Belgija - angleščina - AFMPS (Agence Fédérale des Médicaments et des Produits de Santé)

purna pharmaceuticals - zinc oxide - ointment - zinc oxide 250 mg/g - zinc products

Združene države Amerike - angleščina - 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 )] .

Združene države Amerike - angleščina - 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)] .

Združene države Amerike - angleščina - NLM (National Library of Medicine)

takeda pharmaceuticals america, inc. - lanadelumab (unii: 2372v1tkxk) (lanadelumab - unii:2372v1tkxk) - takhzyro® is indicated for prophylaxis to prevent attacks of hereditary angioedema (hae) in adult and pediatric patients aged 2 years and older. none. risk summary there are no available data on takhzyro use in pregnant women to inform any drug associated risks. monoclonal antibodies such as lanadelumab-flyo are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. an enhanced pre-and postnatal development (eppnd) study conducted in pregnant monkeys at doses resulting in exposures of up to 33 times the exposure achieved (on an auc basis) at the maximum recommended human dose (mrhd) revealed no evidence of harm to the developing fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data in the eppnd study, pregnant cynomolgus monkeys were administered lanadelumab-flyo once weekly at subcutaneous doses resulting in up to 33 times the exposure at the mrhd (on an auc basis with maternal subcutaneous doses up to 50 mg/kg/week) from gestation day 20, at the beginning of organogenesis, through to parturition. there were no lanadelumab-flyo-related effects on maintenance of pregnancy or parturition. maternal lanadelumab-flyo treatment had no effects on embryo-fetal development, survival, growth, or postnatal development of offspring through 3 months of age. lanadelumab-flyo crossed the placenta in monkeys. offspring were exposed to lanadelumab-flyo at approximately 50% of the maternal plasma concentration out to postnatal day 21 (pnd 21). lanadelumab-flyo concentrations were approximately equivalent in maternal and offspring plasma at pnd 90. risk summary there are no data on the presence of lanadelumab-flyo in human milk, its effects on the breastfed infant, or its effects on milk production. lanadelumab-flyo was detected in the milk of lactating cynomolgus monkeys at approximately 0.2% of the maternal plasma concentration. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for takhzyro and any potential adverse effects on the breastfed infant from takhzyro or from the underlying maternal condition. data animal data available pharmacokinetic data in cynomolgus monkeys have shown excretion of lanadelumab-flyo in milk at approximately 0.2% of the maternal plasma level. the safety and effectiveness of takhzyro for prophylaxis to prevent attacks of hereditary angioedema (hae) have been established in pediatric patients 2 years of age and older. use of takhzyro for this indication in patients 12 years of age and older was supported by a subgroup analysis by age of 10 patients aged 12 to <18 years in trial 1 (a randomized, double-blind, placebo-controlled parallel-group study in adult and pediatric patients 12 years of age and older with hae). results of the subgroup analysis by age were consistent with overall study results. an additional 13 pediatric patients aged 12 to <18 years were enrolled in the open-label extension study [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)]. use of takhzyro for this indication in patients 2 to less than 12 years of age was supported by extrapolation of efficacy data from trial 1, an adequate and well controlled study in adult and pediatric (12 to less than 18 years of age) patients, with additional pharmacokinetic analyses showing similar drug exposures between adults (>18 years of age) and pediatric patients (2 to less than 12 years of age), and safety and pharmacodynamic data from an open-label, multicenter study in pediatric patients with hae aged 2 to less than 12 years that enrolled 21 patients (4 patients were aged 2 to less than 6 years and 17 patients were 6 to less than 12 years of age) [see adverse reactions (6.1) and clinical pharmacology (12.3)] . the pharmacodynamic response observed in this trial for pediatric patients 2 to less than 12 years of age was similar to that seen in adult and pediatric patients 12 years of age and older [see clinical pharmacology (12.2)] . the safety and effectiveness of takhzyro in pediatric patients less than 2 years of age have not been established. the safety and effectiveness of takhzyro were evaluated in a subgroup of patients (n=5) aged ≥65 years in trial 1. results of the subgroup analysis by age were consistent with overall study results [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)] . takhzyro® (tak-zye-roe) (lanadelumab-flyo) injection, for subcutaneous use single-dose 1 ml prefilled syringe this instructions for use contains information on how to inject takhzyro. please make sure to read, understand, and follow the instructions for use before injecting takhzyro. a healthcare provider should show you how to