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):

• 123 mg orally once on alternate days.
• Avoid administering the drug on 2 consecutive days.

• Missed doses:

  • In case, a dose is missed, it should only be administered if less than 12 hours have passed since the time of the scheduled dose.
  • If more than twelve hours have passed, the drug should be resumed at the next scheduled time as per the alternate-day dosing schedule.
  • Administering the drug on two consecutive days should be avoided.

Use in children:

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

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

• Its use in pregnancy is not known.

Migalastat use during breastfeeding:

• It is unknown if the drug will be excreted into breast milk.
• Manufacturers recommend that you weigh the benefits and risks of drug therapy for the nursing mother and the infant.

Galafold (migalastat) Dose in Kidney Disease:

• eGFR ≥30 mL/minute/1.73 m²:
  • No adjustment is necessary.
• eGFR <30 mL/minute/1.73 m²:
  • It has not been studied in patients with a CrCl of less than 30 ml/min and should be avoided.
• ESRD requiring dialysis:
  • It has not been studied in patients with ESRD and should be avoided.

Galafold (migalastat) Dose in Liver disease:

It has not been studied in patients with liver disease. Hence, no adjustments in the dose have been recommended.

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 manufacturer's label does not contain any contraindications. Contraindications according to the Canadian labeling

• Hypersensitivity to migalastat, any component of the formulation, or container

Caution and alert

• Renal impairment

  • People with extreme renal disease or ESRD (eGFR 30 mL/minute/1.73 m2) should avoid it

Monitoring parameters:

Before initiating the treatment, determine the presence of an amenable mutant galactosidase alpha (GLA) gene variant. Monitor kidney functions (creatinine clearance).

How to administer Migalastat (Galafold)?

• It is administered orally on alternate days at the same time of the day.
• Administering the drugs on two consecutive days should be avoided.
• It is preferably taken on an empty stomach as food reduces its bioavailability.
• Food should not be taken two hours before and two hours after the drug is administered (a minimum of four hours of fasting is recommended).
• Clear liquids may be consumed during the four hours fast. The capsules may be swallowed whole without cutting, crushing, or chewing it.

Mechanism of action of Galafold (Migalastat):

• Migalastat, an oral medicine, acts as a chaperone.
• It binds to the active site for the mutant forms of the enzyme alpha-galactosidase in a reversible manner, allowing it to be transported from the endoplasmic retina into the lysosomes, where it acts.

Half-life elimination:

• About 4 hours

Protein binding:

• None detected

Metabolism:

• Dehydrogenated to 3 O-glucuronide conjugated minor metabolites (M1 to M3).
• UDPGT is a minor elimination pathway.

Excretion:

• Urine (About 80% is excreted as an unchanged drug)
• feces (About 20% is excreted as unchanged drug)

Bioavailability:

• The bioavailability of the drug is about 75%;
• It is reduced if taken an hour before a high-fat meal (850 calories; 56% from fat) or
• if it is administered one hour before or after a light meal (507 calories; 30% from fat)

Time to peak:

• About 3 hours

International Brands of Migalastat:

• Galafold

Migalastat Brand Names in Pakistan:

No Brands Available in Pakistan.