Overview
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.
Mechanism of Action
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).
Indications
- 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).
Common Doses
- 100 mg
- 70 mL
- 50 mL
- 30 mL
Dosage
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
Contraindications
- 4 CONTRAINDICATIONS None None ( 4 )
Side Effects
- 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,...
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 ).