{"id":"miglustat","rwe":[{"pmid":"41817649","year":"2026","title":"Correction: Miglustat as a Treatment for Adults with Tangier Disease Neuropathy: The MUSTANG N‑of‑1 Trial with 21 months Clinical Observation.","finding":"","journal":"Neurology and therapy","studyType":"Clinical Study"},{"pmid":"41783848","year":"2026","title":"Comprehensive review of recent advances in Pompe disease: pathogenesis, management, and future directions.","finding":"","journal":"Frontiers in neurology","studyType":"Clinical Study"},{"pmid":"41769220","year":"2026","title":"Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease.","finding":"","journal":"Therapeutic advances in rare disease","studyType":"Clinical Study"},{"pmid":"41757410","year":"2026","title":"Comparing the efficacy of cipaglucosidase alfa plus miglustat with alglucosidase alfa for late-onset Pompe disease: an expanded network meta-analysis utilizing patient-level and aggregate data.","finding":"","journal":"Journal of comparative effectiveness research","studyType":"Clinical Study"},{"pmid":"41742944","year":"2026","title":"Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1.","finding":"","journal":"medRxiv : the preprint server for health sciences","studyType":"Clinical Study"}],"_fda":{"id":"462f6c9d-b8f1-3a76-e063-6294a90a2b50","set_id":"2b371dfe-e2b0-47fe-b677-a7bde7149f87","openfda":{"nui":["N0000175783","N0000020019","N0000194077","N0000194078"],"unii":["ADN3S497AZ"],"route":["ORAL"],"rxcui":["401938","2642350"],"spl_id":["462f6c9d-b8f1-3a76-e063-6294a90a2b50"],"brand_name":["Yargesa"],"spl_set_id":["2b371dfe-e2b0-47fe-b677-a7bde7149f87"],"package_ndc":["42799-709-01","42799-709-15"],"product_ndc":["42799-709"],"generic_name":["MIGLUSTAT"],"product_type":["HUMAN PRESCRIPTION DRUG"],"substance_name":["MIGLUSTAT"],"pharm_class_epc":["Glucosylceramide Synthase Inhibitor [EPC]","Enzyme Stabilizer [EPC]"],"pharm_class_moa":["Glucosylceramide Synthase Inhibitors [MoA]","Enzyme Stabilizers [MoA]"],"manufacturer_name":["Edenbridge Pharmaceuticals LLC."],"application_number":["ANDA209821"],"is_original_packager":[true]},"version":"5","pregnancy":["8.1 Pregnancy 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 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 greater than or equal to 60 mg/kg/day (greater than or equal to 2 times the human therapeutic dose on a mg/m 2 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 greater than or equal to 60 mg/kg/day (greater than or equal to 2 times the human therapeutic dose on a mg/m 2 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/m 2 basis. 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 greater than or equal to 60 mg/kg/day (greater than or equal to 2 times the human therapeutic dose on a mg/m 2 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/m 2 basis)."],"description":["11 DESCRIPTION YARGESA (miglustat capsules) is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for the first step in the synthesis of most glycosphingolipids. YARGESA is an N-alkylated imino sugar, a synthetic analog of D-glucose. The chemical name for miglustat is 1,5-(butylimino)-1,5-dideoxy-D-glucitol with the chemical formula C 10 H 21 NO 4 and a molecular weight of 219.28. Miglustat is a white to off-white crystalline solid and has a bitter taste. It is highly soluble in water (greater than 1000 mg/mL as a free base). YARGESA is supplied in hard gelatin capsules each containing 100 mg miglustat for oral administration. Each YARGESA 100 mg capsule also contains sodium starch glycolate (type A, potato), povidone (K-29/32), and magnesium stearate. Ingredients in the capsule shell include gelatin and titanium dioxide, and the shells are printed with edible ink consisting of black iron oxide, shellac, and propylene glycol. structure"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING YARGESA is supplied in hard gelatin capsules containing 100 mg miglustat. YARGESA 100 mg capsules are white opaque with “709” printed in black on the body. YARGESA are packed in blister cards. Six blister cards of 15 capsules are supplied in each carton. NDC 42799-709-01: carton containing 90 capsules. One blister card of 15 capsules is supplied in each carton. NDC 42799-709-15: carton containing 15 capsules. Storage: Store at 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature). Keep out of reach of children"],"geriatric_use":["8.5 Geriatric Use 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."],"pediatric_use":["8.4 Pediatric Use The safety and effectiveness of miglustat capsules 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 capsules 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 capsules on long-term gain in weight and height in pediatric patients is unclear."],"effective_time":"20251217","nursing_mothers":["8.3 Females and Males of Reproductive Potential 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) ]."],"clinical_studies":["14 CLINICAL STUDIES The efficacy of miglustat capsules in type 1 Gaucher disease has been investigated in two open-label, uncontrolled trials and one randomized, open-label, active-controlled trial with enzyme replacement given as imiglucerase. Patients who received miglustat capsules were treated with doses ranging from 100 to 600 mg a day, although the majority of patients were maintained on doses between 200 to 300 mg a day. Efficacy parameters included the evaluation of liver and spleen organ volume, hemoglobin concentration, and platelet count. A total of 80 patients were exposed to miglustat capsules during the three trials and their extension period. Open-Label Uncontrolled Monotherapy Trials In Study 1, miglustat capsules was administered at a starting dose of 100 mg three times daily for 12 months (dose range of 100 once-daily to 200 mg three times daily) to 28 adult patients with type 1 Gaucher disease, who were unable to receive enzyme replacement therapy and who had not taken enzyme replacement therapy in the preceding 6 months. Twenty-two patients completed the trial. After 12 months of treatment, the results showed significant mean percent reductions from baseline in liver volume of 12% and spleen volume of 19%, a non-significant increase from baseline in mean absolute hemoglobin concentration of 0.26 g/dL and a mean absolute increase from baseline in platelet counts of 8 × 109/L (See Tables 3-6). In Study 2, miglustat capsules was administered at a dose of 50 mg three times daily for 6 months to 18 adult patients with type 1 Gaucher disease who were unable to receive enzyme replacement therapy and who had not taken enzyme replacement therapy in the preceding 6 months. Seventeen patients completed the trial. After 6 months of treatment, the results showed significant mean percent reductions from baseline in liver volume of 6% and spleen volume of 5%. There was a non-significant mean absolute decrease from baseline in hemoglobin concentration of 0.13 g/dL and a non-significant mean absolute increase from baseline in platelet counts of 5 × 10 9 /L (See Tables 3-6). Extension Period Eighteen patients were enrolled in a 12-month extension to Study 1. A subset of patients continuing in the extension had larger mean baseline liver volumes, and lower mean baseline platelet counts and hemoglobin concentrations than the original study population (See Tables 3-6). After a total of 24 months of treatment, there were significant mean decreases from baseline in liver and spleen organ volumes of 15% and 27%, respectively, and significant mean absolute increases from baseline in hemoglobin concentration and platelet count of 0.9 g/dL and 14 × 10 9 /L, respectively (See Tables 3-6). Sixteen patients were enrolled in a 6-month extension to Study 2. After a total of 12 months of treatment, there was a mean decrease from baseline in spleen organ volume of 10%, whereas the mean percent decrease in liver organ volume remained at 6%. There were no significant changes in hemoglobin concentrations or platelet counts (See Tables 3-6). Liver volume results from Studies 1 and 2 and their extensions are summarized in Table 3: Table 3: Liver Volume Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period Liver Volume n Absolute Mean (L) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI) Study 1 (starting dose miglustat capsules 100mg three times daily) Baseline (Month 0) 21 2.39 Month 12 Change from baseline -0.28 (-0.38, -0.18) -12.1% (-16.4, 7.9) Study 1 Extension Phase Baseline (Month 0) 12 2.54 Month 24 Change from baseline -0.36 (-0.48, -0.24) -14.5% (-19.3, 9.7) Study 2 (miglustat capsules 50mg three times daily) Baseline (Month 0) 17 2.45 Month 6 Change from baseline -0.14 (-0.25, -0.03) -5.9% (-9.9, -1.9) Study 2 Extension Phase Baseline (Month 0) 13 2.35 Month 12 Change from baseline -0.17 (-0.3, -0.0) -6.2% (-12.0, -0.5) Spleen volume results from Studies 1 and 2 and their extensions are summarized in Table 4: Table 4: Spleen Volume Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period Spleen Volume n Absolute Mean (L) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI) Study 1 (starting dose miglustat capsules 100mg three times daily) Baseline (Month 0) 18 1.64 Month 12 Change from baseline -0.32 (-0.42, -0.22) -19.0% (-23.7, -14.3) Study 1 Extension Phase Baseline (Month 0) 10 1.56 Month 24 Change from baseline -0.42 (-0.53, -0.30) -26.4% (-30.4, -22.4) Study 2 (miglustat capsules 50 mg three times daily) Baseline (Month 0) 11 1.98 Month 6 Change from baseline -0.09 (-0.18, -0.01) -4.5% (-8.2, -0.7) Study 2 Extension Phase Baseline (Month 0) 9 1.98 Month 12 Change from baseline -0.23 (-0.46, 0.00) -10.1% (-20.1, -0.1) Hemoglobin concentration results from Studies 1 and 2 and their extensions are summarized in Table 5: Table 5: Hemoglobin Concentration Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period Hemoglobin Concentration n Absolute Mean (g/dL) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI) Study 1 (starting dose miglustat capsules 100mg three times daily) Baseline (Month 0) 22 11.94 Month 12 Change from baseline 0.26 (-0.05, 0.57) 2.6% (-0.5, 5.7) Study 1 Extension Phase Baseline (Month 0) 13 11.03 Month 24 Change from baseline 0.91 (0.30, 1.53) 9.1% (2.9, 15.2) Study 2 (miglustat capsules 50 mg three times daily) Baseline (Month 0) 17 11.60 Month 6 Change from baseline -0.13 (-0.51, 0.24) -1.3% (-4.4, 1.8) Study 2 Extension Phase Baseline (Month 0) 13 11.94 Month 12 Change from baseline 0.06 (-0.73, 0.85) 1.2% (-5.2, 7.7) Platelet count results from Studies 1 and 2 and their extensions are summarized in Table 6: Table 6: Platelet Count Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period Platelet Count n Absolute Mean (10 9 /L) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI) Study 1 (starting dose miglustat capsules 100mg three times daily) Baseline (Month 0) 22 76.58 Month 12 Change from baseline 8.28 (1.88, 14.69) 16.0% (-0.8, 32.8) Study 1 Extension Phase Baseline (Month 0) 13 72.35 Month 24 Change from baseline 13.58 (7.72, 19.43) 26.1% (14.7, 37.5) Study 2 (miglustat capsules 50 mg three times daily) Baseline (Month 0) 17 116.47 Month 6 Change from baseline 5.35 (-6.31, 17.02) 2.0% (-6.9, 10.8) Study 2 Extension Phase Baseline (Month 0) 13 122.15 Month 12 Change from baseline 14.0 (-3.4, 31.4) 14.7% (-1.4, 30.7) Open-Label Active-Controlled Trial Study 3 was an open-label, randomized, active-controlled study of 36 adult patients with type 1 Gaucher disease, who had been receiving enzyme replacement therapy with imiglucerase for a minimum of 2 years prior to study entry. Patients were randomized 1:1:1 to one of three treatment groups, as follows: • miglustat capsules 100 mg three times daily alone • imiglucerase (patient‘s usual dose) alone • miglustat capsules 100 mg three times daily and imiglucerase (usual dose) Patients were treated for 6 months, and 33 patients completed the study. Because miglustat capsules is only indicated as monotherapy, the results for the monotherapy arms are described below. At Month 6, the results showed a decrease in mean percent change in liver volume in the miglustat capsules treatment group compared to the imiglucerase alone group. There were no significant differences between the groups for mean absolute changes in liver and spleen volume and hemoglobin concentration. However, there was a significant difference between the miglustat capsules alone and imiglucerase alone groups in platelet counts at Month 6, with the miglustat capsules alone group having a mean absolute decrease in platelet count of 21.6 × 10 9 /L and the imiglucerase alone group having a mean absolute increase in platelet count of 10.1 × 10 9 /L (See Tables 7-10). Extension period Twenty-nine patients were enrolled in a 6-month extension to Study 3. In the extension phase, all 29 patients had withdrawn from imiglucerase and received open-label miglustat capsules 100 mg three times daily monotherapy. At Month 12, the results showed non-significant decreases in platelet counts from baseline in all the treatment groups (by original randomization). There was a significant decrease in platelet counts from Month 6 to Month 12 in the group originally randomized to treatment with imiglucerase, and a continued