Siklos 1000 mg film-coated tablets

Siklos is used to prevent painful crises, including sudden chest pain, caused by Sickle Cell Syndrome, in children older than 2 years and adults.
Sickle cell disease is an inherited blood disorder that affects the rounded red cells of the blood. Some cells become abnormal, rigid and take a crescent or sickle shape which leads to anemia. The sickle cells also get stuck in blood vessels, blocking blood flow. This can cause acute pain crises and organ damage.
For the most severe crises, most patients require hospitalisations.Siklos will decrease the number of painful crises as well as the need for hospitalisation linked with the disease.

The active substance of Siklos, i.e. hydroxycarbamide, is a substance which inhibits growth and proliferation of some cells, such as blood cells. These effects lead to a reduction of circulating red, white and coagulation blood cells (myelosuppressive effect). In Sickle Cell Syndrome, hydroxycarbamide helps to prevent red blood cells from taking abnormal shape.

Do not take Siklos

• if you are allergic (hypersensitive) to hydroxycarbamide or any of the other ingredients of Siklos, (see section ?FURTHER INFORMATION?),
• if you suffer from severe liver disease,
• if you suffer from severe kidney disease,
• if you are myelosuppressed (if you have decreased production of red, white, or coagulating blood cells) as described in the section ?HOW TO TAKE SIKLOS? (treatment follow-up),
• if you are breast-feeding (see section ?Pregnancy and breast-feeding?).

Take special care with Siklos

• if you have a liver disease,
• if you have a kidney disease,
• if you have leg ulcers,
• if you are taking other myelosuppressive medicines (decrease production of red, white, or coagulating blood cells) or receiving radiation therapy,
• if you have a known lack of vitamin B12 or folate.

If you experience (or have experienced) any of the above, please tell your doctor.

Taking other medicines

Please inform your doctor or pharmacist if you are taking:

• antiretroviral medicines (those that inhibit or destroy a retrovirus such as HIV), e.g. didanosine, stavudine and indinavir (a median decline in some of your white blood cells called CD4 cells of approximately 100/mm 3 may occur) ,
• myelosuppressive medicines (decrease production of red, white, or coagulating blood cells) and radiation therapy,
• some vaccines (if you have doubts, please ask your pharmacist or your doctor).

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even medecines obtained without a prescription.

Taking Siklos with food and drink

Please take Siklos in the morning before breakfast and, where necessary, with a glass of water or a very small amount of food to ensure optimal absorption.

Pregnancy and breast-feeding

Siklos is not recommended during pregnancy.
If you are a woman you have to use adequate birth control measures during treatment with hydroxycarbamide. The use of effective contraception is strongly recommended.
If you become pregnant or plan to become pregnant while taking Siklos, , your doctor will discuss with you the potential benefits and risks of continuing Siklos.
For the male patients taking Siklos, if your partner becomes pregnant or plans to become pregnant, your doctor will discuss with you the potential benefits and risks of continuing Siklos.

The active substance of Siklos passes into human breast-milk. You must not breast-feed while taking Siklos.

Driving and using machines

Dizziness is an uncommon side effect of Siklos. Do not drive or use any tools or machines if you experience dizziness whilst taking Siklos.

Handling

Siklos is a medicine that must be handled with care.
Any person, in particular pregnant women, who are not taking Siklos should avoid to come in direct contact with the parts when breaking a tablet. Wash your hands before and after contact with the tablets.

In case the prescribed dose requires breaking the tablet in halves or quarters, this should be done out of the reach of food. Powder spilled from the broken tablet should be wiped up with a damp disposable towel which must be thrown out. For the storage of unused broken tablets, see HOW TO STORE SIKLOS.

Dosages

Always take Siklos exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
Your doctor will tell you how much of Siklos to take each day and define the dose in whole, half or quarter tablets.

The prescribed dose of Siklos must be taken once daily, preferably in the morning before breakfast. If necessary, it can be taken with a glass of water or a very small amount of food.
If you cannot swallow the tablets, you can disintegrate them in water immediately before use:

• Place the required dose (preferably broken if Siklos 1000 mg tablet is used) in a teaspoon and add some water.
• As soon as the tablet is disintegrated, swallow the content of the teaspoon. You can add a drop of syrup or mix the content with food to mask a possible bitter taste.
• Then drink a large glass of water or any other drink.

