USA - engelsk - NLM (National Library of Medicine)

torrent pharmaceuticals limited - esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - esomeprazole 20 mg - 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 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

USA - engelsk - NLM (National Library of Medicine)

dr. reddy's laboratories limited - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq), esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - naproxen and esomeprazole magnesium delayed-release tablets, a combination of naproxen and esomeprazole magnesium, is indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric ulcers. the naproxen component of naproxen and esomeprazole magnesium delayed-release tablet is indicated for relief of signs and symptoms of: • osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults.   • juvenile idiopathic arthritis (jia) in adolescent patients. the esomeprazole magnesium component of naproxen and esomeprazole magnesium delayed-release tablet is indicated to decrease the risk of developing naproxen-associated gastric ulcers.   limitations of use :  • do not substitute naproxen and esomeprazole magnesium delayed-release tablet with the single-ingredient products of naproxen and esomeprazole magnesium. • naproxen and esome

USA - engelsk - NLM (National Library of Medicine)

lupin pharmaceuticals, inc. - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq), esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - naproxen and esomeprazole magnesium delayed-release tablets, a combination of naproxen and esomeprazole magnesium, are indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric ulcers. the naproxen component of naproxen and esomeprazole magnesium delayed-release tablets is indicated for relief of signs and symptoms of: -   osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults. -   juvenile idiopathic arthritis (jia) in adolescent patients. the esomeprazole magnesium component of naproxen and esomeprazole magnesium delayed-release tablets is indicated to decrease the risk of developing naproxen-associated gastric ulcers. limitations   of use: -   do not substitute naproxen and esomeprazole magnesium delayed-release tablet with the single-ingredient products of naproxen and esomeprazole magnesium. -   naproxen and esomeprazole magnesium delayed-release tablet is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. -   controlled studies do not extend beyond 6 months [see use in specific populations (8.4), clinical studies (14)] . naproxen and esomeprazole magnesium delayed-release tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. hypersensitivity reactions to esomeprazole may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.7, 5.8, 5.9,5.18), adverse reactions (6.2)] . - history of asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8)] . - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1)] . - proton pump inhibitors (ppis), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . risk summary use of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, can cause premature closure of the fetal ductus arteriosus and fetal and renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of naproxen and esomeprazole magnesium delayed-release tablets use between about 20 and 30 weeks of gestation and avoid naproxen and esomeprazole magnesium delayed-release tablets use at about 30 weeks of gestation and later in pregnancy (see clinical considerations, data) . premature closure of the fetal ductus arteriosus use of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. naproxen and esomeprazole magnesium delayed-release tablet contains naproxen and esomeprazole magnesium. esomeprazole is the s- isomer of omeprazole. naproxen data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, naproxen administered during organogenesis to rats and rabbits at doses less than the maximum recommended human daily dose of 1500 mg/day showed no evidence of harm to the fetus (see data) . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as naproxen resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. esomeprazole there are no human data for esomeprazole. however, available epidemiologic data for omeprazole (esomeprazole is the s-isomer of omeprazole) fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see data) . in animal studies with administration of oral esomeprazole magnesium in rats 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 esomeprazole or 40 mg omeprazole. 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. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, can cause premature closure of the fetal ductus arteriosus (see data). oligohydramnios/neonatal renal impairment if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if naproxen and esomeprazole magnesium delayed-release tablets treatment is needed in pregnant women, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue naproxen and esomeprazole magnesium delayed-release tablets and follow up according to clinical practice (see data). labor or delivery there are no studies on the effects of naproxen and esomeprazole magnesium delayed-release tablets during labor or delivery. in animal studies, nsaids, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data naproxen when used to delay preterm labor, inhibitors of prostaglandin synthesis, including nsaids such naproxen, may