Class: Other Miscellaneous Therapeutic Agents
Chemical Name: (2R,3S,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol
Molecular Formula: C6H13NO4
CAS Number: 108147-54-2
Medically reviewed by Drugs.com. Last updated on Aug 24, 2020.
Migalastat is a pharmacological chaperone that 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.1
Uses for Migalastat
Migalastat hydrochloride has the following uses:
Migalastat hydrochloride is an alpha-galactosidase A (alpha-Gal A) pharmacological chaperone indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.1
This indication is approved under accelerated approval based on reduction in kidney interstitial capillary cell globotriaosylceramide (KIC GL-3) substrate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Migalastat Dosage and Administration
Migalastat hydrochloride is available in the following dosage form(s) and strength(s):
Capsules: 123 mg migalastat.1
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage & Administration
Select adults with confirmed Fabry disease who have an amenable GLA variant for treatment with migalastat hydrochloride. 1
Treatment is indicated for patients with an amenable GLA variant that is interpreted by a clinical genetics professional as causing Fabry disease (pathogenic, likely pathogenic) in the clinical context of the patient. Consultation with a clinical genetics professional is strongly recommended in cases where the amenable GLA variant is of uncertain clinical significance (VUS, variant of uncertain significance) or may be benign (not causing Fabry disease).1
Take on an empty stomach. Do not consume food at least 2 hours before and 2 hours after taking migalastat hydrochloride to give a minimum 4 hours fast.1
Do not take migalastat hydrochloride on 2 consecutive days.1
If a dose is missed entirely for the day, take the missed dose only if it is within 12 hours of the normal time that the dose should have been taken. If more than 12 hours have passed, resume taking migalastat hydrochloride at the next planned dosing day and time and according to the every-other-day dosing schedule.1
Swallow capsules whole; do not cut, crush, or chew.1
Cautions for Migalastat
Risk Summary: There were three pregnant women with Fabry disease exposed to migalastat hydrochloride in clinical trials. As such, the available data are not sufficient to assess drug associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed. 1
The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1
Animal Data: No adverse developmental effects were observed with oral administration of migalastat to pregnant rats and rabbits during organogenesis at doses up to 26 and 54 times, respectively, the recommended dose based on AUC. No effects on post-natal development were observed following oral administration of up to 500 mg/kg migalastat twice daily to pregnant rats (16 times the recommended dose based on AUC) during organogenesis and through lactation.1
Risk Summary: There are no human data available on the presence of migalastat in human milk, the effects on the breastfed infant, or the effects on milk production. Migalastat is present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for migalastat hydrochloride and any potential adverse effects on the breastfed child from migalastat hydrochloride or from the underlying maternal condition. 1
Animal Data: Migalastat concentrations in milk from rats following oral administration of up to 500 mg/kg twice daily (approximately 16 times the recommended human dose based on AUC) was approximately 2.5 times higher than levels in the rat maternal plasma at 4 hours post-dose. The concentration of migalastat in plasma from pups was approximately 11 times lower than the maternal plasma concentrations at 1 hour post-dose.1
Females and Males of Reproductive Potential
The effects of migalastat hydrochloride on fertility in humans have not been studied. Transient and fully reversible infertility in male rats was associated with migalastat treatment at a systemic exposure (AUC) equivalent to the human exposure at the recommended dose. Complete reversibility was seen at 4 weeks after the termination of treatment. Migalastat did not affect fertility in female rats. 1
The safety and effectiveness of migalastat hydrochloride have not been established in pediatric patients.1
Clinical trials of migalastat hydrochloride did not include a sufficient number of patients 65 years and older to determine whether they respond differently from younger patients. 1
Migalastat is substantially excreted by the kidneys. Systemic exposure was significantly increased in subjects with severe renal impairment (eGFR less than 30 mL/min/1.73 m2). Migalastat hydrochloride has not been studied in patients with Fabry disease who have an eGFR less than 30 mL/min/1.73 m2. Migalastat hydrochloride is not recommended for use in patients with severe renal impairment or end-stage renal disease requiring dialysis. No dosage adjustment is required in patients with mild to moderate renal impairment (eGFR at least 30 mL/min/1.73 m2 and above). 1
Common Adverse Effects
Most common adverse drug reactions ≥10% are: headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia.1
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.
Mechanism of Action
Migalastat is a pharmacological chaperone that 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. This binding stabilizes alpha-Gal A allowing its trafficking from the endoplasmic reticulum into the lysosome where it exerts its action. In the lysosome, at a lower pH and at a higher concentration of relevant substrates, migalastat dissociates from alpha-Gal A allowing it to break down the glycosphingolipids globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb 3). Certain GLA variants (mutations) causing Fabry disease result in the production of abnormally folded and less stable forms of the alpha-Gal A protein which, however, retain enzymatic activity. Those GLA variants, referred to as amenable variants, produce alpha-Gal A proteins that may be stabilized by migalastat thereby restoring their trafficking to lysosomes and their intralysosomal activity. 1 For a list of GLA variants which are amenable to treatment with migalastat hydrochloride based on an in vitro assay, consult the manufacturer's labeling.
Advice to Patients
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling. 1
Take migalastat hydrochloride once every other day at the same time of day.1
Take migalastat hydrochloride on an empty stomach. Do not consume food at least 2 hours before and 2 hours after taking migalastat hydrochloride to give a minimum 4 hours fast. Clear liquids can be consumed during this 4-hour period.1
Do not take migalastat hydrochloride on 2 consecutive days.1
If a dose is missed entirely for the day, take the missed dose only if it is within 12 hours of the normal time that the dose should have been taken. If more than 12 hours have passed, resume taking migalastat hydrochloride at the next planned dosing day and time, according to the every-other-day dosing schedule.1
Swallow capsules whole. Do not cut, crush, or chew.1
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.
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.
123 mg (of migalastat)
Amicus Therapeutics U.S. Inc.
AHFS Drug Information. © Copyright 2021, Selected Revisions September 3, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Amicus Therapeutics U.S., Inc. Galafold (migalastat hydrochloride) ORAL prescribing information. 2018 Aug. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66dbd928-0f1c-48b1-a832-54e4abd9f1db
Frequently Asked Questions
More about migalastat
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- Drug class: miscellaneous metabolic agents
Other brands: Galafold