Miglustat, Hydrochloride

Miglustat, Hydrochloride - General Information

Miglustat, Hydrochloride is a drug used to treat Gaucher disease.
It inhibits the enzyme glucosylceramide synthase, an essential enzyme for the synthesis of most glycosphingolipids.
It is only used for patients who cannot be treated with enzyme replacement therapy with imiglucerase.
It is marketed under the trade name Zavesca.
It has also been investigated for use in treating Niemann-Pick disease.


Pharmacology of Miglustat, Hydrochloride

Miglustat, Hydrochloride is an N-alkylated imino sugar, a synthetic analogue of D-glucose. Miglustat, Hydrochloride is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for the first step in the synthesis of most glycosphingolipids.


Miglustat, Hydrochloride for patients

ZAVESCA® (zah-VEHS-kah) (miglustat) 100 mg Capsules

Read the Patient information that comes with ZAVESCA® before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your condition or your treatment.

What is ZAVESCA®?

ZAVESCA® is a prescription medicine taken by mouth for adults with mild to moderate type 1 Gaucher disease. ZAVESCA® is used only in patients who cannot be treated with enzyme replacement therapy.

ZAVESCA® has not been studied in children under 18 years of age.

What is type 1 Gaucher disease?

Type 1 Gaucher disease is an inherited disease that you get from both your parents. People with type 1 Gaucher disease are missing an enzyme that breaks down a chemical in the body called glucosylceramide. Too much glycosylceramide causes liver and spleen enlargement, changes in the blood, and bone disease. ZAVESCA® may stop glucosylceramide from forming.

Who should not take ZAVESCA®?

Do not take ZAVESCA® if you are allergic to any of its ingredients. The active ingredient is miglustat. See the end of this leaflet for a complete list of ingredients.

Tell your doctor before taking ZAVESCA®:

· If you are pregnant or planning to become pregnant. ZAVESCA® may harm your baby. You should use effective birth control while taking ZAVESCA®.

ZAVESCA® may also harm a man's sperm. All men should use effective birth control during treatment with ZAVESCA® and for 3 months after stopping ZAVESCA®. Do not use ZAVESCA® if you plan to become pregnant, or if your partner can become pregnant.

· If you are breast-feeding. It is not known if ZAVESCA® passes into your milk and if it can harm your baby. You should decide either to breast feed or take ZAVESCA®, but not both.

· If you have kidney problems

· About all of your medical conditions

· About all the medicines you take including prescription and non-prescription medicines, vitamins and other dietary supplements. Some medicines may affect ZAVESCA®. ZAVESCA® may affect other medicines.

How should I take ZAVESCA®?

· Take ZAVESCA® exactly as your doctor has prescribed. Check with your doctor or your pharmacist if you are not sure.

· Take ZAVESCA® at the same time or times each day. Your doctor will prescribe the dose that is right for you.

· Swallow ZAVESCA® capsules whole with water. ZAVESCA® may be taken with or without food

· If you miss a dose of ZAVESCA®, skip that dose. Take the next ZAVESCA® capsule at the usual time.

· If you take too much ZAVESCA® or overdose, call your doctor or local poison control center right away.

What should I avoid while taking ZAVESCA®?

Do not get pregnant while taking ZAVESCA®. Men and women should use effective birth control during treatment with ZAVESCA®. Men should keep using effective birth control for 3 months after treatment with ZAVESCA® stops.

What are the possible side effects of ZAVESCA®?

ZAVESCA® can cause problems affecting your nerves (neurologic problems):

· Hand tremors (shaky movements) or worsen a hand tremor that you already have. Tremors may begin within the first month of starting treatment. Sometimes the tremors may go away between 1 to 3 months with continued treatment. Sometimes a lower dose or stopping ZAVESCA® is needed to help the tremors go away. Call your doctor if you get hand tremors while taking ZAVESCA® or the hand tremors you already have get worse.

· Numbness and tingling in your hands, arms, legs, or feet (peripheral neuropathy). Call your doctor right away if you get numbness or tingling in your arms or legs.

Your doctor may test your nerves (neurological exam) before you start ZAVESCA® and may repeat this procedure at a later time.

Diarrhea is the most common side effect for people taking ZAVESCA®. Your doctor may give you another medicine (anti-diarrheal) to treat diarrhea if it is a problem for you, and may recommend changes to your diet. You may also lose weight when you start treatment with ZAVESCA®.

Some of the other side effects with ZAVESCA® are:

· Gas

· Stomach pain

· Headache

· Dizziness

· Nausea

· Constipation

· Muscle cramps

· Weakness

· Cramps

· Do not feel like eating

· Vision problems

· Low platelet count

Call your doctor if you get any side effect that bothers you. Sometimes the side effects will go away. Sometimes a lower dose of ZAVESCA® will help side effects go away.