increase the risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage. naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin e levels in preterm infants. premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. esomeprazole 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 1995-99, 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- 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% 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 there are no reproduction studies in animals with naproxen and esomeprazole magnesium delayed-release tablet, a combination of naproxen and esomeprazole. naproxen reproduction studies with naproxen administered during the period of organogenesis have been performed in rats at 20 mg/kg/day (0.13 times the maximum recommended human daily dose of 1500 mg/day based on body surface area comparison) rabbits at 20 mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area comparison), and mice at 170 mg/kg/day (0.56 times the maximum recommended human daily dose based on body surface area comparison) with no evidence of harm to the fetus due to the drug. 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 42 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis and have revealed no evidence of harm to the fetus due to esomeprazole magnesium. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development were performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times a daily 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 a daily 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     the daily human dose of 40 mg on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in the 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 limited data from published literature report that naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. esomeprazole is the s-isomer of omeprazole and limited data from published literature suggest omeprazole may be present in human milk. there is no information on the effects of naproxen or omeprazole 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 naproxen and esomeprazole magnesium delayed-release tablets and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, may delay or prevent rupture of ovarian follicles that may lead to reversible infertility in some women. small studies in women treated with nsaids have also shown a reversible delay in ovulation. published animal studies have shown that administration of prostaglandin synthesis inhibitors have the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. consider withdrawal of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of naproxen and esomeprazole magnesium delayed-release tablets have been established in adolescent patients 12 years of age and older weighing at least 38 kg for the symptomatic relief of jia and to decrease the risk of developing naproxen-associated gastric ulcers. use of naproxen and esomeprazole magnesium delayed-release tablets in this age group is based on extrapolation of adequate and well-controlled studies in adults and supported by a 6 month safety study including pharmacokinetic assessment of naproxen and esomeprazole magnesium in 36 adolescent patients with jia. based on the limited data, the plasma naproxen and plasma esomeprazole concentrations were found to be within the range to that observed to those found in healthy adults. the safety profile of naproxen and esomeprazole magnesium delayed-release tablets in adolescent patients with jia was similar to adults with ra. the safety and effectiveness of naproxen and esomeprazole magnesium delayed-release tablets in pediatric patients less than 12 years of age or less than 38 kg with jia have not been established. juvenile animal data 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)]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see warnings and precautions (5.1, 5.2, 5.3, 5.6, 5.14)] . of the total number of patients who received naproxen and esomeprazole magnesium delayed-release tablets (n=1157) in clinical trials, 387 were ≥65 years of age, of which 85 patients were 75 years and over. no meaningful differences in efficacy or safety were observed between these subjects and younger subjects [see adverse reactions (6)]. studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. as with other drugs used in the elderly, it is prudent to use the lowest effective dose [see dosage and administration  (2) , clinical pharmacology (12.3)]. experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nsaids. elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. most spontaneous reports of fatal gi events are in the geriatric population [see warnings and precautions (5.2)]. naproxen and its metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nsaids [see warnings and precautions (5.6)] . naproxen and esomeprazole magnesium delayed-release tablets should be avoided in patients with severe hepatic impairment because naproxen may increase the risk of renal failure or bleeding and esomeprazole doses should not exceed 20 mg daily in these patients [see dosage and administration (2), warnings and precautions (5.3 ), clinical pharmacology (12.3)] . naproxen-containing products, including naproxen and esomeprazole magnesium delayed-release tablets, are not recommended for use in patients with advanced renal disease [see dosage and administration (2), warnings and precautions (5.6 )] .

