Overview

  • Generic Name: Miglustat

  • Trade Name: Zavesca

  • Drug Class: Substrate reduction therapy (SRT); glucosylceramide synthase inhibitor

  • Administration: Oral capsules

Indications

  • Gaucher disease type 1 (mild to moderate severity) for patients unable or unwilling to receive enzyme replacement therapy (ERT).

  • Niemann–Pick Disease Type C (NPC), to slow neurological progression.

Mechanism of Action

  • Miglustat is an iminosugar (N-alkylated imino sugar) derivative.

  • Acts by competitively inhibiting glucosylceramide synthase enzyme.

  • Reduces glycosphingolipid accumulation by decreasing substrate production.

Pharmacokinetics

  • Absorption: Rapid oral absorption with peak plasma concentrations in 2-3 hours.

  • Bioavailability: Approximately 80%.

  • Metabolism: Minimal hepatic metabolism; primarily eliminated unchanged.

  • Half-life: Approximately 6-7 hours.

  • Excretion: Predominantly renal.

Dosage and Administration

  • Typical dosage in adults:

    • Gaucher Disease: 100 mg orally three times daily.

    • Niemann–Pick Disease Type C: 200 mg orally three times daily for adults and adolescents; adjusted for pediatric patients based on body surface area.

  • Dosage modifications necessary for renal impairment.

Clinical Efficacy

  • Demonstrated ability to stabilize or slow progression of neurological symptoms in Niemann–Pick Type C.

  • Effective in reducing organomegaly and improving hematological parameters in Gaucher type 1 patients.

Side Effects

  • Gastrointestinal:

    • Diarrhea (most common)

    • Abdominal pain

    • Flatulence

    • Nausea

  • Neurological:

    • Tremor

    • Peripheral neuropathy

    • Dizziness

  • Metabolic:

    • Weight loss

  • Others:

    • Thrombocytopenia

    • Muscle weakness

Contraindications and Precautions

  • Contraindications:

    • Hypersensitivity to miglustat or excipients.

    • Pregnancy and breastfeeding (potential teratogenic effects).

  • Precautions:

    • Monitoring recommended for neurological and hematological adverse effects.

    • Regular renal function tests essential for dose adjustments.

    • Caution advised in patients with pre-existing neuropathy.

Drug Interactions

  • Limited clinically significant interactions known.

  • Concurrent use with drugs that affect renal function may require careful monitoring.

Monitoring

  • Regular neurological assessments.

  • Periodic complete blood counts.

  • Renal function testing (serum creatinine, estimated GFR).

Current Research Areas of Interest

  • Investigation of miglustat as combination therapy with other substrate reduction or enzyme replacement therapies.

  • Exploring benefits in other lysosomal storage disorders (e.g., Tay–Sachs disease, Sandhoff disease).

  • Developing pediatric dosing and safety profiles.

  • Long-term efficacy and safety studies for chronic administration.

Regulatory Status

  • Approved by EMA (European Medicines Agency), FDA (U.S. Food and Drug Administration), and other international health agencies for specific indications.

Conclusion

Miglustat remains an important therapeutic option in managing specific lysosomal storage disorders, particularly Gaucher disease type 1 and Niemann–Pick Disease Type C, with ongoing research focused on expanding indications and optimizing clinical outcomes.