Treatment follow-up

The duration of treatment is the responsibility of your treating doctor and should be based on your physical condition and blood count. The treating doctor will monitor your blood count and adjust your dose accordingly.

When taking Siklos you will have regular blood tests and tests on your liver and kidney functions. Depending on the dose you take, these tests may be performed every two weeks or every two months. According to these results your doctor will adjust your dose of Siklos.

The growth of treated children should be regularly monitored by the treating doctor.

If you take more Siklos than you should

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

• Soreness (touch is painful)
• Redness of the skin
• Swelling of the palms of hands and soles of feet followed by the hands and feet becoming scaly
• Skin becoming strongly pigmented (coloured)
• Soreness or swelling in the mouth.

If you forget to take Siklos

Do not take a double dose to make up for forgotten tablet. Continue as normal when it is time to take the next dose as prescribed by your doctor.

If you stop taking Siklos

Do not stop your treatment unless advised by your doctor.
If you have any further question on the use of this medicine, ask your doctor or pharmacist.

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

ACTIONS TO TAKE IN CASE OF SIDE EFFECTS

Tell your doctor immediately if you experience any of the following:

• A severe infection
• Tiredness and/or looking pale
• Unexplained bruising (accumulation of blood under the tissues) or bleeding
• Headache
• Difficulties in breathing.

All these are serious side effects of Siklos. You may need medical attention.

Tell your doctor as soon as possible if you notice any of the following side effects of Siklos:

• Rash (itching red eruption of the skin)
• Ulcers or wounds on your legs
• Sore (open skin infection) on your skin.
• Fever or chills
• Feeling sick, weak, lacking energy or a general feeling of being unwell
• Disorientation (confusion) and dizziness

DETAILS OF SIDE EFFECTS

Very common side effects (occurring in more than 1 in 10 people):

Low blood cell counts (myelosuppression), enlargement of red blood cells, decreased resistance to infections.

Common side effects (occurring in less than 1 in 10 people, but more than 1 in 100): Reduced number of red blood cells (anemia), low platelet count, headache, skin reactions, inflammation or ulceration of the mouth (oral mucositis).

Uncommon side effects (occurring in less than 1 in 100 people, but more than 1 in 1,000): Dizziness, nausea, itching red eruption of the skin (rash), black nails (melanonychia), hair loss.

Rare side effects (occurring in less than 1 in 1,000 people, but more than 1 in 10,000): Wounds on the legs (leg ulcers), modification of liver function,

Very rare side effects or unknown frequency (frequency cannot be estimated from the available data):

Absence or low amount of sperm in the semen (azoospermia or oligospermia). Siklos may hence decrease the ability of men to father children.
Isolated cases of malignant disease of blood cells (leukaemia), skin cancer in elderly patients, viralinfection with Parvovirus B19, bleeding, gastrointestinal disturbances, vomiting, skin dryness, fever, absence of menstrual cycles (amenorrhoea), and weight gain.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Siklos after the expiry date which is stated on the carton and the bottle after EXP. The expiry date refers to the last day of that month.

Store below 30°C.

Unused Siklos 1000 mg broken tablets must be replaced in the box.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Siklos contains

The active substance is hydroxycarbamide.
Each Siklos 100 mg film-coated tablet contains 100 mg hydroxycarbamide.
Each Siklos 1000 mg film-coated tablet contains 1,000 mg hydroxycarbamide.

The other ingredients are sodium stearyl fumarate, silicified microcrystalline cellulose and methacrylate copolymer.

What Siklos looks like and contents of the pack

Siklos 100 mg film-coated tablets are off-white, round tablets.
Each tablet is embossed 100 on one side.
Siklos 100 mg is supplied in plastic bottles containing 60, 90 or 120 tablets.

