Galafold (migalastat HCl)
Metabolic Disease Enzyme Replacement, Fabry's Disease Oral Capsule
Last reviewed · Source: First Databank (FDB) drug data
Overview
Migalastat hydrochloride is an alpha-galactosidase A (alpha-Gal A) pharmacological chaperone.
Migalastat hydrochloride 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-Gb3).
Certain GLA variants (mutations) causing Fabry disease result in the production of abnormally folded and less stable forms of the alpha-Gal A protein; however, these forms 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. For a list of GLA variants which are amenable to treatment with migalastat based on an in vitro assay, consult the manufacturer's labeling.
The bioavailability of migalastat is approximately 75%. The time to peak plasma concentration is approximately 3 hours. Administration of migalastat 1 hour before a high fat meal (850 calories; 56% from fat) or light meal (507 calories; 30% from fat), or 1 hour after a light meal, reduced the mean migalastat AUC0-infinityby 37% and peak plasma concentration by 15% compared to the fasting state.
Migalastat does not bind to plasma proteins to a significant extent. Migalastat is a substrate for uridine diphosphate glucuronosyltransferase (UDPGT). Approximately 77% of radioactive migalastat was recovered in urine and 20% was recovered in feces with a total recovery of 98%.
In urine, unchanged migalastat accounted for 80% of radioactivity, which equates to 62% of the administered dose. In feces, unchanged migalastat was the only drug-related component. The half-life of migalastat is approximately 4 hours.
USES: This medication is used for long-term treatment in people with a certain inherited disease (Fabry disease). In Fabry disease, a certain enzyme in your body (alpha-galactosidase) does not work the way it should. This leads to a buildup of a certain fatty substance in your kidneys, heart, and other organs.
Migalastat works by helping alpha-galactosidase work better so it can remove the fatty substance. Treatment can decrease some symptoms caused by Fabry disease, such as abdominal cramps, diarrhea, burning pain in the hands and feet, heat intolerance, skin rash, kidney/heart disease, or stroke.
Generic name: migalastat HCl
Pronunciation: (mi-GAL-a-stat)
Drug class: Metabolic Disease Enzyme Replacement, Fabry's Disease
Therapeutic class: Metabolic Modifiers
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Galafold
Indications
The following indications are listed for Galafold:
- Fabry Disease
Also known as: Alpha-Galactosidase A Deficiency, Angiokeratoma Corporis Diffusum, Angiokeratoma Corporis Diffusum Universale, Ceramide Trihexosidase Deficiency, Diffuse Angiokeratoma, Fabry's Disease, Glycolipid Lipidosis.
Dosing
Dosage of migalastat hydrochloride is expressed in terms of migalastat.
The recommended dosage of migalastat 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 is 123 mg orally once every other day.
Administer migalastat hydrochloride orally once every other day at the same time of day, on an empty stomach. The drug is commercially available as an oral capsule.
Do not consume food or caffeine at least 2 hours before and after taking migalastat to give a minimum 4 hours fast. Water (plain, flavored, or sweetened), fruit juices without pulp, and caffeine-free carbonated beverages can be consumed during the fasting period. Do not take migalastat on 2 consecutive days. 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 at the next planned dosing day and time and according to the every-other-day dosing schedule. Swallow capsules whole; do not cut, crush, or chew.
Store in the original packaging to protect from moisture at room temperature (20-25degreesC). Excursions are permitted between 15-30degreesC.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Galafold 123 Mg Capsule | Maintenance | Take 1 capsule (123 mg) by oral route every other day at the same time each day. |
No dosing information is available for this tab.
Drug interactions
Migalastat hydrochloride is not a known inhibitor or inducer of cytochrome P-450 (CYP) enzymes such as CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5 and is not an inhibitor of breast cancer resistance protein (BCRP), multi-drug resistance (MDR) 1, P-glycoprotein (P-gp), bile salt export pump (BSEP) human efflux transporters, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, organic anion transporter 1 (OAT1), OAT3, organic cation transporter 1 (OCT1), OCT2, multidrug and toxin extrusion protein 1 (MATE1), or MATE2-K human uptake transporters. Migalastat is not a substrate of P-gp, BCRP, MDR1 or MATE1, MATE2-K, OAT1, OAT3, or OCT2. Migalastat showed low affinity for sodium/glucose cotransporter 1 (SGLT1) as a substrate or an inhibitor and has no activity for SGLT2.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
Moderate Interaction: Assess the risk to the patient and take action as needed.
Migalastat/Caffeine-Containing Products
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: The mechanism of this interaction is unknown.
CLINICAL EFFECTS: Concurrent use of a caffeine-containing product may result in decreased levels and effectiveness of migalastat.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Avoid coadministration of migalastat with caffeine-containing products. Do not administer caffeine-containing products within 2 hours before and 2 hours after taking migalastat.(1)
DISCUSSION: Coadministration of migalastat with caffeine 190 mg decreased the migalastat maximum concentration (Cmax) by 60% and area-under-curve (AUC) by 55%.(1)
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
- No disease contraindications
Adverse reactions
The most common adverse effects of migalastat reported in >=10% of patients are headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia.
Rare or Very Rare
- Hepatocellular damage
- Hypertension
More Frequent
- Fever
- Headache disorder
- Nausea
- Pharyngitis
- Urinary tract infection
Less Frequent
- Acute abdominal pain
- Back pain
- Constipation
- Cough
- Depression
- Diarrhea
- Dizziness
- Dyspepsia
- Dyspnea
- Epistaxis
- Fatigue
- Fecal urgency
- Hypoesthesia
- Muscle spasm
- Myalgia
- Pain
- Palpitations
- Paresthesia
- Proteinuria
- Pruritus of skin
- Skin rash
- Vertigo
- Weight gain
- Xerostomia
Rare or Very Rare
- Anorexia
- Drowsy
- Erythema
- Hypercholesterolemia
- Memory impairment
- Ocular itching
- Polyuria
- Reduced visual acuity
- Vomiting
Precautions
No enhanced messaging available.
Safety and effectiveness of migalastat have not been established in pediatric patients.
Available data are not sufficient to assess drug associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 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.
An ongoing study collects data on pregnant women with Fabry disease, either exposed or unexposed to migalastat. Healthcare providers are encouraged to register patients or obtain additional information by contacting the Pregnancy Coordinating Center at 1-888-239-0758, emailing fabrypregnancy@ubc.com, or visiting https://fabrypregnancyregistry.com/.
There are no human data available on the presence of migalastat hydrochloride 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 and any potential adverse effects on the breastfed child from migalastat or from the underlying maternal condition.
An ongoing study collects data on the effects of migalastat on lactation for women with Fabry disease and their neonates and infants up to 1 year of age who are exposed through breast milk. Healthcare providers are encouraged to register patients or obtain additional information by contacting the Pregnancy Coordinating Center at 1-888-239-0758, emailing fabrypregnancy@ubc.com, or visiting https://fabrypregnancyregistry.com/.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Experience in patients >=65 years of age is insufficient to determine whether they respond differently to migalastat than younger patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Fabry disease | ||
| E75.21 | ICD10CM | Fabry (-anderson) disease |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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