Miglustat

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.

• 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.

• None None ( 4 )contraindicated

• 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) ].

• 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.

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.

• 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.

Metabolism

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.

• Jul 31, 2003NDANDA021348Actelion
• Apr 17, 2018ANDAANDA208342Ani Pharms
• Aug 6, 2020ANDAANDA209821Edenbridge Pharms
• Sep 28, 2023NDANDA215211Amicus Therap Us
• Mar 14, 2025ANDAANDA219111Navinta Llc

1. 1Diarrhoea16415%
2. 2Death15614%
3. 3Seizure1089.6%
4. 4Weight Decreased988.7%
5. 5Niemann-pick Disease978.6%
6. 6Pneumonia908.0%
7. 7Disease Progression857.5%
8. 8Tremor776.8%
9. 9Condition Aggravated766.7%
10. 10Off Label Use726.4%
11. 11Dysphagia665.9%
12. 12Pyrexia615.4%
13. 13Vomiting474.2%
14. 14Epilepsy443.9%
15. 15Convulsion433.8%

The 10 most recently updated of 32 ClinicalTrials.gov registrations naming Miglustat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Safety and Efficacy of Nizubaglustat (AZ-3102) in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease
  Recruiting · Phase 2 · Interventional · 21 enrolled · Azafaros B.V.
  NCT07399704updated 2026-05-07
• A Global Prospective Observational Registry of Patients With Pompe Disease
  Recruiting · Observational · 500 enrolled · Amicus Therapeutics
  NCT06121011updated 2026-03-10
• A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD)
  Completed · Phase 3 · Interventional · 119 enrolled · Amicus Therapeutics
  NCT04138277updated 2026-03-05
• A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18
  Recruiting · Phase 3 · Interventional · 36 enrolled · Amicus Therapeutics
  NCT04808505updated 2026-01-22
• Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the F508del Mutation
  Completed · Phase 2 · Phase 3 · Interventional · 16 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT02325362updated 2025-11-20
• ZIP Study-OL Study of Safety, PK, Efficacy, PD, Immunogenicity of ATB200/AT2221 in Pediatrics Aged 0 to < 18 y.o. w/LOPD
  Active not recruiting · Phase 3 · Interventional · 21 enrolled · Amicus Therapeutics
  NCT03911505updated 2025-10-27
• First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221
  Completed · Phase 1 · Phase 2 · Interventional · 29 enrolled · Amicus Therapeutics
  NCT02675465updated 2025-10-23
• Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD)
  Terminated · Phase 3 · Interventional · 30 enrolled · Tehran University of Medical Sciences
  NCT03822013updated 2025-09-17
• A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease
  Completed · Phase 3 · Interventional · 125 enrolled · Amicus Therapeutics
  NCT03729362updated 2025-09-11
• Expanded Access for ATB200/AT2221 for the Treatment of IOPD
  Available · Expanded access · Amicus Therapeutics
  NCT04327973updated 2025-09-10

Frequently asked questions

How does Miglustat work?

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.

What is Miglustat used for?

According to FDA labeling, Miglustat carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Miglustat?

Miglustat is classified as Various alimentary tract and metabolism products, Enzyme Stabilizer, Glucosylceramide Synthase Inhibitor, Enzyme Stabilizers, Glucosylceramide Synthase Inhibitors, Glycosphingolipid Synthesis Decrease.

What are the brand names for Miglustat?

Miglustat is marketed under brand names including Opfolda, Yargesa, Zavesca.

What are the contraindications for Miglustat?

Miglustat labeling lists contraindications including: None None ( 4 ). Always consult the full prescribing information and a clinician.