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

remedyrepack inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone tablets are indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] .  adjunctive therapy risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years)   [see clinical studies (14.4)] . risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone, during pregnancy (see clinical considerations) . oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times mrhd based on mg/m 2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m 2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m 2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m 2 body surface area. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. 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 risperidone, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk of major birth defects (rr=1.26, 95% ci 1.02-1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88-1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area: maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m 2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m 2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m 2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations). there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone   and any potential adverse effects on the breastfed child from risperidone or from the mother’s underlying condition. clinical considerations infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d 2 receptor antagonism), treatment with risperidone may result in an increase in serum prolactin levels , which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.6)]. approved pediatric indications schizophrenia the efficacy and safety of risperidone tablets in the treatment of schizophrenia were demonstrated in 417 adolescents, aged 13 to 17 years, in two short-term (6 and 8 weeks, respectively) double-blind controlled trials [see indications and usage (1.1), adverse reactions (6.1), and clinical studies (14.1)] . additional safety and efficacy information was also assessed in one long-term (6-month) open-label extension study in 284 of these adolescent patients with schizophrenia. safety and effectiveness of risperidone tablets in children less than 13 years of age with schizophrenia have not been established. bipolar i disorder the efficacy and safety of risperidone tablets in the short-term treatment of acute manic or mixed episodes associated with bipolar i disorder in 169 children and adolescent patients, aged 10 to 17 years, were demonstrated in one double-blind, placebo-controlled, 3-week trial [see indications and usage (1.2), adverse reactions (6.2), and clinical studies (14.2)] . safety and effectiveness of risperidone tablets in children less than 10 years of age with bipolar disorder have not been established. autistic disorder the efficacy and safety of risperidone tablets in the treatment of irritability associated with autistic disorder were established in two 8-week, double-blind, placebo-controlled trials in 156 children and adolescent patients, aged 5 to 16 years [see indications and usage (1.3),  adverse reactions (6.1) and clinical studies (14.4)] . additional safety information was also assessed in a long-term study in patients with autistic disorder, or in short- and long-term studies in more than 1200 pediatric patients with psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania who were of similar age and weight, and who received similar dosages of risperidone tablets as patients treated for irritability associated with autistic disorder. a third study was a 6-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study to evaluate the efficacy and safety of a lower than recommended dose of risperidone in subjects 5 to 17 years of age with autistic disorder and associated irritability, and related behavioral symptoms. there were two weight-based, fixed doses of risperidone (high-dose and low-dose). the high dose was 1.25 mg per day for patients weighing 20 to < 45 kg, and it was 1.75 mg per day for patients weighing ≥ 45 kg.the low dose was 0.125 mg per day for patients weighing 20 to < 45 kg, and it was 0.175 mg per day for patients weighing ≥ 45 kg. the study demonstrated the efficacy of high-dose risperidone, but it did not demonstrate efficacy for low-dose risperidone. adverse reactions in pediatric patients tardive dyskinesia in clinical trials in 1885 children and adolescents treated with risperidone tablets, 2 (0.1%) patients were reported to have tardive dyskinesia, which resolved on discontinuation of risperidone tablets treatment [see also warnings and precautions (5.4)] . weight gain weight gain has been observed in children and adolescents during treatment with risperidone tablets. clinical monitoring of weight is recommended during treatment. data derive from short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder, or other psychiatric disorders. in the short-term trials (3 to 8 weeks), the mean weight gain for risperidone tablets-treated patients was 2 kg, compared to 0.6 kg for placebo-treated patients. in these trials, approximately 33% of the risperidone tablets group had weight gain ≥7%, compared to 7% in the placebo group. in longer-term, uncontrolled, open-label pediatric studies, the mean weight gain was 5.5 kg at week 24 and 8 kg at week 48 [see warnings and precautions (5.5) and adverse reactions (6.1)]. somnolence somnolence was frequently observed in placebo-controlled clinical trials of pediatric patients with autistic disorder. most cases were mild or moderate in severity. these events were most often of early onset with peak incidence occurring during the first two weeks of treatment, and transient with a median duration of 16 days. somnolence was the most commonly observed adverse reaction in the clinical trial of bipolar disorder in children and adolescents, as well as in the schizophrenia trials in adolescents. as was seen in the autistic disorder trials, these adverse reactions were most often of early onset and transient in duration  [see  adverse reactions (6.1, 6.2)] . patients experiencing persistent somnolence may benefit from a change in dosing regimen [see dosage & administration (2.1, 2.2, and 2.3)] . hyperprolactinemia risperidone tablets have been shown to elevate prolactin levels in children and adolescents as well as in adults [see warnings and precautions (5.6)] . in double-blind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received risperidone tablets had elevated prolactin levels compared to 2% of patients who received placebo. similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82–87% of patients who received risperidone tablets had elevated levels of prolactin compared to 3–7% of patients on placebo. increases were dose-dependent and generally greater in females than in males across indications. in clinical trials in 1885 children and adolescents, galactorrhea was reported in 0.8% of risperidone tablets-treated patients and gynecomastia was reported in 2.3% of risperidone tablets-treated patients. growth and sexual maturation the long-term effects of risperidone tablets on growth and sexual maturation have not been fully evaluated in children and adolescents. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4, and 13.5 times the mrhd of  6 mg/day for children, based on mg/m 2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m 2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. clinical studies of risperidone tablets in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3) and dosage & administration (2.4, 2.5)] . while elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg twice daily followed by careful titration [see warnings and precautions (5.7)] . monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. this drug is substantially excreted by the kidneys, 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 it may be useful to monitor renal function [see dosage & administration (2.4)] . in patients with moderate to severe (clcr 59 to 15 ml/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. risperidone tablets doses should be reduced in patients with renal disease [see dosage and administration (2.4)] . while the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α 1 -acid glycoprotein. risperidone tablets doses should be reduced in patients with liver disease [see dosage and administration (2.4)] . patients with parkinsons disease or dementia with lewy bodies can experience increased sensitivity to risperidone tablets. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone tablets are not a controlled substance. risperidone tablets have not been systematically studied in animals or humans for its potential for abuse. 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. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of risperidone tablets misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). risperidone tablets have not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