prepare and inject takhzyro properly before you use it for the first time. contact your healthcare provider if you have any questions. - takhzyro is a ready to use prefilled syringe (figure a ) for injection under the skin (subcutaneous) to be given to children by their healthcare provider or caregiver. self-injection is not recommended in children (2 to less than 12 years of age). - each takhzyro prefilled syringe contains one 150 mg/1 ml dose. the takhzyro prefilled syringe is for single use only. - store the takhzyro prefilled syringe in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store the takhzyro prefilled syringe in the original carton to protect it from light. - throw away (discard) the takhzyro prefilled syringe if it has been kept out of the refrigerator, frozen, or not kept in the original carton protected from light. - do not shake the takhzyro prefilled syringe. keep the takhzyro prefilled syringe and all medicines out of the reach of children. - do not use if the seal on the carton is open or broken. - your medicine is sensitive to warm temperatures. do not use heat sources such as a microwave or hot water to warm your takhzyro prefilled syringe. - do not remove the needle cap until you are ready to inject. - do not touch or push the plunger rod until you are ready to inject. - do not touch any surface or body part after washing your hands before the injection. - do not use the takhzyro prefilled syringe if the expiration date has passed. if the takhzyro prefilled syringe is expired throw it away (discard) in a sharps container and contact your healthcare provider. - do not use the takhzyro prefilled syringe if the syringe is damaged or cracked. - do not use the takhzyro prefilled syringe if the medicine is discolored, cloudy, or has flakes or particles in it. - you may see air bubbles in the takhzyro prefilled syringe. this is normal and will not affect your dose. - stomach area (abdomen) - thighs - upper arms - do not inject into an area where the skin is irritated, red, bruised, or infected. - the area you choose for injection should be at least 2 inches away from any scars or belly button (navel). - do not fan or blow on the clean site. - do not touch the clean site again before giving your injection. - do not touch or push the plunger rod until you are ready to inject. - do not use the takhzyro prefilled syringe if it has been dropped without the needle cap on. - do not use the takhzyro prefilled syringe if the needle looks damaged or bent. - do not touch the needle or allow the needle to touch anything. - do not recap the needle to avoid a needle-stick injury. - keep pinching until the injection is complete and the needle is removed (figure k ). - do not rub the injection site. there may be a small amount of blood where you injected. this is normal. - cover the injection site with an adhesive bandage if needed. - do not recap the needle to avoid a needle-stick injury. - do not reuse the takhzyro prefilled syringe or any of your injection supplies. - do not throw away (dispose of) the takhzyro prefilled syringe in your household trash. - do not touch the needle. fda-cleared sharps containers are generally available through pharmacies, medical supply companies, healthcare providers, and online. - if you do not have an fda-cleared sharps container, you may use a household container that is: made of a heavy-duty plastic can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use leak-resistant, and properly labeled to warn of hazardous waste inside the container. - made of a heavy-duty plastic - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to fda's website at: http://www.fda.gov/safesharpsdisposal. - important: always keep the sharps disposal container out of the reach of children. - do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. questions? for product or service-related questions, call 1-877-takeda-7 (1-877-825-3327) or go to www.takhzyro.com. manufactured by: takeda pharmaceuticals u.s.a., inc. lexington, ma 02421 u.s. license no. 1898 takhzyro® is a registered trademark of dyax corp., a takeda company. takeda® and the takeda logo® are registered trademarks of takeda pharmaceutical company limited. ©2023 takeda pharmaceuticals u.s.a., inc. all rights reserved. this instructions for use has been approved by the u.s. food and drug administration. approved: 02/2023 takhzyro® (tak-zye-roe) (lanadelumab-flyo) injection, for subcutaneous use single-dose prefilled syringe this instructions for use contains information on how to inject takhzyro. please make sure to read, understand, and follow the instructions for use before injecting takhzyro. a healthcare provider should show you how to prepare and inject takhzyro properly before you use it for the first time. contact your healthcare provider if you have any questions. - takhzyro is a ready to use prefilled syringe (figure a ) for injection under the skin (subcutaneous) to be given by your healthcare provider, caregiver, or by yourself. - each takhzyro prefilled syringe contains one 300 mg/2 ml dose. the takhzyro prefilled syringe is for single use only. - store