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

cotherix, inc. - miglustat (unii: adn3s497az) (miglustat - unii:adn3s497az) - miglustat 100 mg - miglustat is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to allergy, hypersensitivity, or poor venous access). none. risk summary based on findings from animal reproduction studies, miglustat may cause fetal harm when administered to a pregnant woman. available data from postmarketing case reports with miglustat use in pregnancy are insufficient to assess a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. there are risks associated with symptomatic type i gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia (see clinical considerations). advise pregnant women of the potential risks to the fetus. in animal reproduction studies, miglustat was maternally toxic in rabbits at exposures near the expected human therapeutic dose and caused embryo-fetal tox

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

ani pharmaceuticals, inc. - miglustat (unii: adn3s497az) (miglustat - unii:adn3s497az) - miglustat 100 mg - miglustat is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to allergy, hypersensitivity, or poor venous access). none risk summary based on findings from animal reproduction studies, miglustat capsules may cause fetal harm when administered to a pregnant woman. available data from postmarketing case reports with miglustat use in pregnancy are insufficient to assess a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. there are risks associated with symptomatic type i gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia (see clinical considerations) . advise pregnant women of the potential risks to the fetus. in animal reproduction studies, miglustat was maternally toxic in rabbits at exposures near the expected human therapeutic dose and caused embryo-fetal toxicities in rats at doses twice the recommended human dose. no adverse developmental outcomes were observed with administration of miglustat to pregnant rats at dose levels 6 times the recommended human dose (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 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and embryo-fetal risk pregnancy may exacerbate existing type 1 gaucher disease symptoms or result in new disease manifestations. type 1 gaucher disease manifestations may lead to adverse pregnancy outcomes including, hepatosplenomegaly which can interfere with the normal growth of a pregnancy and thrombocytopenia which can lead to increased bleeding and possible hemorrhage. data animal data in female rats given miglustat by oral gavage at doses of 20, 60, 180 mg/kg/day beginning 14 days before mating and continuing through gestation day 17 (organogenesis), increased post implantation loss, decreased embryo-fetal survival and decreased fetal and pup weights were observed at doses ≥60 mg/kg/day (≥2 times the human therapeutic dose on a mg/m2 basis). miglustat was also administered to pregnant rats by oral gavage at doses of 20, 60, 180 mg/kg/day from gestation day 6 through lactation (postpartum day 20). delayed and prolonged parturition with decreased live births were observed at doses ≥60 mg/kg/day (≥2 times the human therapeutic dose on a mg/m2 basis). in pregnant rabbits given miglustat by oral gavage at doses of 15, 30, 45 mg/kg/day during gestation days 6-18 (organogenesis), maternal toxicity, including maternal deaths (all doses), reduced food consumption (30 and 45 mg/kg/day), and decreased body weight gain (15 and 30 mg/kg/day), was observed. the 15 mg/kg/day dose level was 0.97 times the human therapeutic dose on a mg/m2 basis. in a pre- and postnatal development study in rats, miglustat was administered by oral gavage at doses of 20, 60, 180 mg/kg/day from gestation day 6 through day 20 of lactation, decreased live births were observed in dams, as well as decreased body weight gain in the offspring at doses ≥60 mg/kg/day (≥2 times the human therapeutic dose on a mg/m2 basis). there was no effect on behavioral and learning assessments, sexual maturation or reproductive performance of the offspring at doses up to 180 mg/kg/day (about 6 times the human therapeutic dose on a mg/m2 basis). risk summary there are no available data on the presence of miglustat in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. based on the physical properties of miglustat, miglustat is likely to be present in breast milk. because of the potential for serious adverse reactions in breastfed infants, advise women that breastfeeding is not recommended. infertility findings from a small clinical study in seven healthy adult males who received miglustat for six weeks did not indicate effects on male fertility. studies in male rats have shown that miglustat decreased fertility but findings were reversible. studies in female rats have shown increased post-implantation loss and decreased embryo-fetal survival [see use in specific populations (8.1), nonclinical toxicology (13.1)] . the safety and effectiveness of miglustat in pediatric patients have not been established. in a combined clinical trial safety data set of 45 patients less than 18 years of age exposed to miglustat in indications other than type 1 gaucher disease, the median weight and height percentiles adjusted for age and gender decreased during the first year of treatment but then stabilized. the mean length of exposure in these studies ranged from 2 to 2.6 years; some pediatric patients were exposed for up to 4 years. however, the effect of miglustat on long-term gain in weight and height in pediatric patients is unclear. clinical studies of miglustat capsules did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. other reported clinical experience has not identified differences in responses between elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, and cardiac function and of concomitant disease or other drug therapy. miglustat is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function [see clinical pharmacology (12.3)] . in patients with mild renal impairment (adjusted creatinine clearance 50-70 ml/min/1.73m2 ), miglustat capsule administration should commence at a dose of 100 mg twice per day. in patients with moderate renal impairment (adjusted creatinine clearance of 30-50 ml/min/1.73m2 ), miglustat capsule administration should commence at a dose of 100 mg once a day. use of miglustat capsules in patients with severe renal impairment (creatinine clearance < 30 ml/min/1.73m2 ) is not recommended. since 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. the impact of hemodialysis on the disposition of miglustat has not been investigated.

