Miglustat

Pronunciation: MIG-loo-stat
Class: Endocrine and metabolic agent

Trade Names

Zavesca
- Capsule 100 mg

Pharmacology

Competitive and reversible inhibitor of the enzyme glucosylceramide synthase.

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Pharmacokinetics

Absorption

Bioavailability is about 97%. C max observed in 2 to 2.5 h. Effective t ½ is about 6 to 7 h, predicting a steady-state in 1.5 to 2 days.

Distribution

Vd is 83 to 105 L. No protein binding.

Elimination

Excreted unchanged in the urine.

Special Populations

Renal function impairment

Based on CrCl levels, dosage adjustment in mild and moderate renal function impairment is justified.

Indications and Usage

Treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not an option (eg, hypersensitivity).

Contraindications

Pregnancy; standard considerations.

Dosage and Administration

Adults

PO 100 mg 3 times daily at regular intervals. It may be necessary to reduce the dose to 100 mg 1 or 2 times daily in patients experiencing adverse reactions (eg, diarrhea, tremor).

Renal function impairment
Adults

PO CrCl 50 to 70 mL/min, start with 100 mg 2 times daily; CrCl 30 to 50 mL/min, start with 100 mg every day. Administration to patient with severe renal function impairment (CrCl less than 30 mL/min) is not recommended.

Storage/Stability

Store capsules at controlled room temperature (68° to 77°F).

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (22%); tremor, dizziness, leg cramps (11%); unsteady gait, memory loss (8%); paresthesia (7%); migraine (6%).

EENT

Visual disturbance (17%).

GI

Diarrhea (85%); abdominal pain (50%); flatulence (44%); nausea (22%); vomiting (11%); constipation, dry mouth (8%); anorexia, dyspepsia (7%); bloating, epigastric pain (6%).

Genitourinary

Menstrual disorder (6%).

Hematologic

Thrombocytopenia (7%).

Metabolic

Weight loss (65%).

Musculoskeletal

Cramps (11%)

Miscellaneous

Generalized weakness (17%); abdominal distension and gaseous abdominal distension, back pain, heaviness in limbs (8%).

Precautions

Pregnancy

Category X .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution and start at the lower end of the dose range because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Dosage adjustment is recommended.

Peripheral neuropathy

Has been reported.

Patient Information

  • Advise patient to read the patient information leaflet before starting therapy and with each refill.
  • Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs. Advise patient to swallow each capsule whole with a glass of water.
  • Advise patient that diarrhea is most common adverse reaction and that reducing carbohydrate intake may be helpful. If diarrhea develops, advise patient to discuss use of OTC antidiarrheals (eg, loperamide) with health care provider.
  • Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time.
  • Instruct women of childbearing potential to use effective contraception during treatment.
  • Instruct sexually active men to use reliable contraceptive methods during treatment and for 3 mo after therapy has been discontinued.
  • Instruct patient to immediately report the following symptoms to health care provider: numbness, pain, burning, or tingling in hands or feet; tremor; worsening of existing tremor.
  • Advise patient to inform health care provider if persistent diarrhea does not respond to OTC antidiarrheals or unexplained weight loss occurs.

Copyright © 2009 Wolters Kluwer Health.

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