the takhzyro prefilled syringe in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store the takhzyro prefilled syringe in the original carton to protect it from light. - throw away (discard) the takhzyro prefilled syringe if it has been kept out of the refrigerator, frozen, or not kept in the original carton protected from light. - do not shake the takhzyro prefilled syringe. keep the takhzyro prefilled syringe and all medicines out of the reach of children. - do not use if the seal on the carton is open or broken. - your medicine is sensitive to warm temperatures. do not use heat sources such as a microwave or hot water to warm your takhzyro prefilled syringe. - do not remove the needle cap until you are ready to inject. - do not touch or push the plunger rod until you are ready to inject. - do not touch any surface or body part after washing your hands before the injection. - do not use the takhzyro prefilled syringe if the expiration date has passed. if the takhzyro prefilled syringe is expired throw it away (discard) in a sharps container and contact your healthcare provider. - do not use the takhzyro prefilled syringe if the syringe is damaged or cracked. - do not use the takhzyro prefilled syringe if the medicine is discolored, cloudy, or has flakes or particles in it. - you may see air bubbles in the takhzyro prefilled syringe. this is normal and will not affect your dose. - stomach area (abdomen) - thighs - upper arms (only if a healthcare provider or caregiver is giving you the injection) - do not inject into an area of your body where the skin is irritated, red, bruised, or infected. - the area you choose for injection should be at least 2 inches away from any scars or your belly button (navel). - do not fan or blow on the clean site. - do not touch the clean site again before giving your injection. - do not touch or push the plunger rod until you are ready to inject. - do not use the takhzyro prefilled syringe if it has been dropped without the needle cap on. - do not use the takhzyro prefilled syringe if the needle looks damaged or bent. - do not touch the needle or allow the needle to touch anything. - do not recap the needle to avoid a needle-stick injury. - keep pinching until the injection is complete and the needle is removed (figure k ). - do not rub the injection site. there may be a small amount of blood where you injected. this is normal. - cover the injection site with an adhesive bandage if needed. - do not recap the needle to avoid a needle-stick injury. - do not reuse the takhzyro prefilled syringe or any of your injection supplies. - do not throw away (dispose of) the takhzyro prefilled syringe in your household trash. - do not touch the needle. fda-cleared sharps containers are generally available through pharmacies, medical supply companies, healthcare providers, and online. - if you do not have an fda-cleared sharps container, you may use a household container that is: made of a heavy-duty plastic can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use leak-resistant, and properly labeled to warn of hazardous waste inside the container. - made of a heavy-duty plastic - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to fda's website at: http://www.fda.gov/safesharpsdisposal. - important: always keep the sharps disposal container out of the reach of children. - do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. questions? for product or service-related questions, call 1-877-takeda-7 (1-877-825-3327) or go to www.takhzyro.com. manufactured by: takeda pharmaceuticals u.s.a., inc. lexington, ma 02421 u.s. license no. 1898 takhzyro® is a registered trademark of dyax corp., a takeda company. takeda® and the takeda logo® are registered trademarks of takeda pharmaceutical company limited. ©2022 takeda pharmaceuticals u.s.a., inc. all rights reserved. this instructions for use has been approved by the u.s food and drug administration. approved: 02/2022 be sure that you read, understand, and follow the instructions for use before injecting takhzyro. a healthcare provider should show you how to prepare and inject takhzyro properly before you use it for the first time . contact your healthcare provider if you have any questions. important information: - takhzyro is a ready-to-use solution for injection under the skin (subcutaneous). it is supplied in a single-dose, glass vial. - your healthcare provider will prescribe the dose that you should take. - only use the syringes, transfer needles, and injection needles that your healthcare provider prescribes. - only use the syringes, transfer needles and injection needles 1 time. throw away (dispose of) any used syringes and needles. storing takhzyro: - store takhzyro in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store takhzyro in the original carton to protect the vial from light. - do not shake takhzyro. - keep takhzyro and all medicines out of the reach of children. supplies needed for your takhzyro injection step 1: prepare for your injection - gather all supplies and place them on a well-lighted flat work surface. - take the vial out of the