommended [see clinical pharmacology (12.3)] .

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - canagliflozin (unii: 0sac974z85) (canagliflozin anhydrous - unii:6s49dgr869) - invokana (canagliflozin) is indicated: - as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (cvd). - to reduce the risk of end-stage kidney disease (eskd), doubling of serum creatinine, cardiovascular (cv) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. limitations of use invokana is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see warnings and precautions (5.1)] . invokana is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m 2 . invokana is likely to be ineffective in this setting based upon its mechanism of action. invokana is contraindicated in patients with a serious hypersensitivity reaction to invokana, such as anaphylaxis or angioedema [see warnings and precautions (5.8)and adverse reactions (6.1, 6.2)] . risk summary based on animal data showing adverse renal effects, invokana is not recommended during the second and third trimesters of pregnancy. limited data with invokana in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations]. in animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on auc. the estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a hba 1c >7 and has been reported to be as high as 20–25% in women with a hba 1c >10. the estimated background risk of 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 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. animal data canagliflozin dosed directly to juvenile rats from postnatal day (pnd) 21 until pnd 90 at doses of 4, 20, 65, or 100 mg/kg increased kidney weights and dose dependently increased the incidence and severity of renal pelvic and tubular dilatation at all doses tested. exposure at the lowest dose was greater than or equal to 0.5-times the 300 mg clinical dose, based on auc. these outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development. the renal pelvic dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. in embryo-fetal development studies in rats and rabbits, canagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. no developmental toxicities independent of maternal toxicity were observed when canagliflozin was administered at doses up to 100 mg/kg in pregnant rats and 160 mg/kg in pregnant rabbits during embryonic organogenesis or during a study in which maternal rats were dosed from gestation day (gd) 6 through pnd 21, yielding exposures up to approximately 19-times the 300 mg clinical dose, based on auc. risk summary there is no information regarding the presence of invokana in human milk, the effects on the breastfed infant, or the effects on milk production. canagliflozin is present in the milk of lactating rats [see data] . since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. because of the potential for serious adverse reactions in a breastfed infant, advise women that use of invokana is not recommended while breastfeeding. data animal data radiolabeled canagliflozin administered to lactating rats on day 13 post-partum was present at a milk/plasma ratio of 1.40, indicating that canagliflozin and its metabolites are transferred into milk at a concentration comparable to that in plasma. juvenile rats directly exposed to canagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. safety and effectiveness of invokana in pediatric patients under 18 years of age have not been established. in 13 clinical trials of invokana, 2,294 patients 65 years and older, and 351 patients 75 years and older were exposed to invokana [see clinical studies (14.1)] . patients 65 years and older had a higher incidence of adverse reactions related to reduced intravascular volume with invokana (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300 mg daily dose, compared to younger patients; a more prominent increase in the incidence was seen in patients who were 75 years and older [see dosage and administration (2.1)and adverse reactions (6.1)]. smaller reductions in hba 1c with invokana relative to placebo were seen in older (65 years and older; -0.61% with invokana 100 mg and -0.74% with invokana 300 mg relative to placebo) compared to younger patients (-0.72% with invokana 100 mg and -0.87% with invokana 300 mg relative to placebo). the efficacy and safety of invokana for glycemic control were evaluated in a trial that included patients with moderate renal impairment (egfr 30 to less than 50 ml/min/1.73 m 2 ) [see clinical studies (14.1)] . these patients had less overall glycemic efficacy, and patients treated with 300 mg per day had increases in serum potassium, which were transient and similar by the end of study. patients with renal impairment using invokana for glycemic control may also be more likely to experience hypotension and may be at higher risk for acute kidney injury [see warnings and precautions (5.3)] . efficacy and safety studies with invokana did not enroll patients with eskd on dialysis or patients with an egfr less than 30 ml/min/1.73 m 2 [see clinical pharmacology (12.3)] . no dosage adjustment is necessary in patients with mild or moderate hepatic impairment. the use of invokana has not been studied in patients with severe hepatic impairment and is therefore not recommended [see clinical pharmacology (12.3)] .

