Estados Unidos - inglés - NLM (National Library of Medicine)

aurobindo pharma limited - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 2 mg - aripiprazole tablets are indicated for the treatment of: - schizophrenia - irritability associated with autistic disorder - treatment of tourette’s disorder aripiprazole tablets are contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see clinical considerations) . overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data) . there are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including aripiprazole, during pregnancy (see clinical considerations). in animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 19 times, respectively, the maximum recommended human dose (mrhd) of 30 mg/day based on mg/m2 body surface area, produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. oral and intravenous aripiprazole administration during the pre- and post-natal period in rats at doses 10 times the mrhd based on mg/m2 body surface area, produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (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 there is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth. it is not known if this is a direct result of the illness or other comorbid factors.    fetal/neonatal adverse reactions extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including aripiprazole) during the third trimester of pregnancy. these symptoms have varied in severity. monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. data human data published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. a retrospective study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. animal data in animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits. in pregnant rats treated orally with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are approximately 1, 3 and 10 times the mrhd of 30 mg/day based on mg/m2 body surface area, a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes, were observed at 10 times the mrhd. delayed skeletal ossification was observed at 3 and 10 times the mrhd. delivered offspring had increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed at 10 times the mrhd (the other dose groups were not examined for these findings). postnatally, delayed vaginal opening was seen at 3 and 10 times the mrhd. impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) were observed at 10 times the mrhd; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. in pregnant rabbits treated orally with aripiprazole during organogenesis at doses of 10, 30, and 100 mg/kg/day which are 6, 19, and 65 times the mrhd of 30 mg/day based on mg/m2 body surface area, decreased maternal food consumption, and increased abortions as well as increased fetal mortality were observed at 65 times the mrhd. decreased fetal weight and increased incidence of fused sternebrae were observed at 19 and 65 times the mrhd. in rats treated orally with aripiprazole peri- and postnatally from gestation day 17 through postpartum day 21 at doses of 3, 10, and 30 mg/kg/day which are 1, 3, and 10 times the mrhd of 30 mg/day based on mg/m2 body surface area slight maternal toxicity and slightly prolonged gestation were observed at 10 times the mrhd. an increase in stillbirths and, decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. risk summary limited data from published literature report the presence of aripiprazole in human breast milk, at relative infant doses ranging between 0.7% to 8.3% of the maternal weight-adjusted dosage. there are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole. the development and health benefits of breastfeeding should be considered along with the mother’s clinical need for aripiprazole and any potential adverse effects on the breastfed infant from aripiprazole or from the underlying maternal condition. the pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients, 10 to 17 years of age, were similar to those in adults after correcting for the differences in body weight [see clinical pharmacology (12.3)]. schizophrenia safety and effectiveness in pediatric patients with schizophrenia were established in a 6 week, placebo-controlled clinical trial in 202 pediatric patients aged 13 to 17 years [see dosage and administration (2.1), adverse reactions (6.1), and clinical studies (14.1)]. although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.   irritability associated with autistic disorder safety and effectiveness in pediatric patients demonstrating irritability associated with autistic disorder were established in two 8 week, placebo-controlled clinical trials in 212 pediatric patients aged 6 to 17 years [see indications and usage (1), dosage and administration (2.4), adverse reactions (6.1), and clinical studies (14.4)] . a maintenance trial was conducted in pediatric patients (6 to 17 years of age) with irritability associated with autistic disorder. the first phase of this trial was an open-label, flexibly dosed (aripiprazole 2 to 15 mg/day) phase in which patients were stabilized (defined as >25% improvement on the abc-i subscale, and a cgi-i rating of “much improved” or “very much improved”) on aripiprazole for 12 consecutive weeks. overall, 85 patients were stabilized and entered the second, 16 week, double-blind phase where they were randomized to either continue aripiprazole treatment or switch to placebo. in this trial, the efficacy of aripiprazole for the maintenance treatment of irritability associated with autistic disorder was not established. tourette’s disorder safety and effectiveness of aripiprazole in pediatric patients with tourette’s disorder were established in one 8 week (aged 7 to 17 years) and one 10 week trial (aged 6 to 18 years) in 194 pediatric patients [see dosage and administration (2.5), adverse reactions (6.1), and clinical studies (14.5)] . maintenance efficacy in pediatric patients has not been systematically evaluated. juvenile animal studies aripiprazole in juvenile rats caused mortality, cns clinical signs, impaired memory and learning,  and  delayed  sexual  maturation when  administered at  oral  doses  of  10,  20, 40 mg/kg/day  from  weaning  (21  days  old)  through  maturity  (80  days   old).  at 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other cns signs were observed in both genders. in addition, delayed sexual maturation was observed in males. at all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. the changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. a no observed adverse effect level (noael) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2 month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies. aripiprazole in juvenile dogs (2 months old) caused cns clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. a noael could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2 month recovery period. no dosage adjustment is recommended for elderly patients [see boxed warning, warnings and precautions (5.1), and clinical pharmacology (12.3)]. of the 13,543 patients treated with oral aripiprazole in clinical trials, 1,073 (8%) were ≥65 years old and 799 (6%) were ≥75 years old. placebo-controlled studies of oral aripiprazole in schizophrenia, or other indications did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. aripiprazole is not approved for the treatment of patients with psychosis associated with alzheimer’s disease [see boxed warning and warnings and precautions (5.1)]. dosage adjustment is recommended in known cyp2d6 poor metabolizers due to high aripiprazole concentrations. approximately 8% of caucasians and 3 to 8% of black/african americans cannot metabolize cyp2d6 substrates and are classified as poor metabolizers (pm) [see dosage and administration (2.7) and clinical pharmacology (12.3)]. no  dosage  adjustment for  aripiprazole  is  required  on  the  basis  of  a  patient’s  hepatic function (mild to severe hepatic impairment, child-pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 ml/minute) [see clinical pharmacology (12.3)]. no dosage adjustment for aripiprazole is required on the basis of a patient’s sex, race, or smoking status [see clinical pharmacology (12.3)]. aripiprazole is not a controlled substance. aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of aripiprazole misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). in physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. while the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed.

