Zavesca

Zavesca (miglustat capsules, 100 mg) 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. Zavesca is an N-alkylated imino sugar, a synthetic analog of D-glucose.

The chemical name for miglustat is 1,5-(butylimino)-1,5-dideoxy-D-glucitol with the chemical formula C10H21NO4 and a molecular weight of 219.28.

Miglustat is a white to off-white crystalline solid and has a bitter taste. It is highly soluble in water ( > 1000 mg/mL as a free base).

Zavesca is supplied in hard gelatin capsules each containing 100 mg miglustat for oral administration. Each Zavesca 100 mg capsule also contains sodium starch glycollate, povidone (K30), and magnesium stearate. Ingredients in the capsule shell include gelatin and titanium dioxide, and the shells are printed with edible ink consisting of black iron oxide and shellac.

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

Read this Patient Information before you start taking Zavesca and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is Zavesca?

Zavesca is a prescription medicine used alone to treat adults with mild to moderate type 1 Gaucher disease. Zavesca is used only in people who cannot be treated with enzyme replacement therapy.

It is not known if Zavesca is safe and effective in children under 18 years of age.

What should I tell my doctor before taking Zavesca?

Before you take Zavesca tell your doctor if you:

• have kidney problems
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if Zavesca will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if Zavesca passes into your breast milk. You and your doctor should decide if you will breastfeed or take Zavesca. You should not do both.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Zavesca may affect how other medicines work.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take Zavesca?

• Take Zavesca exactly as your doctor has prescribed.
• Take Zavesca at the same time each day.
• If you miss a dose of ZAVESCA, skip that dose. Take the next ZAVESCA capsule at the usual time.

What are the possible side effects of Zavesca?

Zavesca may cause serious side effects including

• Numbness, tingling, pain, or burning in your hands or feet (peripheral neuropathy). Call your doctor right away if you get numbness, tingling, pain, or burning in your hands or feet.
• Your doctor may test your nerves (neurological exam) before you start Zavesca and during treatment with Zavesca.
• New or worsening hand tremors (shaky movements). Tremors are common with Zavesca and may begin within the first month of starting treatment. Sometimes the tremors may go away between 1 to 3 months with continued treatment. Your doctor may lower your dose or stop Zavesca if you develop new or worsening hand tremors. Call your doctor right away if you get new hand tremors while taking Zavesca or if the hand tremors you already have get worse.
• Diarrhea is common with Zavesca and sometimes can be serious. Your doctor may prescribe another medicine (anti-diarrheal) to treat diarrhea if it is a problem for you and may recommend changes to your diet, such as avoiding foods high in carbohydrates. Talk with your doctor about your diet if you have diarrhea.
• Weight loss is common with Zavesca and sometimes can be serious. You may lose weight when you start treatment with Zavesca.
• Low platelet count is common with Zavesca and can be serious. Your doctor may do blood tests to monitor your blood platelet count.

The most common side effects of Zavesca are:

• Weight loss
• Stomach pain
• Gas
• Nausea and vomiting
• Headache, including migraine
• Leg cramps
• Dizziness
• Weakness
• Vision problems
• Muscle cramps
• Back pain
• Constipation
• Dry mouth
• Heaviness in arms and legs
• Memory loss
• Unsteady walking
• Loss of appetite
• Indigestion
• Numbness, tingling, pain, or burning of your skin
• Stomach bloating
• Stomach pain not related to food
• Menstrual changes

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Zavesca. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Zavesca?

• Store Zavesca at room temperature between 68°F to 77°F (20°C to 25°C).

Keep Zavesca and all medicines out of the reach of children.

General information about the safe and effective use of Zavesca.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. 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.

If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Zavesca that is written for health professionals.

For more information about Zavesca call 1-866-228-3546 or go to www.Zavesca.com.

What are the ingredients in Zavesca?

Active ingredient: miglustat

Inactive ingredients: sodium starch glycollate, povidone (K30), and magnesium stearate.

The capsule shell contains: gelatin and titanium dioxide; the edible printing ink contains black iron oxide and shellac.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take imiglucerase (Cerezyme).

This is not a complete list of Zavesca drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Zavesca including the following:

• pain, burning, numbness or tingling in your hands, arms, legs, or feet
• shaking hands that you cannot control
• changes in vision
• easy bruising or bleeding

Zavesca can cause dizziness. Do not drive or operate heavy machinery until you know how Zavesca affects you.

Do not take Zavesca if you are allergic to Zavesca or to any of its ingredients.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• tremor or uncontrolled shaking, especially in your hands;

• numbness, tingling, or burning pain in your hands or feet;

• severe diarrhea and weight loss; or

• easy bruising or bleeding (nosebleeds, bleeding gums).

Common side effects may include:

• diarrhea, constipation, bloating;

• nausea, vomiting, stomach pain, indigestion;

• dry mouth;

• dizziness, weakness;

• headache (including migraine);

• back pain, muscle cramps;

• pain or heavy feeling in your arms or legs;

• memory problems, feeling unsteady, loss of balance;

• vision problems; or

• changes in your menstrual periods.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• diarrhea
• pinpoint red spots on the skin
• trembling or shaking in the hands
• unsteadiness or awkwardness
• unusual bleeding or bruising
• weakness in the arms, hands, legs, or feet
• weight loss

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain
• bloated or full feeling
• blurred or loss of vision
• difficulty having a bowel movement (stool)
• disturbed color perception
• dizziness
• double vision
• dry mouth
• excess air or gas in the stomach or intestines
• halos around lights
• headache
• heartburn
• heaviness in the limbs
• indigestion
• leg cramps
• loss of appetite
• memory loss
• menstrual changes
• nausea
• pain or discomfort in the chest, upper stomach, or throat
• passing gas
• stomach discomfort, upset or pain
• swelling of the abdominal or stomach area
• tunnel vision
• unsteady walk
• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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

• Take with or without food.
• Take with a full glass of water.
• Take Zavesca at the same time of day.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

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 or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very loose stools (diarrhea).
• A burning, numbness, or tingling feeling that is not normal.
• Change in eyesight.
• Any unexplained bruising or bleeding.
• Memory problems or loss.
• Very bad headache.
• Shakiness.
• Trouble walking.