decrease in platelet counts in the group originally randomized to miglustat capsules alone. There were no significant changes in any treatment group for liver volume, spleen volume, or hemoglobin concentration (See Tables 7-10). Liver volume results from Study 3 and extension are summarized in Table 7: Table 7: Liver Volume Changes from Study 3 and Extension Phase Imiglucerase Alone miglustat capsules Alone Study 3 n = 11 n = 10 Month 0 1.81 1.58 Month 6 Change (L) 0.04 -0.05 Month 6 % Change 3.6% -2.9% Adjusted Mean Difference from Imiglucerase (95% CI) -4.5% (-13.2, 4.2) Extension Phase* n = 10 n = 8 Month 0 1.94 1.60 Month 12 Change (L) -0.05 -0.01 Month 12 % Change -0.7% -0.8% * All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12. Spleen volume results from Study 3 and extension are summarized in Table 8: Table 8: Spleen Volume Changes from Study 3 and Extension Phase Imiglucerase Alone miglustat capsules Alone Study 3 n = 8 n = 7 Month 0 0.61 0.69 Month 6 Change (L) -0.02 -0.03 Month 6 % Change -2.1% -4.8% Adjusted % Difference from Imiglucerase (95% CI) -5.8% (-22.1, 10.5) Extension Phase* n = 7 n = 6 Month 0 0.83 0.57 Month 12 Change (L) 0.04 -0.05 Month 12 % Change 1.5% -6.1% * All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12. Hemoglobin concentration results from Study 3 and extension are summarized in Table 9: Table 9: Hemoglobin Concentration Changes from Study 3 and Extension Phase Imiglucerase Alone miglustat capsules Alone Study 3 n = 12 n = 10 Month 0 13.18 12.44 Month 6 Change g/dL -0.15 -0.31 Month 6 % Change -1.2% -2.4% Adjusted % Difference from Imiglucerase (95% CI) -1.9% (-6.4, 2.6) Extension Phase* n = 10 n = 9 Month 0 13.39 12.46 Month 12 Change g/dL -0.48 -0.13 Month 12 % Change -3.1% -1.1% * All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12. Platelet count results from Study 3 and extension are summarized in Table 10: Table 10: Platelet Count Changes from Study 3 and Extension Phase Imiglucerase Alone miglustat capsules Alone Study 3 n = 12 n = 10 Month 0 165.75 170.55 Month 6 Change (10 9 /L) 15.29 -21.60 Month 6 % Change 10.1% -9.6% Adjusted % Difference from Imiglucerase (95% CI) -17.1% (-32.9, -1.3) Extension Phase* n = 10 n = 9 Month 0 170.05 184.83 Month 12 Change (10 9 /L) -3.75 -27.39 Month 12 % Change -3.2% -10.4% * All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12. Patients with platelet counts above 150 × 10 9 /L at baseline who were randomized to miglustat capsules treatment had significant decreases in platelet counts at Month 12."],"pharmacokinetics":["12.3 Pharmacokinetics Absorption: After a 100 mg oral dose, the time to maximum observed plasma concentration of miglustat (t max ) ranged from 2 to 2.5 hours in Gaucher patients. Plasma concentrations show a biexponential decline, characterized by a short distribution phase and a longer elimination phase. The effective half-life of miglustat is approximately 6 to 7 hours, which predicts that steady-state will be achieved by 1.5 to 2 days following the start of three times daily dosing. Miglustat, dosed at 50 and 100 mg three times daily in Gaucher patients, exhibits dose-proportional pharmacokinetics. The pharmacokinetics of miglustat were not altered after repeated dosing three times daily for up to 12 months. In healthy subjects, co-administration of miglustat capsules with food results in a decrease in the rate of absorption of miglustat (maximum plasma concentration [C max ] was decreased by 36% and t max delayed 2 h) but had no statistically significant effect on the extent of absorption of miglustat (area-under-the-plasma-concentration time curve [AUC] was decreased by 14%). The mean oral bioavailability of a 100-mg miglustat capsule is about 97% relative to an oral solution administered under fasting conditions. The pharmacokinetics of miglustat were similar between adult type 1 Gaucher disease patients and healthy subjects after a single dose administration of miglustat 100 mg. Distribution: Miglustat does not bind to plasma proteins. Mean apparent volume of distribution of miglustat is 83-105 liters in Gaucher patients. At steady state, the concentration of miglustat in cerebrospinal fluid of six non-Gaucher patients was 31.4-67.2% of that in plasma, indicating that miglustat crosses the blood brain barrier. Metabolism and Excretion: The major route of excretion of miglustat is via kidney. Following administration of a single dose of 100 mg 14 C-miglustat to healthy volunteers, 83% of the radioactivity was recovered in urine and 12% in feces. In healthy subjects, 67% of the administered dose was excreted unchanged in urine over 72 hours. The most abundant metabolite in urine was miglustat glucuronide accounting for 5% of the dose. The terminal half-life of radioactivity in plasma was 150 hours, suggesting the presence of one or more metabolites with a prolonged half-life. The metabolite accounting for this observation has not been identified but may accumulate and reach concentrations exceeding those of miglustat at steady state. Specific Populations Gender : There was no statistically significant gender difference in miglustat pharmacokinetics, based on pooled data analysis. Race : Ethnic differences in miglustat pharmacokinetics have not been evaluated in Gaucher patients. However, apparent oral clearance of miglustat in patients of Ashkenazi Jewish descent was not statistically different to that in others (1 Asian and 15 Caucasians), based on a cross-study analysis. Hepatic Impairment: No studies have been performed to assess the pharmacokinetics of miglustat in patients with hepatic impairment. Renal Impairment: Limited data in non-Gaucher patients with impaired renal function indicate that the apparent oral clearance (CL/F) of miglustat decreases with decreasing renal function. While the number of subjects with mild and moderate renal impairment was very small, the data suggest an approximate decrease in the apparent oral clearance of 40% and 60% respectively, in mild and moderate renal impairment, justifying the need to decrease the dosing of miglustat in such patients dependent upon creatinine clearance levels [ see Dosage and Administration (2.2) ]. Data in severe renal impairment are limited to two patients with creatinine clearances in the range 18-29 mL/min and cannot be extrapolated below this range. These data suggest a decrease in CL/F by at least 70% in patients with severe renal impairment [ see Dosage and Administration (2.2) and Use in Specific Populations (8.6) ]. Drug Interaction Studies Miglustat does not inhibit the metabolism of various substrates of cytochrome P450 enzymes including, CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP4A11 in vitro; consequently significant interactions via inhibition of these enzymes are unlikely with drugs that are substrates of cytochrome P450 enzymes. Drug interaction between miglustat capsules (miglustat 100 mg orally three times daily) and imiglucerase 7.5 or 15 U/kg/day was assessed in imiglucerase-stabilized patients after one month of co-administration. There was no significant effect of imiglucerase on the pharmacokinetics of miglustat, with the co-administration of imiglucerase and miglustat resulting in a 22% reduction in Cmax and a 14% reduction in the AUC for miglustat. While miglustat capsules appeared to increase the clearance of imiglucerase by 70%, these results are not conclusive because of the small number of subjects studied and because patients took variable doses of imiglucerase [see Drug Interactions (7) ]. Concomitant therapy with loperamide during clinical trials did not appear to significantly alter the pharmacokinetics of miglustat."],"adverse_reactions":["6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Peripheral Neuropathy [ see Warnings and Precautions (5.1) ] • Tremor [ see Warnings and Precautions (5.2) ] • Diarrhea and weight loss [ see Warnings and Precautions (5.3) ] • Reductions in platelet count [ see Warnings and Precautions (5.4) ] The most common adverse reactions (incidence ≥ to 5%) are: diarrhea, weight loss, stomach pain, gas, nausea and vomiting, headache including migraine, tremor, leg cramps, dizziness, weakness, vision problems, thrombocytopenia, muscle cramps, back pain, constipation, dry mouth, heaviness in arms and legs, memory loss, unsteady walking, anorexia, indigestion, paresthesia, stomach bloating, stomach pain not related to food, and menstrual changes ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Edenbridge Pharmaceuticals, LLC at 1-877-381-3336 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure of 80 patients with type 1 Gaucher disease in two open-label, uncontrolled, monotherapy trials, one open-label, active-controlled trial, and two extensions, who received miglustat capsules at doses ranging from 50 mg to 200 mg three times daily. Patients were aged 18 to 69 years at first treatment. The population was evenly distributed by gender. The most common serious adverse reaction reported with miglustat capsules treatment in clinical trials was peripheral neuropathy [ see Warnings and Precautions (5.1) ]. The most commonly reported adverse reactions in patients treated with miglustat capsules (occurring in ≥ to 5%) that were considered related to miglustat capsules are shown in Tables 1 and 2. [ see Warnings and Precautions (5.2 , 5.3) ]. The most common adverse reactions requiring intervention were diarrhea and tremor. [ see Warnings and Precautions (5.2 , 5.3) ]. In two open-label, uncontrolled monotherapy trials, adult type 1 Gaucher disease patients were treated with miglustat capsules at a starting dose of 100 mg three times daily (dose range 100 to 200 mg three times daily) for up to 12 months in 28 patients [Study 1], or at a dose of 50 mg three times daily for up to 6 months in 18 patients [Study 2]. Table 1 below lists adverse reactions that occurred during the trials in ≥ to 5% of patients. Table 1: Adverse Reactions in greater than or equal to 5% of Patients in Two Open-Label, Uncontrolled Monotherapy Trials of miglustat capsules Incidence of adverse reactions Study 1 (starting dose 100mg three times daily) Study 2 (50mg three times daily) Patients entered in Study (n) 28 18 Body System – Preferred Term % of patients reporting % of patients reporting Gastrointestinal System Diarrhea 89 89 Flatulence 29 44 Abdominal Pain 18 50 Nausea 14 22 Vomiting 4 11 Bloating 0 6 Anorexia 7 0 Dyspepsia 7 0 Epigastric pain not food-related 0 6 Metabolic and Nutritional Disorders Weight Decrease 39 67 Central and Peripheral Nervous System Headache 21 22 Tremor 11 11 Dizziness 0 11 Leg cramps 4 11 Paresthesia 7 0 Migraine 0 6 Vision Disorders Visual Disturbance 0 17 Musculoskeletal Disorders Cramps 0 11 Platelet, Bleeding and Clotting Disorders Thrombocytopenia 7 6 Reproductive disorders, female Menstrual disorder 0 6 In an open-label, active-controlled study, 36 adult type 1 Gaucher disease patients were treated with miglustat capsules, imiglucerase, or miglustat capsules plus imiglucerase [Study 3] for up to 12 months. Table 2 lists adverse reactions that occurred during the trial in greater than or equal to 5% of patients. Table 2: Adverse Reactions in greater than or equal to 5% of Patients in Open-Label Active Controlled Study Incidence of adverse reactions Miglustat capsules alone Imiglucerase alone Patients entered in Study (n) 12 12 Body System – Preferred Term % of patients reporting % of patients reporting Gastrointestinal System Diarrhea 100 0 Abdominal Pain 67 0 Flatulence 50 0 Constipation 8 0 Nausea 8 0 Dry Mouth 8 0 Body as Whole Pain 0 8 Generalized weakness 17 0 Abdominal distension 8 0 Back pain 8 0 Heaviness in limbs 8 0 Metabolic and Nutritional Disorders Weight Decrease 67 0 Central Peripheral Nervous System Tremor 17 0 Dizziness 8 0 Leg cramps 8 0 Unsteady gait 8 0 Psychiatric disorders Memory loss 8 0"],"contraindications":["4 CONTRAINDICATIONS None None ( 4 )"],"drug_interactions":["7 DRUG INTERACTIONS While co-administration of miglustat capsules appeared to increase the clearance of imiglucerase by 70%, these results are not conclusive because of the small number of patients studied and because patients took variable doses of imiglucerase [ see Clinical Pharmacology (12.3) ]. Co-administration of YARGESA and imiglucerase may lead to increased clearance of imiglucerase ( 7 )."],"labor_and_delivery":["8.2 Lactation 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 capsules 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."],"mechanism_of_action":["12.1 Mechanism of Action Type 1 Gaucher disease is caused by a functional deficiency of glucocerebrosidase, the enzyme that mediates the degradation of the glycosphingolipid glucosylceramide. Miglustat functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids. Miglustat capsules helps reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to a level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy). In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Type 1 Gaucher disease is caused by a functional deficiency of glucocerebrosidase, the enzyme that mediates the degradation of the glycosphingolipid glucosylceramide. Miglustat functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids. Miglustat capsules helps reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to a level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy). In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids. 12.3 Pharmacokinetics Absorption: After a 100 mg oral dose, the time to maximum observed plasma concentration of miglustat (t max ) ranged from 2 to 2.5 hours in Gaucher patients. Plasma concentrations show a biexponential decline, characterized by a short distribution phase and a longer elimination phase. The effective half-life of miglustat is approximately 6 to 7 hours, which predicts that steady-state will be achieved by 1.5 to 2 days following the start of three times daily dosing. Miglustat, dosed at 50 and 100 mg three times daily in Gaucher patients, exhibits dose-proportional pharmacokinetics. The pharmacokinetics of miglustat were not altered after repeated dosing three times daily for up to 12 months. In healthy subjects, co-administration of miglustat capsules with food results in a decrease in the rate of absorption of miglustat (maximum plasma concentration [C max ] was decreased by 36% and t max delayed 2 h) but had no statistically significant effect on the extent of absorption of miglustat (area-under-the-plasma-concentration time curve [AUC] was decreased by 14%). The mean oral bioavailability of a 100-mg miglustat capsule is about 97% relative to an oral solution administered under fasting conditions. The pharmacokinetics of miglustat were similar between adult type 1 Gaucher disease patients and healthy subjects after a single dose administration of miglustat 100 mg. Distribution: Miglustat does not bind to plasma proteins. Mean apparent volume of distribution of miglustat is 83-105 liters in Gaucher patients. At steady state, the concentration of miglustat in cerebrospinal fluid of six non-Gaucher patients was 31.4-67.2% of that in plasma, indicating that miglustat crosses the blood brain barrier. Metabolism and Excretion: The major route of excretion of miglustat is via kidney. Following administration of a single dose of 100 mg 14 C-miglustat to healthy volunteers, 83% of the radioactivity was recovered in urine and 12% in feces. In healthy subjects, 67% of the administered dose was excreted unchanged in urine over 72 hours. The most abundant metabolite in urine was miglustat glucuronide accounting for 5% of the dose. The terminal half-life of radioactivity in plasma was 150 hours, suggesting the presence of one or more metabolites with a prolonged half-life. The metabolite accounting for this observation has not been identified but may accumulate and reach concentrations exceeding those of miglustat at steady state. Specific Populations Gender : There was no statistically significant gender difference in miglustat pharmacokinetics, based on pooled data analysis. Race : Ethnic differences in miglustat pharmacokinetics have not been evaluated in Gaucher patients. However, apparent oral clearance of miglustat in patients of Ashkenazi Jewish descent was not statistically different to that in others (1 Asian and 15 Caucasians), based on a cross-study analysis. Hepatic Impairment: No studies have been performed to assess the pharmacokinetics of miglustat in patients with hepatic impairment. Renal Impairment: Limited data in non-Gaucher patients with impaired renal function indicate that the apparent oral clearance (CL/F) of miglustat decreases with decreasing renal function. While the number of subjects with mild and moderate renal impairment was very small, the data suggest an approximate decrease in the apparent oral clearance of 40% and 60% respectively, in mild and moderate renal impairment, justifying the need to decrease the dosing of miglustat in such patients dependent upon creatinine clearance levels [ see Dosage and Administration (2.2) ]. Data in severe renal impairment are limited to two patients with creatinine clearances in the range 18-29 mL/min and cannot be extrapolated below this range. These data suggest a decrease in CL/F by at least 70% in patients with severe renal impairment [ see Dosage and Administration (2.2) and Use in Specific Populations (8.6) ]. Drug Interaction Studies Miglustat does not inhibit the metabolism of various substrates of cytochrome P450 enzymes including, CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP4A11 in vitro; consequently significant interactions via inhibition of these enzymes are unlikely with drugs that are substrates of cytochrome P450 enzymes. Drug interaction between miglustat capsules (miglustat 100 mg orally three times daily) and imiglucerase 7.5 or 15 U/kg/day was assessed in imiglucerase-stabilized patients after one month of co-administration. There was no significant effect of imiglucerase on the pharmacokinetics of miglustat, with the co-administration of imiglucerase and miglustat resulting in a 22% reduction in Cmax and a 14% reduction in the AUC for miglustat. While miglustat capsules appeared to increase the clearance of imiglucerase by 70%, these results are not conclusive because of the small number of subjects studied and because patients took variable doses of imiglucerase [see Drug Interactions (7) ]. Concomitant therapy with loperamide during clinical trials did not appear to significantly alter the pharmacokinetics of miglustat."],"indications_and_usage":["1 INDICATIONS AND USAGE YARGESA is a glucosylceramide synthase inhibitor indicated as monotherapy for treatment of adult patients with mild/moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option ( 1.1 ). 1.1 Type 1 Gaucher Disease YARGESA 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)."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS • Peripheral neuropathy: Perform baseline and follow-up neurological evaluations at 6-month intervals in all patients ( 5.1 ). • Tremor: Reduce dose to ameliorate tremor or discontinue treatment if tremor does not resolve within days of dose reduction ( 5.2 ). • Diarrhea and weight loss: Evaluate for underlying gastrointestinal disease in patients who do not respond to usual interventions (e.g. diet modification) ( 5.3 ). • Reductions in Platelet count: Mild reductions in platelet counts without association with bleeding were observed in some patients. Monitoring of platelet counts is recommended. ( 5.4 ) 5.1 Peripheral Neuropathy In clinical trials, cases of peripheral neuropathy have been reported in 3% of Gaucher‘s patients treated with miglustat capsules. All patients receiving miglustat capsules treatment should undergo baseline and repeat neurological evaluations at approximately 6-month intervals. Patients who develop symptoms of peripheral neuropathy such as pain, weakness, numbness and tingling should have a careful re-assessment of the risk/benefit of miglustat therapy, and cessation of treatment may be considered. 5.2 Tremor Approximately 30% of patients have reported tremor or exacerbation of existing tremor on treatment. These tremors were described as an exaggerated physiological tremor of the hands. Tremor usually began within the first month of therapy and in many cases resolved between 1 to 3 months during treatment. Reduce dose to ameliorate tremor or discontinue treatment if tremor does not resolve within days of dose reduction. 5.3 Diarrhea and Weight Loss Diarrhea and weight loss were common in clinical studies of patients treated with miglustat capsules, occurring in approximately 85% and up to 65% of treated patients, respectively. Diarrhea appears to be the result of the inhibitory activity of miglustat on intestinal disaccharidases such as sucrase-isomaltase in the gastrointestinal tract leading to reduced absorption of dietary disaccharides in the small intestine, with a resultant osmotic diarrhea. It is unclear if weight loss results from the diarrhea and associated gastrointestinal complaints, a decrease in food intake, or a combination of these or other factors. The incidence of weight loss was most evident in the first 12 months of treatment. Diarrhea decreased over time with continued miglustat treatment, and may respond to individualized diet modification (e.g., reduction of sucrose, lactose and other carbohydrate intake), to taking miglustat capsules between meals, and/or to anti-diarrheal medications, most commonly loperamide. Patients may be instructed to avoid high carbohydrate content foods during treatment with miglustat capsules if they present with diarrhea. Patients with persistent gastrointestinal events that continue during treatment with miglustat capsules, and who do not respond to usual interventions (e.g. diet modification), should be evaluated to determine whether significant underlying gastrointestinal disease is present. The safety of treatment with miglustat capsules has not been evaluated in patients with significant gastrointestinal disease, such as inflammatory bowel disease, and continued treatment of these patients with miglustat capsules should occur only after consideration of the risks and benefits of continued treatment. 5.4 Reductions in Platelet Count In clinical trials evaluating the use of miglustat capsules for treatment of indications other than type 1 Gaucher disease, mild reductions in platelet counts without association with bleeding were observed in some patients; approximately 40% of patients in this trial had low platelet counts (defined as below 150 × 10 9 /L) before starting treatment with miglustat capsules. Monitoring of platelet counts is recommended in patients with type 1 Gaucher disease. Mild reductions in platelet counts without association with bleeding were observed in patients with type 1 Gaucher disease who were switched from enzyme replacement therapy (ERT) to miglustat capsules."],"clinical_studies_table":["
Table 3: Liver Volume Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period
Liver Volume
n Absolute Mean (L) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI)
Study 1 (starting dose miglustat capsules 100mg three times daily)
Baseline (Month 0) 21 2.39
Month 12 Change from baseline -0.28 (-0.38, -0.18) -12.1% (-16.4, 7.9)
Study 1 Extension Phase
Baseline (Month 0) 12 2.54
Month 24 Change from baseline -0.36 (-0.48, -0.24) -14.5% (-19.3, 9.7)
Study 2 (miglustat capsules 50mg three times daily)
Baseline (Month 0) 17 2.45
Month 6 Change from baseline -0.14 (-0.25, -0.03) -5.9% (-9.9, -1.9)
Study 2 Extension Phase
Baseline (Month 0) 13 2.35
Month 12 Change from baseline -0.17 (-0.3, -0.0) -6.2% (-12.0, -0.5)
","
Table 4: Spleen Volume Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period
Spleen Volume
n Absolute Mean (L) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI)
Study 1 (starting dose miglustat capsules 100mg three times daily)
Baseline (Month 0) 18 1.64
Month 12 Change from baseline -0.32 (-0.42, -0.22) -19.0% (-23.7, -14.3)
Study 1 Extension Phase
Baseline (Month 0) 10 1.56
Month 24 Change from baseline -0.42 (-0.53, -0.30) -26.4% (-30.4, -22.4)
Study 2 (miglustat capsules 50 mg three times daily)
Baseline (Month 0) 11 1.98
Month 6 Change from baseline -0.09 (-0.18, -0.01) -4.5% (-8.2, -0.7)
Study 2 Extension Phase
Baseline (Month 0) 9 1.98
Month 12 Change from baseline -0.23 (-0.46, 0.00) -10.1% (-20.1, -0.1)
","
Table 5: Hemoglobin Concentration Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period
Hemoglobin Concentration
n Absolute Mean (g/dL) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI)
Study 1 (starting dose miglustat capsules 100mg three times daily)
Baseline (Month 0) 22 11.94
Month 12 Change from baseline 0.26 (-0.05, 0.57) 2.6% (-0.5, 5.7)
Study 1 Extension Phase
Baseline (Month 0) 13 11.03
Month 24 Change from baseline 0.91 (0.30, 1.53) 9.1% (2.9, 15.2)
Study 2 (miglustat capsules 50 mg three times daily)
Baseline (Month 0) 17 11.60
Month 6 Change from baseline -0.13 (-0.51, 0.24) -1.3% (-4.4, 1.8)
Study 2 Extension Phase
Baseline (Month 0) 13 11.94
Month 12 Change from baseline 0.06 (-0.73, 0.85) 1.2% (-5.2, 7.7)
","
Table 6: Platelet Count Changes in Two Open-Label Uncontrolled Monotherapy Trials of miglustat capsules with Extension Period
Platelet Count
n Absolute Mean (10 9/L) (2-sided 95% CI) Percent Mean (%) (2-sided 95% CI)
Study 1 (starting dose miglustat capsules 100mg three times daily)
Baseline (Month 0) 22 76.58
Month 12 Change from baseline 8.28 (1.88, 14.69) 16.0% (-0.8, 32.8)
Study 1 Extension Phase
Baseline (Month 0) 13 72.35
Month 24 Change from baseline 13.58 (7.72, 19.43) 26.1% (14.7, 37.5)
Study 2 (miglustat capsules 50 mg three times daily)
Baseline (Month 0) 17 116.47
Month 6 Change from baseline 5.35 (-6.31, 17.02) 2.0% (-6.9, 10.8)
Study 2 Extension Phase
Baseline (Month 0) 13 122.15
Month 12 Change from baseline 14.0 (-3.4, 31.4) 14.7% (-1.4, 30.7)
","
Table 7: Liver Volume Changes from Study 3 and Extension Phase
Imiglucerase Alone miglustat capsules Alone
Study 3 n = 11 n = 10
Month 0 1.81 1.58
Month 6 Change (L) 0.04 -0.05
Month 6 % Change 3.6% -2.9%
Adjusted Mean Difference from Imiglucerase (95% CI) -4.5% (-13.2, 4.2)
Extension Phase* n = 10 n = 8
Month 0 1.94 1.60
Month 12 Change (L) -0.05 -0.01
Month 12 % Change -0.7% -0.8%
* All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12.
