United States - English - NLM (National Library of Medicine)

remedyrepack inc. - ibuprofen (unii: wk2xyi10qm) (ibuprofen - unii:wk2xyi10qm) - carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before deciding to use ibuprofen. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). ibuprofen tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. ibuprofen tablets are indicated for relief of mild to moderate pain. ibuprofen tablets are also indicated for the treatment of primary dysmenorrhea. controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. ibuprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients (see warnings, anaphylactoid reactions and precautions, preexisting asthma). ibuprofen tablets are contraindicated in the setting of coronary artery bypass graft (cabg) surgery (see warnings ).

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - mirtazapine (unii: a051q2099q) (mirtazapine - unii:a051q2099q) - mirtazapine tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)]. mirtazapine tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.3), drug interactions (7)]. - with a known hypersensitivity to mirtazapine or to any ofthe excipients in mirtazapine tablets. severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (dress), stevens-johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine tablets [see warnings and precautions (5.6), adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. risk summary prolonged experience with mirtazapine in pregnant women, based on published observational studies and postmarketing reports, has not reliably identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there are risks associated with untreated depression in pregnancy (see clinical considerations). in animal reproduction studies, oral administration of mirtazpine to pregnant rats and rabbits during the period of organogenesis revealed no evidence of teratogenic effects up to 20 and 17 times the maximum recommended human dose (mrhd) of 45 mg, respectively, based on mg/m 2 body surface area. however, in rats, there was an increase in postimplantation loss at 20 times the mrhd based on mg/m 2 body surface area. oral administration of mirtazapine to pregnant rats during pregnancy and lactation resulted in an increase in pup deaths and a decrease in pup birth weights at doses 20 times the mrhd based on mg/m 2 body surface area (see data). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or 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. data animal data mirtazapine was administered orally to pregnant rats and rabbits during the period of organogenesis at doses of 2.5, 15, and 100 mg/kg/day and 2.5, 10, and 40 mg/kg/day, respectively, which are up to 20 and 17 times the maximum recommended human dose (mrhd) of 45 mg based on mg/m 2 body surface area, respectively. no evidence of teratogenic effects was observed. however, in rats, there was an increase in postimplantation loss in dams treated with mirtazapine at 100 mg/kg/day which is 20 times the mrhd based on mg/m 2 body surface area. oral administration of mirtazapine at doses of 2.5, 15, and 100 mg/kg/day to pregnant rats during pregnancy and lactation resulted in an increase in pup deaths during the first 3 days of lactation and a decrease in pup birth weights at 20 times the mrhd based on mg/m 2 body surface area. the cause of these deaths is not known. the no effect dose level is 3 times the mrhd based on mg/m 2 body surface area. risk summary data from published literature report the presence of mirtazapine in human milk at low levels with relative infant doses for mirtazapine ranging between 0.6 and 2.8% of the maternal weight-adjusted dose (see data) . no adverse effects on the breastfed infant have been reported in most cases of maternal use of mirtazapine. there are no data on the effects of mirtazapine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mirtazapine and any potential adverse effects on the breastfed infant from mirtazapine or from the underlying maternal condition. data in a published pooled analysis of 8 breastfeeding mother-infant pairs, the mean (min, max) total relative infant doses for mirtazapine and its desmethyl metabolite were 1.5% (0.6%, 2.8%) and 0.4% (0.1%, 0.7%) of the maternal weight-adjusted dose (median (min, max) dose of 38 mg (30 mg, 120 mg), respectively). no adverse drug effects were reported for any of the infants. the safety and effectiveness of mirtazapine have not been established in pediatric patients with mdd. two placebo-controlled trials in 258 pediatric patients with mdd have been conducted with mirtazapine, and the data were insufficient to establish the safety and effectiveness of mirtazapine in pediatric patients with mdd. antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see  boxed warningand warnings and precautions (5.1)]. in an 8-week-long clinical trial in pediatric patients receiving doses between 15 to 45 mg per day, 49% of mirtazapine-treated patients had a weight gain of at least 7%, compared to 5.7% of placebo-treated patients. the mean increase in weight was 4 kg (2 kg sd) for mirtazapine-treated patients versus 1 kg (2 kg sd) for placebo-treated patients [see warnings and precautions (5.7)]. approximately 190 patients ≥65 years of age participated in clinical studies with mirtazapine. mirtazapine is known to be substantially excreted by the kidney (75%), and the risk of decreased clearance of this drug is greater in patients with impaired renal function. pharmacokinetic studies revealed a decreased clearance of mirtazapine in the elderly [see clinical pharmacology (12.3)]. sedating drugs, including mirtazapine, may cause confusion and over-sedation in the elderly. elderly patients may be at greater risk of developing hyponatremia. caution is indicated when administering mirtazapine to elderly patients [see warnings and precautions (5.12),  (5.15)and clinical pharmacology (12.3)] . in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. the clearance of mirtazapine is reduced in patients with moderate to severe renal or hepatic impairment. consequently, plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in patients without renal or hepatic impairment. dosage decrease may be necessary when administering mirtazapine to patients with moderate to severe renal or hepatic impairment [see warnings and precautions (5.13), use in specific populations (8.5), and clinical pharmacology (12.3)].

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - ibuprofen (unii: wk2xyi10qm) (ibuprofen - unii:wk2xyi10qm) - carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before deciding to use ibuprofen. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). ibuprofen tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. ibuprofen tablets are indicated for relief of mild to moderate pain. ibuprofen tablets are also indicated for the treatment of primary dysmenorrhea. controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. ibuprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients (see warnings, anaphylactoid reactions and precautions, preexisting asthma). ibuprofen tablets are contraindicated in the setting of coronary artery bypass graft (cabg) surgery (see warnings ).

