Migalastat

Generic name: migalastat
Brand name: Galafold
Dosage form: oral capsule (123 mg)
Drug class: Miscellaneous metabolic agents

Medically reviewed by A Ras MD.

What is migalastat used for?

Migalastat is a prescription medicine that is used to treat Fabry’s disease.

Description

Migalastat, an alpha-galactosidase A (alpha-Gal A) pharmacological chaperone, is a low molecular weight iminosugar and an analogue of the terminal galactose of globotriaosylceramide (GL-3).

Migalastat is present in the form of a hydrochloride salt in GALAFOLD. The chemical name for migalastat hydrochloride is (+)-(2R,3S,4R,5S)-2-(hydroxymethyl) piperidine-3,4,5-triol hydrochloride. Its molecular formula is C6H13NO4•HCl, molecular mass is 199.63 g/mol, and its chemical structure is depicted below.

Migalastat hydrochloride is a white to almost white crystalline solid. It is freely soluble in aqueous media within the pH range of 1.2 to 7.5.

GALAFOLD (migalastat) capsules for oral administration contain 123 mg of migalastat (equivalent to 150 mg migalastat hydrochloride) as a white to pale brown powder and are supplied in a size “2” hard gelatin capsule with an opaque blue cap and an opaque white body imprinted with “A1001” in black ink. The inactive ingredients are magnesium stearate and pregelatinized starch. Capsule shells consist of gelatin, indigotine – FD&C Blue 2, and titanium dioxide. The black ink consists of black iron oxide, potassium hydroxide, and shellac.

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-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 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.

In Vitro Amenability Assay

In an in vitro assay (HEK-293 assay), Human Embryonic Kidney (HEK-293) cell lines were transfected with specific GLA variants (mutations) which produced mutant alpha-Gal A proteins. In the transfected cells, amenability of the GLA variants was assessed after a 5-day incubation with 10 micromol/L migalastat. A GLA variant was categorized as amenable if the resultant mutant alpha-Gal A activity (measured in the cell lysates) met two criteria: 1) it showed a relative increase of at least 20% compared to the pre-treatment alpha-Gal A activity, and 2) it showed an absolute increase of at least 3% of the wild-type (normal) alpha-Gal A activity.

The in vitro assay did not evaluate trafficking of the mutant alpha-Gal A proteins into the lysosome or the dissociation of migalastat from the mutant alpha-Gal A proteins within the lysosome. Also, the in vitro assay did not test whether a GLA variant causes Fabry disease or not.

The GLA variants which are amenable to treatment with GALAFOLD, based on the in vitro assay data, are shown in. Inclusion of GLA variants in this table does not reflect interpretation of their clinical significance in Fabry disease. Whether a certain amenable GLA variant in a patient with Fabry disease is disease-causing or not should be determined by the prescribing physician (in consultation with a clinical genetics professional, if needed) prior to treatment initiation. 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).

Before taking migalastat, tell your doctor:

If you are allergic to migalastat; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
If you have kidney disease.

This is not a list of all drugs or health problems that interact with migalastat.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take migalastat with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take migalastat?

Tell all of your health care providers that you take migalastat. This includes your doctors, nurses, pharmacists, and dentists.
Tell your doctor if you are pregnant, plan on getting pregnant, or are breast-feeding. You will need to talk about the benefits and risks to you and the baby.

How is migalastat best taken?

Use migalastat as ordered by your doctor. Read all information given to you. Follow all instructions closely.

Take on an empty stomach. Do not eat for at least 2 hours before and 2 hours after you take migalastat. You may drink clear liquids during this time.
Swallow whole. Do not chew, break, or crush.
This medicine is not taken every day. Be sure you know how to take it. Talk with your doctor if you have questions.
Take migalastat at the same time of day.

What do I do if I miss a dose?

Take a missed dose as soon as you think about it.
If it has been 12 hours or more since the missed dose, skip the missed dose and go back to your normal time.
Do not take migalastat 2 days in a row.

What are the side effects of migalastat that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.

What are some other side effects of migalastat?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

Headache.
Nose or throat irritation.
Upset stomach.
Mild fever.
Stomach pain or diarrhea.
Back pain.
Cough.
Nosebleed.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out migalastat?

Store in the original container at room temperature.
Store in a dry place. Do not store in a bathroom.
Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.