Niemann-Pick Type C disease: Limited data available (Heron 2012; Patterson 2012): Note: Therapy is recommended for patients with neurological, cognitive, or psychiatric disease manifestations (Patterson 2012). Infant data is very limited; reported infant neurological effects (aside from seizures) have included hypotonia, dysphagia, feeding difficulties (onset: 5 to 12 months of age); earliest reported miglustat therapy is 7 months of age (DiRoccoa 2012; Heron 2012). Doses may be initiated slowly and adjusted for tolerability, particularly GI effects (diarrhea which may require dietary and pharmacologic management (Heron 2012; Patterson 2012). Several months of therapy may be necessary to see clinical benefit (eg, 6 to 12 months) (Patterson 2012).
Infants and Children <12 years: Oral:
BSA ≤0.47 m2: 100 mg once daily
BSA >0.47 to 0.73 m2: 100 mg twice daily
BSA >0.73 to 0.88 m2: 100 mg 3 times daily
BSA >0.88 to 1.25 m2: 200 mg twice daily
BSA >1.25 m2: 200 mg 3 times daily
Children ≥12 years and Adolescents: 200 mg 3 times daily (Zavesca prescribing information [Canada 2012]; Zavesca prescribing information [European Medicines Agency 2012])
Niemann-Pick Type C disease (Zavesca prescribing [Canada] information 2012):
Children <12 years:
CrCl 50 to 70 mL/minute/1.73 m2: Administer two-thirds of regular BSA adjusted dose in 2 equal doses
CrCl 30 to 50 mL/minute/1.73 m2: Administer one-third of regular BSA adjusted dose in 2 equal doses
CrCl <30 mL/minute/1.73 m2: Not recommended
Children ≥12 years and Adolescents:
CrCl 50 to 70 mL/minute/1.73 m2: 200 mg twice daily
CrCl 30 to 50 mL/minute/1.73 m2: 100 mg twice daily
CrCl <30 mL/minute/1.73 m2: Not recommended
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, dosage adjustment unlikely because miglustat is not metabolized by the liver.
(For additional information see "Miglustat: Drug information")
Gaucher disease, type 1: Oral: 100 mg 3 times daily; dose may be reduced to 100 mg 1 to 2 times daily in patients with adverse effects (eg, tremor, diarrhea).
Niemann-Pick type C disease (off-label use): Oral: 200 mg 3 times daily (Patterson 2007; Santos-Lozano 2015).
Gaucher disease, type 1:
CrCl >70 mL/minute/1.73 m2: No dosage adjustment necessary.
CrCl 50 to 70 mL/minute/1.73 m2: 100 mg twice daily.
CrCl 30 to 50 mL/minute/1.73 m2: 100 mg once daily.
CrCl <30 mL/minute/1.73 m2: Use is not recommended.
Niemann-Pick type C disease (off-label use) (Zavesca Canadian product monograph):
CrCl >70 mL/minute/1.73 m2: No dosage adjustment necessary.
CrCl 50 to 70 mL/minute/1.73 m2: 200 mg twice daily.
CrCl 30 to 50 mL/minute/1.73 m2: 100 mg twice daily.
CrCl <30 mL/minute/1.73 m2: Use is not recommended.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, dosage adjustment unlikely because miglustat is not metabolized by the liver.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zavesca: 100 mg [contains soybean lecithin]
Generic: 100 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zavesca: 100 mg [contains soybean lecithin]
Generic: 100 mg
May be administered with or without food; administration between meals may decrease the incidence of diarrhea. Doses should be 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]).
May be administered with or without food; administration between meals may decrease the incidence of diarrhea. Capsules should be 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])
Store at 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: Extended storage information may be available; contact product manufacturer to obtain current recommendations.