refrigerator 15 minutes before use and allow it to reach room temperature before preparing an injection. - check the expiration date on the box and vial label of takhzyro. do not use if the expiration date has passed. - check the supplies for damage. do not use if they appear damaged. - clean your work area and wash your hands before preparing your dose. do not touch any surface or body part, especially your face, after washing your hands before injection. - remove the vial from the packaging. do not use the vial if the plastic cap covering is missing. - gently turn the vial upside down (invert) 3 to 5 times to mix the medicine. do not shake to avoid foaming. - look at the medicine in the vial for visible particles or a change in the color. medicine should be colorless to slightly yellow. do not use if you see particles or a change in color. - remove the plastic cap from the medicine vial. do not remove the medicine vial rubber stopper. - place the vial on a flat surface. clean the medicine vial rubber stopper with an alcohol wipe and allow it to dry. step 2: attach transfer needle to syringe - screw the 18g transfer needle to the 3ml syringe. - pull back the plunger to fill the syringe with air equal to the amount of medicine in the vial. - hold the syringe by the barrel with one hand and the transfer needle cap with the other hand. - pull off the transfer needle cap straight away from the syringe and away from your body. do not pull on the plunger. place the transfer needle cap down on a clean flat surface. - do not touch the needle tip. step 3: transfer takhzyro into syringe and switch to the injection needle - keep the vial on the flat surface and insert the transfer needle into the center of the rubber stopper. - push the plunger down to inject air into the vial and hold the plunger down. - slowly turn the vial upside down with transfer needle and syringe attached. pull back on the plunger to withdraw the full dose in the vial. - remove large air bubbles by gently tapping on the syringe barrel with your fingers until the bubbles rise to the top of the syringe. - slowly push the plunger, allowing air to go back into the vial, until the medicine reaches the top of the syringe. - repeat these steps until large air bubbles are removed. - return the vial to an upright position. - without removing the needle from the vial, unscrew the syringe by holding the needle hub and turning the syringe counter clockwise. - return the syringe to an upright position. - throw away the 18g transfer needle and the vial in a sharps disposal container (see step 6). - screw the 27g ½-inch injection needle to the syringe. step 4: select and prepare injection site - takhzyro can be self-injected in your stomach (abdomen) or thigh. if given by a caregiver, takhzyro may also be injected in the upper arm. - clean your injection site with an alcohol wipe and allow it to dry completely. - you should use a different injection site each time you receive an injection to keep your skin healthy. - the area you choose for injection should be at least 2 inches (5 cm) away from any scars or your belly button (navel). do not choose an area that is bruised, swollen, or painful. - takhzyro should be given within 2 hours of preparing the dosing syringe at room temperature. after the dosing syringe is prepared, it can be refrigerated at 36°f to 46°f (2°c to 8°c) and must be used within 8 hours of preparation. take the dosing syringe out of the refrigerator 15 minutes before use and allow it to reach room temperature prior to injecting. step 5: inject takhzyro - hold the syringe by the barrel with one hand and the injection needle cap with the other hand. - pull off the injection needle cap straight away from the syringe and away from your body. do not pull on the plunger. do not touch the needle tip or allow it to touch any other surface. - gently pinch about 1 inch of skin at your cleaned chosen injection site and insert the needle. - push the plunger slowly until no medicine remains in the syringe. release the skin fold and gently remove the needle. do not recap the needle. step 6: throw away (dispose of) needle and syringe - place the 27g ½-inch injection needle and the syringe in a sharps container. - if you do not have a fda-cleared sharps disposal, you may use a household container that is: made of heavy-duty plastic, can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and - made of heavy-duty plastic, - can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps in the state you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. important: always keep the sharps disposal container out of the reach of children. for more information, visit www.takhzyro.com this instructions for use has been approved by the u.s. food and drug administration. manufactured by: takeda pharmaceuticals u.s.a., inc. lexington, ma 02421 u.s. license no: 1898 takhzyro® is a registered trademark of dyax corp., a takeda company. takeda® and the takeda logo® are registered trademarks of takeda pharmaceutical company limited. ©2021 takeda pharmaceuticals u.s.a., inc. all rights reserved. approved: 11/2021

