SIKLOS 100 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Siklos 100 mg film-coated tablets

Siklos 1000 mg film-coated tablets

hydroxycarbamide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

1. What is Siklos and what is it used for
2. What you need to know before you take Siklos
3. How to take Siklos

1. Possible side effects
2. Storage of Siklos

1. Contents of the pack and further information

1. What is Siklos and what is it used for

Siklos is used to prevent pain crises, including sudden chest pain, caused by sickle cell disease in adults, adolescents and children over 2 years of age.

Sickle cell disease is a hereditary blood disorder that affects the red blood cells.

This disorder causes some cells to become deformed, rigid and sickle-shaped, leading to anaemia.

Additionally, sickled cells stick to blood vessels and block blood flow, which can cause acute pain crises and organ damage.

Most patients need to be hospitalized when they suffer severe crises. Siklos will reduce the number of pain crises and the need for hospitalization due to the disease.

The active substance in Siklos, hydroxycarbamide, is a substance that inhibits the growth and proliferation of some cells, such as blood cells; these effects lead to a reduction in red and white blood cells and blood platelets (myelosuppressive effect). In sickle cell disease, hydroxycarbamide also helps prevent red blood cells from becoming deformed.

2. What you need to know before you take Siklos

Do not take SIKLOS:

• if you are allergic to hydroxycarbamide or any of the other ingredients of this medicine (listed in section 6),
• if you have severe liver disease,
• if you have severe kidney disease,

• if you have myelosuppression (i.e. you have a reduced number of red or white blood cells or platelets), as described in section 3 "How to take Siklos, treatment follow-up”,

• if you are breast-feeding (see section “Pregnancy, breast-feeding and fertility”).

Warnings and precautions

Tell your doctor or pharmacist or nurse before you start taking Siklos

• if you have liver disease,

• if you have kidney disease,
• if you have leg ulcers,
• if you are taking other myelosuppressive medicines (which reduce the production of red or white blood cells or platelets) or if you are receiving radiotherapy,
• if you have a known deficiency of vitamin B12 or folate.

If you experience (or have experienced) any of these disorders, please tell your doctor. If you have any questions, please ask your doctor or pharmacist or nurse.

Patient and/or parents or guardians must be able to follow the instructions for administration of this medicine, its control and care.

Other medicines and Siklos

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Exchange of information is especially important in the following cases

• certain antiretrovirals (medicines that inhibit or destroy retroviruses, such as HIV), e.g. didanosine, stavudine and indinavir (a decrease in white blood cell count may occur),

• myelosuppressive medicines and radiotherapy,
• certain vaccines.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Siklos is not recommended during pregnancy. Please contact your doctor if you think you may be pregnant. The use of effective contraceptive methods is strongly recommended.

If you become pregnant or plan to become pregnant while taking Siklos, your doctor will discuss with you the possible benefits and risks of continuing to use Siklos.

For male patients taking Siklos, if your partner becomes pregnant or plans to become pregnant, your doctor will discuss with you the possible benefits and risks of continuing to use Siklos.

The active substance in Siklos is excreted in breast milk. You must not breast-feed while you are taking Siklos.

Hydroxycarbamide may reduce sperm production in male patients during treatment.

Driving and using machines

Some people may feel dizzy while taking Siklos. Do not drive or use tools or machines if you feel dizzy during treatment with Siklos.

3. How to take Siklos

Take Siklos exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

Dose

Your doctor will tell you what dose of Siklos to take and whether to take the tablets whole or divided into halves or quarters.

The prescribed dose of Siklos should be taken once a day, preferably in the morning before breakfast.

You can take it with a glass of water or with a small amount of food.

If you cannot swallow the tablets, you can dissolve them in water immediately before use:

• Place the prescribed dose (preferably already in pieces if taking Siklos 1000 mg) in a spoon and add water.
• Take the contents of the spoon as soon as the tablet dissolves. You can add a drop of syrup or mix the contents with food to hide any possible bitter taste.
• Then drink a full glass of water or any other drink.

Handling

Siklos is a cytotoxic medicine that must be handled with care.

If a tablet is broken, anyone who is not taking Siklos (especially pregnant women) should avoid contact with the fragments. Wash your hands before and after touching the tablets.

If you need to break the tablet into two or four parts to achieve the required dose, do so away from where food is prepared. Clean up any powder that has fallen with a disposable damp cloth and dispose of it. To store unused broken tablets, see section 5 "Storage of Siklos”.

Treatment follow-up

Your doctor will tell you how long you need to take Siklos.

While taking Siklos, you will have regular blood tests, and liver and kidney checks.

Depending on the dose you take, these tests will be done monthly or every two months.

Depending on the results, your doctor will adjust the dose of Siklos.

If you take more Siklos than you should

If you take more Siklos than you should or if a child takes it, contact your doctor or the nearest hospital immediately, as you may need urgent medical treatment. The most common symptoms of Siklos overdose are:

• Redness of the skin,
• Pain (tender touch) and swelling of the palms of the hands and soles of the feet, followed by peeling of hands and feet,
• Intense skin pigmentation (local colour changes),
• Pain or swelling in the mouth.

