Miglustat

What it is and how it works

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 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).

Mechanism class: Glucosylceramide Synthase Inhibitors · Enzyme Stabilizers

Indications

Miglustat 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 . Type 1 Gaucher Disease Miglustat is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to allergy, hypersensitivity, or poor venous access).

Dosage and administration (summary)

Recommended dosage is 100 mg administered orally three times a day at regular intervals . May reduce dosage to 100 mg once or twice a day in some patients due to tremor or diarrhea . Adjust in patients with renal impairment : 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 Instructions for Administration Therapy should be directed by physicians who are knowledgeable in the management of Gaucher disease.

Contraindications

None. None

Warnings and precautions

Peripheral neuropathy : Perform baseline and follow-up neurological evaluations at 6- month intervals in all patients . Tremor : Reduce dose to ameliorate tremor or discontinue treatment if tremor does not resolve within days of dose reduction . Diarrhea and Weight Loss : Evaluate for underlying gastrointestinal disease in patients who do not respond to usual interventions (e.g. diet modification) . Reductions in Platelet Count : Mild reductions in platelet counts without association with bleeding were observed in some patients. Monitoring of platelet counts is recommended .

Pregnancy

Pregnancy Risk Summary Based on findings from animal reproduction studies, miglustat may cause fetal harm when administered to a pregnant woman. Available data from postmarketing case reports with miglustat use in pregnancy are insufficient to assess a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Storage and supply

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). . Keep out of reach of children.

Source: Miglustat (Miglustat) — US FDA prescribing information, 2023-04-25, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.