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd) in adults. trazodone hydrochloride tablets are contraindicated in: -   patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/ pregnancyregistry/ antidepressants/ risk summary published prospective cohort studies, case series, and case reports over several decades with trazodone hydrochloride tablets use in pregnant women have not identified any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data). trazodone hydrochloride has been shown to cause increased fetal resorption and other adverse effects on the fetus in the rat when given at dose levels approximately 7.3 times to 11 times the maximum recommended human dose (mrhd) of 400 mg/day in adults on a mg/m2 basis. there was also an increase in congenital anomalies in the rabbit at approximately 7.3 times to 22 times the mrhd on a mg/m2 basis (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% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk a prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression that women who continued antidepressants. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. data human data while available studies cannot definitively establish the absence of risk, published data from prospective cohort studies, case series, and case reports over several decades have not identified an association with trazodone use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. all available studies have methodological limitations, including small sample size and inconsistent comparator groups. animal data no teratogenic effects were observed when trazodone was given to pregnant rats and rabbits during the period of organogenesis at oral doses up to 450 mg/kg/day. this dose is 11 times and 22 times, in rats and rabbits, respectively, the maximum recommended human dose (mrhd) of 400 mg/day in adults on a mg/m2 basis. increased fetal resorption and other adverse effects on the fetus in rats at 7.3 times to 11 times the mrhd and increase in congenital anomalies in rabbits at 7.3 times to 22 times the mrhd on a mg/m2 basis were observed. no further details on these studies are available. risk summary data from published literature report the transfer of trazodone into human milk. there are no data on the effect of trazodone on milk production. limited data from postmarketing reports have not identified and association of adverse effects on the breastfed child. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for trazodone hydrochloride tablets and any potential adverse effects on the breastfed child from trazodone hydrochloride tablets or from the underlying maternal condition. safety and effectiveness in the pediatric population have not been established.  antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning, warnings and precautions (5.1) ]. reported clinical literature and experience with trazodone has not identified differences in responses between elderly and younger patients. however, as experience in the elderly with trazodone hydrochloride is limited, it should be used with caution in geriatric patients. serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients who may be at greater risk for this adverse reaction [see warnings and precautions (5.11) ]. trazodone has not been studied in patients with renal impairment. trazodone should be used with caution in this population. trazodone has not been studied in patients with hepatic impairment. trazodone should be used with caution in this population. trazodone hydrochloride tablets are not a controlled substance. although trazodone hydrochloride has not been systematically studied in preclinical or clinical studies for its potential for abuse, no indication of drug-seeking behavior was seen in the clinical studies with trazodone hydrochloride.

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - liraglutide (unii: 839i73s42a) (liraglutide - unii:839i73s42a) - saxenda is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in: limitations of use saxenda is contraindicated in: risk summary saxenda is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see clinical considerations] . there are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. saxenda should not be used during pregnancy. if a patient wishes to become pregnant, or pregnancy occurs, treatment with saxenda should be discontinued. animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (mrhd) of 3 mg/day. in pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the mrhd [see animal data] . the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk a minimum weight gain, and no weight loss, is recommended for all pregnant women, including those who are already overweight or obese, due to the necessary weight gain that occurs in maternal tissues during pregnancy. animal data liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (mrhd) of 3 mg/day based on plasma area under the time-concentration curve (auc) comparison. liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the mrhd based on plasma auc comparison. female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the mrhd based on plasma auc comparison. the number of early embryonic deaths in the 1 mg/kg/day group increased slightly. fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. mottled liver and minimally kinked ribs occurred at the highest dose. the incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day. pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the mrhd of 3 mg/day at all doses, based on plasma auc comparison. liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. the incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group. in pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times exposure in obese humans at the mrhd of 3 mg/day, based on plasma auc comparison. a slight delay in parturition was observed in the majority of treated rats. group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. group mean body weight from birth to postpartum day 14 trended lower in f2 generation rats descended from liraglutide-treated rats compared to f2 generation rats descended from controls, but differences did not reach statistical significance for any group. risk summary there are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. liraglutide was present in the milk of lactating rats (see data ). the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for saxenda and any potential adverse effects on the breastfed infant from saxenda or from the underlying maternal condition. data in lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. the safety and effectiveness of saxenda as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management have been established in pediatric patients aged 12 years and older with body weight above 60 kg and an initial bmi corresponding to 30 kg/m2 or greater for adults (obese) by international cut-offs (see table 2). use of saxenda for this indication is supported by a 56-week double-blind, placebo-controlled clinical trial in 251 pediatric patients aged 12 to 17 years, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see clinical pharmacology (12.3), clinical studies (14.1,14.2)]. in the pediatric clinical trial, there was one death due to suicide in a saxenda-treated patient [see warnings and precautions (5.8)] ; one saxenda-treated patient had an event of pancreatitis [see warnings and precautions (5.2)] ; more episodes of hypoglycemia confirmed by self blood glucose monitoring occurred in saxenda-treated patients compared to placebo [see warnings and precautions (5.4), adverse reactions (6.1)] ; and mean increases in resting heart rate of 3 to 7 bpm from baseline were observed with saxenda-treated patients [see warnings and precautions (5.5)] . the safety and effectiveness of saxenda have not been established in patients less than 12 years of age. in the saxenda clinical trials, 232 (6.9%) of the saxenda-treated patients were 65 years of age and over, and 17 (0.5%) of the saxenda-treated patients were 75 years of age and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. there is limited experience with saxenda in patients with mild, moderate, and severe renal impairment, including end‑stage renal disease. however, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis [see warnings and precautions (5.6), adverse reactions (6.2)] . saxenda should be used with caution in this patient population [see clinical pharmacology (12.3)] . there is limited experience in patients with mild, moderate, or severe hepatic impairment. therefore, saxenda should be used with caution in this patient population [see clinical pharmacology (12.3)] . saxenda slows gastric emptying. saxenda has not been studied in patients with pre-existing gastroparesis. step 1. prepare your pen with a new needle always use a new needle for each injection. this will prevent contamination, infection, leakage of saxenda, and blocked needles leading to the wrong dose. never use a bent or damaged needle. do not attach a new needle to your pen until you are ready to take your injection. step 2. check the saxenda flow with each new pen. always make sure that a drop appears at the needle tip before you use a new pen for the first time. this makes sure that saxenda flows. if no drop appears, you will not inject any saxenda, even though the dose counter may move. this may mean that there is a blocked or damaged needle. a small drop may remain at the needle tip, but it will not be injected. only check the saxenda flow before your first injection with each new pen. step 3. select your dose always use the dose counter and the dose pointer to see how many mg you select. you will hear a “click” every time you turn the dose selector. do not set the dose by counting the number of clicks you hear. do not use the pen scale to set the dose. it does not show exactly how much saxenda is left in your pen. only doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg can be selected with the dose selector. the selected dose must line up exactly with the dose pointer to make sure that you get a correct dose. the dose selector changes the dose. only the dose counter and dose pointer will show how many mg you select for each dose. you can select up to 3 mg each dose. when your pen contains less than 3 mg the dose counter stops before 3 mg is shown. the dose selector clicks differently when turned forward, backwards or past the number of mg left. do not count the pen clicks. how much saxenda is left? if you need more saxenda than what is left in your pen only if trained or told by your healthcare provider, you may split your dose between your current pen and a new pen. use a calculator to plan the doses as instructed by your healthcare provider. be very careful to calculate correctly. if you are not sure how to split your dose using 2 pens, then select and inject the dose you need with a new pen. step 4. inject your dose always watch the dose counter to know how many mg you inject. hold the dose button down until the dose counter shows 0. you may see a drop of saxenda at the needle tip after injecting. this is normal and does not affect your dose. step 5. after your injection if you do not have a sharps container, follow a 1-handed needle recapping method. carefully slip the needle into the outer needle cap. dispose of the needle in a sharps container as soon as possible. never try to put the inner needle cap back on the needle. you may stick yourself with the needle. always remove the needle from your pen. this prevents contamination, infection, leakage of saxenda, and blocked needles leading to the wrong dose. if the needle is blocked, you will not inject any saxenda. always dispose of the needle after each injection . important caring for your pen how should i store my saxenda pen? this medication guide and instructions for use have been approved by the u.s. food and drug administration. december 2020