Združene države Amerike - angleščina - NLM (National Library of Medicine)

ipsen biopharmaceuticals, inc. - mecasermin (unii: 7gr9i2683o) (mecasermin - unii:7gr9i2683o) - mecasermin 40 mg in 4 ml - severe primary igf-1 deficiency (primary igfd) increlex is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with: - severe primary igf-1 deficiency or - growth hormone (gh) gene deletion who have developed neutralizing antibodies to gh. severe primary igf-1 deficiency (igfd) is defined by: - height standard deviation score ≤ –3.0 and - basal igf-1 standard deviation score ≤ –3.0 and - normal or elevated growth hormone (gh). limitations of use: increlex is not a substitute to gh for approved gh indications. increlex is not indicated for use in patients with secondary forms of igf-1 deficiency, such as gh deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory corticosteroids. - known hypersensitivity increlex should not be used by patients who are allergic to mecasermin (rhigf-1) or any of the inactive ingredients in increlex, or who have experienced a severe hypersensitivity to increlex [see warnings and precautions (5.2) and adverse reactions (6.3)]. - closed epiphyses increlex should not be used for growth promotion in patients with closed epiphyses. - malignant neoplasia increlex is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy [see warnings and precautions (5.7) and adverse reactions (6.3)]. risk summary there are no available data on increlex use in pregnant women. exposure to increlex during pregnancy is unlikely because the drug is not indicated for use after epiphyseal closure. in animal reproduction studies, there were no observed embryo-fetal development abnormalities with intravenous administration of increlex to pregnant rats and rabbits during fetal organogenesis given at exposures up to 11 and 3 times the maximum recommended human dose (mrhd) of 0.24 mg/kg/day based on body surface area (bsa), respectively (see data) . the estimated background risk of birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data studies to assess embryo-fetal toxicity evaluated the effects of increlex during organogenesis in sprague dawley rats given 1, 4, and 16 mg/kg/day and in new zealand white rabbits given 0.125, 0.5, and 2 mg/kg/day, administered intravenously. there were no observed embryo-fetal developmental abnormalities in rats given up to 16 mg/kg/day (11 times the mrhd based on bsa comparison). in the rabbit study, the noael for fetal toxicity was 0.5 mg/kg/day (approximately equivalent to the mrhd based on bsa) due to an increase in fetal death at 2 mg/kg. increlex displayed no teratogenicity or maternal toxicity in rabbits given up to 2 mg/kg (3 times the mrhd based on bsa). risk summary there is no information available on the presence of mecasermin in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for increlex and any potential adverse effects on the breast-fed child from increlex or from the underlying maternal condition. toxicity (gasping syndrome) with benzyl alcohol serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and infants in the intensive care unit who received drugs containing benzyl alcohol as a preservative. in these cases, benzyl alcohol dosages of 99 mg/kg/day to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 mmol/l to 1.378 mmol/l). increlex contains 9 mg/ml benzyl alcohol as a preservative. additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. use of increlex in infants is not recommended [see warnings and precautions (5.8)] . safety and effectiveness in pediatric patients below the age of 2 years of age have not been established. the safety and effectiveness of increlex in patients aged 65 and over has not been established. instructions for use increlex® (eenk-ruh-lex) (mecasermin) injection for subcutaneous use read this instructions for use before you start using increlex and each time you get a refill. there may be new information. this information does not take the place of talking to your child's doctor about your child's medical condition or treatment. do not share your child's needles and syringes with another person. your child may give another person an infection or your child could get an infection from them. important : - inject increlex exactly as your child's doctor or nurse has shown you. - follow your doctor's instructions for the type of syringe and needle to use to prepare and inject your child's dose of increlex . - always use a new, unopened needle and syringe for each injection. - only use single-use, disposable needles and syringes. never reuse disposable needles and syringes. - throw away used needles and syringes in a puncture-resistant, disposable sharps container as soon as you finish giving the injection. see step 5 "how should i throw away (dispose of) used needles and syringes? " at the end of these instructions. supplies needed to give the injection: - 1 vial of increlex - 1 alcohol swab - 1 gauze or cotton ball - alcohol (to clean the skin at the injection site) - 1 sharps container for throwing away (disposing of) used needles and syringes. see step 5 "how should i throw away (dispose of) used needles and syringes? " at the end of these instructions. preparing the dose: - wash your hands before getting increlex ready for your child's injection. - check the liquid to make sure it is clear and colorless. do not use if it is cloudy or if you see particles. - check the expiration date printed on the label of the vial. do not use increlex if the expiration date has passed. - if you are using a new vial, remove the protective cap. do not remove the rubber top (see figure 1). figure 1: remove the protective cap - wipe the rubber top on the vial with an alcohol swab (see figure 2). figure 2: wipe rubber top with alcohol swab - before putting the needle into the vial, pull back on plunger to draw air into the syringe equal to the increlex dose. put the needle through the rubber top of the vial and push the plunger to inject air into the vial (see figure 3). figure 3: inject air into vial - leave the syringe in the vial and turn both upside down. hold the syringe and vial firmly (see figure 4). figure 4: prepare to withdraw liquid - make sure the tip of the needle is in the liquid (see figure 5). pull the plunger to withdraw the correct dose into the syringe (see figure 6). figure 5: tip in liquidfigure 6: withdraw correct dose - before you take the needle out of the vial, check the syringe for air bubbles. if bubbles are in the syringe, hold the vial and syringe with needle straight up and tap the side of the syringe until the bubbles float to the top. push the bubbles out with the plunger and draw liquid back in until you have the correct dose (see figure 7). figure 7: remove air bubbles and refill syringe - remove the needle from the vial. do not let the needle touch anything. you are now ready to inject (see figure 8). figure 8: ready to inject injecting the dose: inject increlex exactly as your child's doctor or nurse has shown you. do not give the increlex injection if your child is unable to eat within 20 minutes before or after the injection . - put used needles and syringes in an fda-cleared sharps disposal container right away after use. do not throw away (dispose of) loose needles and syringes in your household trash. - do not try to touch the needle. - if you do not have an fda-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. - made of a heavy-duty plastic, - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how to throw away needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. - for the safety and health of you and others, needles and used syringes must never be re-used. - the used alcohol swabs, cotton balls, and gauze may be placed in your household trash. - do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. - always keep the sharps disposal container out of the reach of children. how should i store increlex? - before opening : store new, unopened vials of increlex in the refrigerator between 36°f to 46°f (2°c to 8°c). - after opening : store opened vials of increlex in the refrigerator between 36°f to 46°f (2°c to 8°c) for 30 days after you start using the vial. throw away any unused increlex after 30 days. - do not freeze increlex. if a vial freezes, throw it away. - keep increlex out of direct light. - do not use increlex after the expiration date printed on the label. keep increlex and all medicines out of reach of children. this instructions for use has been approved by the u.s. food and drug administration. for additional information, call 855-463-5127. manufactured by: ipsen biopharmaceuticals, inc. cambridge, ma 02142 usa u.s. license no. 2194 www.ipsenus.com revised: october 2023