","
Table 8: Spleen Volume Changes from Study 3 and Extension Phase
Imiglucerase Alone miglustat capsules Alone
Study 3 n = 8 n = 7
Month 0 0.61 0.69
Month 6 Change (L) -0.02 -0.03
Month 6 % Change -2.1% -4.8%
Adjusted % Difference from Imiglucerase (95% CI) -5.8% (-22.1, 10.5)
Extension Phase* n = 7 n = 6
Month 0 0.83 0.57
Month 12 Change (L) 0.04 -0.05
Month 12 % Change 1.5% -6.1%
* All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12.
","
Table 9: Hemoglobin Concentration Changes from Study 3 and Extension Phase
Imiglucerase Alone miglustat capsules Alone
Study 3 n = 12 n = 10
Month 0 13.18 12.44
Month 6 Change g/dL -0.15 -0.31
Month 6 % Change -1.2% -2.4%
Adjusted % Difference from Imiglucerase (95% CI) -1.9% (-6.4, 2.6)
Extension Phase* n = 10 n = 9
Month 0 13.39 12.46
Month 12 Change g/dL -0.48 -0.13
Month 12 % Change -3.1% -1.1%
* All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12.
","
Table 10: Platelet Count Changes from Study 3 and Extension Phase
Imiglucerase Alone miglustat capsules Alone
Study 3 n = 12 n = 10
Month 0 165.75 170.55
Month 6 Change (10 9/L) 15.29 -21.60
Month 6 % Change 10.1% -9.6%
Adjusted % Difference from Imiglucerase (95% CI) -17.1% (-32.9, -1.3)
Extension Phase* n = 10 n = 9
Month 0 170.05 184.83
Month 12 Change (10 9/L) -3.75 -27.39
Month 12 % Change -3.2% -10.4%
* All patients received miglustat capsules 100mg three times daily monotherapy from Month 6 to Month 12.
"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis: Two-year carcinogenicity studies have been conducted with miglustat in CD-1 mice at oral doses up to 500 mg/kg/day and in Sprague Dawley rats at oral doses up to 180 mg/kg/day. Oral administration of miglustat for 104 weeks produced mucinous adenocarcinomas of the large intestine at 210, 420 and 500 mg/kg/day (about 3, 6 and 7 times the recommended human dose, respectively, based on the body surface area) in male mice and at 420 and 500 mg/kg/day (about 6 and 7 times the recommended human dose, based on the body surface area) in female mice. The adenocarcinomas were considered rare in CD-1 mice and occurred in the presence of inflammatory and hyperplastic lesions in the large intestine of both males and females. In rats, oral administration of miglustat for 100 weeks produced increased incidences of interstitial cell adenomas of the testis at 30, 60 and 180 mg/kg/day (about 1, 2 and 5 times the recommended human dose, respectively, based on the body surface area). Mutagenesis: Miglustat was not mutagenic or clastogenic in a battery of in vitro and in vivo assays including the bacterial reverse mutation (Ames), chromosomal aberration (in human lymphocytes), gene mutation in mammalian cells (Chinese hamster ovary), and mouse micronucleus assays. Impairment of Fertility: Miglustat was administered by oral gavage to male rats at doses of 20, 60, 180 mg/kg/day beginning at least 14 days prior to mating and continuing through mating. Effects on sperm parameters (concentration, motility and morphology) resulting in decreased fertility were observed at all dose levels (the lowest dose level was 0.65 times the human therapeutic dose on a mg/m 2 basis). Reversibility was demonstrated following 6 weeks of drug withdrawal. Findings of, seminiferous tubule degeneration and atrophy were observed in the testes in rat repeat-dose toxicity studies. Miglustat was administered by oral gavage to female rats at doses of 20, 60, 180 mg/kg/day beginning 14 days before mating and continuing through gestation day 17. There were no effects on mating performance or fertility in female rats at doses up to 180 mg/kg/day. However, increased post implantation loss and decreased embryo-fetal survival were observed at doses greater than or equal to 60 mg/kg/day (≥ 2 times the human therapeutic dose on a mg/m 2 basis). 13.2 Animal Toxicology and/or Pharmacology Histopathology findings in the absence of clinical signs in the central nervous system of the monkey (brain, spine) that included vascular mineralization, in addition to mineralization and necrosis of white matter were observed at greater than 750 mg/kg/day (4 times the human therapeutic systemic exposure based on area-under-the-plasma-concentration curve [AUC] comparisons) in a 52-week oral toxicity study using doses of 750 and 2000 mg/kg/d. Vacuolization of white matter was observed in rats dosed orally by gavage at greater than or equal to 180 mg/kg/d (6 times the human therapeutic exposure based on surface area comparisons, mg/m 2 ) in a 4-week study using doses of 180, 840, and 4200 mg/kg/d. Vacuolization can sometimes occur as an artifact of tissue processing. Findings in dogs included tremor and absent corneal reflexes at 105 mg/kg/day (10 times the human therapeutic systemic exposure, based on body surface area comparisons, mg/m 2 ) after a 4-week oral gavage toxicity study using doses of 35, 70, 105, and 140 mg/kg/d. Ataxia, diminished/absent pupillary, palpebral, or patellar reflexes were observed in a dog at greater than or equal to 495 mg/kg/day (50 times the human therapeutic systemic exposure based on body surface area comparisons, mg/m2), in a 2-week oral gavage toxicity study using doses of 85, 165, 495, and 825 mg/kg/d. Cataracts were observed in rats at greater than or equal to 180 mg/kg/day (4 times the human therapeutic systemic exposure, based on AUC) in a 52-week oral gavage toxicity study using doses of 180, 420, 840, and 1680 mg/kg/d. Gastrointestinal necrosis, inflammation, and hemorrhage were observed in dogs at greater than or equal to 85 mg/kg/day (9 times the human therapeutic systemic exposure based on body surface area comparisons, mg/m 2 ) after a 2-week oral (capsule) toxicity study using doses of 85, 165, 495, and 825 mg/kg/d. Similar GI toxicity occurred in rats at 1200 mg/kg/day (7 times the human therapeutic systemic exposure, based on AUC) in a 26-week oral gavage toxicity study using doses of 300, 600, and 1200 mg/kg/d. In monkeys, similar GI toxicity occurred at greater than or equal to 750 mg/kg/day (6 times the human therapeutic systemic exposure based on AUC) following a 52-week oral gavage toxicity study using doses of 750 and 2000 mg/kg/d."],"adverse_reactions_table":["
Table 1: Adverse Reactions in greater than or equal to 5% of Patients in Two Open-Label, Uncontrolled Monotherapy Trials of miglustat capsules
Incidence of adverse reactions
Study 1 (starting dose 100mg three times daily) Study 2 (50mg three times daily)
Patients entered in Study (n)2818
Body System – Preferred Term% of patients reporting% of patients reporting
Gastrointestinal System
Diarrhea8989
Flatulence2944
Abdominal Pain1850
Nausea1422
Vomiting411
Bloating06
Anorexia70
Dyspepsia70
Epigastric pain not food-related06
Metabolic and Nutritional Disorders
Weight Decrease3967
Central and Peripheral Nervous System
Headache2122
Tremor1111
Dizziness011
Leg cramps411
Paresthesia70
Migraine06
Vision Disorders
Visual Disturbance017
Musculoskeletal Disorders
Cramps011
Platelet, Bleeding and Clotting Disorders
Thrombocytopenia76
Reproductive disorders, female
Menstrual disorder06
","
Table 2: Adverse Reactions in greater than or equal to 5% of Patients in Open-Label Active Controlled Study
Incidence of adverse reactions
Miglustat capsules aloneImiglucerase alone
Patients entered in Study (n)1212
Body System – Preferred Term% of patients reporting% of patients reporting
Gastrointestinal System
Diarrhea1000
Abdominal Pain670
Flatulence500
Constipation80
Nausea80
Dry Mouth80
Body as Whole
Pain08
Generalized weakness170
Abdominal distension80
Back pain80
Heaviness in limbs80
Metabolic and Nutritional Disorders
Weight Decrease670
Central Peripheral Nervous System
Tremor170
Dizziness80
Leg cramps80
Unsteady gait80
Psychiatric disorders
Memory loss80
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) Information for Patients • Advise patients that the most common serious adverse reactions reported with YARGESA are peripheral neuropathy. Advise patients to promptly report any numbness, tingling, pain, or burning in the hands and feet [see Warnings and Precautions (5.1.) ] • Advise patients that other adverse reactions include tremor and reductions in platelet counts. Advise patients to promptly report the development of tremor or worsening in an existing tremor. [see Warnings and Precautions ( 5.2 , 5.4 )] • Advise patients that other serious adverse reactions include diarrhea and weight loss. Advise patients to adhere to dietary instructions [see Warnings and Precautions (5.3) ]. • Advise patients to take the next YARGESA capsule at the next scheduled time if a dose is missed. • Inform patients of the potential risks and benefits of YARGESA and of alternative modes of therapy. Pregnancy Advise pregnant women and females of reproductive potential of the potential risk to a fetus, based on animal data. Advise patients who may become pregnant to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)]. Lactation Advise women not to breastfeed if they are taking YARGESA [see Use in Specific Populations (8.2) ]. Manufactured for: Edenbridge Pharmaceuticals, LLC DBA Dexcel Pharma USA Parsippany, NJ 07054 877-381-3336 Issued: July 2024"],"spl_unclassified_section":["Patient Information YARGESA (yär ges uh) (miglustat) Capsules Read this Patient Information before you start taking YARGESA and each time you get a refill. There may be new information. What is YARGESA ? YARGESA is a prescription medicine used alone to treat adults with mild to moderate type 1 Gaucher disease.YARGESA is used only in people who cannot be treated with enzyme replacement therapy. It is not known if YARGESA is safe and effective in children under 18 years of age. Before taking YARGESA , tell your healthcare provider about all of your medical conditions, including if you: • have kidney problems • are pregnant or plan to become pregnant. Yargesa may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with YARGESA • are breastfeeding or plan to breastfeed. It is not known if YARGESA passes into your breast milk and may harm your baby. Do not breastfeed during treatment with YARGESA. Talk to your healthcare provider about the best way to feed your baby during treatment with YARGESA. Tell your Healthcare Provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. YARGESA may affect how other medicines work. How should I take YARGESA ? • Take YARGESA exactly as your healthcare provider tells you to. • Take YARGESA at the same time each day. • If you miss a dose of YARGESA, skip that dose. Take the next miglustat capsule at the usual time. What are the possible side effects of YARGESA ? YARGESA may cause serious side effects including: • Numbness, tingling, pain, or burning in your hands or feet (peripheral neuropathy) . Call your healthcare provider right away if you get numbness, tingling, pain, or burning in your hands or feet. • Your healthcare provider may test your nerves (neurological exam) before you start YARGESA and during treatment with YARGESA. • New or worsening hand tremors (shaky movements). Tremors are common with YARGESA and may begin within the first month of starting treatment. Sometimes the tremors may go away between 1 to 3 months with continued treatment. Your healthcare provider may lower your dose or stop YARGESA if you develop new or worsening hand tremors. Call your healthcare provider right away if you get new hand tremors during treatment with YARGESA or if the hand tremors you already have get worse. • Diarrhea is common with YARGESA and sometimes can be serious. Your healthcare provider may prescribe another medicine (anti-diarrheal) to treat diarrhea if it is a problem for you and may recommend changes to your diet, such as avoiding foods high in carbohydrates. Talk with your healthcare provider about your diet if you have diarrhea. • Weight loss is common with YARGESA and sometimes can be serious. You may lose weight when you start treatment with YARGESA. • Low platelet count is common with YARGESA and can be serious. Your healthcare provider may do blood tests to monitor your blood platelet count. The most common side effects of YARGESA include: • weight loss • stomach pain • gas • nausea and vomiting • headache, including migraine • back pain • constipation • dry mouth • heaviness in arms and legs • memory loss • unsteady walking • leg cramps • dizziness • weakness • vision problems • muscle cramps • loss of appetite • indigestion • numbness, tingling, pain, or burning of your skin • stomach bloating • stomach pain not related to food • menstrual changes These are not all the possible side effects of YARGESA. For more information, ask your healthcare provider or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store YARGESA ? • Store YARGESA at room temperature between 68ºF to 77ºF (20ºC to 25ºC) Keep YARGESA and all medicines out of the reach of children General information about the safe and effective use of YARGESA . Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use YARGESA for a condition for which it was not prescribed. Do not give YARGESA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about YARGESA that is written for health professionals. What are the ingredients in YARGESA ? Active ingredient : miglustat Inactive ingredients: sodium starch glycolate (type A, potato), povidone (K-29/32), and magnesium stearate. The capsule shell contains : gelatin and titanium dioxide; the edible printing ink contains black iron oxide, shellac, and propylene glycol. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured for: Edenbridge Pharmaceuticals, LLC DBA Dexcel Pharma USA Parsippany, NJ 07054 877-381-3336 Revised: 07/2024"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION • Recommended dosage is 100 mg administered orally three times a day at regular intervals ( 2.1 ). • May reduce dosage to 100 mg once or twice a day in some patients due to tremor or diarrhea ( 2.1 ). • Adjust in patients with renal impairment ( 2.2 ): Renal Impairment Adjusted Creatinine Clearance (in mL/min/1.73 m 2 ) Recommendations Mild 50 – 70 Start dose at 100 mg twice a day Moderate 30 – 50 Start dose at 100 mg once a day Severe < 30 Use is not recommended 2.1 Instructions for Administration Therapy should be directed by physicians who are knowledgeable in the management of Gaucher disease. The recommended dose for the treatment of adult patients with type 1 Gaucher disease is one 100 mg capsule administered orally three times a day at regular intervals. If a dose is missed, the next YARGESA capsule should be taken at the next scheduled time. It may be necessary to reduce the dose to one 100 mg capsule once or twice a day in some patients due to adverse reactions, such as tremor or diarrhea. 2.2 Patients with Renal Insufficiency In patients with mild renal impairment (adjusted creatinine clearance 50-70 mL/min/1.73 m 2 ), initiate YARGESA treatment at a dose of 100 mg twice per day. In patients with moderate renal impairment (adjusted creatinine clearance of 30-50 mL/min/1.73 m 2 ), initiate YARGESA treatment at a dose of one 100 mg capsule per day. YARGESA is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73 m 2 ) [ see Use in Specific Populations (8.6) ]."],"spl_product_data_elements":["Yargesa Miglustat SODIUM STARCH GLYCOLATE TYPE A POTATO POVIDONE MAGNESIUM STEARATE GELATIN TITANIUM DIOXIDE FERROSOFERRIC OXIDE SHELLAC PROPYLENE GLYCOL MIGLUSTAT MIGLUSTAT 709"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Capsules: 100 mg of miglustat, white opaque hard gelatin capsules with “709” printed in black on the body. Capsules: 100 mg ( 3 )"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS • Pregnancy : Based on animal data, may cause fetal harm ( 8.1 ). • Lactation : Breastfeeding not recommend ( 8.2 ). 8.1 Pregnancy 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 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 greater than or equal to 60 mg/kg/day (greater than or equal to 2 times the human therapeutic dose on a mg/m 2 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 greater than or equal to 60 mg/kg/day (greater than or equal to 2 times the human therapeutic dose on a mg/m 2 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/m 2 basis. 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 greater than or equal to 60 mg/kg/day (greater than or equal to 2 times the human therapeutic dose on a mg/m 2 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/m 2 basis). 8.2 Lactation 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 capsules 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. 8.3 Females and Males of Reproductive Potential 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) ]. 8.4 Pediatric Use The safety and effectiveness of miglustat capsules 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 capsules 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 capsules on long-term gain in weight and height in pediatric patients is unclear. 8.5 Geriatric Use 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. 8.6 Renal Impairment 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/1.73 m 2 ), miglustat capsules 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/1.73 m 2 ), miglustat capsules administration should commence at a dose of 100 mg once a day. Use of miglustat capsules in patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73 m 2 ) 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 capsules has not been investigated."],"dosage_and_administration_table":["
Renal Impairment Adjusted Creatinine Clearance (in mL/min/1.73 m 2) Recommendations
Mild 50 – 70 Start dose at 100 mg twice a day
Moderate 30 – 50 Start dose at 100 mg once a day
Severe < 30 Use is not recommended
"],"animal_pharmacology_and_or_toxicology":["13.2 Animal Toxicology and/or Pharmacology Histopathology findings in the absence of clinical signs in the central nervous system of the monkey (brain, spine) that included vascular mineralization, in addition to mineralization and necrosis of white matter were observed at greater than 750 mg/kg/day (4 times the human therapeutic systemic exposure based on area-under-the-plasma-concentration curve [AUC] comparisons) in a 52-week oral toxicity study using doses of 750 and 2000 mg/kg/d. Vacuolization of white matter was observed in rats dosed orally by gavage at greater than or equal to 180 mg/kg/d (6 times the human therapeutic exposure based on surface area comparisons, mg/m 2 ) in a 4-week study using doses of 180, 840, and 4200 mg/kg/d. Vacuolization can sometimes occur as an artifact of tissue processing. Findings in dogs included tremor and absent corneal reflexes at 105 mg/kg/day (10 times the human therapeutic systemic exposure, based on body surface area comparisons, mg/m 2 ) after a 4-week oral gavage toxicity study using doses of 35, 70, 105, and 140 mg/kg/d. Ataxia, diminished/absent pupillary, palpebral, or patellar reflexes were observed in a dog at greater than or equal to 495 mg/kg/day (50 times the human therapeutic systemic exposure based on body surface area comparisons, mg/m2), in a 2-week oral gavage toxicity study using doses of 85, 165, 495, and 825 mg/kg/d. Cataracts were observed in rats at greater than or equal to 180 mg/kg/day (4 times the human therapeutic systemic exposure, based on AUC) in a 52-week oral gavage toxicity study using doses of 180, 420, 840, and 1680 mg/kg/d. Gastrointestinal necrosis, inflammation, and hemorrhage were observed in dogs at greater than or equal to 85 mg/kg/day (9 times the human therapeutic systemic exposure based on body surface area comparisons, mg/m 2 ) after a 2-week oral (capsule) toxicity study using doses of 85, 165, 495, and 825 mg/kg/d. Similar GI toxicity occurred in rats at 1200 mg/kg/day (7 times the human therapeutic systemic exposure, based on AUC) in a 26-week oral gavage toxicity study using doses of 300, 600, and 1200 mg/kg/d. In monkeys, similar GI toxicity occurred at greater than or equal to 750 mg/kg/day (6 times the human therapeutic systemic exposure based on AUC) following a 52-week oral gavage toxicity study using doses of 750 and 2000 mg/kg/d."],"package_label_principal_display_panel":["PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 15ct-carton"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis: Two-year carcinogenicity studies have been conducted with miglustat in CD-1 mice at oral doses up to 500 mg/kg/day and in Sprague Dawley rats at oral doses up to 180 mg/kg/day. Oral administration of miglustat for 104 weeks produced mucinous adenocarcinomas of the large intestine at 210, 420 and 500 mg/kg/day (about 3, 6 and 7 times the recommended human dose, respectively, based on the body surface area) in male mice and at 420 and 500 mg/kg/day (about 6 and 7 times the recommended human dose, based on the body surface area) in female mice. The adenocarcinomas were considered rare in CD-1 mice and occurred in the presence of inflammatory and hyperplastic lesions in the large intestine of both males and females. In rats, oral administration of miglustat for 100 weeks produced increased incidences of interstitial cell adenomas of the testis at 30, 60 and 180 mg/kg/day (about 1, 2 and 5 times the recommended human dose, respectively, based on the body surface area). Mutagenesis: Miglustat was not mutagenic or clastogenic in a battery of in vitro and in vivo assays including the bacterial reverse mutation (Ames), chromosomal aberration (in human lymphocytes), gene mutation in mammalian cells (Chinese hamster ovary), and mouse micronucleus assays. Impairment of Fertility: Miglustat was administered by oral gavage to male rats at doses of 20, 60, 180 mg/kg/day beginning at least 14 days prior to mating and continuing through mating. Effects on sperm parameters (concentration, motility and morphology) resulting in decreased fertility were observed at all dose levels (the lowest dose level was 0.65 times the human therapeutic dose on a mg/m 2 basis). Reversibility was demonstrated following 6 weeks of drug withdrawal. Findings of, seminiferous tubule degeneration and atrophy were observed in the testes in rat repeat-dose toxicity studies. Miglustat was administered by oral gavage to female rats at doses of 20, 60, 180 mg/kg/day beginning 14 days before mating and continuing through gestation day 17. There were no effects on mating performance or fertility in female rats at doses up to 180 mg/kg/day. However, increased post implantation loss and decreased embryo-fetal survival were observed at doses greater than or equal to 60 mg/kg/day (≥ 2 times the human therapeutic dose on a mg/m 2 basis)."]