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline tablets are indicated for the treatment of the following [see clinical studies (14)] : - major depressive disorder (mdd) - obsessive-compulsive disorder (ocd) - panic disorder (pd) - posttraumatic stress disorder (ptsd) - social anxiety disorder (sad) - premenstrual dysphoric disorder (pmdd) sertraline is contraindicated in patients: - taking, or within 14 days of stopping, maois, (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7.1)] . - taking pimozide [ see drug interactions (7.1)] . - with known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [see adverse reactions (6.1, 6.2)]. pregnancy exposure registry  there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers should encourage patients to enroll by calling the national pregnancy registry for antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants. risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with less than 2-fold increase in the risk of postpartum hemorrhage  [see warnings and precautions (5.3)and clinical considerations]. overall, available published epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in comparator populations. some studies have reported increases for specific major birth defects; however, these study results are inconclusive [see data]. there are clinical considerations regarding neonates exposed to ssris and snris, including sertraline, during the third trimester of pregnancy [see clinical considerations]. although no teratogenicity was observed in animal reproduction studies, delayed fetal ossification was observed when sertraline was administered during the period of organogenesis at doses less than the maximum recommended human dose (mrhd) in rats and doses 3.1 times the mrhd in rabbits on a mg/m2 basis in adolescents. when sertraline was administered to female rats during the last third of gestation, there was an increase in the number of stillborn pups and pup deaths during the first four days after birth at the mrhd [see data]. the background risk of major birth defects and miscarriage for the indicated population are 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. advise a pregnant woman of possible risks to the fetus when prescribing sertraline. clinical considerations disease-associated maternal and/or embryo/fetal risk a prospective longitudinal study followed 201 pregnant women with a history of major depression who were euthymic taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of sertraline in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.3)]. fetal/neonatal adverse reactions exposure to ssris and snris, including sertraline in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (pphn). when treating a pregnant woman with sertraline during the third trimester, carefully consider both the potential risks and benefits of treatment. monitor neonates who were exposed to sertraline in the third trimester of pregnancy for pphn and drug discontinuation syndrome [see data]. data human data third trimester exposure neonates exposed to sertraline and other ssris or snris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. these findings are based on post-marketing reports. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. in some cases, the clinical picture was consistent with serotonin syndrome [see warnings and precautions (5.2)] . exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. in a retrospective case-control study of 377 women whose infants were born with pphn and 836 women whose infants were born healthy, the risk for developing pphn was approximately six-fold higher for infants exposed to ssris after the 20 th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. a study of 831,324 infants born in sweden in 1997-2005 found a pphn risk ratio of 2.4 (95% ci 1.2-4.3) associated with patient-reported maternal use of ssris “in early pregnancy” and a pphn risk ratio of 3.6 (95% ci 1.2-8.3) associated with a combination of patient-reported maternal use of ssris “in early pregnancy” and an antenatal ssri prescription “in later pregnancy”. first trimester exposure the weight of evidence from epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in pregnant women who were not exposed to sertraline. a meta-analysis of studies suggest no increase in the risk of total malformations (summary odds ratio=1.01, 95% ci=0.88-1.17) or cardiac malformations (summary odds ratio=0.93, 95% ci=0.70-1.23) among offspring of women with first trimester exposure to sertraline. an increased risk of congenital cardiac defects, specifically septal defects, the most common type of congenital heart defect, was observed in some published epidemiologic studies with first trimester sertraline exposure; however, most of these studies were limited by the use of comparison populations that did not allow for the control of confounders such as the underlying depression and associated conditions and behaviors, which may be factors associated with increased risk of these malformations. animal data reproduction studies have been performed in rats and rabbits at doses up to 80 mg/kg/day and 40 mg/kg/day, respectively. these doses correspond to approximately 3.1 times the maximum recommended human dose (mrhd) of 200 mg/day on a mg/m2 basis in adolescents. there was no evidence of teratogenicity at any dose level. when pregnant rats and rabbits were given sertraline during the period of organogenesis, delayed ossification was observed in fetuses at doses of 10 mg/kg (0.4 times the mrhd on a mg/m2 basis) in rats and 40 mg/kg (3.1 times the mrhd on a mg/m2 basis) in rabbits. when female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in stillborn pups and pup deaths during the first 4 days after birth. pup body weights were also decreased during the first four days after birth. these effects occurred at a dose of 20 mg/kg (0.8 times the mrhd on a mg/m2 basis). the no effect dose for rat pup mortality was 10 mg/kg (0.4 times the mrhd on a mg/m2 basis). the decrease in pup survival was shown to be due to in utero exposure to sertraline. the clinical significance of these effects is unknown. risk summary available data from published literature demonstrate low levels of sertraline and its metabolites in human milk [see data] . there are no data on the effects of sertraline on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sertralineand any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. data in a published pooled analysis of 53 mother-infant pairs, exclusively human milk-fed infants had an average of 2% (range 0% to 15%) of the sertraline serum levels measured in their mothers. no adverse reactions were observed in these infants. the safety and efficacy of sertralinehave been established in the treatment of ocd in pediatric patients aged 6 to 17 [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)] . safety and effectiveness in pediatric patients in patients with ocd below the age of 6 have not been established. safety and effectiveness have not been established in pediatric patients