Estados Unidos - inglés - NLM (National Library of Medicine)

torrent pharmaceuticals limited - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 2 mg - aripiprazole oral tablets are indicated for the treatment of: - schizophrenia  - acute treatment of manic and mixed episodes associated with bipolar i disorder  - adjunctive treatment of major depressive disorder  - irritability associated with autistic disorder  - treatment of tourette's disorder  aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions ( 6.2) ]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see clinical considerations) . overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data) . there are risks to the mother associated with untreated schizophrenia, bipolar i disorder, or major depressive disorder, and with exposure to antipsychotics, including aripiprazole, during pregnancy (see clinical considerations) . in animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 19 times, respectively, the maximum recommended human dose (mrhd) of 30 mg/day based on mg/m 2 body  surface area, produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. oral and intravenous aripiprazole administration during the pre- and post- natal period in rats at doses 10 times the mrhd based on mg/m 2  body surface area, produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (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 there is a risk to the mother from untreated schizophrenia or bipolar i disorder, including increased risk of relapse, hospitalization, and suicide. schizophrenia and bipolar i disorder are associated with increased adverse perinatal outcomes, including preterm birth. it is not known if this is a direct result of the illness or other comorbid factors. a prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. fetal/neonatal adverse reactions extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including aripiprazole) during the third trimester of pregnancy. these symptoms have varied in severity. monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. monitor neonates for extrapyramidal and/or withdrawal symptoms. data human data published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. a retrospective study from a medicaid database of 9,258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. animal data in animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits. in pregnant rats treated orally with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are approximately 1, 3 and 10 times the mrhd of 30 mg/day based on mg/m 2  body surface area, a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes, were observed at 10 times the mrhd. delayed skeletal ossification was observed at 3 and 10 times the mrhd. delivered offspring had increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed at 10 times the mrhd (the other dose groups were not examined for these findings). postnatally, delayed vaginal opening was seen at 3 and 10 times the mrhd. impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) were observed at 10 times the mrhd; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. in pregnant rats injected intravenously with aripiprazole during organogenesis at doses of 3, 9, and 27 mg/kg/day, which are 1, 3, and 9 times the mrhd of 30 mg/day based on mg/m 2  body surface area, decreased fetal weight and delayed skeletal ossification were observed at 9 times the mrhd; this dose also caused maternal toxicity. in pregnant rabbits treated orally with aripiprazole during organogenesis at doses of 10, 30, and 100 mg/kg/day which are 6, 19, and 65 times the mrhd of 30 mg/day based on mg/m 2  body surface area, decreased maternal food consumption, and increased abortions as well as increased fetal mortality were observed at 65 times the mrhd. decreased fetal weight and increased incidence of fused sternebrae were observed at 19 and 65 times the mrhd. in pregnant rabbits injected intravenously with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are 2, 6, and 19 times the mrhd of 30 mg/day based on mg/m 2  body surface area, decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification were observed at 19 times the mrhd; this dose also caused maternal toxicity. the fetal no-effect dose was 10 mg/kg/day, which is 6 times the mrhd. in rats treated orally with aripiprazole peri- and post-natally from gestation day 17 through postpartum day 21 at doses of 3, 10, and 30 mg/kg/day which are 1, 3, and 10 times the mrhd of 30 mg/day based on mg/m 2  body surface area slight maternal toxicity and slightly prolonged gestation were observed at 10 times the mrhd. an increase in stillbirths and, decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. in rats injected intravenously with aripiprazole from gestation day 6 through lactation day 20 at doses of 3, 8, and 20 mg/kg/day, which are 1, 3, and 6 times the mrhd of 30 mg/day based on mg/m 2  body surface area, increased stillbirths were observed at 3 and 6 times the mrhd; and decreases in early postnatal pup weight and survival were observed at 6 times the mrhd; these doses also caused some maternal toxicity. there were no effects on postnatal behavioral and reproductive development. risk summary limited data from published literature report the presence of aripiprazole in human breast milk, at relative infant doses ranging between 0.7% to 8.3% of the maternal weight-adjusted dosage. there are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole. the development and health benefits of breastfeeding should be considered along with the mother's clinical need for aripiprazole and any potential adverse effects on the breastfed infant from aripiprazole or from the underlying maternal condition.  