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

remedyrepack inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone tablets are indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] .  adjunctive therapy risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years)   [see clinical studies (14.4)] . risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone, during pregnancy (see clinical considerations) . oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times mrhd based on mg/m 2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m 2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m 2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m 2 body surface area. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. 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 risperidone, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk of major birth defects (rr=1.26, 95% ci 1.02-1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88-1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area: maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m 2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m 2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m 2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations). there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone   and any potential adverse effects on the breastfed child from risperidone or from the mother’s underlying condition. clinical considerations infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d 2 receptor antagonism), treatment with risperidone may result in an increase in serum prolactin levels , which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.6)]. approved pediatric indications schizophrenia the efficacy and safety of risperidone tablets in the treatment of schizophrenia were demonstrated in 417 adolescents, aged 13 to 17 years, in two short-term (6 and 8 weeks, respectively) double-blind controlled trials [see indications and usage (1.1), adverse reactions (6.1), and clinical studies (14.1)] . additional safety and efficacy information was also assessed in one long-term (6-month) open-label extension study in 284 of these adolescent patients with schizophrenia. safety and effectiveness of risperidone tablets in children less than 13 years of age with schizophrenia have not been established. bipolar i disorder the efficacy and safety of risperidone tablets in the short-term treatment of acute manic or mixed episodes associated with bipolar i disorder in 169 children and adolescent patients, aged 10 to 17 years, were demonstrated in one double-blind, placebo-controlled, 3-week trial [see indications and usage (1.2), adverse reactions (6.2), and clinical studies (14.2)] . safety and effectiveness of risperidone tablets in children less than 10 years of age with bipolar disorder have not been established. autistic disorder the efficacy and safety of risperidone tablets in the treatment of irritability associated with autistic disorder were established in two 8-week, double-blind, placebo-controlled trials in 156 children and adolescent patients, aged 5 to 16 years [see indications and usage (1.3),  adverse reactions (6.1) and clinical studies (14.4)] . additional safety information was also assessed in a long-term study in patients with autistic disorder, or in short- and long-term studies in more than 1200 pediatric patients with psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania who were of similar age and weight, and who received similar dosages of risperidone tablets as patients treated for irritability associated with autistic disorder. a third study was a 6-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study to evaluate the efficacy and safety of a lower than recommended dose of risperidone in subjects 5 to 17 years of age with autistic disorder and associated irritability, and related behavioral symptoms. there were two weight-based, fixed doses of risperidone (high-dose and low-dose). the high dose was 1.25 mg per day for patients weighing 20 to < 45 kg, and it was 1.75 mg per day for patients weighing ≥ 45 kg.the low dose was 0.125 mg per day for patients weighing 20 to < 45 kg, and it was 0.175 mg per day for patients weighing ≥ 45 kg. the study demonstrated the efficacy of high-dose risperidone, but it did not demonstrate efficacy for low-dose risperidone. adverse reactions in pediatric patients tardive dyskinesia in clinical trials in 1885 children and adolescents treated with risperidone tablets, 2 (0.1%) patients were reported to have tardive dyskinesia, which resolved on discontinuation of risperidone tablets treatment [see also warnings and precautions (5.4)] . weight gain weight gain has been observed in children and adolescents during treatment with risperidone tablets. clinical monitoring of weight is recommended during treatment. data derive from short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder, or other psychiatric disorders. in the short-term trials (3 to 8 weeks), the mean weight gain for risperidone tablets-treated patients was 2 kg, compared to 0.6 kg for placebo-treated patients. in these trials, approximately 33% of the risperidone tablets group had weight gain ≥7%, compared to 7% in the placebo group. in longer-term, uncontrolled, open-label pediatric studies, the mean weight gain was 5.5 kg at week 24 and 8 kg at week 48 [see warnings and precautions (5.5) and adverse reactions (6.1)]. somnolence somnolence was frequently observed in placebo-controlled clinical trials of pediatric patients with autistic disorder. most cases were mild or moderate in severity. these events were most often of early onset with peak incidence occurring during the first two weeks of treatment, and transient with a median duration of 16 days. somnolence was the most commonly observed adverse reaction in the clinical trial of bipolar disorder in children and adolescents, as well as in the schizophrenia trials in adolescents. as was seen in the autistic disorder trials, these adverse reactions were most often of early onset and transient in duration  [see  adverse reactions (6.1, 6.2)] . patients experiencing persistent somnolence may benefit from a change in dosing regimen [see dosage & administration (2.1, 2.2, and 2.3)] . hyperprolactinemia risperidone tablets have been shown to elevate prolactin levels in children and adolescents as well as in adults [see warnings and precautions (5.6)] . in double-blind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received risperidone tablets had elevated prolactin levels compared to 2% of patients who received placebo. similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82–87% of patients who received risperidone tablets had elevated levels of prolactin compared to 3–7% of patients on placebo. increases were dose-dependent and generally greater in females than in males across indications. in clinical trials in 1885 children and adolescents, galactorrhea was reported in 0.8% of risperidone tablets-treated patients and gynecomastia was reported in 2.3% of risperidone tablets-treated patients. growth and sexual maturation the long-term effects of risperidone tablets on growth and sexual maturation have not been fully evaluated in children and adolescents. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4, and 13.5 times the mrhd of  6 mg/day for children, based on mg/m 2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m 2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. clinical studies of risperidone tablets in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3) and dosage & administration (2.4, 2.5)] . while elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg twice daily followed by careful titration [see warnings and precautions (5.7)] . monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. this drug is substantially excreted by the kidneys, 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 it may be useful to monitor renal function [see dosage & administration (2.4)] . in patients with moderate to severe (clcr 59 to 15 ml/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. risperidone tablets doses should be reduced in patients with renal disease [see dosage and administration (2.4)] . while the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α 1 -acid glycoprotein. risperidone tablets doses should be reduced in patients with liver disease [see dosage and administration (2.4)] . patients with parkinsons disease or dementia with lewy bodies can experience increased sensitivity to risperidone tablets. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone tablets are not a controlled substance. risperidone tablets have not been systematically studied in animals or humans for its potential for abuse. 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. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of risperidone tablets misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). risperidone tablets have not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