for indications other than ocd. two placebo-controlled trials were conducted in pediatric patients with mdd, but the data were not sufficient to support an indication for use in pediatric patients. monitoring pediatric patients treated with sertraline monitor all patients being treated with antidepressants for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during the initial few months of treatment, or at times of dose increases or decreases [see boxed warning, warnings and precautions (5.1)] . decreased appetite and weight loss have been observed with the use of ssris. monitor weight and growth in pediatric patients treated with an ssri such as sertraline. weight loss in studies in pediatric patients with mdd in a pooled analysis of two 10-week, double-blind, placebo-controlled, flexible dose (50-200 mg) outpatient trials for mdd (n=373), there was a difference in weight change between sertralineand placebo of roughly 1 kg, for both children (ages 6-11) and adolescents (ages 12-17), in both age groups representing a slight weight loss for the sertralinegroup compared to a slight gain for the placebo group. for children, about 7% of the sertraline-treated patients had a weight loss greater than 7% of body weight compared to 0% of the placebo-treated patients; for adolescents, about 2% of sertraline-treated patients had a weight loss > 7% of body weight compared to about 1% of placebo-treated patients. a subset of patients who completed the randomized controlled trials in patients with mdd (sertralinen=99, placebo n=122) were continued into a 24-week, flexible-dose, open-label, extension study. those subjects who completed 34 weeks of sertralinetreatment (10 weeks in a placebo-controlled trial + 24 weeks open-label, n=68) had weight gain that was similar to that expected using data from age-adjusted peers. however, there are no studies that directly evaluate the long-term effects of sertralineon the growth, development, and maturation in pediatric patients. juvenile animal data a study conducted in juvenile rats at clinically relevant doses showed delay in sexual maturation, but there was no effect on fertility in either males or females. in this study in which juvenile rats were treated with oral doses of sertraline at 0, 10, 40 or 80 mg/kg/day from postnatal day 21 to 56, a delay in sexual maturation was observed in males treated with 80 mg/kg/day and females treated with doses ≥10 mg/kg/day. there was no effect on male and female reproductive endpoints or neurobehavioral development up to the highest dose tested (80 mg/kg/day), except a decrease in auditory startle response in females at 40 and 80 mg/kg/day at the end of treatment but not at the end of the drug –free period. the highest dose of 80 mg/kg/day produced plasma levels (auc) of sertraline 5 times those seen in pediatric patients (6 – 17 years of age) receiving the maximum recommended dose of sertraline (200 mg/day). of the total number of patients in clinical studies of sertraline in patients with mdd, ocd, pd, ptsd, sad and pmdd, 797 (17%) were ≥ 65 years old, while 197 (4%) were ≥ 75 years old. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. in 354 geriatric subjects treated with sertraline in mdd placebo-controlled trials, the overall profile of adverse reactions was generally similar to that shown in table 3 [see adverse reactions (6.1)], except for tinnitus, arthralgia with an incidence of at least 2% and at a rate greater than placebo in geriatric patients. snris and ssris, including sertraline, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.8) ] . the recommended dosage in patients with mild hepatic impairment (child-pugh score 5 or 6) is half the recommended dosage due to increased exposure in this patient population. the use of sertraline in patients with moderate (child-pugh score 7 to 10) or severe hepatic impairment (child-pugh score 10-15) is not recommended, because sertraline is extensively metabolized, and the effects of sertraline in patients with moderate and severe hepatic impairment have not been studied  [see dosage and administration (2.4), clinical pharmacology (12.3)] . no dose adjustment is needed in patients with mild to severe renal impairment. sertraline exposure does not appear to be affected by renal impairment [see clinical pharmacology (12.3)] . sertraline is not a controlled substance. in a placebo-controlled, double-blind, randomized study of the comparative abuse liability of sertraline, alprazolam, and d-amphetamine in humans, sertraline did not produce the positive subjective effects indicative of abuse potential, such as euphoria or drug liking, that were observed with the other two drugs.

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole sodium  delayed-release tablets are indicated for: pantoprazole sodium is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (ee). for those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium may be considered. safety of treatment beyond 8 weeks in pediatric patients has not been established. pantoprazole sodium is indicated for maintenance of healing of ee and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gerd. controlled studies did not extend beyond 12 months. pantoprazole sodium is indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison (ze) syndrome. - pantoprazole sodium is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6)]. - proton pump inhibitors (ppis), including pantoprazole sodium, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . risk summary available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole. in animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see data) . a pre-and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (gd) 6 through lactation day (ld) 21. changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (pnd) 4 through pnd 21 [see use in specific populations (8.4)]. there were no drug-related findings in maternal animals. advise pregnant women of the potential risk of fetal harm. 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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (ppis). there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=0.55, [95% confidence interval (ci) 0.08 to 3.95]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations or=1.12 ([95% ci 0.86 to 1.45] and for spontaneous abortions or=1.29 [95% ci 0.84 to 1.97]). animal data reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. the studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. a pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (gd) 6 through lactation day (ld) 21. on postnatal day (pnd 4) through pnd 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (auc) in humans at a dose of 40 mg). there were no drug-related findings in maternal animals. during the preweaning dosing phase (pnd 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (auc) in humans receiving the 40 mg dose) and higher doses. on pnd 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (auc) in humans at the 40 mg dose) and higher doses. the femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. there were no microscopic changes in the distal femur, proximal tibia, or stifle joints. changes in bone parameters were partially reversible following a recovery period, with findings on pnd 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (auc) in humans at the 40 mg dose) and higher doses. risk summary pantoprazole has been detected in breast milk of a nursing mother after a single 40 mg oral dose of pantoprazole. there were no effects on the breastfed infant (see data) . there are no data on pantoprazole effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pantoprazole sodium and any potential adverse effects on the breastfed child from pantoprazole or from the underlying maternal condition. data the breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10 months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole present in the breast milk. pantoprazole was detectable in milk only 2 and 4 hours after the dose with milk levels of approximately 36 mcg/l and 24 mcg/l, respectively. a milk-to-plasma ratio of 0.022 was observed at 2 hours after drug administration. pantoprazole was not detectable (<10 mcg/l) in milk at 6, 8 and 24 hours after the dose. the relative dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to 0.14% of the weight-adjusted maternal dose. no adverse events in the infant were reported by the mother. the safety and effectiveness of pantoprazole sodium for short-term treatment (up to eight weeks) of  ee associated with gerd have been established in pediatric patients 1 year through 16 years of age. effectiveness for ee has not been demonstrated in patients less than 1 year of age. in addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. therefore, pantoprazole sodium are indicated for the short-term treatment of ee associated with gerd for patients 5 years and older. the safety and effectiveness of pantoprazole sodium for pediatric uses other than ee have not been established. 1 year through 16 years of age use of pantoprazole sodium in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of ee associated with gerd is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of pantoprazole sodium for treatment of ee associated with gerd in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see clinical studies (14.1), clinical pharmacology (12.3)]. safety of pantoprazole sodium in the treatment of ee associated with gerd in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with ee (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). the children ages 1 year to 5 years with endoscopically diagnosed ee (defined as an endoscopic hetzel-dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole sodium (approximating 0.6 mg/kg or 1.2 mg/kg). all 4 of these patients with ee were healed (hetzel-dent score of 0 or 1) at 8 weeks. because ee is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic gerd were also included in these studies. patients were treated with a range of doses of pantoprazole sodium once daily for 8 weeks. for safety findings see adverse reactions (6.1) . because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of pantoprazole sodium for symptomatic gerd in the pediatric population. the effectiveness of pantoprazole sodium for treating symptomatic gerd in pediatric patients has not been established. although the data from the clinical trials support use of pantoprazole sodium for the short-term treatment of ee associated with gerd in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see dosage and administration (2) ]. in a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven gerd had a median value of 2.4 l/h. following a 1.2 mg/kg equivalent dose (15 mg for ≤12.5 kg and 20 mg for >12.5 to <25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. the estimated auc for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean auc value of 6.8 mcg•hr/ml. neonates to less than one year of age pantoprazole sodium were not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. patients were enrolled if they had symptomatic gerd based on medical history and had not responded to non-pharmacologic interventions for gerd for two weeks. patients received pantoprazole sodium daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive pantoprazole sodium treatment or placebo for the subsequent four weeks in a double-blind manner. efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. there was no statistically significant difference between pantoprazole sodium and placebo in the rate of discontinuation. in this trial, the adverse reactions that were reported more commonly (difference of ≥4%) in the treated population compared to the placebo population were elevated ck, otitis media, rhinitis, and laryngitis. in a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with gerd compared to adults who received a single 40 mg dose (geometric mean auc was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of pantoprazole sodium, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). in these patients, the apparent clearance (cl/f) increased with age (median clearance: 0.6 l/hr, range: 0.03 to 3.2 l/hr). these doses resulted in pharmacodynamic effects on gastric but not esophageal ph. following once daily dosing of 2.5 mg of pantoprazole sodium in preterm infants and neonates, there was an increase in the mean gastric ph (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric ph was > 4 (from 60% at baseline to 80% at steady-state). following once daily dosing of approximately 1.2 mg/kg of pantoprazole sodium in infants 1 through 11 months of age, there was an increase in the mean gastric ph (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric ph was > 4 (from 32% at baseline to 60% at steady-state). however, no significant changes were observed in mean intraesophageal ph or % time that esophageal ph was <4 in either age group. because pantoprazole sodium were not shown to be effective in the randomized, placebo-controlled study in this age group, the use of pantoprazole sodium for treatment of symptomatic gerd in infants less than 1 year of age is not indicated. animal toxicity data in a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (auc) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (pnd 4) through pnd 21, in addition to lactational exposure through milk. on pnd 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (auc) in children aged 6 to 11 years at the 40 mg dose) and higher doses. changes in bone parameters were partially reversible following a recovery period.   in neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. an increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. full to partial recovery of these effects were noted in animals of both age groups following a recovery period.       in short-term u.s. clinical trials, ee healing rates in the 107 elderly patients (≥65 years old) treated with pantoprazole sodium were similar to those found in patients under the age of 65. the incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.    