Združene države Amerike - angleščina - NLM (National Library of Medicine)

nucare pharmaceuticals, inc. - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole 30 mg - lansoprazole delayed-release capsules are indicated for short-term treatment (for 4 weeks) for healing and symptom relief of active duodenal ulcer. [see clinical studies (14)] triple therapy: lansoprazole delayed-release capsules /amoxicillin /clarithromycin lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate h. pylori. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. [see clinical studies (14) ] please refer to the full prescribing information for amoxicillin and clarithromycin. dual therapy: lansoprazole delayed-release capsules /amoxicillin dual therapy: lansoprazole delayed-release capsules /amoxicillinlansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated for the treatment of patients with h. pylori infection and

Združene države Amerike - angleščina - NLM (National Library of Medicine)

preferred pharmaceuticals, inc. - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole 30 mg - lansoprazole delayed-release capsules are indicated for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies (14)] . lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy are indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate h. pylori . eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14)] . please refer to the full prescribing information for amoxicillin and clarithromycin. lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy are indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the c

Združene države Amerike - angleščina - NLM (National Library of Medicine)

preferred pharmaceuticals, inc. - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 30 mg - duloxetine delayed-release capsules are indicated for the treatment of major depressive disorder (mdd). the efficacy of duloxetine was established in four short term and one maintenance trial in adults [see clinical studies (14.1) ]. a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or a suicide attempt or suicidal ideation. duloxetine delayed-release capsules are indicated for the treatment of generalized anxiety disorder (gad). the efficacy of duloxetine was established in three short-term trials and one maintenance trial in adults [see clinical studies