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

remedyrepack inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone tablets are indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] .  adjunctive therapy risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years)   [see clinical studies (14.4)] . risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone, during pregnancy (see clinical considerations) . oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times mrhd based on mg/m 2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m 2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m 2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m 2 body surface area. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. 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 risperidone, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk of major birth defects (rr=1.26, 95% ci 1.02-1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88-1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area: maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m 2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m 2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m 2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations). there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone   and any potential adverse effects on the breastfed child from risperidone or from the mother’s underlying condition. clinical considerations infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d 2 receptor antagonism), treatment with risperidone may result in an increase in serum prolactin levels , which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.6)]. approved pediatric indications schizophrenia the efficacy and safety of risperidone tablets in the treatment of schizophrenia were demonstrated in 417 adolescents, aged 13 to 17 years, in two short-term (6 and 8 weeks, respectively) double-blind controlled trials [see indications and usage (1.1), adverse reactions (6.1), and clinical studies (14.1)] . additional safety and efficacy information was also assessed in one long-term (6-month) open-label extension study in 284 of these adolescent patients with schizophrenia. safety and effectiveness of risperidone tablets in children less than 13 years of age with schizophrenia have not been established. bipolar i disorder the efficacy and safety of risperidone tablets in the short-term treatment of acute manic or mixed episodes associated with bipolar i disorder in 169 children and adolescent patients, aged 10 to 17 years, were demonstrated in one double-blind, placebo-controlled, 3-week trial [see indications and usage (1.2), adverse reactions (6.2), and clinical studies (14.2)] . safety and effectiveness of risperidone tablets in children less than 10 years of age with bipolar disorder have not been established. autistic disorder the efficacy and safety of risperidone tablets in the treatment of irritability associated with autistic disorder were established in two 8-week, double-blind, placebo-controlled trials in 156 children and adolescent patients, aged 5 to 16 years [see indications and usage (1.3),  adverse reactions (6.1) and clinical studies (14.4)] . additional safety information was also assessed in a long-term study in patients with autistic disorder, or in short- and long-term studies in more than 1200 pediatric patients with psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania who were of similar age and weight, and who received similar dosages of risperidone tablets as patients treated for irritability associated with autistic disorder. a third study was a 6-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study to evaluate the efficacy and safety of a lower than recommended dose of risperidone in subjects 5 to 17 years of age with autistic disorder and associated irritability, and related behavioral symptoms. there were two weight-based, fixed doses of risperidone (high-dose and low-dose). the high dose was 1.25 mg per day for patients weighing 20 to < 45 kg, and it was 1.75 mg per day for patients weighing ≥ 45 kg.the low dose was 0.125 mg per day for patients weighing 20 to < 45 kg, and it was 0.175 mg per day for patients weighing ≥ 45 kg. the study demonstrated the efficacy of high-dose risperidone, but it did not demonstrate efficacy for low-dose risperidone. adverse reactions in pediatric patients tardive dyskinesia in clinical trials in 1885 children and adolescents treated with risperidone tablets, 2 (0.1%) patients were reported to have tardive dyskinesia, which resolved on discontinuation of risperidone tablets treatment [see also warnings and precautions (5.4)] . weight gain weight gain has been observed in children and adolescents during treatment with risperidone tablets. clinical monitoring of weight is recommended during treatment. data derive from short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder, or other psychiatric disorders. in the short-term trials (3 to 8 weeks), the mean weight gain for risperidone tablets-treated patients was 2 kg, compared to 0.6 kg for placebo-treated patients. in these trials, approximately 33% of the risperidone tablets group had weight gain ≥7%, compared to 7% in the placebo group. in longer-term, uncontrolled, open-label pediatric studies, the mean weight gain was 5.5 kg at week 24 and 8 kg at week 48 [see warnings and precautions (5.5) and adverse reactions (6.1)]. somnolence somnolence was frequently observed in placebo-controlled clinical trials of pediatric patients with autistic disorder. most cases were mild or moderate in severity. these events were most often of early onset with peak incidence occurring during the first two weeks of treatment, and transient with a median duration of 16 days. somnolence was the most commonly observed adverse reaction in the clinical trial of bipolar disorder in children and adolescents, as well as in the schizophrenia trials in adolescents. as was seen in the autistic disorder trials, these adverse reactions were most often of early onset and transient in duration  [see  adverse reactions (6.1, 6.2)] . patients experiencing persistent somnolence may benefit from a change in dosing regimen [see dosage & administration (2.1, 2.2, and 2.3)] . hyperprolactinemia risperidone tablets have been shown to elevate prolactin levels in children and adolescents as well as in adults [see warnings and precautions (5.6)] . in double-blind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received risperidone tablets had elevated prolactin levels compared to 2% of patients who received placebo. similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82–87% of patients who received risperidone tablets had elevated levels of prolactin compared to 3–7% of patients on placebo. increases were dose-dependent and generally greater in females than in males across indications. in clinical trials in 1885 children and adolescents, galactorrhea was reported in 0.8% of risperidone tablets-treated patients and gynecomastia was reported in 2.3% of risperidone tablets-treated patients. growth and sexual maturation the long-term effects of risperidone tablets on growth and sexual maturation have not been fully evaluated in children and adolescents. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4, and 13.5 times the mrhd of  6 mg/day for children, based on mg/m 2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m 2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. clinical studies of risperidone tablets in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3) and dosage & administration (2.4, 2.5)] . while elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg twice daily followed by careful titration [see warnings and precautions (5.7)] . monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. this drug is substantially excreted by the kidneys, 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 it may be useful to monitor renal function [see dosage & administration (2.4)] . in patients with moderate to severe (clcr 59 to 15 ml/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. risperidone tablets doses should be reduced in patients with renal disease [see dosage and administration (2.4)] . while the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α 1 -acid glycoprotein. risperidone tablets doses should be reduced in patients with liver disease [see dosage and administration (2.4)] . patients with parkinsons disease or dementia with lewy bodies can experience increased sensitivity to risperidone tablets. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone tablets are not a controlled substance. risperidone tablets have not been systematically studied in animals or humans for its potential for abuse. 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. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of risperidone tablets misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). risperidone tablets have not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

