Migalastat is a medication used for the treatment of Fabry disease in individuals with certain types of gene mutations. Fabry disease is a rare genetic disorder caused by a deficiency of the enzyme alpha-galactosidase A, leading to a buildup of a specific type of fat called globotriaosylceramide (GL-3) in the body's cells. This accumulation can cause damage to various organs, including the skin, eyes, kidneys, heart, and nervous system.

Galafold (migalastat) is an FDA-labeled "Orphan Drug" that has been developed by Amicus Therapeutics for the treatment of the rare multisystemic disease, Fabry Disease.

Migalastat (Gallafold) Uses:

• Fabry disease:
  • Based on results from in vitro assays, it is recommended for the treatment of adult patients with a definitive diagnosis of Fabry disease and an amenable mutant variation of the galactosidase alpha gene (GLA).

Migalastat Dose in Adults:

Note: Before initiating the treatment, determine the presence of an amenable mutant variant of the galactosidase alpha (GLA) gene.

Galafold (migalastat) dose in the treatment of Fabry disease (with amenable GLA gene variant):

• Take one 123 mg pill of Migalastat by mouth every two days.
• So, if you take it on Monday, the next dose would be on Wednesday.
• Never take it two days in a row.

If you forget a dose:

• If you miss your pill, and it's been less than 12 hours since you were supposed to take it, go ahead and take the missed dose.
• But if more than 12 hours have passed, skip that dose and just take your next one as scheduled. Again, never take it on back-to-back days.

Use in children:

The safety and efficacy of the drug in children have not been established.

Galafold (migalastat) Pregnancy Risk Category: N (Not assigned)

• We don't have a lot of information about how Migalastat affects pregnancy.

Migalastat use during breastfeeding:

• We're not sure if migalastat gets into breast milk.
• If you're thinking of breastfeeding while taking it, weigh the possible risks to the baby against the benefits of breastfeeding and the medicine's benefits for you.

Galafold (migalastat) Dose in Kidney Disease:

• If your kidney function is good (eGFR ≥30 mL/minute/1.73 m), you don't need to change the dosage of migalastat.
• If your kidney function is not so good (eGFR <30 mL/minute/1.73 m) or if you need dialysis because your kidneys have failed, it's not recommended to use migalastat because there hasn't been enough study to know if it's safe in these situations.

Galafold (migalastat) Dose in Liver disease:

• For people with liver problems, the maker of migalastat hasn't given any special dose instructions because they haven't studied it in such cases.

Side Effects of Migalastat (Galafold):

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Nausea
• Genitourinary:
  • Urinary tract infection
• Respiratory:
  • Nasopharyngitis
• Miscellaneous:
  • Fever

Less Common Side Effects of Migalastat (Galafold):

• Gastrointestinal:
  • Abdominal pain
  • Diarrhea
• Neuromuscular & skeletal:
  • Back pain
• Respiratory:
  • Cough
  • Epistaxis

Contraindications to Migalastat (Galafold):

• The maker of migalastat doesn't list any reasons not to use it in their U.S. instructions.
• But in Canada, if you're allergic to migalastat or anything else in the pill or its container, you shouldn't take it.

Caution and alert

Renal impairment

• If you have serious kidney problems (eGFR <30 mL/minute/1.73 m) or if you're on dialysis because your kidneys have failed, it's not recommended to use migalastat.

Monitoring parameters:

Before Starting Treatment:

• Check if the patient has the right type of GLA gene change that migalastat can help with.

Regular Checks:

• Keep an eye on kidney health by measuring creatinine clearance.

How to administer Migalastat (Galafold)?

When:

• Take it every two days, always at the same time. Don't take it two days in a row.

Food:

• Don't eat for 2 hours before and 2 hours after taking the pill.
• That's a total of 4 hours without food.
• But, you can have clear drinks during this time.

Taking the Pill:

• Swallow the capsule as it is. Don't cut, crush, or chew it.

Mechanism of action of Galafold (Migalastat):

• Migalastat is a medication that works like a helper for a specific enzyme called alpha-galactosidase A (alpha-Gal A).
• In people with Fabry disease, this enzyme doesn't work correctly because of a genetic issue.
• Migalastat helps by sticking to the active part of this enzyme.
• This makes the enzyme more stable and helps it move from where it's made in the cell (endoplasmic reticulum) to where it needs to work (lysosome).
• This process is essential for treating Fabry disease (Germain 2016).

Distribution:

• Once in the body, it spreads out in an average space of about 89 liters (though this can range from 77 to 133 liters).

Protein Binding:

• It doesn't stick to proteins in the blood.

Metabolism:

• The body slightly changes migalastat, creating minor versions (called M1 to M3).
• A tiny part gets processed through a pathway called UDPGT.

How well it's absorbed:

• About 75% of migalastat is used by the body.
• However, if taken 1 hour before a big, fatty meal or 1 hour before or after a light meal, the body doesn't use it as effectively.

How long it stays in the body:

• It lasts about 4 hours (that's the half-life).

Peak level in blood:

• It reaches its highest level in the blood about 3 hours after taking it.

Getting rid of it:

• Around 77% leaves the body through urine (and 80% of that is still as migalastat without any change).
• About 20% leaves through feces as the unchanged drug.

International Brands of Migalastat:

• Galafold

Migalastat Brand Names in Pakistan:

Not Available.