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remedyrepack inc. - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see warnings and precautions ( 5.7) and use in specific populations ( 8.1)] . warfarin sodium can cause fetal harm when administered to a pregnant woman. warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. if warfarin sodium is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see use in specific populations ( 8.1)] . warfarin sodium is contraindicated in patients with: - hemorrhagic tendencies or blood dyscrasias - recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see warnings and precautions ( 5.8)] - bleeding tendencies associated with: − active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract − central nervous system hemorrhage − cerebral aneurysms, dissecting aorta − pericarditis and pericardial effusions − bacterial endocarditis - threatened abortion, eclampsia, and preeclampsia - unsupervised patients with conditions associated with potential high level of non-compliance - spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding - hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see adverse reactions ( 6)] - major regional or lumbar block anesthesia - malignant hypertension risk summary warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of warfarin sodium may outweigh the risks [see warnings and precautions ( 5.7)] . warfarin sodium can cause fetal harm. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the u.s. general population and may not reflect the incidences observed in practice. consider the benefits and risks of warfarin sodium and possible risks to the fetus when prescribing warfarin sodium to a pregnant woman. adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions in humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, dandy-walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see contraindications ( 4)] . risk summary warfarin was not present in human milk from mothers treated with warfarin from a limited published study. because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for warfarin sodium and any potential adverse effects on the breastfed infant from warfarin sodium or from the underlying maternal condition before prescribing warfarin sodium to a lactating woman. clinical considerations monitor breastfeeding infants for bruising or bleeding. data human data based on published data in 15 nursing mothers, warfarin was not detected in human milk. among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. prothrombin times were not obtained for the other 9 nursing infants. effects in premature infants have not been evaluated. pregnancy testing warfarin sodium can cause fetal harm [see use in specific populations ( 8.1)] . verify the pregnancy status of females of reproductive potential prior to initiating warfarin sodium therapy. contraception females advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of warfarin sodium. adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. pediatric patients administered warfarin sodium should avoid any activity or sport that may result in traumatic injury. the developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target inrs. because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target inr ranges may be difficult to achieve and maintain in pediatric patients, and more frequent inr determinations are recommended. bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. infants and children receiving vitamin k-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy. of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. no overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. patients 60 years or older appear to exhibit greater than expected inr response to the anticoagulant effects of warfarin [see clinical pharmacology ( 12.3)] . warfarin sodium is contraindicated in any unsupervised patient with senility. conduct more frequent monitoring for bleeding with administration of warfarin sodium to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. consider lower initiation and maintenance doses of warfarin sodium in elderly patients [see dosage and administration ( 2.2, 2.3)] . renal clearance is considered to be a minor determinant of anticoagulant response to warfarin. no dosage adjustment is necessary for patients with renal impairment. instruct patients with renal impairment taking warfarin to monitor their inr more frequently [see warnings and precautions ( 5.4)] . hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. conduct more frequent monitoring for bleeding when using warfarin sodium in these patients.

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remedyrepack inc. - lamotrigine (unii: u3h27498ks) (lamotrigine - unii:u3h27498ks) - adjunctive therapy: lamotrigine is indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: - partial-onset seizures. - primary generalized tonic-clonic (pgtc) seizures. - generalized seizures of lennox-gastaut syndrome. monotherapy: lamotrigine is indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (aed). safety and effectiveness of lamotrigine have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from aeds other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant aeds. lamotrigine is indicated for the maintenance treatment of bipolar i disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see clinical studies (14.2)] . limitations of use: treatment of acute manic or mixed episodes is not recommended. effectiveness of lamotrigine in the acute treatment of mood episodes has not been established. lamotrigine is contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients [see boxed warning, warnings and precautions (5.1, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, including lamotrigine, during pregnancy. encourage women who are taking lamotrigine tablets during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population (see data) . the majority of lamotrigine pregnancy exposure data are from women with epilepsy. in animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities) at doses lower than those administered clinically. lamotrigine decreased fetal folate concentrations in rats, an effect known to be associated with adverse pregnancy outcomes in animals and humans (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations as with other aeds, physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. there have been reports of decreased lamotrigine concentrations during pregnancy and restoration of pre-pregnancy concentrations after delivery. dose adjustments may be necessary to maintain clinical response. data human data: data from several international pregnancy registries have not shown an increased risk for malformations overall. the international lamotrigine pregnancy registry reported major congenital malformations in 2.2% (95% ci: 1.6%, 3.1%) of 1,558 infants exposed to lamotrigine monotherapy in the first trimester of pregnancy. the naaed pregnancy registry reported major congenital malformations among 2.0% of 1,562 infants exposed to lamotrigine monotherapy in the first trimester. eurap, a large international pregnancy registry focused outside of north america, reported major birth defects in 2.9% (95% ci: 2.3%, 3.7%) of 2,514 exposures to lamotrigine monotherapy in the first trimester. the frequency of major congenital malformations was similar to estimates from the general population. the naaed pregnancy registry observed an increased risk of isolated oral clefts: among 2,200 infants exposed to lamotrigine early in pregnancy, the risk of oral clefts was 3.2 per 1,000 (95% ci: 1.4, 6.3), a 