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

remedyrepack inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone tablets are indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] .  adjunctive therapy risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years)   [see clinical studies (14.4)] . risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone, during pregnancy (see clinical considerations) . oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times mrhd based on mg/m 2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m 2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m 2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m 2 body surface area. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. 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 risperidone, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk of major birth defects (rr=1.26, 95% ci 1.02-1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88-1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area: maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m 2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m 2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m 2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations). there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone   and any potential adverse effects on the breastfed child from risperidone or from the mother’s underlying condition. clinical considerations infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d 2 receptor antagonism), treatment with risperidone may result in an increase in serum prolactin levels , which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.6)]. approved pediatric indications schizophrenia the efficacy and safety of risperidone tablets in the treatment of schizophrenia were demonstrated in 417 adolescents, aged 13 to 17 years, in two short-term (6 and 8 weeks, respectively) double-blind controlled trials [see indications and usage (1.1), adverse reactions (6.1), and clinical studies (14.1)] . additional safety and efficacy information was also assessed in one long-term (6-month) open-label extension study in 284 of these adolescent patients with schizophrenia. safety and effectiveness of risperidone tablets in children less than 13 years of age with schizophrenia have not been established. bipolar i disorder the efficacy and safety of risperidone tablets in the short-term treatment of acute manic or mixed episodes associated with bipolar i disorder in 169 children and adolescent patients, aged 10 to 17 years, were demonstrated in one double-blind, placebo-controlled, 3-week trial [see indications and usage (1.2), adverse reactions (6.2), and clinical studies (14.2)] . safety and effectiveness of risperidone tablets in children less than 10 years of age with bipolar disorder have not been established. autistic disorder the efficacy and safety of risperidone tablets in the treatment of irritability associated with autistic disorder were established in two 8-week, double-blind, placebo-controlled trials in 156 children and adolescent patients, aged 5 to 16 years [see indications and usage (1.3),  adverse reactions (6.1)and clinical studies (14.4)] . additional safety information was also assessed in a long-term study in patients with autistic disorder, or in short- and long-term studies in more than 1200 pediatric patients with psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania who were of similar age and weight, and who received similar dosages of risperidone tablets as patients treated for irritability associated with autistic disorder. a third study was a 6-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study to evaluate the efficacy and safety of a lower than recommended dose of risperidone in subjects 5 to 17 years of age with autistic disorder and associated irritability, and related behavioral symptoms. there were two weight-based, fixed doses of risperidone (high-dose and low-dose). the high dose was 1.25 mg per day for patients weighing 20 to < 45 kg, and it was 1.75 mg per day for patients weighing ≥ 45 kg.the low dose was 0.125 mg per day for patients weighing 20 to < 45 kg, and it was 0.175 mg per day for patients weighing ≥ 45 kg. the study demonstrated the efficacy of high-dose risperidone, but it did not demonstrate efficacy for low-dose risperidone. adverse reactions in pediatric patients tardive dyskinesia in clinical trials in 1885 children and adolescents treated with risperidone tablets, 2 (0.1%) patients were reported to have tardive dyskinesia, which resolved on discontinuation of risperidone tablets treatment [see also warnings and precautions (5.4)] . weight gain weight gain has been observed in children and adolescents during treatment with risperidone tablets. clinical monitoring of weight is recommended during treatment. data derive from short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder, or other psychiatric disorders. in the short-term trials (3 to 8 weeks), the mean weight gain for risperidone tablets-treated patients was 2 kg, compared to 0.6 kg for placebo-treated patients. in these trials, approximately 33% of the risperidone tablets group had weight gain ≥7%, compared to 7% in the placebo group. in longer-term, uncontrolled, open-label pediatric studies, the mean weight gain was 5.5 kg at week 24 and 8 kg at week 48 [see warnings and precautions (5.5)and adverse reactions (6.1)]. somnolence somnolence was frequently observed in placebo-controlled clinical trials of pediatric patients with autistic disorder. most cases were mild or moderate in severity. these events were most often of early onset with peak incidence occurring during the first two weeks of treatment, and transient with a median duration of 16 days. somnolence was the most commonly observed adverse reaction in the clinical trial of bipolar disorder in children and adolescents, as well as in the schizophrenia trials in adolescents. as was seen in the autistic disorder trials, these adverse reactions were most often of early onset and transient in duration  [see  adverse reactions (6.1, 6.2)] . patients experiencing persistent somnolence may benefit from a change in dosing regimen [see dosage & administration (2.1, 2.2, and 2.3)] . hyperprolactinemia risperidone tablets have been shown to elevate prolactin levels in children and adolescents as well as in adults [see warnings and precautions (5.6)] . in double-blind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received risperidone tablets had elevated prolactin levels compared to 2% of patients who received placebo. similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82–87% of patients who received risperidone tablets had elevated levels of prolactin compared to 3–7% of patients on placebo. increases were dose-dependent and generally greater in females than in males across indications. in clinical trials in 1885 children and adolescents, galactorrhea was reported in 0.8% of risperidone tablets-treated patients and gynecomastia was reported in 2.3% of risperidone tablets-treated patients. growth and sexual maturation the long-term effects of risperidone tablets on growth and sexual maturation have not been fully evaluated in children and adolescents. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4, and 13.5 times the mrhd of  6 mg/day for children, based on mg/m 2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m 2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. clinical studies of risperidone tablets in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3)and dosage & administration (2.4, 2.5)] . while elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg twice daily followed by careful titration [see warnings and precautions (5.7)] . monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. this drug is substantially excreted by the kidneys, 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 it may be useful to monitor renal function [see dosage & administration (2.4)] . in patients with moderate to severe (clcr 59 to 15 ml/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. risperidone tablets doses should be reduced in patients with renal disease [see dosage and administration (2.4)] . while the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α 1 -acid glycoprotein. risperidone tablets doses should be reduced in patients with liver disease [see dosage and administration (2.4)] . patients with parkinsons disease or dementia with lewy bodies can experience increased sensitivity to risperidone tablets. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone tablets are not a controlled substance. risperidone tablets have not been systematically studied in animals or humans for its potential for abuse. 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. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of risperidone tablets misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). risperidone tablets have not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