USA - engelsk - NLM (National Library of Medicine)

sciegen pharmaceuticals, inc - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq), esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - naproxen and esomeprazole magnesium delayed-release tablets, a combination of naproxen and esomeprazole magnesium, is indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric ulcers. the naproxen component of naproxen and esomeprazole magnesium delayed-release tablets are indicated for relief of signs and symptoms of: - osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults. - juvenile idiopathic arthritis (jia) in adolescent patients. the esomeprazole magnesium component of naproxen and esomeprazole magnesium delayed-release tablets are indicated to decrease the risk of developing naproxen-associated gastric ulcers. limitations of use: - do not substitute naproxen and esomeprazole magnesium delayed-release tablets with the single-ingredient products of naproxen and esomeprazole magnesium. - naproxen and esomeprazole magnesium delayed-release tablets are not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. - controlled studies do not extend beyond 6 months [see use in specific populations (8.4), clinical studies (14)] . naproxen and esomeprazole magnesium delayed-release tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. hypersensitivity reactions to esomeprazole may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.7, 5.8, 5.9, 5.18), adverse reactions (6.2)] . - history of asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8)] . - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1)] . - proton pump inhibitors (ppis), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . risk summary use of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, can cause premature closure of the fetal ductus arteriosus and fetal and renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of naproxen and esomeprazole magnesium delayed-release tablets use between about 20 and 30 weeks of gestation and avoid naproxen and esomeprazole magnesium delayed-release tablets use at about 30 weeks of gestation and later in pregnancy (see clinical considerations, data) . premature closure of the fetal ductus arteriosus use of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. naproxen and esomeprazole magnesium delayed-release tablets contain naproxen and esomeprazole magnesium. esomeprazole is the s- isomer of omeprazole. naproxen data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, naproxen administered during organogenesis to rats and rabbits at doses less than the maximum recommended human daily dose of 1500 mg/day showed no evidence of harm to the fetus (see data) . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as naproxen resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. esomeprazole there are no human data for esomeprazole. however, available epidemiologic data for omeprazole (esomeprazole is the s-isomer of omeprazole) fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see data) . in animal studies with administration of oral esomeprazole magnesium in rats, 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 esomeprazole or 40 mg omeprazole. 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. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, can cause premature closure of the fetal ductus arteriosus (see data). oligohydramnios/neonatal renal impairment if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if naproxen and esomeprazole magnesium delayed-release tablets treatment is needed in pregnant women, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue naproxen and esomeprazole magnesium delayed-release tablets and follow up according to clinical practice (see data). labor or delivery there are no studies on the effects of naproxen and esomeprazole magnesium delayed-release tablets during labor or delivery. in animal studies, nsaids, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data naproxen when used to delay preterm labor, inhibitors of prostaglandin synthesis, including nsaids such naproxen, may increase the risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage. naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin e levels in preterm infants. premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. esomeprazole 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 1995-99, 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 19962009, 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% 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 there are no reproduction studies in animals with naproxen and esomeprazole magnesium delayed-release tablets, a combination of naproxen and esomeprazole. naproxen reproduction studies with naproxen administered during the period of organogenesis have been performed in rats at 20 mg/kg/day (0.13 times the maximum recommended human daily dose of 1500 mg/day based on body surface area comparison) rabbits at 20 mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area comparison), and mice at 170 mg/kg/day (0.56 times the maximum recommended human daily dose based on body surface area comparison) with no evidence of harm to the fetus due to the drug. 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 42 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis and have revealed no evidence of harm to the fetus due to esomeprazole magnesium. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development were performed with esomeprazole magnesium at oral doses of 14 mg/kg/day to 280 mg/kg/day (about 3.4 to 68 times a daily 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 a daily 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 the daily human dose of 40 mg on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in the pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 mg /kg/day 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 limited data from published literature report that naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. esomeprazole is the s-isomer of omeprazole and limited data from published literature suggest omeprazole may be present in human milk. there is no information on the effects of naproxen or omeprazole 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 naproxen and esomeprazole magnesium delayed-release tablets and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, may delay or prevent rupture of ovarian follicles that may lead to reversible infertility in some women. small studies in women treated with nsaids have also shown a reversible delay in ovulation. published animal studies have shown that administration of prostaglandin synthesis inhibitors have the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. consider withdrawal of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of naproxen and esomeprazole magnesium delayed-release tablets have been established in adolescent patients 12 years of age and older weighing at least 38 kg for the symptomatic relief of jia and to decrease the risk of developing naproxen-associated gastric ulcers. use of naproxen and esomeprazole magnesium delayed-release tablets in this age group is based on extrapolation of adequate and well-controlled studies in adults and supported by a 6 month safety study including pharmacokinetic assessment of naproxen and esomeprazole magnesium in 36 adolescent patients with jia. based on the limited data, the plasma naproxen and plasma esomeprazole concentrations were found to be within the range to that observed to those found in healthy adults. the safety profile of naproxen and esomeprazole magnesium delayed-release tablets in adolescent patients with jia was similar to adults with ra. the safety and effectiveness of naproxen and esomeprazole magnesium delayed-release tablets in pediatric patients less than 12 years of age or less than 38 kg with jia have not been established. juvenile animal data 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)]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see warnings and precautions (5.1, 5.2, 5.3, 5.6, 5.14)] . of the total number of patients who received naproxen and esomeprazole magnesium delayed-release tablets (n=1157) in clinical trials, 387 were ≥ 65 years of age, of which 85 patients were 75 years and over. no meaningful differences in efficacy or safety were observed between these subjects and younger subjects [see adverse reactions (6)]. studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. as with other drugs used in the elderly, it is prudent to use the lowest effective dose [see dosage and administration (2), clinical pharmacology (12.3)]. experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nsaids. elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. most spontaneous reports of fatal gi events are in the geriatric population [see warnings and precautions (5.2)]. naproxen and its metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nsaids [see warnings and precautions (5.6)] . naproxen and esomeprazole magnesium delayed-release tablets should be avoided in patients with severe hepatic impairment because naproxen may increase the risk of renal failure or bleeding and esomeprazole doses should not exceed 20 mg daily in these patients [see dosage and administration (2), warnings and precautions (5.3), clinical pharmacology (12.3)] . naproxen-containing products, including naproxen and esomeprazole magnesium delayed-release tablets, are not recommended for use in patients with advanced renal disease [see dosage and administration (2), warnings and precautions (5.6)] .