safety and effectiveness in pediatric patients with major depressive disorder or agitation associated with schizophrenia or bipolar mania have not been established. the pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients, 10 to 17 years of age, were similar to those in adults after correcting for the differences in body weight [see clinical pharmacology ( 12.3) ] . schizophrenia safety and effectiveness in pediatric patients with schizophrenia were established in a 6 week, placebo-controlled clinical trial in 202 pediatric patients aged 13 to 17 years [see dosage and administration ( 2.1), adverse reactions ( 6.1) , and clinical studies ( 14.1) ] . although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. bipolar i disorder safety and effectiveness in pediatric patients with bipolar mania were established in a 4 week, placebo-controlled clinical trial in 197 pediatric patients aged 10 to 17 years [see dosage and administration ( 2.2), adverse reactions ( 6.1) , and clinical studies ( 14.2)] . although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. the efficacy of adjunctive aripiprazole with concomitant lithium or valproate in the treatment of manic or mixed episodes in pediatric patients has not been systematically evaluated. however, such efficacy and lack of pharmacokinetic interaction between aripiprazole and lithium or valproate can be extrapolated from adult data, along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. irritability associated with autistic disorder safety and effectiveness in pediatric patients demonstrating irritability associated with autistic disorder were established in two 8 week, placebo-controlled clinical trials in 212 pediatric patients aged 6 to 17 years [see indications and usage ( 1), dosage and administration ( 2.4), adverse reactions ( 6.1) , and clinical studies ( 14.4)] . a maintenance trial was conducted in pediatric patients (6 to 17 years of age) with irritability associated with autistic disorder. the first phase of this trial was an open-label, flexibly dosed (aripiprazole 2 to 15 mg/day) phase in which patients were stabilized (defined as >25% improvement on the abc-i subscale, and a cgi-i rating of "much improved" or "very much improved") on aripiprazole for 12 consecutive weeks. overall, 85 patients were stabilized and entered the second, 16 week, double-blind phase where they were randomized to either continue aripiprazole treatment or switch to placebo. in this trial, the efficacy of aripiprazole for the maintenance treatment of irritability associated with autistic disorder was not established. tourette's disorder safety and effectiveness of aripiprazole in pediatric patients with tourette's disorder were established in one 8 week (aged 7 to 17 years) and one 10 week trial (aged 6 to 18 years) in 194 pediatric patients [see dosage and administration ( 2.5), adverse reactions ( 6.1), and clinical studies ( 14.5) ]. maintenance efficacy in pediatric patients has not been systematically evaluated. juvenile animal studies aripiprazole in juvenile rats caused mortality, cns clinical signs, impaired memory and learning, and delayed sexual maturation when administered at oral doses of 10, 20, 40 mg/kg/day from weaning (21 days old) through maturity (80 days old). at 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other cns signs were observed in both genders. in addition, delayed sexual maturation was observed in males. at all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. the changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. a no observed adverse effect level (noael) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (auc 0 to 24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2 month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies. aripiprazole in juvenile dogs (2 months old) caused cns clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. a noael could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (auc 0 to 24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2 month recovery period. no dosage adjustment is recommended for elderly patients [see boxed warning, warnings and precautions ( 5.1) , and clinical pharmacology ( 12.3) ] . of the 13,543 patients treated with oral aripiprazole in clinical trials, 1,073 (8%) were ≥65 years old and 799 (6%) were ≥75 years old. placebo-controlled studies of oral aripiprazole in schizophrenia, bipolar mania, or major depressive disorder did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. aripiprazole is not approved for the treatment of patients with psychosis associated with alzheimer's disease [see boxed warning and warnings and precautions ( 5.1) ] . dosage adjustment is recommended in known cyp2d6 poor metabolizers due to high aripiprazole concentrations. approximately 8% of caucasians and 3 to 8% of black/african americans cannot metabolize cyp2d6 substrates and are classified as poor metabolizers (pm) [see dosage and administration ( 2.7) and clinical pharmacology ( 12.3) ]. no dosage adjustment for aripiprazole is required on the basis of a patient's hepatic function (mild to severe hepatic impairment, child-pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 ml/minute) [see clinical pharmacology ( 12.3) ] . no dosage adjustment for aripiprazole is required on the basis of a patient's sex, race, or smoking status [see clinical pharmacology ( 12.3) ] . aripiprazole is not a controlled substance. aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of aripiprazole misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). in physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. while the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed.