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

remedyrepack inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone tablets are indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] .  adjunctive therapy risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years)   [see clinical studies (14.4)] . risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone, during pregnancy (see clinical considerations) . oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times mrhd based on mg/m 2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m 2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m 2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m 2 body surface area. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. 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 risperidone, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk of major birth defects (rr=1.26, 95% ci 1.02-1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88-1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area: maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m 2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m 2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m 2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations). there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone   and any potential adverse effects on the breastfed child from risperidone or from the mother’s underlying condition. clinical considerations infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d 2 receptor antagonism), treatment with risperidone may result in an increase in serum prolactin levels , which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.6)]. approved pediatric indications schizophrenia the efficacy and safety of risperidone tablets in the treatment of schizophrenia were demonstrated in 417 adolescents, aged 13 to 17 years, in two short-term (6 and 8 weeks, respectively) double-blind controlled trials [see indications and usage (1.1), adverse reactions (6.1), and clinical studies (14.1)] . additional safety and efficacy information was also assessed in one long-term (6-month) open-label extension study in 284 of these adolescent patients with schizophrenia. safety and effectiveness of risperidone tablets in children less than 13 years of age with schizophrenia have not been established. bipolar i disorder the efficacy and safety of risperidone tablets in the short-term treatment of acute manic or mixed episodes associated with bipolar i disorder in 169 children and adolescent patients, aged 10 to 17 years, were demonstrated in one double-blind, placebo-controlled, 3-week trial [see indications and usage (1.2), adverse reactions (6.2), and clinical studies (14.2)] . safety and effectiveness of risperidone tablets in children less than 10 years of age with bipolar disorder have not been established. autistic disorder the efficacy and safety of risperidone tablets in the treatment of irritability associated with autistic disorder were established in two 8-week, double-blind, placebo-controlled trials in 156 children and adolescent patients, aged 5 to 16 years [see indications and usage (1.3),  adverse reactions (6.1) and clinical studies (14.4)] . additional safety information was also assessed in a long-term study in patients with autistic disorder, or in short- and long-term studies in more than 1200 pediatric patients with psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania who were of similar age and weight, and who received similar dosages of risperidone tablets as patients treated for irritability associated with autistic disorder. a third study was a 6-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study to evaluate the efficacy and safety of a lower than recommended dose of risperidone in subjects 5 to 17 years of age with autistic disorder and associated irritability, and related behavioral symptoms. there were two weight-based, fixed doses of risperidone (high-dose and low-dose). the high dose was 1.25 mg per day for patients weighing 20 to < 45 kg, and it was 1.75 mg per day for patients weighing ≥ 45 kg.the low dose was 0.125 mg per day for patients weighing 20 to < 45 kg, and it was 0.175 mg per day for patients weighing ≥ 45 kg. the study demonstrated the efficacy of high-dose risperidone, but it did not demonstrate efficacy for low-dose risperidone. adverse reactions in pediatric patients tardive dyskinesia in clinical trials in 1885 children and adolescents treated with risperidone tablets, 2 (0.1%) patients were reported to have tardive dyskinesia, which resolved on discontinuation of risperidone tablets treatment [see also warnings and precautions (5.4)] . weight gain weight gain has been observed in children and adolescents during treatment with risperidone tablets. clinical monitoring of weight is recommended during treatment. data derive from short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder, or other psychiatric disorders. in the short-term trials (3 to 8 weeks), the mean weight gain for risperidone tablets-treated patients was 2 kg, compared to 0.6 kg for placebo-treated patients. in these trials, approximately 33% of the risperidone tablets group had weight gain ≥7%, compared to 7% in the placebo group. in longer-term, uncontrolled, open-label pediatric studies, the mean weight gain was 5.5 kg at week 24 and 8 kg at week 48 [see warnings and precautions (5.5) and adverse reactions (6.1)]. somnolence somnolence was frequently observed in placebo-controlled clinical trials of pediatric patients with autistic disorder. most cases were mild or moderate in severity. these events were most often of early onset with peak incidence occurring during the first two weeks of treatment, and transient with a median duration of 16 days. somnolence was the most commonly observed adverse reaction in the clinical trial of bipolar disorder in children and adolescents, as well as in the schizophrenia trials in adolescents. as was seen in the autistic disorder trials, these adverse reactions were most often of early onset and transient in duration  [see  adverse reactions (6.1, 6.2)] . patients experiencing persistent somnolence may benefit from a change in dosing regimen [see dosage & administration (2.1, 2.2, and 2.3)] . hyperprolactinemia risperidone tablets have been shown to elevate prolactin levels in children and adolescents as well as in adults [see warnings and precautions (5.6)] . in double-blind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received risperidone tablets had elevated prolactin levels compared to 2% of patients who received placebo. similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82–87% of patients who received risperidone tablets had elevated levels of prolactin compared to 3–7% of patients on placebo. increases were dose-dependent and generally greater in females than in males across indications. in clinical trials in 1885 children and adolescents, galactorrhea was reported in 0.8% of risperidone tablets-treated patients and gynecomastia was reported in 2.3% of risperidone tablets-treated patients. growth and sexual maturation the long-term effects of risperidone tablets on growth and sexual maturation have not been fully evaluated in children and adolescents. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4, and 13.5 times the mrhd of  6 mg/day for children, based on mg/m 2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m 2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. clinical studies of risperidone tablets in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3) and dosage & administration (2.4, 2.5)] . while elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg twice daily followed by careful titration [see warnings and precautions (5.7)] . monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. this drug is substantially excreted by the kidneys, 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 it may be useful to monitor renal function [see dosage & administration (2.4)] . in patients with moderate to severe (clcr 59 to 15 ml/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. risperidone tablets doses should be reduced in patients with renal disease [see dosage and administration (2.4)] . while the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α 1 -acid glycoprotein. risperidone tablets doses should be reduced in patients with liver disease [see dosage and administration (2.4)] . patients with parkinsons disease or dementia with lewy bodies can experience increased sensitivity to risperidone tablets. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone tablets are not a controlled substance. risperidone tablets have not been systematically studied in animals or humans for its potential for abuse. 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. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of risperidone tablets misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). risperidone tablets have not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