3-fold increased risk versus unexposed healthy controls. this finding has not been observed in other large international pregnancy registries. furthermore, a case-control study based on 21 congenital anomaly registries covering over 10 million births in europe reported an adjusted odds ratio for isolated oral clefts with lamotrigine exposure of 1.45 (95% ci: 0.8, 2.63). several meta-analyses have not reported an increased risk of major congenital malformations following lamotrigine exposure in pregnancy compared with healthy and disease-matched controls. no patterns of specific malformation types were observed. the same meta-analyses evaluated the risk of additional maternal and infant outcomes including fetal death, stillbirth, preterm birth, small for gestational age, and neurodevelopmental delay. although there are no data suggesting an increased risk of these outcomes with lamotrigine monotherapy exposure, differences in outcome definition, ascertainment methods, and comparator groups limit the conclusions that can be drawn. animal data: when lamotrigine was administered to pregnant mice, rats, or rabbits during the period of organogenesis (oral doses of up to 125, 25, and 30 mg/kg, respectively), reduced fetal body weight and increased incidences of fetal skeletal variations were seen in mice and rats at doses that were also maternally toxic. the no-effect doses for embryofetal developmental toxicity in mice, rats, and rabbits (75, 6.25, and 30 mg/kg, respectively) are similar to (mice and rabbits) or less than (rats) the human dose of 400 mg/day on a body surface area (mg/m 2 ) basis. in a study in which pregnant rats were administered lamotrigine (oral doses of 0, 5, or 25 mg/kg) during the period of organogenesis and offspring were evaluated postnatally, neurobehavioral abnormalities were observed in exposed offspring at both doses. the lowest effect dose for developmental neurotoxicity in rats is less than the human dose of 400 mg/day on a mg/m 2 basis. maternal toxicity was observed at the higher dose tested. when pregnant rats were administered lamotrigine (oral doses of 0, 5, 10, or 20 mg/kg) during the latter part of gestation and throughout lactation, increased offspring mortality (including stillbirths) was seen at all doses. the lowest effect dose for pre- and post-natal developmental toxicity in rats is less than the human dose of 400 mg/day on a mg/m 2 basis. maternal toxicity was observed at the 2 highest doses tested. when administered to pregnant rats, lamotrigine decreased fetal folate concentrations at doses greater than or equal to 5 mg/kg/day, which is less than the human dose of 400 mg/day on a mg/m 2 basis. risk summary lamotrigine is present in milk from lactating women taking lamotrigine tablets (see data) . neonates and young infants are at risk for high serum levels because maternal serum and milk levels can rise to high levels postpartum if lamotrigine dosage has been increased during pregnancy but is not reduced after delivery to the pre-pregnancy dosage. glucuronidation is required for drug clearance. glucuronidation capacity is immature in the infant and this may also contribute to the level of lamotrigine exposure. events including rash, apnea, drowsiness, poor sucking, and poor weight gain (requiring hospitalization in some cases) have been reported in infants who have been human milk-fed by mothers using lamotrigine; whether or not these events were caused by lamotrigine is unknown. no data are available on 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 lamotrigine tablets and any potential adverse effects on the breastfed infant from lamotrigine or from the underlying maternal condition. clinical considerations human milk-fed infants should be closely monitored for adverse events resulting from lamotrigine. measurement of infant serum levels should be performed to rule out toxicity if concerns arise. human milk-feeding should be discontinued in infants with lamotrigine toxicity. data data from multiple small studies indicate that lamotrigine plasma levels in nursing infants have been reported to be as high as 50% of maternal plasma concentrations. epilepsy lamotrigine is indicated as adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of lennox-gastaut syndrome, and pgtc seizures. safety and efficacy of lamotrigine used as adjunctive treatment for partial-onset seizures were not demonstrated in a small, randomized, double-blind, placebo-controlled withdrawal trial in very young pediatric patients (aged 1 to 24 months). lamotrigine was associated with an increased risk for infectious adverse reactions (lamotrigine 37%, placebo 5%), and respiratory adverse reactions (lamotrigine 26%, placebo 5%). infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection. respiratory adverse reactions included nasal congestion, cough, and apnea. bipolar disorder safety and efficacy of lamotrigine for the maintenance treatment of bipolar disorder were not established in a double-blind, randomized withdrawal, placebo-controlled trial that evaluated 301 pediatric patients aged 10 to 17 years with a current manic/hypomanic, depressed, or mixed mood episode as defined by dsm-iv-tr. in the randomized phase of the trial, adverse reactions that occurred in at least 5% of patients taking lamotrigine (n = 87) and were twice as common compared with patients taking placebo (n = 86) were influenza (lamotrigine 8%, placebo 2%), oropharyngeal pain (lamotrigine 8%, placebo 2%), vomiting (lamotrigine 6%, placebo 2%), contact dermatitis (lamotrigine 5%, placebo 2%), upper abdominal pain (lamotrigine 5%, placebo 1%), and suicidal ideation (lamotrigine 5%, placebo 0%). juvenile animal data in a juvenile animal study in which lamotrigine (oral doses of 0, 5, 15, or 30 mg/kg) was administered to young rats from postnatal day 7 to 62, decreased viability and growth were seen at the highest dose tested and long-term neurobehavioral abnormalities (decreased locomotor activity, increased reactivity, and learning deficits in animals tested as adults) were observed at the 2 highest doses. the no-effect dose for adverse developmental effects in juvenile animals is less than the human dose of 400 mg/day on a mg/m 2 basis. clinical trials of lamotrigine for epilepsy and bipolar disorder did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients or exhibit a different safety profile than that of younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. experience in patients with hepatic impairment is limited. based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment [see clinical pharmacology (12.3)] , the following general recommendations can be made. no dosage adjustment is needed in patients with mild liver impairment. initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. escalation and maintenance doses may be adjusted according to clinical response [see dosage and administration (2.1)]. lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites being recovered in the urine. in a small study comparing a single dose of lamotrigine in subjects with varying degrees of renal impairment with healthy volunteers, the plasma half-life of lamotrigine was approximately twice as long in the subjects with chronic renal failure [see clinical pharmacology (12.3)] . initial doses of lamotrigine should be based on patients' aed regimens; reduced maintenance doses may be effective for patients with significant renal impairment. few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. because there is inadequate experience in this population, lamotrigine should be used with caution in these patients [see dosage and administration (2.1)] .