Združene države Amerike - angleščina - NLM (National Library of Medicine)

lupin pharmaceuticals, inc. - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults and pediatric patients 13 years of age and older - chronic musculoskeletal pain in adults  the use of maois intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.8) and warnings and precautions  (5.4)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors the pregnancy outcomes in women exposed to antidepressants, including duloxetine, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for antidepressants at 1-866-961-2388 or online at  https://womensmentalhealth.org/research/pregnancyregistry/. risk summary data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see data). there are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to snris and ssris, including duloxetine, during pregnancy (see clinical considerations) . in rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (mrhd) of 120 mg/day given to adolescents on a mg/m2 basis. when duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the mrhd given to adolescents on a mg/m2 basis. at this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. post-weaning growth was not adversely affected. 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 embryo/fetal risk: women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis. it is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. maternal adverse reactions: use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.5)]. fetal/neonatal adverse reaction: neonates exposed to duloxetine and other 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 findings are consistent with either a direct toxic effect of the snris or ssris, 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 (5.4)] . data human data: data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% ci: 1.08 to 2.18). the same study did not find a clinically meaningful increase in the risk for major birth defects in the comparison of 2532 women exposed to duloxetine in the first trimester of pregnancy to 1,284,827 unexposed women after adjusting for several confounders. methodologic limitations include possible residual confounding, misclassification of exposure and outcomes, lack of direct measures of disease severity, and lack of information about alcohol use, nutrition, and over-the-counter medication exposures. animal data: in animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. when duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of malformations or developmental variations at doses up to 45 mg/kg/day [3 and 6 times, respectively, the mrhd of 120 mg/day given to adolescents on a mg/m2 basis]. however, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (approximately equal to the mrhd in rats and 2 times the mrhd in rabbits). when duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (2 times the mrhd given to adolescents on a mg/m2 basis); the no-effect dose was 10 mg/kg/day. furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment.   risk summary data from published literature report the presence of duloxetine in human milk (see data) . there are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk (see clinical considerations) . there are no data on the effect of duloxetine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for duloxetine and any potential adverse effects on the breastfed child from duloxetine or from the underlying maternal condition. clinical considerations infants exposed to duloxetine should be monitored for sedation, poor feeding and poor weight gain. data disposition of duloxetine was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants. the women were given 40 mg of duloxetine twice daily for 3.5 days. the peak concentration measured in breast milk occurred at a median of 3 hours after the dose. the amount of duloxetine in breast milk was approximately 7 mcg/day while on that dose; the estimated daily infant dose was approximately 2 mcg/kg/day, which is less than 1% of the maternal dose. the presence of duloxetine metabolites in breast milk was not examined.   the safety and effectiveness of duloxetine have been established for treatment of generalized anxiety disorder (gad) in patients 7 to 17 years of age. the safety and effectiveness of duloxetine have not been established in pediatric patients with major depressive disorder (mdd), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain. antidepressants increased the risk of suicidal thoughts and behavior in pediatric patients. monitor all pediatric patients being treated with antidepressants for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment, or at times of dosage changes [see warnings and precautions (5.1)] . perform regular monitoring of weight and growth in pediatric patients treated with duloxetine [see adverse reactions (6.1)] . generalized anxiety disorder use of duloxetine for the treatment of gad in patients 7 to 17 years of age is supported by one 10-week, placebo-controlled trial (gad-6). the study included 272 pediatric patients with gad of which 47% were 7 to 11 years of age (53% were 12 to 17 years of age). duloxetine demonstrated superiority over placebo as measured by greater improvement in the pediatric anxiety rating scale (pars) for gad severity score [see clinical studies (14.3)] . the safety and effectiveness of duloxetine for the treatment of gad in pediatric patients less than 7 years of age have not been established. fibromyalgia use of duloxetine for treatment of fibromyalgia in patients 13 to 17 years of age is supported by a 13-week placebo-controlled trial in 184 patients with juvenile fibromyalgia syndrome (study fm- 4). duloxetine