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

remedyrepack inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone tablets are indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] .  adjunctive therapy risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years)   [see clinical studies (14.4)] . risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone, during pregnancy (see clinical considerations) . oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times mrhd based on mg/m 2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m 2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m 2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m 2 body surface area. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. 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 risperidone, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk of major birth defects (rr=1.26, 95% ci 1.02-1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88-1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area: maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m 2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m 2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m 2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m 2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations). there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone   and any potential adverse effects on the breastfed child from risperidone or from the mother’s underlying condition. clinical considerations infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d 2 receptor antagonism), treatment with risperidone may result in an increase in serum prolactin levels , which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.6)]. approved pediatric indications schizophrenia the efficacy and safety of risperidone tablets in the treatment of schizophrenia were demonstrated in 417 adolescents, aged 13 to 17 years, in two short-term (6 and 8 weeks, respectively) double-blind controlled trials [see indications and usage (1.1), adverse reactions (6.1), and clinical studies (14.1)] . additional safety and efficacy information was also assessed in one long-term (6-month) open-label extension study in 284 of these adolescent patients with schizophrenia. safety and effectiveness of risperidone tablets in children less than 13 years of age with schizophrenia have not been established. bipolar i disorder the efficacy and safety of risperidone tablets in the short-term treatment of acute manic or mixed episodes associated with bipolar i disorder in 169 children and adolescent patients, aged 10 to 17 years, were demonstrated in one double-blind, placebo-controlled, 3-week trial [see indications and usage (1.2), adverse reactions (6.2), and clinical studies (14.2)] . safety and effectiveness of risperidone tablets in children less than 10 years of age with bipolar disorder have not been established. autistic disorder the efficacy and safety of risperidone tablets in the treatment of irritability associated with autistic disorder were established in two 8-week, double-blind, placebo-controlled trials in 156 children and adolescent patients, aged 5 to 16 years [see indications and usage (1.3),  adverse reactions (6.1) and clinical studies (14.4)] . additional safety information was also assessed in a long-term study in patients with autistic disorder, or in short- and long-term studies in more than 1200 pediatric patients with psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania who were of similar age and weight, and who received similar dosages of risperidone tablets as patients treated for irritability associated with autistic disorder. a third study was a 6-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study to evaluate the efficacy and safety of a lower than recommended dose of risperidone in subjects 5 to 17 years of age with autistic disorder and associated irritability, and related behavioral symptoms. there were two weight-based, fixed doses of risperidone (high-dose and low-dose). the high dose was 1.25 mg per day for patients weighing 20 to < 45 kg, and it was 1.75 mg per day for patients weighing ≥ 45 kg.the low dose was 0.125 mg per day for patients weighing 20 to < 45 kg, and it was 0.175 mg per day for patients weighing ≥ 45 kg. the study demonstrated the efficacy of high-dose risperidone, but it did not demonstrate efficacy for low-dose risperidone. adverse reactions in pediatric patients tardive dyskinesia in clinical trials in 1885 children and adolescents treated with risperidone tablets, 2 (0.1%) patients were reported to have tardive dyskinesia, which resolved on discontinuation of risperidone tablets treatment [see also warnings and precautions (5.4)] . weight gain weight gain has been observed in children and adolescents during treatment with risperidone tablets. clinical monitoring of weight is recommended during treatment. data derive from short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder, or other psychiatric disorders. in the short-term trials (3 to 8 weeks), the mean weight gain for risperidone tablets-treated patients was 2 kg, compared to 0.6 kg for placebo-treated patients. in these trials, approximately 33% of the risperidone tablets group had weight gain ≥7%, compared to 7% in the placebo group. in longer-term, uncontrolled, open-label pediatric studies, the mean weight gain was 5.5 kg at week 24 and 8 kg at week 48 [see warnings and precautions (5.5) and adverse reactions (6.1)]. somnolence somnolence was frequently observed in placebo-controlled clinical trials of pediatric patients with autistic disorder. most cases were mild or moderate in severity. these events were most often of early onset with peak incidence occurring during the first two weeks of treatment, and transient with a median duration of 16 days. somnolence was the most commonly observed adverse reaction in the clinical trial of bipolar disorder in children and adolescents, as well as in the schizophrenia trials in adolescents. as was seen in the autistic disorder trials, these adverse reactions were most often of early onset and transient in duration  [see  adverse reactions (6.1, 6.2)] . patients experiencing persistent somnolence may benefit from a change in dosing regimen [see dosage & administration (2.1, 2.2, and 2.3)] . hyperprolactinemia risperidone tablets have been shown to elevate prolactin levels in children and adolescents as well as in adults [see warnings and precautions (5.6)] . in double-blind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received risperidone tablets had elevated prolactin levels compared to 2% of patients who received placebo. similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82–87% of patients who received risperidone tablets had elevated levels of prolactin compared to 3–7% of patients on placebo. increases were dose-dependent and generally greater in females than in males across indications. in clinical trials in 1885 children and adolescents, galactorrhea was reported in 0.8% of risperidone tablets-treated patients and gynecomastia was reported in 2.3% of risperidone tablets-treated patients. growth and sexual maturation the long-term effects of risperidone tablets on growth and sexual maturation have not been fully evaluated in children and adolescents. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4, and 13.5 times the mrhd of  6 mg/day for children, based on mg/m 2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m 2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. clinical studies of risperidone tablets in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3) and dosage & administration (2.4, 2.5)] . while elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg twice daily followed by careful titration [see warnings and precautions (5.7)] . monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. this drug is substantially excreted by the kidneys, 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 it may be useful to monitor renal function [see dosage & administration (2.4)] . in patients with moderate to severe (clcr 59 to 15 ml/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. risperidone tablets doses should be reduced in patients with renal disease [see dosage and administration (2.4)] . while the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α 1 -acid glycoprotein. risperidone tablets doses should be reduced in patients with liver disease [see dosage and administration (2.4)] . patients with parkinsons disease or dementia with lewy bodies can experience increased sensitivity to risperidone tablets. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone tablets are not a controlled substance. risperidone tablets have not been systematically studied in animals or humans for its potential for abuse. 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. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of risperidone tablets misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). risperidone tablets have not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