USA - engelsk - NLM (National Library of Medicine)

seroyal usa - magnesium phosphate, dibasic (unii: a1y870209z) (magnesium phosphate, dibasic - unii:a1y870209z) - magnesium phosphate, dibasic 1 [hp_x] - indications for the temporary relief of cramp and pain indications for the temporary relief of cramp and pain directions adults: take five granules three times daily or as recommended by your healthcare practitioner. children: take three granules and follow adult directions.

USA - engelsk - NLM (National Library of Medicine)

seroyal usa - magnesium carbonate (unii: 0e53j927na) (carbonate ion - unii:7ujq5ope7d) - magnesium carbonate 1 [hp_x] - indications for the temporary relief of fatigue and constipation indications for the temporary relief of fatigue and constipation directions adults: take five granules three times daily or as recommended by your healthcare practitioner. children: take three granules and follow adult directions.

USA - engelsk - NLM (National Library of Medicine)

standard homeopathic company - magnesium phosphate, dibasic trihydrate (unii: hf539g9l3q) (magnesium cation - unii:t6v3lhy838) - magnesium phosphate, dibasic trihydrate 30 [hp_x] in 1 g - muscle cramps, menstrual cramps or pain

USA - engelsk - NLM (National Library of Medicine)

rxhomeo private limited d.b.a. rxhomeo, inc - magnesium phosphate, dibasic trihydrate (unii: hf539g9l3q) (magnesium cation - unii:t6v3lhy838) - magnesium phosphate, dibasic trihydrate 1 [hp_x] - uses: temporary relief - running colic * * claims based on traditional homeopathic practice, not accepted medical evidence. not fda evaluated. condition listed above or as directed by the physician

USA - engelsk - NLM (National Library of Medicine)

seroyal usa - magnesium phosphate, dibasic trihydrate (unii: hf539g9l3q) (magnesium cation - unii:t6v3lhy838) - magnesium phosphate, dibasic trihydrate 6 [hp_x] - uses for the temporary relief of minor muscle cramps menstrual cramps uses for the temporary relief of minor muscle cramps menstrual cramps directions tip bottle slightly allowing for tablets to fall into the cap. use cap to drop tablets into mouth and allow them to dissolve under the tongue. adults and adolescents (12 years and older): take 1 to 4 tablets, one to four times daily, or as recommended by your healthcare practitioner. children (under 12 years): take under the direction of your healthcare practitioner. uses helps to promote general bone and joint health. support general normal growth. uses helps to promote general bone and joint health. support general normal growth. directions tip bottle slightly allowing for tablets to fall into the cap. use cap to drop tablets into mouth and allow them to dissolve under the tongue. adults and adolescents (12 years and older) take 1 to 4 tablets, one to four times daily, or as recommended by your healthcare practitio

USA - engelsk - NLM (National Library of Medicine)

hyland's inc. - magnesium phosphate, dibasic trihydrate (unii: hf539g9l3q) (magnesium cation - unii:t6v3lhy838) - magnesium phosphate, dibasic trihydrate 6 [hp_x] - relief of symptoms of muscular cramps and pains (e.g. menstrual cramps) relieved by warmth,stomach cramps,headaches with darting pains.