Israel - English - Ministry of Health

mbi pharma ltd., israel - miglustat - hard capsule - miglustat 100 mg - miglustat - miglustat dipharma is indicated for the oral treatment of mild to moderate type i gaucher disease. miglustat dipharma may be used only in the treatment of patients for whom enzyme replacement therapy is unsuitable. miglustat dipharma is indicated for the treatment of progressive neurological manifestations in adult patients and paediatric patients with niemann-pick type c disease.

European Union - English - EMA (European Medicines Agency)

gen.orph - miglustat - gaucher disease - other alimentary tract and metabolism products, - miglustat gen.orph is indicated for the oral treatment of adult patients with mild to moderate type 1 gaucher disease. miglustat gen.orph may be used only in the treatment of patients for whom enzyme replacement therapy is unsuitable.miglustat gen.orph is indicated for the treatment of progressive neurological manifestations in adult patients and paediatric patients with niemann-pick type c disease.

European Union - English - EMA (European Medicines Agency)

dipharma arzneimittel gmbh - miglustat - gaucher disease - other alimentary tract and metabolism products - miglustat dipharma is indicated for the oral treatment of adult patients with mild to moderate type 1 gaucher disease.miglustat dipharma may be used only in the treatment of patients for whom enzyme replacement therapy is unsuitable.miglustat dipharma is indicated for the treatment of progressive neurological manifestations in adult patients and paediatric patients with niemann-pick type c disease.

Israel - English - Ministry of Health

a.l. medi-market ltd. - miglustat - capsules - miglustat 100 mg - miglustat - miglustat g.l. is indicated for the oral treatment of mild to moderate type i gaucher disease. miglustat g.l. may be used only in the treatment of patients for whom enzyme replacement therapy is unsuitable. miglustat g.l. is indicated for the treatment of progressive neurological manifestations in adult patients and paediatric patients with niemann-pick type c disease.

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

breckenridge pharmaceutical, inc. - miglustat (unii: adn3s497az) (miglustat - unii:adn3s497az) - miglustat capsules are indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to allergy, hypersensitivity, or poor venous access). none risk summary based on findings from animal reproduction studies, miglustat capsules may cause fetal harm when administered to a pregnant woman. available data from postmarketing case reports with miglustat capsules use in pregnancy are insufficient to assess a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. there are risks associated with symptomatic type i gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia (see clinical considerations) . advise pregnant women of the potential risks to the fetus. in animal reproduction studies, miglustat was maternally toxic in rabbits at exposures near the expected human therapeutic dose and caused embryo-fetal toxicities in rats at doses tw

