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Pronunciation
(MIG loo stat)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of mild-to-moderate type 1 Gaucher disease when enzyme replacement therapy is not a therapeutic option
Pregnancy Risk Factor
X
Pregnancy Considerations
Decreased fetus weight, fetal loss, and difficult or delayed births were observed in animal studies. Women with reproduction potential should use effective contraception during therapy. In addition, adverse effects on spermatogenesis and reduced fertility were observed in male animal studies. The manufacturer recommends that male patients use reliable contraception during therapy and for 3 months following treatment.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to miglustat or any component of the formulation; pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Diarrhea: Observed in the majority of patients, many also reported weight loss. Incidence decreases over time; foods with high carbohydrate content should be avoided. If symptoms persist, patients should be evaluated for underlying GI disease.
• Peripheral neuropathy: Has been reported; neurologic monitoring is required. Weigh risk versus benefit of therapy if patient develops numbness and tingling.
• Tremor: Exacerbations of existing tremor or tremor may occur; may resolve over time or respond to dosage reduction.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustments recommended. Not recommended in patients with severe impairment.
• Severe type 1 Gaucher disease: Safety and efficacy have not been established in severe type 1 Gaucher disease.
Concurrent drug therapy issues:
• Imiglucerase: Miglustat increases the clearance of imiglucerase; combination therapy is not indicated.
Adverse Reactions
Percentages reported from open-label, uncontrolled monotherapy trials.
>10%:
Central nervous system: Headache (21% to 22%), dizziness (up to 11%)
Gastrointestinal: Diarrhea (89% to 100%), weight loss (39% to 67%), abdominal pain (18% to 67%), flatulence (29% to 50%), nausea (8% to 22%), vomiting (4% to 11%)
Neuromuscular & skeletal: Tremor (11% to 30%), weakness (17%), leg cramps (4% to 11%)
Ocular: Visual disturbances (up to 17%)
1% to 10%:
Central nervous system: Memory impairment (8%), migraine (up to 6%)
Endocrine & metabolic: Menstrual disorder (up to 6%)
Gastrointestinal: Constipation (8%), xerostomia (8%), bloating (up to 8%), anorexia (up to 7%), dyspepsia (up to 7%), epigastric pain (up to 6%)
Hematologic: Thrombocytopenia (6% to 7%)
Neuromuscular & skeletal: Paresthesia (up to 7%)
Drug Interactions
There are no known significant interactions.
Ethanol/Nutrition/Herb Interactions
Food: Food decreases the rate, but not the extent, of absorption.
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Miglustat competitively and reversibly inhibits the enzyme needed to produce glycosphingolipids and decreases the rate of glycosphingolipid glucosylceramide formation. Glucosylceramide accumulates in type 1 Gaucher disease, causing complications specific to this disease.
Pharmacodynamics/Kinetics
Distribution: Vd: 83-105 L
Protein binding: No binding to plasma proteins
Metabolism: No evidence of metabolism in humans
Bioavailability: 97%
Half-life elimination: 6-7 hours
Time to peak, plasma: 2-2.5 hours
Excretion: Urine (as unchanged drug)
Dosage
Oral: Adults: Type 1 Gaucher disease: 100 mg 3 times/day; dose may be reduced to 100 mg 1-2 times/day in patients with adverse effects (ie, tremor, GI distress)
Dosage adjustment in renal impairment:
Clcr 50-75 mL/minute: 100 mg twice daily
Clcr 30-50 mL/minute: 100 mg once daily
Clcr <30 mL/minute: Not recommended
Administration: Oral
Capsules should be swallowed whole and taken at the same time each day. May be taken with or without food.
Monitoring Parameters
Neurologic evaluations baseline and repeated every 6 months; adverse effects; weight
Dietary Considerations
May be taken with or without food. Patients with diarrhea should avoid foods with high carbohydrate content.
Patient Education
Capsules should be swallowed whole and taken at the same time each day, with or without food. May cause headache and dizziness (use caution when driving or engaging in hazardous tasks until response to drug is known); nausea, vomiting, or loss of appetite (small, frequent meals and good mouth care may help); or diarrhea (buttermilk, boiled milk, or yogurt may help). Notify prescriber at once of persistent diarrhea, numbness or tingling in extremities, change in vision, or other adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. This drug can cause fetal abnormalities. Both females and males should use (consult prescriber) appropriate contraception during therapy. Males should continue contraceptive use for 3 months following therapy. Breast-feeding is not recommended.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common
Mental Health: Effects on Psychiatric Treatment
GI side effects are common; use caution with SSRIs
Nursing: Physical Assessment/Monitoring
Use caution with renal impairment. Not to be used in combination with imiglucerase. Assess results of neurological evaluations at beginning of therapy and every 6 months during therapy. Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report (tremor, peripheral neuropathy). Pregnancy risk factor X: Determine that patient is not pregnant before beginning treatment. Do not give to women of childbearing age or males who may have intercourse with childbearing age females unless they are capable of complying with effective contraceptive measures during therapy. Men should continue contraceptive measures for 3 months following treatment.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Zavesca®: 100 mg
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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