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - lamotrigine (unii: u3h27498ks) (lamotrigine - unii:u3h27498ks) - adjunctive therapy lamotrigine tablets are indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: - partial-onset seizures. - primary generalized tonic-clonic (pgtc) seizures. - generalized seizures of lennox-gastaut syndrome. monotherapy lamotrigine tablets are indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (aed). safety and effectiveness of lamotrigine tablets have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from aeds other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant aeds. lamotrigine tablets are indicated for the maintenance treatment of bipolar i disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see clinical studies ( 14.2)]. limitations of use treatment of acute manic or mixed episodes is not recommended. effectiveness of lamotrigine tablets in the acute treatment of mood episodes has not been established. lamotrigine tablets are contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients [see boxed warning, warnings and precautions ( 5.1, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, including lamotrigine, during pregnancy. encourage women who are taking lamotrigine during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population ( see data ). the majority of lamotrigine pregnancy exposure data are from women with epilepsy. in animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities) at doses lower than those administered clinically. lamotrigine decreased fetal folate concentrations in rats, an effect known to be associated with adverse pregnancy outcomes in animals and humans ( see data ). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations as with other aeds, physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. there have been reports of decreased lamotrigine concentrations during pregnancy and restoration of pre-pregnancy concentrations after delivery. dose adjustments may be necessary to maintain clinical response. data human data : data from several international pregnancy registries have not shown an increased risk for malformations overall. the international lamotrigine pregnancy registry reported major congenital malformations in 2.2% (95% ci: 1.6%, 3.1%) of 1,558 infants exposed to lamotrigine monotherapy in the first trimester of pregnancy. the naaed pregnancy registry reported major congenital malformations among 2.0% of 1,562 infants exposed to lamotrigine monotherapy in the first trimester. eurap, a large international pregnancy registry focused outside of north america, reported major birth defects in 2.9% (95% ci: 2.3%, 3.7%) of 2,514 exposures to lamotrigine monotherapy in the first trimester. the frequency of major congenital malformations was similar to estimates from the general population. the naaed pregnancy registry observed an increased risk of isolated oral clefts: among 2,200 infants exposed to lamotrigine early in pregnancy, the risk of oral clefts was 3.2 per 1,000 (95% ci: 1.4, 6.3), a 3-fold increased risk versus unexposed healthy controls. this finding has not been observed in other large international pregnancy registries. furthermore, a case-control study based on 21 congenital anomaly registries covering over 10 million births in europe reported an adjusted odds ratio for isolated oral clefts with lamotrigine exposure of 1.45 (95% ci: 0.8, 2.63). several meta-analyses have not reported an increased risk of major congenital malformations following lamotrigine exposure in pregnancy compared with healthy and disease-matched controls. no patterns of specific malformation types were observed. the same meta-analyses evaluated the risk of additional maternal and infant outcomes including fetal death, stillbirth, preterm birth, small for gestational age, and neurodevelopmental delay. although there are no data suggesting an increased risk of these outcomes with lamotrigine monotherapy exposure, differences in outcome definition, ascertainment methods, and comparator groups limit the conclusions that can be drawn. animal data : when lamotrigine was administered to pregnant mice, rats, or rabbits during the period of organogenesis (oral doses of up to 125, 25, and 30 mg/kg, respectively), reduced fetal body weight and increased incidences of fetal skeletal variations were seen in mice and rats at doses that were also maternally toxic. the no-effect doses for embryofetal developmental toxicity in mice, rats, and rabbits (75, 6.25, and 30 mg/kg, respectively) are similar to (mice and rabbits) or less than (rats) the human dose of 400 mg/day on a body surface area (mg/m 2 ) basis. in a study in which pregnant rats were administered lamotrigine (oral doses of 0, 5, or 25 mg/kg) during the period of organogenesis and offspring were evaluated postnatally, neurobehavioral abnormalities were observed in exposed offspring at both doses. the lowest effect dose for developmental neurotoxicity in rats is less than the human dose of 400 mg/day on a mg/m 2 basis. maternal toxicity was observed at the higher dose tested. when pregnant rats were administered lamotrigine (oral doses of 0, 5, 10, or 20 mg/kg) during the latter part of gestation and throughout lactation, increased offspring mortality (including stillbirths) was seen at all doses. the lowest effect dose for pre- and postnatal developmental toxicity in rats is less than the human dose of 400 mg/day on a mg/m 2 basis. maternal toxicity was observed at the 2 highest doses tested. when administered to pregnant rats, lamotrigine decreased fetal folate concentrations at doses greater than or equal to 5 mg/kg/day, which is less than the human dose of 400 mg/day on a mg/m 2 basis. risk summary lamotrigine is present in milk from lactating women taking lamotrigine (see data) . neonates and young infants are at risk for high serum levels because maternal serum and milk levels can rise to high levels postpartum if lamotrigine dosage has been increased during pregnancy but is not reduced after delivery to the pre-pregnancy dosage. glucuronidation is required for drug clearance. glucuronidation capacity is immature in the infant and this may also contribute to the level of lamotrigine exposure. events including rash, apnea, drowsiness, poor sucking, and poor weight gain (requiring hospitalization in some cases) have been reported in infants who have been human milk-fed by mothers using lamotrigine; whether or not these events were caused by lamotrigine is unknown. no data are available on 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 lamotrigine and any potential adverse effects on the breastfed infant from lamotrigine or from the underlying maternal condition. clinical considerations human milk-fed infants should be closely monitored for adverse events resulting from lamotrigine. measurement of infant serum levels should be performed to rule out toxicity if concerns arise. human milk-feeding should be discontinued in infants with lamotrigine toxicity. data data from multiple small studies indicate that lamotrigine plasma levels in nursing infants have been reported to be as high as 50% of maternal plasma concentrations. epilepsy lamotrigine is indicated as adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of lennox-gastaut syndrome, and pgtc seizures. safety and efficacy of lamotrigine used as adjunctive treatment for partial-onset seizures were not demonstrated in a small, randomized, double-blind, placebo-controlled withdrawal trial in very young pediatric patients (aged 1 to 24 months). lamotrigine was associated with an increased risk for infectious adverse reactions (lamotrigine 37%, placebo 5%), and respiratory adverse reactions (lamotrigine 26%, placebo 5%). infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection. respiratory adverse reactions included nasal congestion, cough, and apnea. bipolar disorder safety and efficacy of lamotrigine for the maintenance treatment of bipolar disorder were not established in a double-blind, randomized