},"tags":[{"label":"Glucosylceramide Synthase Inhibitor","category":"class"},{"label":"Small Molecule","category":"modality"},{"label":"Lysosomal alpha-glucosidase","category":"target"},{"label":"GAA","category":"gene"},{"label":"GBA2","category":"gene"},{"label":"SI","category":"gene"},{"label":"A16AX06","category":"atc"},{"label":"Oral","category":"route"},{"label":"Capsule","category":"form"},{"label":"Off-Patent","category":"patent"},{"label":"Generic Available","category":"availability"},{"label":"Mature","category":"status"},{"label":"Glucosylceramide beta-glucosidase deficiency","category":"indication"},{"label":"Lateonset Pompe disease","category":"indication"},{"label":"Niemann-Pick disease, type C","category":"indication"},{"label":"Actelion","category":"company"},{"label":"Approved 2000s","category":"decade"},{"label":"Anti-HIV Agents","category":"pharmacology"},{"label":"Anti-Infective Agents","category":"pharmacology"},{"label":"Anti-Retroviral Agents","category":"pharmacology"},{"label":"Antiviral Agents","category":"pharmacology"},{"label":"Enzyme Inhibitors","category":"pharmacology"},{"label":"Glycoside Hydrolase Inhibitors","category":"pharmacology"},{"label":"Hypoglycemic Agents","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":[],"safetySignals":[{"llr":260.703,"date":"","count":132,"signal":"Seizure","source":"DrugCentral FAERS","actionTaken":"Reported 132 times (LLR=261)"},{"llr":134.798,"date":"","count":26,"signal":"Gastrostomy","source":"DrugCentral FAERS","actionTaken":"Reported 26 times (LLR=135)"},{"llr":121.748,"date":"","count":134,"signal":"Death","source":"DrugCentral FAERS","actionTaken":"Reported 134 times (LLR=122)"},{"llr":103.769,"date":"","count":43,"signal":"Epilepsy","source":"DrugCentral FAERS","actionTaken":"Reported 43 times (LLR=104)"},{"llr":103.493,"date":"","count":145,"signal":"Diarrhoea","source":"DrugCentral FAERS","actionTaken":"Reported 145 times (LLR=103)"},{"llr":101.047,"date":"","count":31,"signal":"Concomitant disease aggravated","source":"DrugCentral FAERS","actionTaken":"Reported 31 times (LLR=101)"},{"llr":97.175,"date":"","count":47,"signal":"Pneumonia aspiration","source":"DrugCentral FAERS","actionTaken":"Reported 47 times (LLR=97)"},{"llr":94.904,"date":"","count":70,"signal":"Disease progression","source":"DrugCentral FAERS","actionTaken":"Reported 70 times (LLR=95)"},{"llr":94.883,"date":"","count":58,"signal":"Dysphagia","source":"DrugCentral FAERS","actionTaken":"Reported 58 times (LLR=95)"},{"llr":83.723,"date":"","count":61,"signal":"Tremor","source":"DrugCentral FAERS","actionTaken":"Reported 61 times (LLR=84)"},{"llr":78.154,"date":"","count":82,"signal":"Weight decreased","source":"DrugCentral FAERS","actionTaken":"Reported 82 times (LLR=78)"},{"llr":69.813,"date":"","count":19,"signal":"Neurological decompensation","source":"DrugCentral FAERS","actionTaken":"Reported 19 times (LLR=70)"},{"llr":53.562,"date":"","count":12,"signal":"Tracheostomy","source":"DrugCentral FAERS","actionTaken":"Reported 12 times (LLR=54)"},{"llr":52.718,"date":"","count":13,"signal":"Gastrointestinal tube insertion","source":"DrugCentral FAERS","actionTaken":"Reported 13 times (LLR=53)"},{"llr":49.509,"date":"","count":22,"signal":"Ataxia","source":"DrugCentral FAERS","actionTaken":"Reported 22 times (LLR=50)"}],"commonSideEffects":[{"effect":"Diarrhea","drugRate":"89%","severity":"common","_validated":true},{"effect":"Weight loss","drugRate":"67%","severity":"common","_validated":true},{"effect":"Abdominal Pain","drugRate":"50%","severity":"common","_validated":true},{"effect":"Flatulence","drugRate":"44%","severity":"common","_validated":true},{"effect":"Nausea","drugRate":"22%","severity":"common","_validated":true},{"effect":"Vomiting","drugRate":"11%","severity":"mild","_validated":true},{"effect":"Headache","drugRate":"21%","severity":"common","_validated":true},{"effect":"Tremor","drugRate":"11%","severity":"mild","_validated":true},{"effect":"Dizziness","drugRate":"11%","severity":"mild","_validated":true},{"effect":"Leg cramps","drugRate":"11%","severity":"mild","_validated":true},{"effect":"Visual Disturbance","drugRate":"17%","severity":"common","_validated":true},{"effect":"Thrombocytopenia","drugRate":"6%","severity":"mild","_validated":true},{"effect":"Menstrual disorder","drugRate":"6%","severity":"mild","_validated":true},{"effect":"Constipation","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Dry Mouth","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Generalized weakness","drugRate":"17%","severity":"common","_validated":true},{"effect":"Abdominal distension","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Back pain","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Heaviness in limbs","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Memory loss","drugRate":"0%","severity":"unknown","_validated":true},{"effect":"Anorexia","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Dyspepsia","drugRate":"0%","severity":"mild","_validated":true},{"effect":"Epigastric pain not food-related","drugRate":"6%","severity":"mild","_validated":true},{"effect":"Bloating","drugRate":"6%","severity":"mild","_validated":true},{"effect":"Paresthesia","drugRate":"0%","severity":"unknown","_validated":true},{"effect":"Migraine","drugRate":"6%","severity":"mild","_validated":true},{"effect":"Unsteady gait","drugRate":"0%","severity":"unknown","_validated":true}],"contraindications":["Breastfeeding (mother)","Impaired renal function disorder","Peripheral nerve disease","Pregnancy, function"],"specialPopulations":{"Pregnancy":"Based on findings from animal reproduction studies, miglustat may cause fetal harm when administered to pregnant woman. Available data from postmarketing case reports with miglustat use in pregnancy are insufficient to assess drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks associated with symptomatic Type Gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have 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% overall. The risks associated with symptomatic Type Gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia, are not well characterized. 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 times the recommended human dose.","Geriatric use":"Clinical studies of miglustat 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 concomitant disease or other drug therapy with advancing age.","Paediatric use":"The safety and effectiveness of miglustat in pediatric patients have not been established. In combined clinical trial safety data set of 45 patients less than 18 years of age exposed to miglustat in indications other than type 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 to 2.6 years; some pediatric patients were exposed for up to 2.6 years.","Nursing mothers":"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."}},"trials":[],"aliases":[],"company":"AstraZeneca","patents":[{"type":"Method of Use","number":"12419937","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2033-03-07"},{"type":"Method of Use","number":"12414985","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2036-12-29"},{"type":"Method of Use","number":"12246062","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2038-09-16"},{"type":"Method of Use","number":"11753632","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2035-09-30"},{"type":"Formulation","number":"11278601","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2036-12-29"},{"type":"Method of Use","number":"11278599","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2033-03-07"},{"type":"Method of Use","number":"10961522","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2035-09-30"},{"type":"Method of Use","number":"10857212","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2037-08-12"},{"type":"Method of Use","number":"10512677","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2033-03-07"},{"type":"Compound","number":"10208299","applicant":"AMICUS THERAPEUTICS US LLC","territory":"US","tradeName":"OPFOLDA","expiryDate":"2035-09-30"}],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=MIGLUSTAT","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T03:19:03.153373+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-20T03:19:03.153295+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Miglustat","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-20T03:19:11.059891+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T03:19:08.749481+00:00"},"regulatory.eu":{"url":"","method":"api_direct","source":"European Medicines Agency","rawText":"","confidence":1,"sourceType":"ema_api","retrievedAt":"2026-04-20T03:19:03.225233+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=MIGLUSTAT","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T03:19:09.232671+00:00"},"mechanism.drugClass":{"url":"https://api.fda.gov/drug/label.json","method":"deterministic","source":"FDA Label (EPC)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:19:02.035813+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:19:02.035843+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:19:02.035852+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Ceramide glucosyltransferase inhibitor","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:19:11.059833+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1029/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:19:10.134527+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"ANDA209821","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:19:02.035856+00:00"}},"allNames":"zavesca","offLabel":[],"synonyms":["miglustat","N-Butyldeoxynojirimycin","N-Butylmoranoline","zavesca"],"timeline":[{"date":"2002-11-20","type":"positive","source":"DrugCentral","milestone":"EMA approval"},{"date":"2003-01-01","type":"neutral","source":"FDA Orange Book","milestone":"Rights transferred from ACTELION PHARMS LTD to Actelion"},{"date":"2003-07-31","type":"positive","source":"DrugCentral","milestone":"FDA approval (Actelion Pharms Ltd)"},{"date":"2018-04-17","type":"neutral","source":"FDA Orange Book","milestone":"Generic entry — 1 manufacturer approved"},{"date":"2023-09-28","type":"positive","source":"FDA Orange Book","milestone":"Opfolda approved — 65MG"}],"aiSummary":"Zavesca (MIGLUSTAT) is a small molecule glucosylceramide synthase inhibitor developed by ACTELION PHARMS LTD and currently owned by Actelion. It targets lysosomal alpha-glucosidase and is used to treat various lysosomal storage disorders, including Gaucher's disease, Late-onset Pompe disease, and Niemann-Pick disease type C. Zavesca was FDA-approved in 2003 and is now available as a generic medication. The commercial status of Zavesca is off-patent, with four generic manufacturers available. Key safety considerations include monitoring for gastrointestinal side effects and potential interactions with other medications.","approvals":[{"date":"2002-11-20","orphan":true,"company":"","regulator":"EMA"},{"date":"2003-07-31","orphan":true,"company":"ACTELION PHARMS LTD","regulator":"FDA"}],"brandName":"Zavesca","ecosystem":[{"indication":"Glucosylceramide beta-glucosidase deficiency","otherDrugs":[{"name":"eliglustat","slug":"eliglustat","company":"Genzyme Corp"},{"name":"imiglucerase","slug":"imiglucerase","company":"Genzyme"}],"globalPrevalence":null},{"indication":"Lateonset Pompe disease","otherDrugs":[],"globalPrevalence":null},{"indication":"Niemann-Pick disease, type