Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Galafold: 123 mg [contains fd&c blue #2 (indigotine)]
Pharmacology
Mechanism of Action
Migalastat is an oral pharmacological chaperone that stabilizes certain mutant variants of alpha-galactosidase to increase enzyme trafficking to lysosomes (Germain 2016). Migalastat reversibly binds to the active site of the alpha-galactosidase A (alpha-Gal A) protein (encoded by the galactosidase alpha gene, GLA), which is deficient in Fabry disease. Binding to the active site stabilizes alpha-Gal A allowing trafficking from the endoplasmic reticulum into the site of action, the lysosome.
Pharmacokinetics/Pharmacodynamics
Distribution
Vz/F: ~89 L (range: 77 to 133 L)
Metabolism
Dehydrogenated to 3 O-glucuronide conjugated minor metabolites (M1 to M3). UDPGT is a minor elimination pathway.
Excretion
Urine (~77%; 80% as unchanged drug); feces (~20% as unchanged drug)
Time to Peak
~3 hours
Half-Life Elimination
~4 hours
Protein Binding
None detected
Use in Specific Populations
Special Populations: Renal Function Impairment
Systemic exposure is increased (significantly) in subjects with eGFR <30 mL/minute/1.73 m2
Use: Labeled Indications
Fabry disease: Treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to migalastat or any component of the formulation or container
Dosage and Administration
Dosing: Adult
Note: Determine presence of an amenable galactosidase alpha (GLA) gene variant prior to therapy.
Fabry disease (with amenable GLA gene variant): Oral: 123 mg once every other day (do not administer on 2 consecutive days).
Missed doses: If a dose is missed entirely for the day, administer the missed dose only if it is within 12 hours of the normal time that the dose should have been administered. If more than 12 hours have passed, resume at the next planned dosing day and time, according to the every-other-day dosing schedule. Do not administer on 2 consecutive days.
Dosing: Geriatric
Refer to adult dosing.
Administration
Oral: Administer every other day at the same time of day. Do not administer on 2 consecutive days. Administer on an empty stomach; do not consume food at least 2 hours before or 2 hours after the migalastat dose (for a minimum of 4 hours of fasting), although clear liquids may be consumed during the 4-hour fast. Swallow capsule whole; do not cut, crush, or chew.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%:
Central nervous system: Headache (35%)
Gastrointestinal: Nausea (12%)
Genitourinary: Urinary tract infection (15%)
Respiratory: Nasopharyngitis (18%)
Miscellaneous: Fever (12%)
1% to 10%:
Gastrointestinal: Abdominal pain (9%), diarrhea (9%)
Neuromuscular & skeletal: Back pain (9%)
Respiratory: Cough (9%), epistaxis (9%)
Warnings/Precautions
Disease-related concerns
- Renal impairment: Use is not recommended in patients with severe renal impairment (eGFR <30 mL/minute/1.73 m2) or with ESRD requiring dialysis.
Other warnings/precautions:
- Conversion: Migalastat 123 mg is equivalent to 150 mg of migalastat hydrochloride.
- Medication safety: Due to potential sound-alike/look-alike issues (migalastat may be confused with miglustat), use caution when selecting product for computerized order entry and for dispensing.
- Patient selection criteria: Select patients with confirmed Fabry disease for migalastat treatment if an amenable galactosidase alpha (GLA) variant is present. Migalastat is indicated for patients with an amenable GLA gene variant that is interpreted by a clinical geneticist as causing Fabry disease (pathogenic, likely pathogenic) in the patient's clinical context. Consultation with a clinical geneticist is strongly recommended in cases where clinical significance of the amenable GLA variant is uncertain or may be benign (not the cause of Fabry disease). For further information on amenable GLA variants, refer to the prescribing information or the manufacturer at 1-877-426-4287.
Monitoring Parameters
Determine presence of an amenable galactosidase alpha (GLA) gene variant (prior to therapy); monitor renal function (creatinine clearance).
Pregnancy
Pregnancy Considerations
Information related to use in pregnancy is limited.
Patient Education
What is this drug used for?
- It is used to treat Fabry disease.
Frequently reported side effects of this drug
- Headache
- Stuffy nose
- Sore throat
- Nausea
- Abdominal pain
- Back pain
- Cough
- Diarrhea
- Nosebleed
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