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

teva pharmaceuticals, inc. - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone for extended-release injectable suspension is indicated for the treatment of schizophrenia [see clinical studies (14.1)] . risperidone for extended-release injectable suspension is indicated as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar i disorder [see clinical studies (14.2, 14.3)] . risperidone for extended-release injectable suspension is contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone for extended-release injectable suspension formulation. hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. paliperidone is a metabolite of risperidone. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone for extended-release injectable suspension, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary neonates exposed to antipsychotic drugs 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 risperidone 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 or bipolar i disorder and with exposure to antipsychotics, including risperidone for extended-release injectable suspension, during pregnancy (see clinical considerations) . risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of risperidone for extended-release injectable suspension [see clinical pharmacology (12.3)] . the clinical significance of risperidone for extended-release injectable suspension administered before pregnancy or anytime during pregnancy is not known. oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (mrhd) with maternal toxicity observed at 4-times the mrhd based on mg/m2 body surface area. risperidone was not teratogenic in rats or rabbits at doses up to 6-times the mrhd based on mg/m2 body surface area. increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the mrhd based on mg/m2 body surface area. learning was impaired in offspring of rats when the dams were dosed at 0.6-times the mrhd and offspring mortality increased at doses 0.1 to 3 times the mrhd based on mg/m2 body surface area. 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. 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 risperidone for extended-release injectable suspension, 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 prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. there was a small increase in the risk major of birth defects (rr=1.26, 95% ci 1.02 to 1.56) and of cardiac malformations (rr=1.26, 95% ci 0.88 to 1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates. animal data oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the mrhd of 16 mg/day based on mg/m2 body surface area; maternal toxicity occurred at 4 times the mrhd. risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the mrhd of 16 mg/day risperidone based on mg/m2 body surface area. learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the mrhd and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the mrhd based on mg/m2 body surface area; postnatal development and growth of the offspring were also delayed. rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the mrhd of 16 mg/day based on mg/m2 body surface area. it is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. the rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the mrhd based on mg/m2 body surface area. in a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats. in addition, the number of deaths increased by day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. all of these effects occurred at 5 mg/kg which is 3 times the mrhd based on mg/m2 and the only dose tested in the study. risk summary limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted dosage. there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone (see clinical considerations) . risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of risperidone for extended-release injectable suspension [see clinical pharmacology (12.3)] , and the clinical significance on the breastfed infant is not known. there is no information on the effects of risperidone on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for risperidone for extended-release injectable suspension and any potential adverse effects on the breastfed child from risperidone for extended-release injectable suspension or from the mother’s underlying condition. clinical considerations infants exposed to risperidone for extended-release injectable suspension through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of risperidone (d2 receptor antagonism), treatment with risperidone for extended-release injectable suspension may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions (5.6)] . safety and effectiveness of risperidone for extended-release injectable suspension in pediatric patients have not been established. however, juvenile animal toxicology studies have been conducted with oral risperidone. juvenile animal studies juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4 and 13.5 times the mrhd of 6 mg/day for children, based on mg/m2 body surface area. bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma auc of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the mrhd of 6 mg/day. in addition, sexual maturation was delayed at all doses in both males and females. the above effects showed little or no reversibility in females after a 12 week drug-free recovery period. juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the mrhd of 6 mg/day for children, based on mg/m2 body surface area. this dose produced plasma auc of risperidone plus paliperidone about half the exposure observed in humans at the mrhd. no other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the mrhd and produced plasma auc of risperidone plus paliperidone that were about two thirds of those observed in humans at the mrhd of 6 mg/day for children. in an open-label study, 57 clinically stable, elderly patients (≥ 65 years old) with schizophrenia or schizoaffective disorder received risperidone for extended-release injectable suspension every 2 weeks for up to 12 months. in general, no differences in the tolerability of risperidone for extended-release injectable suspension were observed between otherwise healthy elderly and nonelderly patients. therefore, dosing recommendations for otherwise healthy elderly patients are the same as for nonelderly patients. because elderly patients exhibit a greater tendency to orthostatic hypotension than nonelderly patients, elderly patients should be instructed in nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position). in addition, monitoring of orthostatic vital signs should be considered in elderly patients for whom orthostatic hypotension is of concern [see warnings and precautions (5.7)] . concomitant use with furosemide in elderly patients with dementia-related psychosis in two of four placebo-controlled trials in elderly patients with dementia-related psychosis, a higher incidence of mortality was observed in patients treated with furosemide plus oral risperidone when compared to patients treated with oral risperidone alone or with oral placebo plus furosemide. no pathological mechanism has been identified to explain this finding, and no consistent pattern for cause of death was observed. an increase of mortality in elderly patients with dementia-related psychosis was seen with the use of oral risperidone regardless of concomitant use with furosemide. risperidone for extended-release injectable suspension is not approved for the treatment of patients with dementia-related psychosis [see boxed warning and warnings and precautions (5.1)]. in patients with renal or hepatic impairment, carefully titrate with oral risperidone prior to initiating treatment with risperidone for extended-release injectable suspension [see dosage and administration (2.4)] . patients with renal impairment may have less ability to eliminate risperidone than patients with normal renal function. patients with impaired hepatic function may have an increase in the free fraction of risperidone, possibly resulting in an enhanced effect [see clinical pharmacology (12.3)] . patients with parkinson’s disease or dementia with lewy bodies can experience increased sensitivity to risperidone for extended-release injectable