showed improvement over placebo on the primary endpoint, change from baseline to end-of-treatment on the brief pain inventory (bpi) – modified short form: adolescent version 24-hour average pain severity rating [see clinical studies (14.5)] . the safety and effectiveness of duloxetine for the treatment of fibromyalgia in patients less than13 years of age have not been established. major depressive disorder the safety and effectiveness of duloxetine have not been established in pediatric patients for the treatment of mdd. efficacy of duloxetine was not demonstrated in two 10-week, placebo-controlled trials with 800 pediatric patients aged 7 to 17 years old with mdd (mdd-6 and mdd-7). neither duloxetine nor an active control (approved for treatment of pediatric mdd) was superior to placebo. the most frequently observed adverse reactions in the mdd pediatric clinical trials included nausea, headache, decreased weight, and abdominal pain. decreased appetite and weight loss have been observed in association with the use of ssris and snris. juvenile animal toxicology data duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued. these effects were observed at the high dose of 45 mg/kg/day (2 times the mrhd, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the mrhd, for a child). geriatric exposure in premarketing clinical trials of duloxetine - of the 2,418 patients in mdd trials, 6% (143) were 65 years of age or over. - of the 1041 patients in clbp trials, 21% (221) were 65 years of age or over. - of the 487 patients in oa trials, 41% (197) were 65 years of age or over. - of the 1,074 patients in the dpnp trials, 33% (357) were 65 years of age or over. - of the 1,761 patients in fm trials, 8% (140) were 65 years of age or over. in the mdd, gad, dpnp, fm, oa, and clbp studies, no overall differences in safety or effectiveness were generally observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between these geriatric and younger adult patients, but greater sensitivity of some older patients cannot be ruled out. ssris and snris, including duloxetine have been associated with clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.13)]. in an analysis of data from all placebo-controlled-trials, duloxetine-treated patients reported a higher rate of falls compared to placebo-treated patients. the increased risk appears to be proportional to a patient's underlying risk for falls. underlying risk appears to increase steadily with age. as geriatric patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during duloxetine treatment is unclear. falls with serious consequences including bone fractures and hospitalizations have been reported with duloxetine use [see warnings and  precautions (5.3) and adverse reactions (6.1)]. the pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 to 77 years) and healthy middle-age females (32 to 50 years). there was no difference in the cmax, but the auc of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females. population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. dosage adjustment based on the age of the adult patient is not necessary. duloxetine's half-life is similar in men and women. dosage adjustment based on gender is not necessary. duloxetine bioavailability (auc) appears to be reduced by about one-third in smokers. dosage modifications are not recommended for smokers. no specific pharmacokinetic study was conducted to investigate the effects of race. patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination. after a single 20 mg dose of duloxetine, 6 cirrhotic patients with moderate liver impairment (child-pugh class b) had a mean plasma duloxetine clearance about 15% that of age- and gender-matched healthy subjects, with a 5-fold increase in mean exposure (auc). although cmax was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see dosage and administration (2.7) and warnings and precautions (5.14)] . limited data are available on the effects of duloxetine in patients with end-stage renal disease (esrd). after a single 60 mg dose of duloxetine, cmax and auc values were approximately 100% greater in patients with esrd receiving chronic intermittent hemodialysis than in subjects with normal renal function. the elimination half-life, however, was similar in both groups. the aucs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. population pk analyses suggest that mild to moderate degrees of renal impairment (estimated crcl 30 to 80 ml/min) have no significant effect on duloxetine apparent clearance [see dosage and administration (2.7) and warnings and precautions (5.14)] . in animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. while duloxetine has not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior). in drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

Združene države Amerike - angleščina - NLM (National Library of Medicine)

pd-rx pharmaceuticals, inc. - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 60 mg - cymbalta ® is indicated for the treatment of: - major depressive disorder [see clinical studies ( 14.1)] - generalized anxiety disorder [see clinical studies ( 14.2)] - diabetic peripheral neuropathy [see clinical studies ( 14.3)] - fibromyalgia [see clinical studies ( 14.4)] - chronic musculoskeletal pain [see clinical studies ( 14.5)] monoamine oxidase inhibitors (maois) — the use of maois intended to treat psychiatric disorders with cymbalta or within 5 days of stopping treatment with cymbalta is contraindicated because of an increased risk of serotonin syndrome. the use of cymbalta within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration ( 2.8) and warnings and precautions ( 5.4)] . starting cymbalt