Estados Unidos - inglés - NLM (National Library of Medicine)

aurobindo pharma limited - pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s) - pioglitazone 15 mg - monotherapy and combination therapy pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see clinical studies (14)] . important limitations of use pioglitazone tablets exert its antihyperglycemic effect only in the presence of endogenous insulin. pioglitazone tablets should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. use caution in patients with liver disease [see warnings and precautions (5.3)] . - initiation in patients with established nyha class iii or iv heart failure [see boxed warning]. -  use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. risk summary limited data with pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated

Estados Unidos - inglés - NLM (National Library of Medicine)

dr. reddy's laboratories limited - citalopram hydrobromide (unii: i1e9d14f36) (citalopram - unii:0dhu5b8d6v) - citalopram 10 mg - citalopram tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies ( 14)] . citalopram tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois (including maois such as linezolid or intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions ( 5.3), drug interactions ( 7)]. - taking pimozide because of risk of qt prolongation [see drug interactions ( 7)] . - with known hypersensitivity to citalopram or any of the inactive ingredients in citalopram tablets. reactions have included angioedema and anaphylaxis [see adverse reactions ( 6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healhcare 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/resea

Estados Unidos - inglés - NLM (National Library of Medicine)

aurobindo pharma limited - atomoxetine hydrochloride (unii: 57wvb6i2w0) (atomoxetine - unii:asw034s0b8) - atomoxetine 10 mg - atomoxetine capsules are indicated for the treatment of attention-deficit/hyperactivity disorder (adhd). the efficacy of atomoxetine capsules was established in seven clinical trials in outpatients with adhd: four 6 to 9-week trials in pediatric patients (ages 6 to 18), two 10-week trial in adults, and one maintenance trial in pediatrics (ages 6 to 15) [see clinical studies (14)] . a diagnosis of adhd (dsm-iv) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years. the symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and must be present in 2 or more settings, e.g., school (or work) and at home. the symptoms must not be better accounted for by another mental disorder. the specific etiology of adhd is unknown, and there is no single diagnostic test. adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. learning may or may not be impaired. the diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of dsm-iv characteristics. for the inattentive type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes, lack of sustained attention, poor listener, failure to follow through on tasks, poor organization, avoids tasks requiring sustained mental effort, loses things, easily distracted, forgetful. for the hyperactive-impulsive type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming, leaving seat, inappropriate running/climbing, difficulty with quiet activities, “on the go,” excessive talking, blurting answers, can’t wait turn, intrusive. for a combined type diagnosis, both inattentive and hyperactive-impulsive criteria must be met. atomoxetine capsules are indicated as an integral part of a total treatment program for adhd that may include other measures (psychological, educational, social) for patients with this syndrome. drug treatment may not be indicated for all patients with this syndrome. drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. appropriate educational placement is essential in children and adolescents with this diagnosis and psychosocial intervention is often helpful. when remedial measures alone are insufficient, the decision to prescribe drug treatment medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms. atomoxetine capsules are contraindicated in patients known to be hypersensitive to atomoxetine or other constituents of the product [see warnings and precautions (5.8)] . atomoxetine capsules should not be taken with an maoi, or within 2 weeks after discontinuing an maoi. treatment with an maoi should not be initiated within 2 weeks after discontinuing atomoxetine capsules. with other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an maoi. some cases presented with features resembling neuroleptic malignant syndrome. such reactions may occur when these drugs are given concurrently or in close proximity [see drug interactions (7.1)] . in clinical trials, atomoxetine capsules use was associated with an increased risk of mydriasis and therefore its use is not recommended in patients with narrow angle glaucoma. serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or