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.

None

The following serious adverse reactions are described below and elsewhere in the labeling:

• Peripheral Neuropathy [see Warnings and Precautions (5.1)]
• Tremor [see Warnings and Precautions (5.2)]
• Diarrhea and weight loss [see Warnings and Precautions (5.3)]
• Reductions in platelet count [see Warnings and Precautions (5.4)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure of 80 patients with type 1 Gaucher disease in two open-label, uncontrolled, monotherapy trials, one open-label, active-controlled trial, and two extensions, who received Zavesca at doses ranging from 50mg to 200 mg three times daily. Patients were aged 18 to 69 years at first treatment. The population was evenly distributed by gender.

The most common serious adverse reaction reported with Zavesca treatment in clinical trials was peripheral neuropathy [see Warnings and Precautions (5.1)].

The most commonly reported adverse reactions in patients treated with Zavesca (occuring in ≥5%) that were considered related to Zavesca are shown in Tables 1 and 2. [see Warnings and Precautions (5.2 ,5.3)].

The most common adverse reactions requiring intervention were diarrhea and tremor. [see Warnings and Precautions (5.2, 5.3)].

In two open-label, uncontrolled monotherapy trials, adult type 1 Gaucher disease patients were treated with Zavesca at a starting dose of 100 mg three times daily (dose range 100 to 200 mg three times daily) for up to 12 months in 28 patients [Study 1], or at a dose of 50 mg three times daily for up to 6 months in 18 patients [Study 2]. Table 1 below lists adverse reactions that occurred during the trials in ≥5% of patients.

In an open-label, active-controlled study, 36 adult type 1 Gaucher disease patients were treated with Zavesca, imiglucerase, or Zavesca plus imiglucerase [Study 3] for up to 12 months. Table 2 lists adverse reactions that occurred during the trial in ≥5% of patients.

Read this Patient Information before you start taking Zavesca and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is Zavesca?

Zavesca is a prescription medicine used alone to treat adults with mild to moderate type 1 Gaucher disease. Zavesca is used only in people who cannot be treated with enzyme replacement therapy.

It is not known if Zavesca is safe and effective in children under 18 years of age.

What should I tell my doctor before taking Zavesca?

Before you take Zavesca tell your doctor if you:

• have kidney problems
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if Zavesca will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if Zavesca passes into your breast milk. You and your doctor should decide if you will breastfeed or take Zavesca. You should not do both.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Zavesca may affect how other medicines work.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take Zavesca?

• Take Zavesca exactly as your doctor has prescribed.
• Take Zavesca at the same time each day.
• If you miss a dose of Zavesca, skip that dose. Take the next Zavesca capsule at the usual time.

What are the possible side effects of Zavesca?

Zavesca may cause serious side effects including:

• Numbness, tingling, pain, or burning in your hands or feet (peripheral neuropathy). Call your doctor right away if you get numbness, tingling, pain, or burning in your hands or feet.
• Your doctor may test your nerves (neurological exam) before you start Zavesca and during treatment with Zavesca.
• New or worsening hand tremors (shaky movements). Tremors are common with Zavesca and may begin within the first month of starting treatment. Sometimes the tremors may go away between 1 to 3 months with continued treatment. Your doctor may lower your dose or stop Zavesca if you develop new or worsening hand tremors. Call your doctor right away if you get new hand tremors while taking Zavesca or if the hand tremors you already have get worse.
• Diarrhea is common with Zavesca and sometimes can be serious. Your doctor may prescribe another medicine (anti-diarrheal) to treat diarrhea if it is a problem for you and may recommend changes to your diet, such as avoiding foods high in carbohydrates. Talk with your doctor about your diet if you have diarrhea.
• Weight loss is common with Zavesca and sometimes can be serious. You may lose weight when you start treatment with Zavesca.
• Low platelet count is common with Zavesca and can be serious. Your doctor may do blood tests to monitor your blood platelet count.

The most common side effects of Zavesca are:

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Zavesca. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Zavesca?

• Store Zavesca at room temperature between 68°F to 77°F (20°C to 25°C).

Keep Zavesca and all medicines out of the reach of children.

General information about the safe and effective use of Zavesca.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. 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.

If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Zavesca that is written for health professionals.

For more information about Zavesca call 1-866-228-3546 or go to www.Zavesca.com.

What are the ingredients in Zavesca?

Active ingredient: miglustat

Inactive ingredients: sodium starch glycollate, povidone (K30), and magnesium stearate.

The capsule shell contains: gelatin and titanium dioxide; the edible printing ink contains black iron oxide and shellac.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Manufactured for:
Actelion Pharmaceuticals US Inc
5000 Shoreline Court, Ste 200
South San Francisco, CA 94080, US
(650) 624 6900
Revised: 07/2015

©2015 Actelion Pharmaceuticals US, Inc.
ACT20150722

If you miss a dose of Zavesca, skip the missed dose and only take the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.