These are not all the side effects with ZAVESCA®. For more information, ask your doctor or your pharmacist.

How do I store ZAVESCA®?

· Store ZAVESCA® between 20ºC to 25ºC (68ºF to 77ºF)

· Do not use ZAVESCA® that has expired.

· Keep ZAVESCA® and all medicines out of the reach of children.

General information about ZAVESCA®

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ZAVESCA® for a condition for which it was not prescribed. Do not give ZAVESCA® to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about ZAVESCA®. If you would like more information, talk with your doctor. You can ask you doctor or pharmacist for information about ZAVESCA® that is written for health professionals. For more information about ZAVESCA® contact:

Medical Information Department

Actelion Pharmaceuticals US Inc.,

601 Gateway Boulevard, Suite

100 South San Francisco, CA 94080 US.

Tel: toll-free (866) 228 3546

What are the ingredients of ZAVESCA®?

Active Ingredient: miglustat

Inactive Ingredients: sodium starch glycollate, povidone (K30) and magnesium stearate in the capsule; the capsule shell contains gelatin and titanium dioxide; the edible printing ink contains, black iron oxide, shellac, soya lecithin and antifoam.


Miglustat, Hydrochloride Interactions

While co-administration of ZAVESCA® appeared to increase the clearance of Cerezyme by 70%, these results are not conclusive because of the small number of subjects studied and because patients took variable doses of Cerezyme. Combination therapy with Cerezyme® (imiglucerase) and ZAVESCA® is not indicated.


Miglustat, Hydrochloride Contraindications

ZAVESCA® is contraindicated in patients who have demonstrated hypersensitivity to the active substance or any of the excipients.

Pregnancy Category X.

Miglustat may cause fetal harm when administered to a pregnant woman. In female rats given miglustat by oral gavage at doses of 20, 60, 180 mg/kg/day beginning 14 days before mating and continuing through gestation day 17 (organogenesis), decreased live births including complete litter loss and decreased fetal weight was observed in the mid and high-dose groups (systemic exposures ³2 times the human therapeutic systemic exposure based on body surface area comparison). In pregnant rats given miglustat by oral gavage at doses of 20, 60, 180 mg/kg/day from gestation day 6 through lactation (postpartum day 20), dystocia and delayed parturition were observed in the mid- and high-dose groups (systemic exposures ³2 times the human therapeutic systemic exposure, based on body surface area comparison), in addition decreased live births and pup body weights were observed at >20 mg/kg/day (systemic exposures less than the human therapeutic systemic exposure, based on body surface area comparison).

In pregnant rabbits given miglustat by oral gavage at doses of 15, 30, 45 mg/kg/day during gestation days 6-18 (organogenesis), maternal death and decreased body weight gain were observed at 15 mg/kg/day (systemic exposures less than the human therapeutic systemic exposure, based on body surface area comparisons).

ZAVESCA® is contraindicated in women who are or may become pregnant. If this drug is administered to a woman with reproductive potential, the patient should be apprised of the potential hazard to a fetus.


Additional information about Miglustat, Hydrochloride

Miglustat, Hydrochloride Indication: For the treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to constraints such as allergy, hypersensitivity, or poor venous access).
Mechanism Of Action: Miglustat, Hydrochloride functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids. The goal of treatment with miglustat is to reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to a level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy). In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids. In clinical trials, miglustat improved liver and spleen volume, as well as hemoglobin concentration and platelet count.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Miglustat
Synonyms: Not Available
Drug Category: Anti-HIV Agents; Enzyme Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Miglustat: Miglustat, Hydrochloride; Zavesca;
Absorption: Mean oral bioavailability is 97%.
Toxicity (Overdose): Miglustat has been administered at doses of up to 3000 mg/day (approximately 10 times the recommended starting dose administered to Gaucher patients) for up to six months in Human Immunodeficiency Virus (HIV)-positive patients. Adverse events observed in the HIV studies included granulocytopenia, dizziness, and paresthesia. Leukopenia and neutropenia have also been observed in a similar group of patients receiving 800 mg/day or above.
Protein Binding: Miglustat does not bind to plasma proteins.
Biotransformation: There is no evidence that miglustat is metabolized in humans.
Half Life: The effective half-life of miglustat is approximately 6 to 7 hours.
Dosage Forms of Miglustat, Hydrochloride: Capsule Oral
Chemical IUPAC Name: (2R,3R,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol
Chemical Formula: C10H21NO4
Miglustat on Wikipedia:
Organisms Affected: Humans and other mammals