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - amiodarone hydrochloride (unii: 976728sy6z) (amiodarone - unii:n3rq532iut) - amiodarone hydrochloride tablets are indicated for the treatment of documented, life-threatening recurrent ventricular fibrillation and life-threatening recurrent hemodynamically unstable tachycardia in adults who have not responded to adequate doses of other available antiarrhythmics or when alternative agents cannot be tolerated. - cardiogenic shock. - sick sinus syndrome, second- or third-degree atrioventricular block, bradycardia leading to syncope without a functioning pacemaker. - known hypersensitivity to the drug or to any of its components, including iodine. risk summary available data from postmarketing reports and published case series indicate that amiodarone use in pregnant women may increase the risk for fetal adverse effects including neonatal hypo- and hyperthyroidism, neonatal bradycardia, neurodevelopmental abnormalities, preterm birth and fetal growth restriction. amiodarone and its metabolite, desethylamiodarone (dea), cross the placenta. untreated underlying arrhythmias, including ventric

Amerika Serikat - Inggris - NLM (National Library of Medicine)

a-s medication solutions - esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - adults esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed ee in adults. for those patients who have not healed after 4 to 8 weeks of treatment, an additional 4 to 8 week course of esomeprazole magnesium delayed-release capsules may be considered. pediatric patients 12 years to 17 years of age esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) for the healing of ee in pediatric patients 12 years to 17 years of age.  esomeprazole magnesium delayed-release capsules are indicated for the maintenance of healing of ee in adults. controlled studies do not extend beyond 6 months. adults esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with gerd in adults. pediatric patients 12 years to 17 years of age esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 weeks) of heartburn and other symptoms associated with gerd in pediatric patients 12 years to 17 years of age. esomeprazole magnesium delayed-release capsules are indicated for the reduction in the occurrence of gastric ulcers associated with continuous nsaid therapy in adult patients at risk for developing gastric ulcers. patients are considered to be at risk due to their age (60 years and older) and/or documented history of gastric ulcers. controlled studies do not extend beyond 6 months. eradication of h.pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy  esomeprazole magnesium delayed-release capsules, in combination with amoxicillin and clarithromycin, are indicated for the treatment of adult patients with h. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate h. pylori . in patients who fail therapy, susceptibility testing should be done. if resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see clinical pharmacology (12.4) and the prescribing information for clarithromyci n].  esomeprazole magnesium delayed-release capsules are indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome, in adults. - esomeprazole magnesium is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6.2)]. - for information about contraindications of amoxicillin and clarithromycin, indicated in combination with esomeprazole magnesium for h. pylori eradication to reduce the risk of duodenal ulcer recurrence, refer to the contraindications section of the respective prescribing information. - proton pump inhibitors (ppis), including esomeprazole, are contraindicated in patients receiving rilpivirine containing products [see drug interactions (7)]. risk summary there are no adequate and well-controlled studies with esomeprazole in pregnant women. esomeprazole is the s-isomer of omeprazole. available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see data). reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole magnesium in rats and rabbits with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg (based on a body surface area basis for a 60 kg person). changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age (see data).  