a history of pheochromocytoma who received atomoxetine capsules. therefore, atomoxetine capsules should not be taken by patients with pheochromocytoma or a history of pheochromocytoma. atomoxetine capsules should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experience increases in blood pressure or heart rate that could be clinically important (for example, 15 to 20 mm hg in blood pressure or 20 beats per minute in heart rate) [see warnings and precautions (5.4)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including atomoxetine, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/. risk summary available published studies with atomoxetine use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. some animal reproduction studies of atomoxetine had adverse developmental outcomes. one of 3 studies in pregnant rabbits dosed during organogenesis resulted in decreased live fetuses and an increase in early resorptions, as well as slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery. these effects were observed at plasma levels (auc) 3 times and 0.4 times the human plasma levels in extensive and poor metabolizers receiving the maximum recommended human dose (mrhd), respectively. in rats dosed prior to mating and during organogenesis a decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at a dose approximately 5 times the mrhd on a mg/m2 basis. in one of 2 studies in which rats were dosed prior to mating through the periods of organogenesis and lactation, decreased pup weight and decreased pup survival were observed at doses corresponding to 5 to 6 times the mrhd on a mg/m2 basis. no adverse fetal effects were seen in pregnant rats dosed during the organogenesis period (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. data animal data pregnant rabbits were treated with up to 100 mg/kg/day of atomoxetine by gavage throughout the period of organogenesis. at this dose, in 1 of 3 studies, a decrease in live fetuses and an increase in early resorptions was observed. slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery were observed. these findings were observed at doses that caused slight maternal toxicity. the no-effect dose for these findings was 30 mg/kg/day. the 100 mg/kg dose is approximately 23 times the mrhd on a mg/m2 basis; plasma levels (auc) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (extensive metabolizers) or 0.4 times (poor metabolizers) those in humans receiving the mrhd. rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately 6 times the mrhd on a mg/m2 basis) in the diet from 2 weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. in 1 of 2 studies, decreases in pup weight and pup survival were observed. the decreased pup survival was also seen at 25 mg/kg (but not at 13 mg/kg). in a study in which rats were treated with atomoxetine in the diet from 2 weeks (females) or 10 weeks (males) prior to mating throughout the period of organogenesis, a decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at 40 mg/kg/day (approximately 5 times the mrhd on a mg/m2 basis) but not at 20 mg/kg/day. no adverse fetal effects were seen when pregnant rats were treated with up to 150 mg/kg/day (approximately 17 times the mrhd on a mg/m2 basis) by gavage throughout the period of organogenesis. risk summary there are no data on the presence of atomoxetine or its metabolite in human milk, the effects on the breastfed child, or the effects on milk production. atomoxetine is present in animal milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for atomoxetine and any potential adverse effects on the breastfed child from atomoxetine or from the underlying maternal condition. anyone considering the use of atomoxetine in a child or adolescent must balance the potential risks with the clinical need [see boxed warning and warnings and precautions (5.1)] . the pharmacokinetics of atomoxetine in children and adolescents are similar to those in adults. the safety, efficacy, and pharmacokinetics of atomoxetine in pediatric patients less than 6 years of age have not been evaluated. a study was conducted in young rats to evaluate the effects of atomoxetine on growth and neurobehavioral and sexual development. rats were treated with 1, 10, or 50 mg/kg/day (approximately 0.2, 2, and 8 times, respectively, the maximum human dose on a mg/m2 basis) of atomoxetine given by gavage from the early postnatal period (day 10 of age) through adulthood. slight delays in onset of vaginal patency (all doses) and preputial separation (10 and 50 mg/kg), slight decreases in epididymal weight and sperm number (10 and 50 mg/kg), and a slight decrease in corpora lutea (50 mg/kg) were seen, but there were no effects on fertility or reproductive performance. a slight delay in onset of incisor eruption was seen at 50 mg/kg. a slight increase in motor activity was seen on day 15 (males at 10 