Miglustat (Pompe Disease) (Monograph)

Brand name: Opfolda
Drug class:

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Miglustat, a synthetic analog of Dglucose, is an enzyme stabilizer.

Uses for Miglustat (Pompe Disease)

Miglustat has the following uses:

Miglustat is indicated, in combination with cipaglucosidase alfa-atga, a hydrolytic lysosomal glycogen-specific enzyme, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).

Miglustat (Pompe Disease) Dosage and Administration

General

Miglustat is available in the following dosage form(s) and strength(s):

Capsules: 65 mg

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Verify pregnancy status in females of reproductive potential prior to initiating treatment.
Miglustat must be administered in combination with cipaglucosidase alfa-atga (Pombiliti). Refer to the Pombiliti Prescribing Information for dosage and administration recommendations.
Recommended miglustat dosage (based on actual body weight), administered orally every other week, is 260 mg for patients weighing ≥50 kg or 195 mg for patients weighing ≥40 kg to <50 kg.
Start miglustat in combination with cipaglucosidase alfa 2 weeks after the last ERT dose.
Swallow miglustat capsules whole with an unsweetened beverage approximately 1 hour before the start of cipaglucosidase alfa-atga infusion; do not consume other beverages or food for at least 2 hours prior to and 2 hours after taking miglustat.
If the miglustat dosage is missed, cipaglucosidase alfa should not be administered and treatment should be rescheduled at least 24 hours after miglustat was last taken. If both drugs are missed, re-start treatment as soon as possible.
See full prescribing information for recommended miglustat dosage in patients with renal impairment.

Cautions for Miglustat (Pompe Disease)

Contraindications

Pregnancy.

Warnings/Precautions

Embryo-fetal Toxicity

Verify the pregnancy status in females of reproductive potential prior to initiating treatment with miglustat in combination with cipaglucosidase alfa. Advise females of reproductive potential to use effective contraception during treatment with the combination therapy and for at least 60 days after the last dose.

Risks Associated with Cipaglucosidase alfa-atga

Miglustat must be administered in combination with cipaglucosidase alfa-atga. Refer to the cipaglucosidase alfa-atga (Pombiliti) Prescribing Information for a description of additional risks including, but not limited to, the warnings and precautions for the drug.

Specific Populations

Pregnancy

Based on findings from animal reproduction studies, miglustat in combination with cipaglucosidase alfa may cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy. In a rabbit embryo-fetal development study, great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with miglustat in combination with cipaglucosidase alfa-atga at 3-fold and 16-fold, respectively, the MRHD of miglustat and cipaglucosidase alfa-atga based on plasma AUC exposure. A No Observed Adverse Effect Level (NOAEL) was not identified for the combination. In a pre- and post-natal development study in rats, increases in pup mortality were seen following maternal treatment with miglustat in combination with cipaglucosidase alfa-atga (400 mg/kg), or with cipaglucosidase alfa-atga (400 mg/kg) alone. The NOAEL for cipaglucosidase alfa-atga alone is 150 mg/kg (5-fold the cipaglucosidase alfa-atga MRHD margin). A NOAEL for the combination was not identified. Margins at the lowest observed adverse effect level (LOAEL), relative to exposures at the MRHD of miglustat and cipaglucosidase alfa-atga were 4-fold and 21-fold, respectively, based on plasma AUC exposure.

There are no available human data on miglustat in combination with cipaglucosidase alfa use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation

There are no data on the presence of miglustat, alone or in combination with cipaglucosidase alfa-atga, in human milk, the effects on the breastfed infant, or the effects on milk production. Miglustat is present in animal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Based on findings in animal studies, the use of miglustat in combination with cipaglucosidase alfa may lead to serious adverse reactions in breastfed infants. Advise females that breastfeeding is not recommended while on treatment with miglustat in combination with cipaglucosidase alfa.

Females and Males of Reproductive Potential

Miglustat in combination with cipaglucosidase alfa may cause embryo-fetal harm when administered to a pregnant female. Verify the pregnancy status in females of reproductive potential prior to initiating treatment with the combination therapy.

Advise females of reproductive potential to use effective contraception during treatment with miglustat in combination with cipaglucosidase alfa and for at least 60 days after the last dose.

Based on preimplantation loss observed in female rats treated with oral miglustat (60 mg/kg) in combination with IV cipaglucosidase alfa-atga (400 mg/kg) every other day for 14 days prior to mating and continuing through GD 7, the combination treatment may impair human female fertility. A NOAEL for the combination was not identified. The LOAEL margins are 4-fold and 21-fold the MRHD for miglustat and cipaglucosidase alfa-atga, respectively. It is not known whether this preimplantation loss in female rats would be sustained if dosing with the combination were discontinued prior to mating.

Based on reversible increases in preimplantation loss in male rats treated with the combination every other day for 28 days prior to mating, miglustat in combination with cipaglucosidase alfa may impair human male fertility. A NOAEL for the combination was not identified. The LOAEL margins are 4-fold and 21-fold the MRHD for miglustat and cipaglucosidase alfa, respectively.

For additional information about male fertility with the use of cipaglucosidase alfa-atga, see the Pombiliti Prescribing Information.

Pediatric Use

Safety and effectiveness of miglustat in combination with cipaglucosidase alfa have not been established in pediatric patients with late-onset Pompe disease.

Geriatric Use

Of the total number of patients treated with miglustat in combination with cipaglucosidase alfa in clinical trials for late-onset Pompe disease, 17 (11%) were 65 to 74 years of age, and none were 75 years of age and older.

Clinical trials of miglustat in combination with cipaglucosidase alfa did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

Renal Impairment

Plasma concentrations of miglustat increased in patients with renal impairment. No dosage adjustment of miglustat is recommended in patients with mild (CLcr 60 to 89 mL/minute, estimated by Cockcroft-Gault) renal impairment. Reduce the miglustat dosage in patients with moderate (CLcr 30 to 59 mL/minute) or severe (CLcr 15 to 29 mL/minute) renal impairment. The pharmacokinetics of miglustat have not been evaluated in patients with end stage renal disease.

Common Adverse Effects

Most common adverse reactions ≥5% are headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Miglustat binds with, stabilizes, and reduces inactivation of cipaglucosidase alfa-atga in the blood after infusion. The bound miglustat is dissociated from cipaglucosidase alfa after it is internalized and transported into lysosomes. Miglustat alone has no pharmacological activity in cleaving glycogen.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Miglustat must be administered in combination with cipaglucosidase alfa-atga (Pombiliti). Refer to the cipaglucosidase alfa-atga (Pombiliti) Prescribing Information for patient counseling information.
Advise the patient and caregiver to follow the timeline recommendations for taking miglustat prior to the IV infusion with cipaglucosidase alfa-atga and to follow the fasting recommendation. Advise the patient and caregiver that miglustat should be swallowed only with unsweetened beverages.
Miglustat in combination with cipaglucosidase alfa may cause embryo-fetal harm. Advise a female patient and caregiver to inform their healthcare provider of a known or suspected pregnancy.
Advise a female of reproductive potential to use effective contraception during treatment with miglustat in combination with cipaglucosidase alfa and for at least 60 days after the last dose.
Advise a lactating female not to breastfeed during treatment with miglustat in combination with cipaglucosidase alfa.
Advise the male or female of reproductive potential that miglustat in combination with cipaglucosidase alfa may impair fertility.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.