the estimated background risks of major birth defects and miscarriage for the indicated population are 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% to 4% and 15% to 20%, respectively. data human data esomeprazole is the s-isomer of omeprazole. four epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to h2 receptor antagonists or other controls. a population-based retrospective cohort epidemiological study from the swedish medical birth registry, covering approximately 99% of pregnancies, from 1995 to 1999, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. the number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low apgar score, or hospitalization was similar to the number observed in this population. the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. a population-based retrospective cohort study covering all live births in denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837, 317 live births whose mothers did not use any proton pump inhibitor. the overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. a retrospective cohort study reported on 689 pregnant women exposed to either h2 blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. the overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an h2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). the reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease paired controls. rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. animal data omeprazole reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. in rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. in rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis), administered prior to mating through the lactation period. esomeprazole no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 41 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis. a pre-and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis). neonatal/early postnatal (birth to weaning) survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). body weight and body weight gain were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to or greater than 69 mg/kg/day (about 17 times an oral human dose of 40 mg on a body surface area basis). in addition, decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times an oral human dose of 40 mg on a body surface area basis). physeal dysplasia in the femur was observed in offspring of rats treated with oral doses of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in a pre-and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis). when rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). a pre-and postnatal development study in rats with esomeprazole strontium (using equimolar doses compared to esomeprazole magnesium study) produced similar results in dams and pups as described above. a follow up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age. risk summary esomeprazole is the s-isomer of omeprazole and limited data suggest that omeprazole may be present in human milk. there are no clinical data on the effects of esomeprazole 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 esomeprazole magnesium and any potential adverse effects on the breastfed infant from esomeprazole magnesium or from the underlying maternal condition. healing of ee pediatric patients 1 year to 17 years of age the safety and effectiveness of esomeprazole magnesium delayed-release capsules have been established in pediatric patients 12 years to 17 years for short-term treatment (4 to 8 weeks) for healing of ee. use of esomeprazole magnesium for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data in pediatric patients 1 year to 17 years of age. the safety profile in pediatric patients 1 year to 17 years of age was similar to adults [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.4)]. symptomatic gerd pediatric patients 1 year to 17 years of age the safety and effectiveness of esomeprazole magnesium delayed-release capsules have been established in pediatric patients 12 years to 17 years of age for the short-term treatment (4 weeks) of heartburn and other symptoms associated with gerd. use of esomeprazole magnesium for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data in pediatric patients 1 year to 17 years of age. the safety profile in pediatric patients 1 year to 17 years of age was similar to adults [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.4)]. the safety and effectiveness of esomeprazole magnesium for the treatment of symptomatic gerd in pediatric patients less than 1 year of age have not been established. other conditions the safety and effectiveness of esomeprazole magnesium delayed-release capsules for the risk reduction of nsaid-associated gastric ulcer, h. pylori eradication to reduce the risk of duodenal ulcer recurrence and treatment of pathological hypersecretory conditions have not been established in pediatric patients. juvenile animal toxicity studies in a juvenile rat toxicity study, esomeprazole was administered with both magnesium and strontium salts at oral doses about 34 to 68 times a daily human dose of 40 mg based on body surface area. increases in death were seen at the high dose, and at all doses of esomeprazole, there were decreases in body weight, body weight gain, femur weight and femur length, and decreases in overall growth [see nonclinical toxicology (13.2)]. of the total number of patients who received esomeprazole magnesium in clinical trials, 1,459 were 65 to 74 years of age and 354 patients were 75 years of age and older. no overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. in patients with severe hepatic impairment (child-pugh class c) exposure to esomeprazole substantially increased compared to healthy subjects. dosage modification of esomeprazole magnesium delayed-release capsules are recommended for patients with severe hepatic impairment for the healing of ee, risk reduction of nsaid-associated gastric ulcer, h. pylori eradication to reduce the risk of duodenal ulcer recurrence, and pathological hypersecretory conditions including zollinger-ellison syndrome [see dosage and administration (2.1), clinical pharmacology (12.3)]. in patients with mild to moderate liver impairment (child-pugh classes a and b), no dosage adjustment is necessary.