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

genzyme corporation - eliglustat (unii: dr40j4wa67) (eliglustat - unii:dr40j4wa67) - eliglustat 84 mg - cerdelga is indicated for the long-term treatment of adult patients with gaucher disease type 1 (gd1) who are cyp2d6 extensive metabolizers (ems), intermediate metabolizers (ims), or poor metabolizers (pms) as detected by an fda-cleared test [see dosage and administration (2.1)] . limitations of use : - patients who are cyp2d6 ultra-rapid metabolizers (urms) may not achieve adequate concentrations of cerdelga to achieve a therapeutic effect [see clinical studies (14)] . - a specific dosage cannot be recommended for those patients whose cyp2d6 genotype cannot be determined (indeterminate metabolizers) [see clinical studies (14)] . cerdelga is contraindicated in the following patients based on cyp2d6 metabolizer status due to the risk of cardiac arrhythmias from prolongation of the pr, qtc, and/or qrs cardiac intervals. ems - taking a strong or moderate cyp2d6 inhibitor concomitantly with a strong or moderate cyp3a inhibitor [see drug interactions (7.1)] - moderate or severe hepatic impairment [see use in specific populations (8.7)] - mild hepatic impairment and taking a strong or moderate cyp2d6 inhibitor [see use in specific populations (8.7)] ims - taking a strong or moderate cyp2d6 inhibitor concomitantly with a strong or moderate cyp3a inhibitor [see drug interactions (7.1)] - taking a strong cyp3a inhibitor [see drug interactions (7.1)] - any degree of hepatic impairment [see use in specific populations (8.7)] pms - taking a strong cyp3a inhibitor [see drug interactions (7.1)] - any degree of hepatic impairment [see use in specific populations (8.7)] risk summary available data on cerdelga use in pregnant women includes 20 pregnancies that occurred during the clinical development program and a small number of post-marketing case reports. these data are not sufficient to assess drug-associated risks major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies in pregnant rats administered oral eliglustat during organogenesis, a spectrum of various developmental abnormalities were observed at doses 6 times the recommended human dose. no adverse developmental outcomes were observed with oral administration of eliglustat to pregnant rabbits at dose levels 10 times the recommended human dose [see data] . the estimated background risk of major birth defects and miscarriage in the indicated population is unknown. all pregnancies have a background risk of birth defect, loss or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk women with gaucher disease type 1 have an increased risk of spontaneous abortion, especially if disease symptoms are not treated and controlled pre-conception and during a pregnancy. pregnancy may exacerbate existing gaucher disease type 1 symptoms or result in new disease manifestations. gaucher disease type 1 manifestations may lead to adverse pregnancy outcomes including, hepatosplenomegaly which can interfere with the normal growth of a pregnancy and thrombocytopenia which can lead to increased bleeding and possible hemorrhage. data animal data reproduction studies have been performed in pregnant rats at oral doses up to 120 mg/kg/day (about 6 times the recommended human dose based on body surface area) and in pregnant rabbits at oral doses up to 100 mg/kg/day (about 10 times the recommended human dose based on body surface area) following administration of eliglustat during the period of organogenesis (gestation days 6 to 17 in the rat and 6 to 18 in the rabbit). in rats, at 120 mg/kg/day (about 6 times the recommended human dose based on body surface area), eliglustat increased the number of late resorptions, dead fetuses and post implantation loss, reduced fetal body weight, and caused fetal cerebral variations (dilated cerebral ventricles), fetal skeletal variations (poor bone ossification) and fetal skeletal malformations (abnormal number of ribs or lumbar vertebra). eliglustat-related effects on fetal rats were observed in association with signs of maternal toxicity. eliglustat did not cause fetal harm in rabbits at oral doses up to 100 mg/kg/day (about 10 times the recommended human dose based on body surface area). mild maternal toxicity was observed at the 100 mg/kg/day dose. in a pre and postnatal development study in rats (dosed daily from gestation day 6 to postpartum day 21), eliglustat did not show any significant adverse effects on pre and postnatal development at doses up to 100 mg/kg/day (about 5 times the recommended human dose based on body surface area). risk summary there are no human data available on the presence of eliglustat in human milk, the effects on the breastfed infant, or the effects on milk production. eliglustat and its metabolites were present in the milk of lactating rats [see data] . when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for cerdelga and any potential adverse effects on the breastfed child from cerdelga or from the underlying maternal condition. data in a milk excretion study in the rat, a single oral dose of 30 mg/kg [14 c]-labeled eliglustat was administered to lactating female rats at day 11 postpartum. approximately 0.23% of the administered radioactivity was excreted into the milk within 24 hours of dose administration. the concentration in the milk at 24 hours post dose was 16.3-fold higher than the plasma concentration. safety and effectiveness in pediatric patients have not been established. clinical studies of cerdelga did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. clinical experience has not identified differences in responses between the elderly and younger patients. use cerdelga in patients with renal impairment based on the patient's cyp2d6 metabolizer status [see clinical pharmacology (12.3)] . ems - avoid cerdelga in patients with end-stage renal disease (esrd) (estimated creatinine clearance (eclcr) less than 15 ml/min not on dialysis or requiring dialysis). - no dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment (eclcr at least 15 ml/min). ims and pms - avoid cerdelga in patients with any degree of renal impairment. use cerdelga in patients with hepatic impairment based on cyp2d6 metabolizer status and concomitant use of cyp2d6 or cyp3a inhibitors [see clinical pharmacology (12.3)] . ems - cerdelga is contraindicated in patients with [see contraindications (4)] : severe (child-pugh class c) hepatic impairment moderate (child-pugh class b) hepatic impairment mild (child-pugh class a) hepatic impairment taking a strong or moderate cyp2d6 inhibitor - severe (child-pugh class c) hepatic impairment - moderate (child-pugh class b) hepatic impairment - mild (child-pugh class a) hepatic impairment taking a strong or moderate cyp2d6 inhibitor - reduce dosage frequency of cerdelga 84 mg to once daily [see dosage and administration (2.3)] in patients with mild hepatic impairment taking: a weak cyp2d6 inhibitor a strong, moderate, or weak cyp3a inhibitor - a weak cyp2d6 inhibitor - a strong, moderate, or weak cyp3a inhibitor - no dosage adjustment is recommended in patients with mild hepatic impairment, unless otherwise specified above. ims and pms - cerdelga is contraindicated in patients with any degree of hepatic impairment [see contraindications (4)] .

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

veranova, l.p. - miglustat (unii: adn3s497az) (miglustat - unii:adn3s497az) - miglustat 1 kg in 1 kg

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

actelion pharmaceuticals us, inc. - miglustat (unii: adn3s497az) (miglustat - unii:adn3s497az) - miglustat 100 mg - zavesca is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to allergy, hypersensitivity, or poor venous access). none. risk summary based on findings from animal reproduction studies, zavesca may cause fetal harm when administered to a pregnant woman. available data from postmarketing case reports with zavesca use in pregnancy are insufficient to assess a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. there are risks associated with symptomatic type i gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia (see clinical considerations). advise pregnant women of the potential risks to the fetus. in animal reproduction studies, miglustat was maternally toxic in rabbits at exposures near the expected human therapeutic dose and caused embryo-fetal toxicitie