Package Insert: Information for the User

Miglustat Dipharma 100 mg Hard Capsules EFG

miglustat

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Miglustat Dipharma contains the active ingredient miglustat, which belongs to a group of medications that affect metabolism. It is used to treat two disorders:

• Miglustat Dipharma is used to treat mild to moderate Gaucher's disease type 1 in adults.

In Gaucher's disease type 1, your body cannot eliminate a substance called glucosylceramide. As a result, it accumulates in some cells of your immune system. This can lead to an enlarged liver and spleen, changes in the blood, and bone diseases.

The usual treatment for Gaucher's disease type 1 consists of enzyme replacement therapy (ERT). Miglustat Dipharma will only be used in cases where enzyme replacement therapy is not considered suitable for the patient.

• Miglustat Dipharma is also used to treat the progressive neurological symptoms of Niemann-Pick disease type C in adults and children.

If you have Niemann-Pick disease C, lipids such as glycosphingolipids may accumulate in the cells of your brain. This can lead to neurological function alterations such as slow eye movements, balance, swallowing, memory, or seizures.

Miglustat Dipharma acts by inhibiting the enzyme called glucosylceramide synthase, responsible for the first step in the synthesis of most glycosphingolipids.

Do not take Miglustat Dipharma:

• if you are allergic to miglustat or any of the other ingredients of this medication (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Miglustat Dipharma

• if you have kidney disease
• if you have liver disease

Your doctor will perform the following tests before and during treatment with Miglustat Dipharma:

• physical examination of the nerves in the arms and legs
• measurement of vitamin B12 levels
• monitoring of growth in children or adolescents with Niemann-Pick type C disease
• blood platelet count control

These tests are necessary because some patients have reported symptoms such as tingling or numbness in hands and feet, or weight loss during treatment with Miglustat Dipharma. The tests will help your doctor determine if these effects are due to your disease or existing conditions or are side effects of Miglustat Dipharma (see section 4 for more details).

If you have diarrhea, your doctor may ask you to modify your diet to reduce lactose and carbohydrate intake such as sucrose (sugar cane), or not take Miglustat Dipharma with food, or temporarily reduce the dose. In some cases, your doctor may prescribe medications to treat diarrhea, such as loperamide. Consult your doctor if diarrhea does not respond to these measures or if you experience any other abdominal discomfort. In this case, your doctor may decide to perform additional tests.

It is recommended that male patients use reliable contraceptive methods during treatment with Miglustat Dipharma and for three months after completing treatment.

Children and adolescents

Do not administer this medication to children and adolescents (under 18 years of age) with Gaucher's disease type 1 because its effectiveness in this disease is unknown.

Other medications and Miglustat Dipharma

Inform your doctor or pharmacist if you are taking or have taken recently or may need to take any other medication.

Inform your doctor if you are taking medications containing imiglucerase, which are sometimes used at the same time as Miglustat Dipharma. They may decrease the amount of Miglustat Dipharma in your body.

Pregnancy, breastfeeding, and fertility

Do not take Miglustat Dipharma if you are pregnant or intend to become pregnant. For more information, consult your doctor or pharmacist. You will need to use an effective contraceptive method while taking Miglustat Dipharma. Do not continue breastfeeding while taking Miglustat Dipharma.

Male patients should use a reliable contraceptive method during treatment with Miglustat Dipharma, and for three months after completing treatment.

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

Miglustat Dipharma may cause dizziness. Do not drive or operate tools or machines if you feel dizzy.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

• For Gaucher's disease type 1 : In adults, the usual dose is one capsule (100 mg) three times a day (morning, afternoon, night), which represents a maximum daily dose of three capsules (300 mg).
• For Niemann-Pick disease type C : In adults and adolescents (over 12 years), the usual dose is two capsules (200 mg) three times a day (morning, afternoon, and night). This represents a maximum daily dose of six capsules (600 mg).

For children under 12 years old, your doctor will adjust the dose for Niemann-Pick disease type C.

If you have kidney problems, your doctor may prescribe a lower initial dose. Your doctor may reduce the dose of Miglustat Dipharma to one capsule (100 mg) once or twice a day if diarrhea occurs during treatment with Miglustat Dipharma (see section 4). Your doctor will indicate the duration of treatment.

Miglustat Dipharma can be taken with or without food. The capsule should be swallowed whole with a glass of water.

If you take more Miglustat Dipharma than you should

If you take more capsules than indicated, consult your doctor immediately. In clinical trials, miglustat was used at doses of up to 3000 mg: this caused a reduction in white blood cells and other adverse effects similar to those described in section 4.

If you forget to take Miglustat Dipharma

Take the next capsule when it is due. Do not take a double dose to compensate for the missed dose.

If you interrupt treatment with Miglustat Dipharma

Do not stop treatment with Miglustat Dipharma without consulting your doctor.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

More serious side effects

Some patients have experienced tingling or numbness in the hands and feet (observed frequently). These could be signs of peripheral neuropathy, due to side effects of Miglustat Dipharma or could be due to existing diseases. Your doctor will perform tests before and during treatment with Miglustat Dipharma to evaluate your case (see section 2).

If you experience any of these side effects, inform your doctor as soon as possible.

If youexperience a slight tremor, usuallyhand tremor, informyour doctor as soon as possible. Tremor often resolves without the need to interrupt treatment. Occasionally, your doctor may need to reduce the dose and even discontinue treatment with Miglustat Dipharma to control the tremor.

Very common– may affect more than 1 in 10 patients

Among the most frequent side effects are diarrhea, flatulence (gas), abdominal pain (stomach), weight loss, and decreased appetite.

If you lose some weightwhen starting treatment with Miglustat Dipharma, do not worry, usually people stop losing weight with continued treatment.

Common– may affect up to 1 in 10 patients

Common side effects are headache, dizziness, paresthesias (tingling or numbness), coordination disturbances, hypoaesthesia (reduced tactile sensation), dyspepsia (stomach burning), nausea (feeling sick), constipation, and vomiting, abdominal swelling or discomfort, and thrombocytopenia (decreased platelet levels). Neurological symptoms and thrombocytopenia may be due to underlying disease.

Other possible side effects are muscle spasms or weakness, fatigue, chills, and general discomfort, difficulty sleeping, forgetfulness, and decreased libido.

Most patients notice one or more of these side effects, usually when starting treatment or at different times during treatment. Most are mild and resolve quickly. If any of these side effects cause problems, consult your doctor. They may reduce the dose of Miglustat Dipharma or prescribe other medications to control side effects.

Reporting side effects

If you experience side effects, consult your doctor or pharmacist, even if they are side effects not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the blister and packaging after “EXP/CAD”. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

• The active ingredient is miglustat. Each hard capsule contains 100 mg of miglustat.
• The other components are magnesium stearate, gelatin, titanium dioxide (E171), printing ink (which consists of iron oxide black (E172), propylene glycol (E1520), potassium hydroxide, shellac).

Appearance of the product and contents of the container

Miglustat Dipharma is a white opaque capsule of 100 mg printed in black ink with “DPH02” on top and “100” in the body. The capsules are presented in PCTFE/PVC and aluminum blister packs, in container sizes of 84 capsules in unperforated blisters and 84x1 capsules in perforated single-dose blisters.

Only some container sizes may be commercially available.

Marketing Authorization Holder

Dipharma Arzneimittel GmbH

Offheimer Weg 33

65549 Limburg a. d. Lahn

Germany

Manufacturer

Doppel Farmaceutici S.r.l

Via Volturno 48

20089 Quinto day Stampi - Rozzano (MI)

Italy

Last review date of this leaflet:{MM/AAAA}.

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.