C","otherDrugs":[],"globalPrevalence":null}],"mechanism":{"target":"Lysosomal alpha-glucosidase","novelty":"Follow-on","targets":[{"gene":"GAA","source":"DrugCentral","target":"Lysosomal alpha-glucosidase","protein":"Lysosomal alpha-glucosidase"},{"gene":"GBA2","source":"DrugCentral","target":"Non-lysosomal glucosylceramidase","protein":"Non-lysosomal glucosylceramidase"},{"gene":"SI","source":"DrugCentral","target":"Sucrase-isomaltase, intestinal","protein":"Sucrase-isomaltase, intestinal"},{"gene":"MGAM","source":"DrugCentral","target":"Maltase-glucoamylase, intestinal","protein":"Maltase-glucoamylase, intestinal"},{"gene":"UGCG","source":"DrugCentral","target":"Ceramide glucosyltransferase","protein":"Ceramide glucosyltransferase"},{"gene":"AGL","source":"DrugCentral","target":"Glycogen debranching enzyme","protein":"Glycogen debranching enzyme"}],"moaClass":"Glucosylceramide Synthase Inhibitors","modality":"Small Molecule","drugClass":"Glucosylceramide Synthase Inhibitor [EPC]","explanation":"Type Gaucher disease is caused by functional deficiency of glucocerebrosidase, the enzyme that mediates the degradation of the glycosphingolipid glucosylceramide.Miglustat functions as competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in series of reactions which results in the synthesis of most glycosphingolipids.miglustat helps reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy). In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids.","oneSentence":"Zavesca works by inhibiting the enzyme glucosylceramide synthase, which is involved in the production of a toxic lipid that accumulates in cells of patients with certain lysosomal storage disorders.","technicalDetail":"Zavesca (MIGLUSTAT) acts as a competitive inhibitor of glucosylceramide synthase, the enzyme responsible for catalyzing the condensation of glucose and ceramide to form glucosylceramide, thereby reducing the accumulation of this toxic lipid in cells.","_target_confidence":0.5},"_wikipedia":{"url":"https://en.wikipedia.org/wiki/Miglustat","title":"Miglustat","extract":"Miglustat, sold under the brand name Zavesca among others, is a medication used to treat type I Gaucher disease and Pompe disease.","wiki_society_and_culture":"== Society and culture ==\n=== Legal status ===\nMiglustat has been approved in the EU, Canada, and Japan for treating progressive neurological complications in people with Niemann–Pick disease, type C (NPC).\n\nOn 26 April 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Opfolda, intended for the treatment of glycogen storage disease type II (Pompe disease) in combination with cipaglucosidase alfa. Opfolda is a hybrid medicine of Zavesca which has been authorized in the EU since 2002."},"commercial":{"launchDate":"2003","_launchSource":"DrugCentral (FDA 2003-07-31, ACTELION PHARMS LTD)"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/1807","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=MIGLUSTAT","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=MIGLUSTAT","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://en.wikipedia.org/wiki/Miglustat","fields":["history","overview"],"source":"Wikipedia"},{"id":5,"url":"https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files","fields":["patents","exclusivity","genericManufacturers"],"source":"FDA Orange Book"}],"_emaChecked":true,"_enrichedAt":"2026-03-30T14:31:58.331199","_validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T03:19:14.522350+00:00","fieldsConflicting":1,"overallConfidence":0.8},"biosimilars":[],"competitors":[{"drugName":"thioctic acid","drugSlug":"thioctic-acid","fdaApproval":"","relationship":"same-class"},{"drugName":"phenylbutanoic acid","drugSlug":"phenylbutanoic-acid","fdaApproval":"1996-04-30","relationship":"same-class"},{"drugName":"nitisinone","drugSlug":"nitisinone","fdaApproval":"2002-01-18","patentExpiry":"Jan 5, 2035","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"zinc acetate","drugSlug":"zinc-acetate","fdaApproval":"1980-02-22","patentStatus":"Unknown","relationship":"same-class"},{"drugName":"sapropterin","drugSlug":"sapropterin","fdaApproval":"2007-12-13","patentExpiry":"Nov 1, 2032","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"teduglutide","drugSlug":"teduglutide","fdaApproval":"2012-12-21","patentExpiry":"May 1, 2026","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"glycerol phenylbutyrate","drugSlug":"glycerol-phenylbutyrate","fdaApproval":"2013-02-01","patentExpiry":"Sep 22, 2030","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"eliglustat","drugSlug":"eliglustat","fdaApproval":"2014-08-19","patentExpiry":"Nov 24, 2030","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"sodium benzoate","drugSlug":"sodium-benzoate","fdaApproval":"1987-12-23","relationship":"same-class"},{"drugName":"trientine","drugSlug":"trientine","fdaApproval":"1985-11-08","genericCount":13,"patentStatus":"Off-patent — generic available","relationship":"same-class"},{"drugName":"uridine triacetate","drugSlug":"uridine-triacetate","fdaApproval":"2015-09-04","patentExpiry":"Aug 17, 2027","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"migalastat","drugSlug":"migalastat","fdaApproval":"2018-08-08","patentExpiry":"Oct 20, 2031","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"givosiran","drugSlug":"givosiran","fdaApproval":"2019-11-20","patentExpiry":"Oct 3, 2034","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"triheptanoin","drugSlug":"triheptanoin","fdaApproval":"2020-06-30","patentExpiry":"Nov 14, 2034","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"lumasiran","drugSlug":"lumasiran","fdaApproval":"2020-11-23","patentExpiry":"Oct 9, 2035","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"fosdenopterin","drugSlug":"fosdenopterin","fdaApproval":"2021-02-26","patentExpiry":"Apr 9, 2029","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"lonafarnib","drugSlug":"lonafarnib","fdaApproval":"2020-11-20","patentExpiry":"Jul 26, 2029","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"phenylacetic acid","drugSlug":"phenylacetic-acid","fdaApproval":"1987-12-23","relationship":"same-class"}],"genericName":"miglustat","indications":{"approved":[{"name":"Glucosylceramide beta-glucosidase deficiency","source":"DrugCentral","snomedId":190794006,"regulator":"FDA"},{"name":"Lateonset Pompe disease","source":"DrugCentral","snomedId":722343009,"regulator":"FDA"},{"name":"Niemann-Pick disease, type C","source":"DrugCentral","snomedId":66751000,"regulator":"FDA"}],"offLabel":[],"pipeline":[]},"currentOwner":"Actelion","drugCategory":"mature","labelChanges":[],"patentStatus":"Off-patent — no active Orange Book patents","relatedDrugs":[{"drugId":"thioctic-acid","brandName":"thioctic acid","genericName":"thioctic acid","approvalYear":"","relationship":"same-class"},{"drugId":"phenylbutanoic-acid","brandName":"phenylbutanoic acid","genericName":"phenylbutanoic acid","approvalYear":"1996","relationship":"same-class"},{"drugId":"nitisinone","brandName":"nitisinone","genericName":"nitisinone","approvalYear":"2002","relationship":"same-class"},{"drugId":"zinc-acetate","brandName":"zinc acetate","genericName":"zinc acetate","approvalYear":"1980","relationship":"same-class"},{"drugId":"sapropterin","brandName":"sapropterin","genericName":"sapropterin","approvalYear":"2007","relationship":"same-class"},{"drugId":"teduglutide","brandName":"teduglutide","genericName":"teduglutide","approvalYear":"2012","relationship":"same-class"},{"drugId":"glycerol-phenylbutyrate","brandName":"glycerol phenylbutyrate","genericName":"glycerol phenylbutyrate","approvalYear":"2013","relationship":"same-class"},{"drugId":"eliglustat","brandName":"eliglustat","genericName":"eliglustat","approvalYear":"2014","relationship":"same-class"},{"drugId":"sodium-benzoate","brandName":"sodium benzoate","genericName":"sodium benzoate","approvalYear":"1987","relationship":"same-class"},{"drugId":"trientine","brandName":"trientine","genericName":"trientine","approvalYear":"1985","relationship":"same-class"}],"trialDetails":[{"nctId":"NCT07399704","phase":"PHASE2","title":"A Study to Evaluate the Safety and Efficacy of Nizubaglustat (AZ-3102) in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease","status":"RECRUITING","sponsor":"Azafaros A.G.","startDate":"2026-02-04","conditions":["GM2 Gangliosidosis","Niemann-Pick Type C Disease"],"enrollment":21,"completionDate":"2030-08-07"},{"nctId":"NCT06121011","phase":"","title":"A Global Prospective Observational Registry of Patients With Pompe Disease","status":"RECRUITING","sponsor":"Amicus Therapeutics","startDate":"2024-02-16","conditions":["Pompe Disease"],"enrollment":500,"completionDate":"2034-12-20"},{"nctId":"NCT04138277","phase":"PHASE3","title":"A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD)","status":"COMPLETED","sponsor":"Amicus Therapeutics","startDate":"2019-12-18","conditions":["Pompe Disease (Late-onset)"],"enrollment":119,"completionDate":"2024-12-31"},{"nctId":"NCT04808505","phase":"PHASE3","title":"A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18","status":"RECRUITING","sponsor":"Amicus Therapeutics","startDate":"2023-07-18","conditions":["Glycogen Storage Disease Type II Infantile Onset"],"enrollment":36,"completionDate":"2027-07"},{"nctId":"NCT02325362","phase":"PHASE2,PHASE3","title":"Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the F508del Mutation","status":"COMPLETED","sponsor":"Assistance Publique - Hôpitaux de Paris","startDate":"2015-03-17","conditions":["Cystic Fibrosis"],"enrollment":16,"completionDate":"2017-04-03"},{"nctId":"NCT03911505","phase":"PHASE3","title":"ZIP Study-OL Study of Safety, PK, Efficacy, PD, Immunogenicity of ATB200/AT2221 in Pediatrics Aged 0 to < 18 y.o. w/LOPD","status":"ACTIVE_NOT_RECRUITING","sponsor":"Amicus Therapeutics","startDate":"2020-02-13","conditions":["Pompe Disease (Late-onset)"],"enrollment":21,"completionDate":"2026-06"},{"nctId":"NCT02675465","phase":"PHASE1,PHASE2","title":"First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221","status":"COMPLETED","sponsor":"Amicus Therapeutics","startDate":"2016-04","conditions":["Pompe Disease"],"enrollment":29,"completionDate":"2024-08-22"},{"nctId":"NCT03822013","phase":"PHASE3","title":"Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD)","status":"TERMINATED","sponsor":"Tehran University of Medical Sciences","startDate":"2019-01-14","conditions":["GM2 Gangliosidosis","Supportive Care"],"enrollment":30,"completionDate":"2025-09-10"},{"nctId":"NCT03729362","phase":"PHASE3","title":"A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease","status":"COMPLETED","sponsor":"Amicus Therapeutics","startDate":"2018-12-04","conditions":["Pompe Disease (Late-onset)"],"enrollment":125,"completionDate":"2021-01-15"},{"nctId":"NCT04327973","phase":"","title":"Expanded Access for ATB200/AT2221 for the Treatment of IOPD","status":"AVAILABLE","sponsor":"Amicus Therapeutics","startDate":"","conditions":["Pompe Disease Infantile-Onset"],"enrollment":0,"completionDate":""},{"nctId":"NCT05174039","phase":"PHASE1,PHASE2","title":"An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of Subjects With Batten Ceroid Lipofuscinosis, Neuronal 3 (CLN3) Disease","status":"COMPLETED","sponsor":"Beyond Batten Disease Foundation","startDate":"2022-03-10","conditions":["Batten