and 50 mg/kg and females at 50 mg/kg) and on day 30 (females at 50 mg/kg) but not on day 60 of age. there were no effects on learning and memory tests. the significance of these findings to humans is unknown. the safety, efficacy and pharmacokinetics of atomoxetine in geriatric patients have not been evaluated. atomoxetine exposure (auc) is increased, compared with normal subjects, in em subjects with moderate (child-pugh class b) (2-fold increase) and severe (child-pugh class c) (4-fold increase) hepatic insufficiency. dosage adjustment is recommended for patients with moderate or severe hepatic insufficiency [see dosage and administration (2.3)] . em subjects with end stage renal disease had higher systemic exposure to atomoxetine than healthy subjects (about a 65% increase), but there was no difference when exposure was corrected for mg/kg dose. atomoxetine can therefore be administered to adhd patients with end stage renal disease or lesser degrees of renal insufficiency using the normal dosing regimen. gender did not influence atomoxetine disposition. ethnic origin did not influence atomoxetine disposition (except that pms are more common in caucasians). tics in patients with adhd and comorbid tourette’s disorder — atomoxetine administered in a flexible dose range of 0.5 to 1.5 mg/kg/day (mean dose of 1.3 mg/kg/day) and placebo were compared in 148 randomized pediatric (age 7 to 17 years) subjects with a dsm-iv diagnosis of adhd and comorbid tic disorder in an 18 week, double-blind, placebo-controlled study in which the majority (80%) enrolled in this trial with tourette’s disorder (tourette’s disorder: 116 subjects; chronic motor tic disorder: 29 subjects). a non-inferiority analysis revealed that atomoxetine did not worsen tics in these patients as determined by the yale global tic severity scale total score (ygtss). out of 148 patients who entered the acute treatment phase, 103 (69.6%) patients discontinued the study. the primary reason for discontinuation in both the atomoxetine (38 of 76 patients, 50.0%) and placebo (45 of 72 patients, 62.5%) treatment groups was identified as lack of efficacy with most of the patients discontinuing at week 12. this was the first visit where patients with a cgi-s≥4 could also meet the criteria for “clinical non-responder” (cgi-s remained the same or increased from study baseline) and be eligible to enter an open-label extension study with atomoxetine. there have been postmarketing reports of tics [see adverse reactions (6.2)]. anxiety in patients with adhd and comorbid anxiety disorders – in two post-marketing, double-blind, placebo-controlled trials, it has been demonstrated that treating patients with adhd and comorbid anxiety disorders with atomoxetine does not worsen their anxiety. in a 12-week double-blind, placebo-controlled trial, 176 patients, aged 8 to 17, who met dsm-iv criteria for adhd and at least one of the anxiety disorders of separation anxiety disorder, generalized anxiety disorder or social phobia were randomized. following a 2-week double-blind placebo lead-in, atomoxetine was initiated at 0.8 mg/kg/day with increase to a target dose of 1.2 mg/kg/day (median dose 1.3 mg/kg/day +/- 0.29 mg/kg/day). atomoxetine did not worsen anxiety in these patients as determined by the pediatric anxiety rating scale (pars). of the 158 patients who completed the double-blind placebo lead-in, 26 (16%) patients discontinued the study. in a separate 16-week, double-blind, placebo-controlled trial, 442 patients aged 18 to 65, who met dsm-iv criteria for adult adhd and social anxiety disorder (23% of whom also had generalized anxiety disorder) were randomized. following a 2-week double-blind placebo lead-in, atomoxetine was initiated at 40 mg/day to a maximum dose of 100 mg/day (mean daily dose 83 mg/day +/- 19.5 mg/day). atomoxetine did not worsen anxiety in these patients as determined by the liebowitz social anxiety scale (lsas). of the 413 patients who completed the double-blind placebo lead-in, 149 (36.1%) patients discontinued the study. there have been postmarketing reports of anxiety [see adverse reactions (6.2)] . atomoxetine is not a controlled substance. in a randomized, double-blind, placebo-controlled, abuse-potential study in adults comparing effects of atomoxetine and placebo, atomoxetine was not associated with a pattern of response that suggested stimulant or euphoriant properties. clinical study data in over 2000 children, adolescents, and adults with adhd and over 1200 adults with depression showed only isolated incidents of drug diversion or inappropriate self-administration associated with atomoxetine. there was no evidence of symptom rebound or adverse reactions suggesting a drug-discontinuation or withdrawal syndrome. animal experience — drug discrimination studies in rats and monkeys showed inconsistent stimulus generalization between atomoxetine and cocaine.