If you forget to take Siklos

Do not take a double dose to make up for a forgotten dose. Take the next tablet at the usual time, as prescribed by your doctor.

If you stop taking Siklos

Do not stop treatment unless your doctor tells you to.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Siklos can cause side effects, although not everybody gets them.

If you experience any of the following serious side effects, tell your doctor immediately:

• Severe infection,
• Fatigue or paleness,

• Bleeding or bruising without cause,
• Uncommon headache,
• Difficulty breathing.

If you notice any of the following side effects, tell your doctor as soon as possible:

• Fever or chills,
• Feeling unwell or general malaise,

• Rash (red skin rash that itches),
• Ulcers or sores on the legs,
• Sores (visible skin infection) on the skin,

• Disorientation (confusion) and dizziness.

DETAILS OF SIDE EFFECTS

Very common side effects (may affect more than 1 in 10 people):Reduction in the number of blood cells (myelosuppression), increase in red blood cell size.

Absence or reduction of sperm in the semen (azoospermia or oligospermia). Therefore, Siklos may reduce the ability of men to father a child.

Common side effects (may affect up to 1 in 10 people):

Reduction in red blood cells (anaemia), reduction in platelets, headache, skin reactions, inflammation or ulceration of the mouth (oral mucositis).

Uncommon side effects (may affect up to 1 in 100 people):

Dizziness, nausea, red skin rash with itching (exanthema), black nails (melanonychia), and hair loss.

Rare side effects (may affect up to 1 in 1,000 people):

Leg ulcers (ulcers) and changes in liver function.

Very rare side effects (may affect up to 1 in 10,000 people) or frequency not known (cannot be estimated from the available data):

Skin inflammation causing red, scaly patches and possibly accompanied by joint pain.

Isolated cases of blood cell cancer (leukaemia), skin cancer in elderly patients, bleeding, gastrointestinal disorders, vomiting, dry skin, fever, absence of menstrual cycles (amenorrhoea) and weight gain.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Siklos

Keep out of the sight and reach of children.

Do not use Siklos after the expiry date which is stated on the carton and blister after EXP.

Store below 30°C.

Unused broken tablets (fractionated) should be put back in the carton and used within three months.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and further information

Composition of Siklos

• The active substance is hydroxycarbamide.

Each Siklos 100 mg film-coated tablet contains 100 mg of hydroxycarbamide. Each Siklos 1000 mg film-coated tablet contains 1000 mg of hydroxycarbamide.

• The other ingredients are sodium stearyl fumarate, silicified microcrystalline cellulose, basic butylated methacrylate copolymer.

Appearance of the product and pack size

Siklos 100 mg film-coated tablets are oblong and white with a score line on both sides. The tablet can be divided into two equal parts. Each half of the tablet is engraved with “H” on one side.

Siklos 100 mg is available in plastic bottles containing 60, 90 or 120 tablets.

Siklos 1000 mg film-coated tablets are white and capsule-shaped, and have three score lines on each side. The tablet can be divided into four equal parts.

Each quarter of the tablet is engraved with “T” on one side.

Siklos 1000 mg is available in bottles of 30 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Addmedica

37 rue de Caumartin

75009 Paris

France

Manufacturer

Delpharm Lille

Parc d’Activités Roubaix-Est

22 rue de Toufflers

CS 50070

59452 Lys-lez-Lannoy

France

You can request more information about this medicine from the local representative of the Marketing Authorisation Holder:

België/Belgique/BelgienLietuva

Addmedica Addmedica

Tel: +32-(0)2-808 2973 37 rue de Caumartin

75009 Paris - France

Tel: +33 (0)1 72 69 01 86

????????Luxembourg/Luxemburg

Addmedica Addmedica

37 rue de Caumartin 37 rue de Caumartin

75009 Paris - ??????? 75009 Paris/Parijs

Tel: +33 (0)1 72 69 01 86 France/Frankreich/Frankrijk

Tel: +33 (0)1 72 69 01 86

Ceská republikaMagyarország

Addmedica Addmedica

37 rue de Caumartin 37 rue de Caumartin

75009 Paris - Francie 75009 Párizs - Franciaország

Tel: +33 (0)1 72 69 01 86 Tel: +33 (0)1 72 69 01 86

DanmarkMalta

Addmedica Addmedica

37 rue de Caumartin 37 rue de Caumartin

75009 Paris - Frankrig 75009 Parigi - Franza

Tel: +33 (0)1 72 69 01 86 Tel: +33 (0)1 72 69 01 86

DeutschlandNederland

Addmedica Addmedica

Tel: +49-(0)30-8878 9408 Tel: +31-(0)20-208 2161

EestiNorge

Addmedica Addmedica

37 rue de Caumartin 37 rue de Caumartin

75009 Pariis - Prantsusmaa 75009 Paris - Frankrike

Tel: +33 (0)1 72 69 01 86 Tel: +33 (0)1 72 69 01 86

Ελλ?δαÖsterreich

DEMO ABEE Addmedica

Τηλ: +30 210 81 61 802 37 rue de Caumartin

75009 Paris - Frankreich

Tel: +33 (0)1 72 69 01 86

Date of last revision of this leaflet

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/. There are also links to other web sites about rare diseases and orphan medicines.