withdrawal, placebo-controlled trial that evaluated 301 pediatric patients aged 10 to 17 years with a current manic/hypomanic, depressed, or mixed mood episode as defined by dsm-iv-tr. in the randomized phase of the trial, adverse reactions that occurred in at least 5% of patients taking lamotrigine (n = 87) and were twice as common compared with patients taking placebo (n = 86) were influenza (lamotrigine 8%, placebo 2%), oropharyngeal pain (lamotrigine 8%, placebo 2%), vomiting (lamotrigine 6%, placebo 2%), contact dermatitis (lamotrigine 5%, placebo 2%), upper abdominal pain (lamotrigine 5%, placebo 1%), and suicidal ideation (lamotrigine 5%, placebo 0%). juvenile animal data in a juvenile animal study in which lamotrigine (oral doses of 0, 5, 15, or 30 mg/kg) was administered to young rats from postnatal day 7 to 62, decreased viability and growth were seen at the highest dose tested and long-term neurobehavioral abnormalities (decreased locomotor activity, increased reactivity, and learning deficits in animals tested as adults) were observed at the 2 highest doses. the no-effect dose for adverse developmental effects in juvenile animals is less than the human dose of 400 mg/day on a mg/m 2 basis. clinical trials of lamotrigine for epilepsy and bipolar disorder did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients or exhibit a different safety profile than that of younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. experience in patients with hepatic impairment is limited. based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment [see clinical pharmacology ( 12.3)] , the following general recommendations can be made. no dosage adjustment is needed in patients with mild liver impairment. initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. escalation and maintenance doses may be adjusted according to clinical response [see dosage and administration ( 2.1)] . lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites being recovered in the urine. in a small study comparing a single dose of lamotrigine in subjects with varying degrees of renal impairment with healthy volunteers, the plasma half-life of lamotrigine was approximately twice as long in the subjects with chronic renal failure [see clinical pharmacology ( 12.3)] . initial doses of lamotrigine should be based on patients' aed regimens; reduced maintenance doses may be effective for patients with significant renal impairment. few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. because there is inadequate experience in this population, lamotrigine should be used with caution in these patients [see dosage and administration ( 2.1)] .

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - gabapentin (unii: 6cw7f3g59x) (gabapentin - unii:6cw7f3g59x) - gabapentin is indicated for: • management of postherpetic neuralgia in adults • adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), such as gabapentin, during pregnancy. encourage women who are taking gabapentin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women. in nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to or lower than those used clinically [see data]. 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data   when pregnant mice received oral doses of gabapentin (500, 1000, or 3000 mg/kg/day) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses. the no-effect dose for embryofetal developmental toxicity in mice (500 mg/kg/day) is less than the maximum recommended human dose (mrhd) of 3600 mg on a body surface area (mg/m 2 ) basis. in studies in which rats received oral doses of gabapentin (500 to 2000 mg/kg/day) during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. the lowest dose tested is similar to the mrhd on a mg/m 2 basis. when pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryofetal mortality was observed at all doses tested (60, 300, or 1500 mg/kg). the lowest dose tested is less than the mrhd on a mg/m 2 basis. in a published study, gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair. gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. the clinical significance of these findings is unknown. risk summary gabapentin is secreted in human milk following oral administration. the effects on the breastfed infant and on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for gabapentin and any potential adverse effects on the breastfed infant from gabapentin or from the underlying maternal condition. safety and effectiveness of gabapentin in the management of postherpetic neuralgia in pediatric patients have not been established. safety and effectiveness as adjunctive therapy in the treatment of partial seizures in pediatric patients below the age of 3 years has not been established  [see clinical studies (14.2)]. the total number of patients treated with gabapentin in controlled clinical trials in patients with postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were 75 years of age and older. there was a larger treatment effect in patients 75 years of age and older compared to younger patients who received the same dosage.    since gabapentin is almost exclusively eliminated by renal excretion, the larger treatment effect observed in patients ≥ 75 years may be a consequence of increased gabapentin exposure for a given dose that results from an age-related decrease in renal function. however, other factors cannot be excluded. the types and incidence of adverse reactions were similar across age groups except for peripheral edema and ataxia, which tended to increase in incidence with age. clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. this drug is known to be substantially excreted by the kidney, and the risk of toxic 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 dose should be adjusted based on creatinine clearance values in these patients [see dosage and administration (2.4), adverse reactions (6), and clinical pharmacology (12.3)] . dosage adjustment in adult patients with compromised renal function is necessary [see  dosage and administration (2.3) and clinical pharmacology (12.3)] . pediatric patients with renal insufficiency have not been studied. dosage adjustment in patients undergoing hemodialysis is necessary [see dosage and administration (2.3) and clinical pharmacology (12.3)] . gabapentin is not a scheduled drug. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. gabapentin does not exhibit affinity for benzodiazepine, opioid (mu, delta or kappa), or cannabinoid 1 receptor sites. gabapentin misuse and abuse have been reported in the postmarketing setting and published literature. most of the individuals described in these reports had a history of polysubstance abuse. some of these individuals were taking higher than recommended doses of gabapentin for unapproved uses. when prescribing gabapentin, carefully evaluate patients for a history of drug abuse and observe them for signs and symptoms of gabapentin misuse or abuse (e.g., self-dose escalation and drug-seeking behavior). the abuse potential of gabapentin has not been evaluated in human studies. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. there are rare postmarketing reports of individuals experiencing withdrawal symptoms shortly after discontinuing higher than recommended doses of gabapentin used to treat illnesses for which the drug is not approved. such symptoms included agitation, disorientation and confusion after suddenly discontinuing gabapentin that resolved after restarting gabapentin. the dependence potential of gabapentin has not been evaluated in human studies.

United States - English - NLM (National Library of Medicine)

remedyrepack inc. - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd) in adults. trazodone hydrochloride tablets are contraindicated in: - patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions ( 5.2), drug interactions ( 7.1)]. patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions ( 5.2), drug interactions ( 7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to registe