Treatment of mild to moderate type 1 Gaucher disease when enzyme replacement therapy is not a therapeutic option (eg, due to allergy, hypersensitivity, or poor venous access) (FDA approved in adults); has also been used to treat Neimann-Pick Type C Disease
Miglustat may be confused with migalastat, miglitol
Zavesca: Brand name for miglustat [US, Canada, and multiple international markets], but also brand name for escitalopram [in multiple international markets; ISMP April 21, 2010]
The following adverse drug reactions are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Weight loss
Gastrointestinal: Abdominal pain, diarrhea, flatulence, nausea, vomiting
Nervous system: Asthenia, dizziness, headache, tremor
Neuromuscular & skeletal: Lower limb cramp, muscle cramps
Ophthalmic: Visual disturbance
1% to 10%:
Endocrine & metabolic: Menstrual disease
Gastrointestinal: Abdominal distention, anorexia, bloating, constipation, dyspepsia, epigastric pain, xerostomia
Hematologic & oncologic: Thrombocytopenia
Nervous system: Feeling of heaviness (limbs), memory impairment, migraine, paresthesia, peripheral neuropathy, unsteady gait
Neuromuscular & skeletal: Back pain
Postmarketing: Nervous system: Psychosis (Yekedüz 2022)
There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Hypersensitivity to miglustat or any component of the formulation; females who are or may become pregnant.
Concerns related to adverse effects:
• Diarrhea: Observed in the majority of patients, many also reported weight loss (within first 12 months of treatment). Diarrhea decreased over time with continued treatment, and may respond to diet modification (eg, reduction of sucrose, lactose and other carbohydrate intake), taking miglustat between meals, and/or to anti-diarrheal medications. If diarrhea occurs during treatment, instruct patients to avoid foods with high carbohydrate content. If symptoms persist, evaluate patients for underlying GI disease.
• Peripheral neuropathy: Peripheral neuropathy has been reported; neurologic monitoring is required. Weigh risk versus benefit of therapy if patient develops symptoms (eg, numbness and tingling); treatment discontinuation may be necessary.
• Platelet counts decreased: Mild decrease in platelet counts (without bleeding) has been observed in patients with type 1 Gaucher disease switched from enzyme replacement therapy; monitor platelet counts during therapy.
• Tremor: New-onset or exacerbations of existing tremor may occur. Tremor typically begins within the first month of treatment and may resolve over time (1-3 months) or respond to dosage reduction. Treatment discontinuation may be necessary if tremor does not respond within days of dose reduction.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustments recommended. Not recommended in patients with severe impairment.
Other warnings/precautions:
• Experienced physician: Should be administered under the supervision of a physician experienced in treatment of Gaucher disease.
• Registry: A registry has been established and all patients with Gaucher disease, and physicians who treat Gaucher disease are encouraged to participate. Information on the International Collaborative Gaucher Group (ICGG) Gaucher Registry may be obtained at https://www.registrynxt.com or by calling 1-888-404-4413.
Growth reductions, both weight and height, has been reported in pediatric patients with Neimann-Pick type C disease on miglustat therapy; initially with therapy, a weight loss was observed that may be accompanied with or followed by a decrease in height velocity. Monitor height and weight with therapy, assess risk/benefit periodically of miglustat therapy (Zavesca prescribing information [European Medicines Agency 2012]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
There are no known significant interactions.
Food decreases the rate, but not the extent, of absorption. Management: Administer without regard to meals.
Patients with diarrhea should avoid foods with high carbohydrate content.
Based on a 6-week study of 7 healthy patients, miglustat is not expected to decrease male fertility.
Based on data from animal reproduction studies, in utero exposure to miglustat may cause fetal harm.
Uncontrolled type 1 Gaucher disease is associated an increased risk of spontaneous abortion; maternal hepatosplenomegaly and thrombocytopenia may also occur and lead to adverse pregnancy outcomes.
Neurologic evaluations baseline and repeated every 6 months; platelet count; renal function; growth parameters in pediatric patients (height, weight, head circumference) (Patterson 2012)
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.
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)
Altered kidney function: Limited data suggests that the clearance of miglustat decreases 40% and 60% with mild and moderate renal impairment, respectively. A decreased clearance of 70% has been suggested in patients with severe renal impairment.
Capsules (migLUstat Oral)
100 mg (per each): $321.48
Capsules (Zavesca Oral)
100 mg (per each): $357.60
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