Siklos 1000 mg film-coated tablets are off-white, capsule-shaped tablets marked with three score lines on both sides. The tablet can be divided into four equal parts.
Siklos 1000 mg is supplied in plastic bottle of 30 tablets.

All pack sizes may not be marketed.

Marketing Authorisation Holder

Addmedica
101 rue Saint Lazare
75009 Paris
France

Manufacturer

Elaiapharm
2881 Route des Crêtes
Z.I. Les Bouillides - Sophia Antipolis
06560 Valbonne
France

Delpharm Lille
Z.I de Roubaix Est
Rue de Toufflers

59390 Lys-Lez-Lannoy

France

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Nordic Pharma Laanstraat 16 B-2610 Wilrijk Tel 32 03 820 52 24 LuxembourgLuxemburg Nordic Pharma Laanstraat 16 B-2610 Wilrijk BelgiëBelgiqueBelgien Tel 32 03 820 52 24

Addmedica 101 rue Saint Lazare 75009 Paris - Tel 33 01 72 69 01 86 Magyarország Addmedica 101 rue Saint Lazare 75009 Párizs - Franciaország Tel 33 01 72 69 01 86

eská republika 101 rue Saint Lazare 75009 Paris - Francie Telefon 33 01 72 69 01 86 Malta Addmedica 101 rue Saint Lazare 75009 Parii - Franza Tel 33 01 72 69 01 86

Danmark Addmedica 101 rue Saint Lazare 75009 Paris - Frankrig Telefon 33 01 72 69 01 86 Deutschland Nordic Pharma GmbH Fraunhoferstrasse 4 85737 Ismaning Tel. 49 089 88 96 90 680 Nederland Nordic Pharma B.V. Tolweg 15, 3741 LM Baarn Tel. 31 035-5480580 Email infonordicpharma.nl Norge Addmedica 101 rue Saint Lazare 75009 Paris - Frankrike Tel 33 01 72 69 01 86

Eesti Addmedica 101 rue Saint Lazare 75009 Pariis - Prantsusmaa Tel 33 01 72 69 01 86 Österreich Addmedica 101 rue Saint Lazare 75009 Paris - Frankreich Tel 33 01 72 69 01 86

DEMO ABEE . 30 210 81 61 802 Polska Addmedica 101 rue Saint Lazare 75009 Pary - Francja Tel 33 01 72 69 01 86

España Laboratorios Farmacéuticos ROVI, S.A. Tel 34 91 375 62 30 Portugal Laboratórios Farmacêuticos ROVI, S.A. Tel 351 213 105 610

France Addmedica 101 rue Saint Lazare 75009 Paris Tel 33 01 72 69 01 86 România Addmedica 101 rue Saint Lazare 75009 Paris - Frana Tel 33 01 72 69 01 86

Ireland Nordic Pharma Ltd. Reading, Berkshire RG7 4SA - UK Tel 44 0118 929 82 33 Slovenija Addmedica 101 rue Saint Lazare 75009 Pariz - Francija Tel 33 01 72 69 01 86

Ísland Addmedica 101 rue Saint Lazare 75009 Paris - Frakkland Tel 33 01 72 69 01 86 Slovenská republika Addmedica 101 rue Saint Lazare 75009 Paris - Francúzsko Tel 33 01 72 69 01 86

Italia Addmedica 101 rue Saint Lazare 75009 Parigi - Francia Tel 33 01 72 69 01 86 SuomiFinland Addmedica 101 rue Saint Lazare 75009 Pariisi -Ranska Tel 33 01 72 69 01 86

The Star Medicines Importers Co Ltd . 357 25 37 1056 Sverige Addmedica 101 rue Saint Lazare 75009 Paris - Frankrike Tel 33 01 72 69 01 86

United Kingdom Nordic Pharma Ltd. Reading, Berkshire RG7 4SA - UK Tel 44 0118 929 82 33 Latvija Addmedica 101 rue Saint Lazare 75009 Paris - Francija Tel 33 01 72 69 01 86

Lietuva
Addmedica
101 rue Saint Lazare
75009 Paris - Pranczija
Tel: +33 (0)1 72 69 01 86

This leaflet was last approved in .