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Pronunciation
(MIG loo stat)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of mild-to-moderate type 1 Gaucher disease when enzyme replacement therapy is not a therapeutic option
Canadian labeling: Additional use (not in U.S. labeling): Treatment to delay the progression of neurological manifestations in Niemann-Pick Type C disease
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.
• Platelet counts decreased: Mild decrease in platelet counts (without bleeding) has been observed with use in Niemann-Pick Type C disease (not an approved use in the U.S.); monitor platelet counts in this patient population during therapy.
• Tremor: Exacerbations of existing tremor or tremor may occur; may resolve over time or respond to dosage reduction. Treatment discontinuation may be necessary.
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; however, the clinical significance of this is not known; 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: Abdominal distension (8%), constipation (8%), xerostomia (8%), bloating (up to 6%), anorexia (up to 7%), dyspepsia (up to 7%), epigastric pain (up to 6%)
Hematologic: Thrombocytopenia (6% to 7%)
Neuromuscular & skeletal: Back pain (8%), gait instability (8%), paresthesia (up to 7%)
Metabolism/Transport Effects
None known.
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). Brief exposure to 15°C to 30°C (59°F to 86°F) permitted. Note: Limited stability data suggests that when dosages <100 mg are required, powder packets may be prepared by opening miglustat capsules and mixing the powder with D-mannitol. Resulting mixture was stored for up to 8 weeks at room temperature (data on file [Actelion Pharmaceuticals Ltd, 2011]).
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:
Type 1 Gaucher disease: Adults: 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)
Niemann-Pick Type C disease (Canadian labeling; not in U.S. labeling):
Children <12 years: Note: Children <4 years of age were not included in clinical trials; dose based on body surface area (BSA):
BSA >1.25 m2: Miglustat 200 mg 3 times/day
BSA >0.88-1.25 m2: Miglustat 200 mg 2 times/day
BSA >0.73-0.88 m2: Miglustat 100 mg 3 times/day
BSA >0.47-0.73 m2: Miglustat 100 mg 2 times/day
BSA ≤0.47 m2: Miglustat 100 mg once daily
Children ≥12 and Adults: 200 mg 3 times/day
Dosage adjustment in renal impairment:
Gaucher disease: Adults:
Clcr 50-70 mL/minute/1.73 m2: 100 mg twice daily
Clcr 30-50 mL/minute/1.73 m2: 100 mg once daily
Clcr <30 mL/minute/1.73 m2: Not recommended
Niemann-Pick Type C disease Canadian labeling (not in U.S. labeling):
Children <12 years:
Clcr 50-70 mL/minute/1.73 m2: Administer two-thirds of regular dose in 2 equal doses (adjusted for BSA)
Clcr 30-50 mL/minute/1.73 m2: Administer one-third of regular dose in 2 equal doses (adjusted for BSA)
Clcr <30 mL/minute/1.73 m2: Not recommended
Children ≥12 years and Adults:
Clcr 50-70 mL/minute/1.73 m2: 200 mg twice daily
Clcr 30-50 mL/minute/1.73 m2: 100 mg twice daily
Clcr <30 mL/minute/1.73 m2: Not recommended
Administration: Oral
May be administered with or without food. Capsules should be swallowed whole and taken at the same time each day at regular intervals. If patient is unable to tolerate or swallow capsule whole and powder is administered, mix powder into a liquid immediately prior to use (do not store); sweetening agents are not expected to interact (data on file [Actelion Pharmaceuticals Ltd, 2011])
Monitoring Parameters
Neurologic evaluations baseline and repeated every 6 months; adverse effects; weight; vitamin B12; platelet counts and renal function in Niemann-Pick Type C patients (Canadian labeling recommendation); pregnancy test prior to therapy in women of reproductive age
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 (do not crush or break) and taken at the same time each day, with or without food. May cause headache, dizziness, nausea, vomiting, shakiness, weight loss, or diarrhea. Notify prescriber of persistent diarrhea or numbness or tingling in extremities. Monitor your weight and report steady, significant weight loss to prescriber.
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. Assess results of neurological evaluations at beginning of therapy and every 6 months during therapy. Instruct patient to report tremor and peripheral neuropathy. Monitor nutritional status closely.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
Zavesca®: 100 mg
International Brand Names
Lexi-Comp.com
Last full review/revision December 2011
Content last modified December 2011
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