The enzyme glucosylceramide synthase is inhibited by the drug miglustat (Zavesca, Yargesa). Patients with mild to severe type 1 Gaucher disease who cannot be treated with imiglucerase, an enzyme replacement therapy, are prescribed it.

Miglustat Uses:

• Gaucher disease:
  • Used to treat people with mild-to-moderate type 1 Gaucher disease if other treatment alternatives such as enzyme replacement therapy are not available (eg, due to allergy, hypersensitivity, or poor venous access)
• Off Label Use of Miglustat in Adults:
  • Type C Niemann-Pick disease

Miglustat (Zavesca, Yargesa) Dose in Adults:

Management of Type 1 Gaucher disease with the drug miglustat (Zavesca, Yargesa) dose:

• Take 100 mg by mouth three times a day.
• If side effects like shaking or diarrhea occur, the dose can be lowered to 100 mg once or twice a day.

Niemann-Pick Type C illness therapy with miglustat (Zavesca, Yargesa) dosage:

• Take 200 mg by mouth three times a day.

Miglustat (Zavesca, Yargesa) Dose in Children:

Niemann-Pick Type C illness therapy with miglustat (Zavesca, Yargesa) dosage

Note:

• It's recommended for patients with issues related to the brain, thinking, or mood (Patterson 2012).
• There's limited data on treating babies. Some babies treated with miglustat had muscle weakness, trouble swallowing, and feeding problems. The youngest baby given miglustat was 7 months old.
• Start with a low dose and increase if needed, especially if there's stomach upset or diarrhea. It might take 6-12 months of treatment before seeing benefits.

Dose based on Body Surface Area (BSA) for Kids under 12 years:

• BSA up to 0.47 m^2: 100 mg once a day
• BSA 0.47-0.73 m^2: 100 mg twice a day
• BSA 0.73-0.88 m^2: 100 mg three times a day
• BSA 0.88-1.25 m^2: 200 mg twice a day
• BSA over 1.25 m^2: 200 mg three times a day

For Kids 12 years and older:

• Take 200 mg three times a day.

Pregnancy Risk Factor C

• Tests on animals found problems related to pregnancy.
• Women with untreated type 1 Gaucher disease are more likely to have a miscarriage. They might also have an enlarged liver and spleen, and low platelet counts, which can cause complications during pregnancy.

Use of Miglustat while breastfeeding

• We don't know if miglustat gets into breast milk.
• Because the medicine might harm a breastfeeding baby, you have to decide: either stop breastfeeding or stop taking the drug. Consider how important the medicine is for the mother when making this choice.

Miglustat (Zavesca, Yargesa) Dose in Kidney Disease:

For Gaucher Disease:

• If kidney function is really good (CrCl >70): Usual dose, no changes needed.
• If kidney function is okay (CrCl 50-70): Take 100 mg two times a day.
• If kidney function is lower (CrCl 30-50): Take 100 mg once a day.
• If kidney function is quite low (CrCl <30): It's best not to use the medicine.

For Niemann-Pick Type C Disease (not the usual use, info from the Canadian guide):

• If kidney function is okay (CrCl 50-70): Take 200 mg two times a day.
• If kidney function is lower (CrCl 30-50): Take 100 mg two times a day.
• If kidney function is quite low (CrCl <30): It's best not to use the medicine.

Miglustat (Zavesca, Yargesa) Dose in Liver disease:

• The manufacturer hasn't given any dose changes for liver issues (they haven't studied it).
• But it's likely that no dose changes are needed because miglustat isn't broken down by the liver.

