Miglustat (Pompe Disease) (Monograph)

Brand name: Opfolda
Drug class: Enzyme Inhibitors

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

Introduction

Synthetic analog of D-glucose; enzyme stabilizer.

Uses for Miglustat (Pompe Disease)

Pompe Disease

Treatment of late-onset Pompe disease in combination with cipaglucosidase alfa-atga (a lysosomal glycogen-specific recombinant human α-glucosidase) in adult patients weighing ≥40 kg who are not improving on current enzyme replacement therapy; designated an orphan drug by FDA for this use.

The standard of care for Pompe disease is supportive care and administration of enzyme-replacement therapy in the form of recombinant human acid α-glucosidase.

Miglustat (Pompe Disease) Dosage and Administration

General

Pretreatment Screening

• Verify the pregnancy status of females of reproductive potential prior to initiation.

Administration

Administer orally.

Must be used in combination with cipaglucosidase alfa-atga; take miglustat approximately 1 hour before IV administration of cipaglucosidase alfa-atga.

Initiate combination therapy 2 weeks after the last dose of enzyme replacement therapy.

Swallow capsules whole with unsweetened beverage (e.g., water, tea or coffee with no cream, sugar, or sweeteners). Do not consume other beverages or food for at least 2 hours prior to and 2 hours after administration.

If a dose of miglustat is missed, do not administer cipaglucosidase alfa-atga; reschedule treatment at least 24 hours after miglustat was last taken. If both miglustat and cipaglucosidase alfa-atga doses are missed, re-start treatment as soon as possible.

Dosage

Adults

Pompe Disease

Oral

Dosage based on actual body weight.

For patients weighing ≥40 kg to <50 kg, 195 mg every other week.

For patients weighing ≥50 kg, 260 mg every other week.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

Dosage adjustments recommended in moderate (Cl_cr 30—59 mL/minute) and severe (Cl_cr 15—29 mL/minute) renal impairment (see Table 1). No dosage adjustments recommended in mild renal impairment (Cl_cr 60—89 mL/minute).

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Miglustat (Pompe Disease)

Contraindications

• Pregnancy.

Warnings/Precautions

Embyro-fetal Toxicity

Based on findings from animal reproduction studies, miglustat with cipaglucosidase alfa-atga may cause embryo-fetal harm when administered to a pregnant female and is contraindicated.

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

Risks Associated with Cipaglucosidase Alfa-atga

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

Specific Populations

Pregnancy

Insufficient evidence in pregnant women to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Lactation

No data on presence of miglustat in human milk, effects on breast-fed child, or effects on milk production. Based on animal studies, use of miglustat in combination with cipaglucosidase alfa-atga may lead to serious adverse reactions in breast-fed infants.

Advise females that breastfeeding is not recommended while receiving treatment with miglustat and cipaglucosidase alfa-atga.

Females and Males of Reproductive Potential

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

Advise females of reproductive potential to use effective contraception during treatment and for at least 60 days after last dose.

Based on animal studies, may impair male and female fertility.

Pediatric Use

Safety and effectiveness in pediatric patients not established.

Geriatric Use

Clinical studies with miglustat did not include sufficient numbers of patientts ≥65 years of age to determine whether they respond differently than younger patients.

Hepatic Impairment

Safety and effectiveness in patients with hepatic impairment not established.

Renal Impairment

Plasma concentrations increase in patients with renal impairment. No dosage adjustment recommended in mild (Cl_cr 60—89 mL/minute) renal impairment. Dosage should be reduced in moderate (Cl_cr30—59 mL/minute) or severe (Cl_cr 15—29 mL/minute) renal impairment.

Pharmacokinetics not established in end stage renal disease.

Common Adverse Effects

Most common adverse effects (≥5%): headache, diarrhea, fatigue, nausea, abdominal pain, pyrexia.

Drug Interactions

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Miglustat is not a known substrate or inhibitor of CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, or CYP4A11.

Interaction of miglustat with other microsomal enzymes not known.

Drugs Affecting or Affected by Transport Systems

Miglustat is not an inhibitor or a substrate of P-glycoprotein.

Interaction of miglustat with other transport systems not known.

Miglustat (Pompe Disease) Pharmacokinetics

Absorption

Bioavailability

Maximum concentration (C_max) and AUC increase proportionally over dose range of 130 mg to 260 mg.

Onset

Mean time to reach maximum concentration (T_max): 2—3 hours

Effect of Food

Co-administration with food is predicted to result in delayed absorption and decreased C_max in healthy subjects.

Elimination

Half-life

Approximately 6 hours.

Special Populations

AUC_0-24hr increased by 21%, 32%, and 41% in mild (Cl_cr 60—89 mL/minute), moderate (Cl_cr 30—59 mL/minute), and severe (Cl_cr 15—29 mL/minute) renal impairment, respectively, compared to normal renal function. Effect of end stage renal disease on pharmacokinetics not known.

No clinically significant differences in pharmacokinetics observed based on age (18—74 years) and sex.

Effect of hepatic impairment on pharmacokinetics not known.

Stability

Storage

Oral

Capsules

Store at 20-25°C; excursions permitted between 15-30°C. Store in original container to protect from light.

Actions

• N-alkylated iminosugar, synthetic analog of D-glucose; classified as an enzyme stabilizer.

• Used in combination with cipaglucosidase alfa (a lysosomal glycogen-specific recombinant human α-glucosidase); miglustat binds with, stabilizes, and reduces inactivation of cipaglucosidase alfa.

• Bound miglustat is dissociated from cipaglucosidase alfa after it is internalized and transported into lysosomes.

• Has no pharmacological activity in cleaving glycogen.

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information).

• Advise the patient and/or caregiver that miglustat must be administered in combination with cipaglucosidase alfa-atga. Advise patient and/or caregiver that miglustat should be started 2 weeks after the last dose of enzyme replacement therapy.

• Advise the patient and/or caregiver that miglustat should be taken approximately 1 hour before IV administration of cipaglucosidase alfa-atga. Advise the patient and/or caregiver that miglustat should be swallowed whole with an unsweetened beverage (e.g., water, tea or coffee with no cream, sugar, or sweeteners). Advise patient and/or caregiver that they should not consume other beverages or food for at least 2 hours prior to and 2 hours after administration of miglustat.

• Advise patient and/or caregiver that if a dose of miglustat is missed, cipaglucosidase alfa-atga should not be administered and treatment should be rescheduled at least 24 hours after miglustat was last taken. If both miglustat and cipaglucosidase alfa-atga doses are missed, re-start treatment as soon as possible.

• Advise patient that miglustat in combination with cipaglucosidase alfa-atga may cause embryo-fetal harm when administered to a pregnant female. Advise females of reproductive potential to inform their clinician of a known or suspected pregnancy. Inform patient that their clinician will verify pregnancy status prior to initiating treatment with miglustat. Advise females of reproductive potential to use effective contraception during treatment with miglustat in combination with cipaglucosidase alfa-atga and for at least 60 days after the last dose.

• Advise males and females of reproductive potential that miglustat in combination with cipaglucosidase alfa-atga may impair fertility.

• Advise females that breastfeeding is not recommended while receiving treatment with miglustat and cipaglucosidase alfa-atga.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

• Refer to the prescribing information available from the manufacturer of cipaglucosidase alfa-atga for additional patient counseling information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

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