Disease"],"enrollment":6,"completionDate":"2024-05-30"},{"nctId":"NCT03910621","phase":"PHASE4","title":"Safety and Efficacy of Miglustat in Chinese NPC Patients","status":"COMPLETED","sponsor":"Actelion","startDate":"2020-04-02","conditions":["Niemann-Pick Disease, Type C"],"enrollment":17,"completionDate":"2022-03-25"},{"nctId":"NCT00517153","phase":"PHASE2","title":"Miglustat in Niemann-Pick Type C Disease","status":"COMPLETED","sponsor":"Actelion","startDate":"2002-01","conditions":["Niemann-Pick Type C Disease"],"enrollment":29,"completionDate":"2008-01"},{"nctId":"NCT00319046","phase":"PHASE3","title":"Clinical Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Miglustat in Patients With Stable Type 1 Gaucher Disease","status":"COMPLETED","sponsor":"Actelion","startDate":"2006-02-01","conditions":["Gaucher Disease Type 1"],"enrollment":42,"completionDate":"2010-07-01"},{"nctId":"NCT04768166","phase":"PHASE2","title":"Testing Miglustat Administration in Subjects With Spastic Paraplegia 11","status":"COMPLETED","sponsor":"IRCCS Fondazione Stella Maris","startDate":"2021-06-15","conditions":["Hereditary Spastic Paraparesis"],"enrollment":10,"completionDate":"2021-09-15"},{"nctId":"NCT02030015","phase":"PHASE4","title":"Synergistic Enteral Regimen for Treatment of the Gangliosidoses","status":"TERMINATED","sponsor":"University of Minnesota","startDate":"2015-12-22","conditions":["GM1 Gangliosidoses","GM2 Gangliosidoses","Tay-Sachs Disease","Sandhoff Disease"],"enrollment":16,"completionDate":"2019-07-31"},{"nctId":"NCT02520934","phase":"NA","title":"Miglustat on Gaucher Disease Type IIIB","status":"UNKNOWN","sponsor":"National Taiwan University Hospital","startDate":"2015-07","conditions":["Gaucher Disease"],"enrollment":19,"completionDate":"2019-12"},{"nctId":"NCT02185651","phase":"PHASE1","title":"A Pilot Study of Zavesca® in Patients With Pompe Disease and Infusion Associated Reaction","status":"TERMINATED","sponsor":"University of Florida","startDate":"2016-10","conditions":["Pompe Disease","Hypersensitivity Reaction"],"enrollment":2,"completionDate":"2018-07"},{"nctId":"NCT01451879","phase":"","title":"Observational Study for Subjects With Pompe Disease Undergoing Immune Modulation Therapies","status":"COMPLETED","sponsor":"University of Florida","startDate":"2008-10","conditions":["Pompe Disease"],"enrollment":11,"completionDate":"2017-10"},{"nctId":"NCT00316498","phase":"PHASE1","title":"Saccadic Eye Movements in Patients With Niemann-Pick Type C Disease","status":"COMPLETED","sponsor":"National Eye Institute (NEI)","startDate":"2002-10-17","conditions":["Niemann Pick Diseases"],"enrollment":30,"completionDate":"2007-08-15"},{"nctId":"NCT00041535","phase":"PHASE2","title":"OGT 918-006: A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease","status":"COMPLETED","sponsor":"National Institute of Neurological Disorders and Stroke (NINDS)","startDate":"2002-07-05","conditions":["Gaucher Disease"],"enrollment":30,"completionDate":"2007-03-21"},{"nctId":"NCT00418847","phase":"PHASE2","title":"Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis","status":"COMPLETED","sponsor":"The Hospital for Sick Children","startDate":"2004-07","conditions":["Gangliosidoses GM2"],"enrollment":5,"completionDate":"2009-04"},{"nctId":"NCT01822028","phase":"PHASE1","title":"Two Period / Two Treatment Cross-over to Assess the Effect of Florastor® on Gastrointestinal Tolerability, Safety, and PK in Healthy Subjects Receiving Zavesca®","status":"COMPLETED","sponsor":"Actelion","startDate":"2013-03","conditions":["Diarrhea"],"enrollment":42,"completionDate":"2013-08"},{"nctId":"NCT00742092","phase":"PHASE2","title":"Miglustat in Cystic Fibrosis","status":"COMPLETED","sponsor":"Actelion","startDate":"2008-08","conditions":["Cystic Fibrosis"],"enrollment":11,"completionDate":"2008-12"},{"nctId":"NCT01760564","phase":"PHASE3","title":"Application of Miglustat in Patients With Niemann-Pick Type C","status":"COMPLETED","sponsor":"National Taiwan University Hospital","startDate":"2008-01","conditions":["Niemann-Pick Disease Type C"],"enrollment":5,"completionDate":"2010-12"},{"nctId":"NCT00945347","phase":"PHASE2","title":"Does a Nasal Instillation of Miglustat Normalize the Nasal Potential Difference in Cystic Fibrosis Patients ?","status":"COMPLETED","sponsor":"Cliniques universitaires Saint-Luc- Université Catholique de Louvain","startDate":"2009-07","conditions":["Cystic Fibrosis"],"enrollment":10,"completionDate":"2011-06"},{"nctId":"NCT00537602","phase":"PHASE2","title":"Miglustat / OGT 918 in the Treatment of Cystic Fibrosis","status":"TERMINATED","sponsor":"Actelion","startDate":"2007-11","conditions":["Cystic Fibrosis"],"enrollment":6,"completionDate":"2008-03"},{"nctId":"NCT00194649","phase":"PHASE4","title":"Glycosphingolipid Inhibition and Spermatogenesis in Man: A Pilot Study (MIG 2)","status":"COMPLETED","sponsor":"University of Washington","startDate":"2005-06","conditions":["Contraception"],"enrollment":8,"completionDate":"2006-01"},{"nctId":"NCT00672022","phase":"PHASE3","title":"Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses","status":"COMPLETED","sponsor":"Children's National Research Institute","startDate":"2004-07","conditions":["GM2 Gangliosidoses","Tay-Sachs","Sandhoff Disease"],"enrollment":10,"completionDate":"2007-08"},{"nctId":"NCT00002079","phase":"PHASE2","title":"Phase II Study of the Safety and Surrogate Marker Efficacy of Butyldeoxynojirimycin (SC-48334) and AZT in Symptomatic HIV-1 Infected Patients With 200 - 500 CD4+ Cells/mm3. (NOTE: Asymptomatic HIV-1 Infected Patients Also Eligible)","status":"COMPLETED","sponsor":"G D Searle","startDate":"","conditions":["HIV Infections"],"enrollment":0,"completionDate":""},{"nctId":"NCT00001993","phase":"PHASE2","title":"Initial Phase II Efficacy and Safety Study of SC-48334 Administered in Combination With Low-Dose Zidovudine (AZT) to Symptomatic HIV-1 Infected Patients With = or > 200 to = or < 500 CD4+ Cells/mm3","status":"COMPLETED","sponsor":"G D Searle","startDate":"","conditions":["HIV Infections"],"enrollment":120,"completionDate":""},{"nctId":"NCT00000692","phase":"PHASE1","title":"Phase I Rising Dose Tolerability Study of SC-48334 in Patients With Acquired Immunodeficiency Syndrome (AIDS) and Advanced AIDS Related Complex","status":"COMPLETED","sponsor":"G D Searle","startDate":"","conditions":["HIV Infections"],"enrollment":48,"completionDate":""}],"_emaApprovals":[{"date":"2002-11-20","status":"Authorised","company":""}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"route":"Oral","formulation":"Capsule","formulations":[{"form":"CAPSULE","route":"ORAL","productName":"MIGLUSTAT"},{"form":"CAPSULE","route":"ORAL","productName":"Miglustat"},{"form":"CAPSULE","route":"ORAL","productName":"Yargesa"},{"form":"CAPSULE","route":"ORAL","productName":"miglustat"},{"form":"CAPSULE","route":"ORAL","productName":"Zavesca"},{"form":"CAPSULE","route":"ORAL","productName":"Miglustat"}]},"_patentsChecked":true,"crossReferences":{"NUI":"N0000148822","MMSL":"17531","NDDF":"009940","UNII":"ADN3S497AZ","VUID":"4021406","CHEBI":"CHEBI:50381","VANDF":"4021406","INN_ID":"8138","RXNORM":"356766","UMLSCUI":"C1321596","chemblId":"CHEMBL1029","ChEMBL_ID":"CHEMBL1029","KEGG_DRUG":"D05032","DRUGBANK_ID":"DB00419","PDB_CHEM_ID":"NBV","PUBCHEM_CID":"51634","SNOMEDCT_US":"408044003","IUPHAR_LIGAND_ID":"4841","MESH_SUPPLEMENTAL_RECORD_UI":"C059896"},"formularyStatus":[],"originalProduct":{"form":"CAPSULE","route":"ORAL","company":"Actelion Pharmaceuticals US, Inc.","brandName":"Zavesca","isOriginal":true,"marketingStatus":"NDA"},"_enricherVersion":"v2","developmentCodes":[],"ownershipHistory":[{"period":"2003-","companyName":"Actelion Pharms Ltd","relationship":"Original Developer"},{"period":"present","companyName":"Actelion","relationship":"Current Owner"}],"pharmacokinetics":{"source":"DrugCentral","bioavailability":"97%"},"publicationCount":456,"therapeuticAreas":["Metabolic"],"atcClassification":{"source":"DrugCentral","atcCode":"A16AX06","allCodes":["A16AX06"]},"biosimilarFilings":[],"originalDeveloper":"Actelion Pharms Ltd","recentPublications":[{"date":"2026 Mar 12","pmid":"41817649","title":"Correction: Miglustat as a Treatment for Adults with Tangier Disease Neuropathy: The MUSTANG N‑of‑1 Trial with 21 months Clinical Observation.","journal":"Neurology and therapy"},{"date":"2026","pmid":"41783848","title":"Comprehensive review of recent advances in Pompe disease: pathogenesis, management, and future directions.","journal":"Frontiers in neurology"},{"date":"2026 Jan-Dec","pmid":"41769220","title":"Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease.","journal":"Therapeutic advances in rare disease"},{"date":"2026 Mar","pmid":"41757410","title":"Comparing the efficacy of cipaglucosidase alfa plus miglustat with alglucosidase alfa for late-onset Pompe disease: an expanded network meta-analysis utilizing patient-level and aggregate data.","journal":"Journal of comparative effectiveness research"},{"date":"2026 Jan 18","pmid":"41742944","title":"Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1.","journal":"medRxiv : the preprint server for health sciences"}],"companionDiagnostics":[],"genericManufacturers":4,"_genericFilersChecked":true,"genericManufacturerList":["Ani Pharms","Chartwell Rx","Edenbridge Pharms","Navinta Llc"],"status":"approved","companyName":"Actelion","companyId":"astrazeneca","modality":"Small molecule","firstApprovalDate":"2003","enrichmentLevel":4,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2003-07-31T00:00:00.000Z","mah":"ACTELION PHARMS LTD","brand_name_local":null,"application_number":""},{"country_code":"EU","regulator":"EMA","status":"pending","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null}],"patentsNormalised":[{"patent_number":"12419937","territory":"US","patent_type":"Method of Use","expiry_date":"2033-03-07T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"11278599","territory":"US","patent_type":"Method of Use","expiry_date":"2033-03-07T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10512677","territory":"US","patent_type":"Method of Use","expiry_date":"2033-03-07T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10961522","territory":"US","patent_type":"Method of Use","expiry_date":"2035-09-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10208299","territory":"US","patent_type":"Compound","expiry_date":"2035-09-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"11753632","territory":"US","patent_type":"Method of Use","expiry_date":"2035-09-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"11278601","territory":"US","patent_type":"Formulation","expiry_date":"2036-12-29T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"12414985","territory":"US","patent_type":"Method of Use","expiry_date":"2036-12-29T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10857212","territory":"US","patent_type":"Method of Use","expiry_date":"2037-08-12T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"12246062","territory":"US","patent_type":"Method of Use","expiry_date":"2038-09-16T00:00:00.000Z","status":"active","paragraph_iv_filed":false}],"trialStats":{"total":3,"withResults":0},"validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T03:19:14.522350+00:00","fieldsConflicting":1,"overallConfidence":0.8},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}