Common Side Effects of Miglustat (Zavesca, Yargesa):

• Endocrine & metabolic:
  • Weight loss
• Neuromuscular & skeletal:
  • Weakness
  • Tremor
  • Leg cramps
• Central nervous system:
  • Dizziness
  • Headache
• Ophthalmic:
  • Visual disturbance
• Gastrointestinal:
  • Flatulence
  • Diarrhea
  • Vomiting
  • Abdominal pain
  • Nausea

Less Common Side Effects of Miglustat (Zavesca, Yargesa):

• Central nervous system:
  • Unsteady gait
  • Memory issues
  • Paresthesia
  • Migraine
• Gastrointestinal:
  • Constipation
  • Dyspepsia
  • Xerostomia
  • Abdominal distension
  • Epigastric pain
  • Anorexia
  • Bloating
• Neuromuscular & skeletal:
  • Back pain
• Endocrine & metabolic:
  • Menstrual disease
• Hematologic & oncologic:
  • Thrombocytopenia

Contraindications to Miglustat (Zavesca, Yargesa):

• The manufacturer doesn't list any situations where the drug shouldn't be used.
• In Canada, the drug shouldn't be used by anyone who's allergic to miglustat or its ingredients, and women who are or might become pregnant.

Warnings and precautions

Diarrhea:

• Most people who take this drug get diarrhea, and many lose weight in the first year.
• The diarrhea usually gets better over time with continued use.
• To help with diarrhea:
  • Try changing your diet: eat fewer sugary foods and avoid lactose and other carbs.
  • Take miglustat between meals.
  • Consider anti-diarrhea medicine.
• If diarrhea happens while on the drug, stay away from high-carb foods.

Peripheral neuropathy:

• Some people taking this drug have nerve problems.
• Regular nerve checks are needed.
• If someone starts feeling symptoms like numbness or tingling, think about whether the medicine's benefits are worth the risks.
• If these nerve problems get bad, stopping the medicine might be needed.

Platelet counts decreased:

• Some people with type 1 Gaucher disease who switched from another treatment to miglustat have seen a small drop in their platelet numbers. But they didn't bleed because of this.
• If on miglustat, it's important to check platelet levels regularly.

Tremor:

• Starting miglustat can cause new shakiness (tremor) or make existing shakiness worse.
• This shakiness usually starts within the first month of using the drug.
• It might go away on its own in 1-3 months or get better if you take a lower dose.
• If reducing the dose doesn't help quickly, stopping the medicine might be needed.

Renal impairment

• Be careful when using miglustat in people with kidney issues.
• Those with kidney problems might need a different dose.
• If someone has really bad kidney problems, they shouldn't take miglustat.

Monitoring parameters:

Neurologic Checks

• Start with a check before treatment.
• Repeat every 6 months.

Adverse Effects

• Keep an eye out for any bad reactions or side effects.

Weight Monitoring

• Track weight to see any changes.

Platelet Count

• Check the number of platelets in the blood.

Kidney (Renal) Health

• Monitor how well the kidneys are working.

How to administer Miglustat (Zavesca, Yargesa)?

Taking Miglustat Capsules

• Can be taken with or without food.
• Taking it between meals might help reduce diarrhea.
• Always take the capsules at the same time each day, spaced evenly.

If Can't Swallow Capsules

• If someone can't swallow the capsule, they can use the inside powder.
• Mix the powder into a drink right before using it. Don't keep it for later.
• It's okay to add sweeteners; they shouldn't cause any problems.

Mechanism of action of Miglustat (Zavesca, Yargesa):

• Miglustat blocks an enzyme that makes glycosphingolipids.
• By doing this, it slows down the creation of a specific glycosphingolipid called glucosylceramide.
• In type 1 Gaucher disease, too much glucosylceramide piles up, leading to problems specific to this condition.

Distribution:

• It spreads out in the body, occupying 83-105 liters of space.

Protein Binding:

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

Metabolism:

• Our body doesn't seem to change it.

Bioavailability:

• 97% of the drug is usable by the body once taken.

Half-life:

• It takes 6-7 hours for half of the drug to leave the body.

Peak Time:

• It reaches its highest level in the blood in about 2-2.5 hours.

Excretion:

• It leaves the body through the urine, unchanged.

International Brand Names of Miglustat:

• Zavesca
• Brazaves
• Yargesa

Miglustat Brand Names in Pakistan:

Not Available.