Estados Unidos - inglés - NLM (National Library of Medicine)

torrent pharmaceuticals limited - valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i) - valsartan 40 mg - valsartan tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which valsartan principally belongs. there are no controlled trials in hypertensive patients demonstrating risk reduction with valsartan tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint national committee on prevention, detection,

Estados Unidos - inglés - NLM (National Library of Medicine)

torrent pharmaceuticals limited - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i) - amlodipine 5 mg - amlodipine and valsartan tablets, usp are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including amlodipine and the arb class to which valsartan principally belongs. there are no controlled trials demonstrating risk reduction with amlodipine and valsartan tablets, usp. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint national com

Estados Unidos - inglés - NLM (National Library of Medicine)

aurobindo pharma limited - didanosine (unii: k3gdh6oh08) (didanosine - unii:k3gdh6oh08) - didanosine 125 mg - didanosine delayed-release capsules, also known as ddi, in combination with other antiretroviral agents are indicated for the treatment of human immunodeficiency virus (hiv)-1 infection [see clinical studies (14) ] . didanosine delayed-release capsules are contraindicated when coadministered with the following medications: - stavudine- potential for serious and/or life-threatening events, notably pancreatitis, lactic acidosis, hepatotoxicity, and peripheral neuropathy [see warnings and precautions (5.1, 5.2, 5.3, 5.5)] . - allopurinol- systemic exposures of didanosine are increased, which may increase didanosine-associated toxicity [see clinical pharmacology (12.3) ]. - ribavirin- exposures of the active metabolite of didanosine (dideoxyadenosine 5′-triphosphate) are increased. fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving both didanosine and ribavirin. pregnancy exposure registry there is a preg

Estados Unidos - inglés - NLM (National Library of Medicine)

dr.reddy's laboratories limited - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole 20 mg - pantoprazole sodium delayed-release tablets are indicated for: pantoprazole sodium delayed-release tablets are 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 delayed-release tablets may be considered. safety of treatment beyond 8 weeks in pediatric patients has not been established.  pantoprazole sodium delayed-release tablets are 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 delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison (ze) syndrome. • pantoprazole sodium delayed-release tablets are 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 delayed-release tablets, 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) 0.08-3.95]. 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 0.86-1.45] and for spontaneous abortions or=1.29 [95% ci 0.84-1.97]). 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 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 is 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 was 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 was 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.

Estados Unidos - inglés - NLM (National Library of Medicine)

aurobindo pharma limited - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules are 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)] - chronic musculoskeletal pain [see clinical studies (14.5)] monoamine oxidase inhibitors (maois) — the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules 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 duloxetine delayed-release capsules in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of seroto