suspension. manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome. risperidone for extended-release injectable suspension is not a controlled substance. risperidone for extended-release injectable suspension has not been systematically studied in animals or humans for its potential for abuse. because risperidone for extended-release injectable suspension is to be administered by health care professionals, the potential for misuse or abuse by patients is low. risperidone for extended-release injectable suspension has not been systematically studied in animals or humans for its potential for tolerance or physical dependence. risperidone (ris per’ i done) for extended-release injectable suspension for deltoid or gluteal intramuscular injection only each injection should be administered by a healthcare professional. important resources for additional information call teva at 1-888-838-2872. risperidone for extended-release injectable suspension requires close attention to these step-by-step instructions for use to help ensure successful administration. single-dose device do not reuse. medical devices require specific material characteristics to perform as intended. these characteristics have been verified for single-dose only. any attempt to re-process the device for subsequent re-use may adversely affect the integrity of the device or lead to deterioration in performance. important information use components provided the components in this dose pack are specifically designed for use with risperidone for extended-release injectable suspension. risperidone for extended-release injectable suspension must be reconstituted only in the diluent supplied in the dose pack. do not substitute any components of the dose pack. do not store suspension after reconstitution administer dose as soon as possible after reconstitution to avoid settling. proper dosing the entire contents of the vial must be administered to ensure intended dose of risperidone for extended-release injectable suspension is delivered. dose pack contents step 1 assemble components take out dose pack                connect vial adapter to vial wait 30 minutes remove dose pack from the refrigerator and allow to sit at room temperature for at least 30 minutes before reconstituting. do not warm any other way. remove cap from vial flip off colored cap from vial. wipe top of the grey stopper with an alcohol swab . allow to air dry. do not remove grey rubber stopper. prepare vial adapter hold sterile blister as shown. peel the blister film from backing and remove the vial adapter from its packaging by holding between the white luer cap and the skirt. do not touch spike tip and luer tip connector of the vial adapter at any time. this will result in contamination. connect vial adapter to vial place vial on a hard surface and hold by the base. center vial adapter over the grey rubber stopper. push vial adapter straight down onto vial top until it snaps securely into place.  clean the luer tip of the vial adapter with an alcohol wipe do not place vial adapter on at an angle or diluent may leak upon transfer to the vial. do not shake. do not touch exposed luer tip connector on vial adapter. this will result in contamination. connect prefilled syringe to vial adapter use proper grip hold by white collar at the tip of the syringe. do not hold syringe by the glass barrel during assembly. remove cap holding the white collar, snap off the white cap. do not twist or cut off the white cap. do not touch syringe tip. this will result in contamination. the broken-off cap can be discarded. connect syringe to vial adapter hold vial adapter by skirt to keep stationary. hold syringe by white collar then insert tip into the luer tip connector of the vial adapter. do not hold the glass syringe barrel. this may cause the white collar to loosen or detach. attach the syringe to the vial adapter with a firm clockwise twisting motion   until it feels snug. do not over-tighten. over-tightening may cause the syringe tip to break. step 2 reconstitute microspheres inject diluent inject entire amount of diluent from syringe into the vial. suspend microspheres in diluent continuing to hold down the plunger rod, shake vigorously for at least 10 seconds , as shown. check the suspension. when properly mixed, the suspension appears uniform, thick and milky in color. microspheres will be visible in the liquid. immediately proceed to the next step so suspension does not settle. transfer suspension to syringe invert vial completely. slowly pull plunger rod down to withdraw entire contents from the vial into the syringe. remove vial adapter hold white collar on the syringe and unscrew from vial adapter. tear section of the vial label at the perforation. apply detached label to the syringe for identification purposes. discard both vial and vial adapter appropriately. step 3 attach needle select appropriate needle choose needle based on injection location (gluteal or deltoid). attach needle peel blister pouch open part way and use to grasp the base of the needle, as shown. holding the white collar on the syringe , attach syringe to needle luer connection with a firm clockwise twisting motion until snug. do not touch needle luer opening. this will result in contamination. resuspend microspheres fully remove the blister pouch. just before injection, shake syringe vigorously again, as some settling will have occurred. step 4 inject dose remove transparent needle protector move the needle safety device back towards the syringe, as shown. then hold white collar on syringe and carefully pull the transparent needle protector straight off. do not twist transparent needle protector, as the luer connection may loosen. remove air bubbles hold needle upright and tap gently to make any air bubbles rise to the top. slowly and carefully press plunger rod upward to remove air. inject immediately inject entire contents of syringe intramuscularly (im) into the gluteal or deltoid muscle of the patient. gluteal injection should be made into the upper-outer quadrant of the gluteal area. do not administer intravenously. secure needle in safety device using one hand , place needle safety device at a 45-degree angle on a hard, flat surface. press down with a firm, quick motion until needle is fully engaged in safety device. avoid needle stick injury: do not use two hands. do not intentionally disengage or mishandle the needle safety device. do not attempt to straighten the needle or engage the safety device if the needle is bent or damaged. properly dispose of needles check to confirm needle safety device is fully engaged. discard in an approved sharps container. also discard the unused needle provided in the dose pack. manufactured in greece by: pharmathen international s.a. rodopi, 69300, greece manufactured for: teva pharmaceuticals parsippany, nj 07054   iss. 3/2023

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

aphena pharma solutions - tennessee, llc - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone is indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] . adjunctive therapy risperidone adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone is indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing

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

aphena pharma solutions - tennessee, llc - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone is indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] . adjunctive therapy risperidone adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone is indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing

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

aphena pharma solutions - tennessee, llc - risperidone (unii: l6uh7zf8hc) (risperidone - unii:l6uh7zf8hc) - risperidone is indicated for the treatment of schizophrenia. efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see clinical studies (14.1)] . monotherapy risperidone is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see clinical studies (14.2)] . adjunctive therapy risperidone adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with bipolar i disorder. efficacy was established in one short-term trial in adults [see clinical studies (14.3)] . risperidone is indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing