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

asclemed usa, inc. - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies ( 14)] . patients who develop angioedema after treatment with ramelteon should not be rechallenged with the drug. patients should not take ramelteon in conjunction with fluvoxamine [see drug interactions ( 7)] . risk summary available data from postmarketing reports with ramelteon use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effect

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

actavis pharma, inc. - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)] . patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7)] . risk summary available data from postmarketing reports with ramelteon tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than 36 times the recommended human dose (rhd) of 8 mg/day based on body surface area (mg/m2 ) (see data ). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data oral administration of ramelteon (10, 40, 150 or 600 mg/kg/day) to pregnant rats during the period of organogenesis was associated with increased incidences of fetal structural abnormalities (malformations and variations) at doses greater than 40 mg/kg/day. the no-effect dose is approximately 50 times the rhd based on mg/m2 . treatment of pregnant rabbits during the period of organogenesis produced no evidence of embryo-fetal toxicity at oral doses of up to 300 mg/kg/day (or up to 720 times the rhd based on mg/m2 ). when rats were orally administered ramelteon (30, 100, or 300 mg/kg/day) throughout gestation and lactation, growth retardation, developmental delay, and behavioral changes were observed in the offspring at doses greater than 30 mg/kg/day. the no-effect dose is 36 times the rhd based on mg/m2 . increased incidences of malformation and death among offspring were seen at the highest dose. risk summary there are no data regarding the presence of ramelteon or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. ramelteon and/or its metabolites are present in rat milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk. because of the mechanism of action of ramelteon, there is a potential risk for somnolence in a breastfed infant (see clinical considerations) . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ramelteon tablets and any potential adverse effects on the breastfed infant from ramelteon tablets or from the underlying maternal condition. clinical considerations infants exposed to ramelteon tablets through breastmilk should be monitored for somnolence and feeding problems. a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 25 hours (approximately 5 elimination half-lives) after ramelteon tablets administration in order to minimize drug exposure to a breastfed infant. safety and effectiveness of ramelteon tablets in pediatric patients have not been established. further study is needed prior to determining that this product may be used safely in prepubescent and pubescent patients. a total of 654 subjects in double-blind, placebo-controlled, efficacy trials who received ramelteon tablets were at least 65 years of age; of these, 199 were 75 years of age or older. no overall differences in safety or efficacy were observed between elderly and younger adult subjects. a double-blind, randomized, placebo-controlled study in elderly subjects with insomnia (n=33) evaluated the effect of a single dose of ramelteon tablets on balance, mobility, and memory functions after middle of the night awakening. there is no information on the effect of multiple dosing. night time dosing of ramelteon tablets 8 mg did not impair middle of the night balance, mobility, or memory functions relative to placebo. the effects on night balance in the elderly cannot be definitively known from this study. the respiratory depressant effect of ramelteon tablets was evaluated in a crossover design study of subjects (n=26) with mild to moderate copd after administering a single 16 mg dose or placebo, and in a separate study (n=25), the effects of ramelteon tablets on respiratory parameters were evaluated after administering an 8 mg dose or placebo in a crossover design to patients with moderate to severe copd, defined as patients who had forced expiratory volume at one second (fev1 )/forced vital capacity ratio of <70%, and a fev1 <80% of predicted with <12% reversibility to albuterol. treatment with a single dose of ramelteon tablets has no demonstrable respiratory depressant effects in subjects with mild to severe copd, as measured by arterial o2 saturation (sao2). there is no available information on the respiratory effects of multiple doses of ramelteon tablets in patients with copd. the respiratory depressant effects in patients with copd cannot be definitively known from this study. the effects of ramelteon tablets were evaluated after administering a 16 mg dose or placebo in a crossover design to subjects (n=26) with mild to moderate obstructive sleep apnea. treatment with ramelteon tablets 16 mg for one night showed no difference compared with placebo on the apnea/hypopnea index (the primary outcome variable), apnea index, hypopnea index, central apnea index, mixed apnea index, and obstructive apnea index. treatment with a single dose of ramelteon tablets does not exacerbate mild to moderate obstructive sleep apnea. there is no available information on the respiratory effects of multiple doses of ramelteon tablets in patients with sleep apnea. the effects on exacerbation in patients with mild to moderate sleep apnea cannot be definitively known from this study. ramelteon has not been studied in subjects with severe obstructive sleep apnea; use of ramelteon tablets is not recommended in such patients. exposure to ramelteon tablets was increased by four-fold in subjects with mild hepatic impairment and by more than ten-fold in subjects with moderate hepatic impairment. ramelteon tablets should be used with caution in patients with moderate hepatic impairment [see clinical pharmacology (12.4)] . ramelteon tablets are not recommended in patients with severe hepatic impairment. no effects on cmax and auc0-t of parent drug or m-ii were seen. no adjustment of ramelteon tablets dosage is required in patients with renal impairment [see clinical pharmacology (12.4)] . ramelteon tablets are not a controlled substance. discontinuation of ramelteon in animals or in humans after chronic administration did not produce withdrawal signs. ramelteon does not appear to produce physical dependence. human data a laboratory abuse potential study was performed with ramelteon tablets [see clinical studies (14.2)] . animal data ramelteon did not produce any signals from animal behavioral studies indicating that the drug produces rewarding effects. monkeys did not self-administer ramelteon and the drug did not induce a conditioned place preference in rats. there was no generalization between ramelteon and midazolam. ramelteon did not affect rotorod performance, an indicator of disruption of motor function, and it did not potentiate the ability of diazepam to interfere with rotorod performance.

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

avkare - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [ see clinical studies (14) ]. patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7) ]. risk summary available data from post marketing reported with ramelteon use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than 36 times the recommended human dose (rhd) of 8 mg/day based on body surface area (mg/m) (see data). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data oral administration of ramelteon (10, 40, 150 or 600 mg/kg/day) to pregnant rats during the period of organogenesis was associated with increased incidences of fetal structural abnormalities (malformations and variations) at doses greater than 40 mg/kg/day. the no-effect dose is approximately 50 times the rhd based on mg/m 2 . treatment of pregnant rabbits during the period of organogenesis produced no evidence of embryo-fetal toxicity at oral doses of up to 300 mg/kg/day (or up to 720 times the rhd based on mg/m 2 ). when rats were orally administered ramelteon (30, 100, or 300 mg/kg/day) throughout gestation and lactation, growth retardation, developmental delay, and behavioral changes were observed in the offspring at doses greater than 30 mg/kg/day. the no-effect dose is 36 times the rhd on a based on mg/m 2 . increased incidences of malformation and death among offspring were seen at the highest dose. risk summary there are no data regarding the presence of ramelteon or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. ramelteon and/or its metabolites are present in rat milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk. because of the mechanism of action of ramelteon, there is a potential risk for somnolence in a breastfed infant ( see clinical considerations) . the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for ramelteon tablets and any potential adverse effects on the breastfed infant from ramelteon tablets or from the underlying maternal condition. clinical considerations infants exposed to ramelteon tablets through breastmilk should be monitored for somnolence and feeding problems. a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 25 hours (approximately 5 elimination half-lives) after ramelteon tablets administration in order to minimize drug exposure to a breastfed infant. safety and effectiveness of ramelteon tablets in pediatric patients have not been established. further study is needed prior to determining that this product may be used safely in prepubescent and pubescent patients. a total of 654 subjects in double-blind, placebo-controlled, efficacy trials who received ramelteon tablets were at least 65 years of age; of these, 199 were 75 years of age or older. no overall differences in safety or efficacy were observed between elderly and younger adult subjects. a double-blind, randomized, placebo-controlled study in elderly subjects with insomnia (n=33) evaluated the effect of a single dose of ramelteon tablets on balance, mobility, and memory functions after middle of the night awakening. there is no information on the effect of multiple dosing. night time dosing of ramelteon tablets, 8 mg did not impair middle of the night balance, mobility, or memory functions relative to placebo. the effects on night balance in the elderly cannot be definitively known from this study. the respiratory depressant effect of ramelteon was evaluated in a crossover design study of subjects (n=26) with mild to moderate copd after administering a single 16 mg dose or placebo, and in a separate study (n=25), the effects of ramelteon on respiratory parameters were evaluated after administering an 8 mg dose or placebo in a crossover design to patients with moderate to severe copd, defined as patients who had forced expiratory volume at one second (fev 1 )/forced vital capacity ratio of <70%, and a fev 1 <80% of predicted with <12% reversibility to albuterol. treatment with a single dose of ramelteon tablets has no demonstrable respiratory depressant effects in subjects with mild to severe copd, as measured by arterial o 2 saturation (sao 2 ). there is no available information on the respiratory effects of multiple doses of ramelteon tablets in patients with copd. the respiratory depressant effects in patients with copd cannot be definitively known from this study. the effects of ramelteon tablets were evaluated after administering a 16 mg dose or placebo in a crossover design to subjects (n=26) with mild to moderate obstructive sleep apnea. treatment with ramelteon tablets 16 mg for one night showed no difference compared with placebo on the apnea/hypopnea index (the primary outcome variable), apnea index, hypopnea index, central apnea index, mixed apnea index, and obstructive apnea index. treatment with a single dose of ramelteon tablets does not exacerbate mild to moderate obstructive sleep apnea. there is no available information on the respiratory effects of multiple doses of ramelteon tablets in patients with sleep apnea. the effects on exacerbation in patients with mild to moderate sleep apnea cannot be definitively known from this study. ramelteon tablets have not been studied in subjects with severe obstructive sleep apnea; use of ramelteon tablets are not recommended in such patients. exposure to ramelteon tablets were increased by four-fold in subjects with mild hepatic impairment and by more than ten-fold in subjects with moderate hepatic impairment. ramelteon tablets should be used with caution in patients with moderate hepatic impairment [see clinical pharmacology (12.4) ]. ramelteon tablets are not recommended in patients with severe hepatic impairment. no effects on c max and auc 0-t of parent drug or m-ii were seen. no adjustment of ramelteon dosage is required in patients with renal impairment [see clinical pharmacology (12.4) ]. ramelteon tablet is not a controlled substance. discontinuation of ramelteon in animals or in humans after chronic administration did not produce withdrawal signs. ramelteon does not appear to produce physical dependence. human data a laboratory abuse potential study was performed with ramelteon tablets [see clinical studies (14.2) ] . animal data ramelteon did not produce any signals from animal behavioral studies indicating that the drug produces rewarding effects. monkeys did not self-administer ramelteon and the drug did not induce a conditioned place preference in rats. there was no generalization between ramelteon and midazolam. ramelteon did not affect rotorod performance, an indicator of disruption of motor function, and it did not potentiate the ability of diazepam to interfere with rotorod performance.

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

zydus pharmaceuticals usa inc. - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)] . patients who develop angioedema after treatment with ramelteon should not be rechallenged with the drug. patients should not take ramelteon in conjunction with fluvoxamine [see drug interactions (7)] . risk summary available data from postmarketing reports with ramelteon use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than

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

bryant ranch prepack - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)] . patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7)] . risk summary available data from postmarketing reports with ramelteon tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in ra

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

i3 pharmaceuticals, llc - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)]. patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7)]. risk summary available data from postmarketing reports with ramelteon tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic ef

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

trupharma, llc - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)]. patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7)]. risk summary available data from postmarketing reports with ramelteon tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic ef

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

quality care products, llc - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)]. patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7)]. risk summary available data from postmarketing reports with ramelteon tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats

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

upsher-smith laboratories, llc - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six month studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)] . patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. patients should not take ramelteon tablets in conjunction with fluvoxamine [see drug interactions (7)] . risk summary available data from postmarketing reports with ramelteon use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at

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

bryant ranch prepack - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)] . patients who develop angioedema after treatment with ramelteon should not be rechallenged with the drug. patients should not take ramelteon in conjunction with fluvoxamine [see drug interactions (7)] . risk summary available data from postmarketing reports with ramelteon use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than