Package Insert: Information for the User

Siklos 100 mg Film-Coated Tablets

Siklos 1000 mg Film-Coated Tablets

hydroxyurea

Read this package insert carefully before starting to take the medicine, as 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, pharmacist, or nurse.

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

1. Possible Adverse Effects
2. Storage of Siklos

1. Contents of the Package and Additional Information

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

Sickle cell anemia is a hereditary blood disorder that affects the disk-shaped red blood cells.

This disorder causes some cells to deform, become rigid, and adopt a sickle or crescent shape that leads to anemia.

Additionally, sickle-shaped cells adhere to blood vessels and obstruct blood flow, which can cause acute pain crises and organ damage.

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

The active ingredient of Siklos, hydroxyurea, 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 platelets (myelosuppressive effect). In sickle cell anemia, hydroxyurea also helps prevent red blood cells from deforming.

Do not take SIKLOS:

• if you are allergic to hydroxyurea or to any of the other components of this medication (listed in section 6),
• if you have a severe liver disorder,
• if you have a severe kidney disorder,

• if you are experiencing myelosuppression (i.e., a reduction in red or white blood cells or platelets), as described in section 3 "How to take Siklos, follow-up treatment",

• if you are breastfeeding (see section "Pregnancy, breastfeeding, and fertility").

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Siklos

• if you have a liver disorder,

• if you have a kidney disorder,
• if you have leg ulcers,
• if you are taking other myelosuppressive medications (that reduce the production of red or white blood cells or platelets) or if you are receiving radiation therapy,
• if you have a known deficiency of vitamin B12 or folate.

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

Patients and/or parents or guardians must be able to follow the administration instructions, control, and care of this medication.

Other medications and Siklos

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

The exchange of information is especially important in the following cases

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

• myelosuppressants (medications that reduce the production of red or white blood cells or platelets) and radiation therapy,
• some vaccines.

Pregnancy, breastfeeding, and fertility

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

Do not take Siklos during pregnancy. Please contact your doctor if you think you may be pregnant. Effective contraceptive methods are strongly recommended.

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

The active ingredient of Siklos is eliminated through breast milk. Do not breastfeed while using Siklos.

Hydroxyurea may reduce sperm production in male patients during treatment.

Driving and operating machinery

Some people may experience dizziness while taking Siklos. Do not drive or operate tools or machinery if you experience dizziness during Siklos treatment.

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

Dose

Your doctor will indicate the daily dose of Siklos and whether you should 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 very small amount of food.

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

• Place the indicated dose (preferably already in pieces if taking Siklos 1000 mg) on 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 its possible bitter taste.
• Then, drink a full glass of water or any other beverage.

Handling

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

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

If you need to break the tablet to get the necessary dose, do it away from food. Clean up the powder that falls when breaking the tablet with a disposable damp cloth and dispose of it. To store unused broken tablets, see section 5 “Storage of Siklos”.

Follow-up treatment

Your doctor will indicate for how long you should take Siklos.

While taking Siklos, you will have periodic 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 you take it by a child, 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 (tactile pain) and swelling of the palms of the hands and soles of the feet, followed by peeling of hands and feet,
• Intense pigmentation (local color changes) of the skin,
• Pain or swelling in the mouth.

If you forgot to take Siklos

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

If you interrupt treatment with Siklos

Do not interrupt treatment unless your doctor tells you to.

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

Like all medicines, Siklos can cause side effects, although not everyone will experience them.

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

• Severe infection,
• Fatigue or paleness,

• Bleeding under the skin (hematomas) or unexplained bleeding,
• Infrequent headache,
• Difficulty breathing.

If you notice any of the following adverse reactions, report them to your doctor as soon as possible:

• Fever or chills,
• General feeling of discomfort or malaise,

• Exanthema (red, itchy rash on the skin),
• Ulcers or wounds on the legs,
• Visible skin infections (abrasions),

• Disorientation (confusion) and dizziness.

ADVERSE REACTION DETAILS

Very common adverse reactions (may affect more than 1 in 10 people):Reduction in the number of blood cells (myelosuppression), increased size of red blood cells.

Absence or reduction in the number of sperm in semen (azoospermia or oligospermia). Therefore, Siklos may reduce the ability of males to conceive.

Common adverse reactions (may affect up to 1 in 10 people):

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

Rare adverse reactions (may affect up to 1 in 100 people):

Dizziness, nausea, red, itchy rash on the skin (exanthema), black nails (melanoniquia), and hair loss.

Uncommon adverse reactions (may affect up to 1 in 1,000 people):

Leg wounds (ulcers) and liver function modification.

Very rare adverse reactions (may affect up to 1 in 10,000 people) or unknown frequency (cannot be estimated from available data):

Dermatitis that causes red, scaly patches on the skin and may be accompanied by joint pain.

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

Reporting adverse reactions

If you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect that does not appear in this prospectus.You can also report them directly through the national notification system included in theAppendix V.By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not use Siklos after the expiration date that appears on the box and the bottle after CAD.

Store below 30°C.

Unused broken (fractured) tablets must be put back in the box and used within three months.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medicines you no longer need. This will help protect the environment.

Composition of Siklos

• The active ingredient is hydroxy-carbamide.

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

• The other components are sodium stearyl fumarate, microcrystalline cellulose, and basic butylated methacrylate copolymer.

Appearance of the product and contents of the pack

Siklos 100 mg film-coated tablets are oval and white with a notch 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 presented in plastic bottles containing 60, 90 or 120 tablets.

Siklos 1000 mg film-coated tablets are white and capsule-shaped, with three notches 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 presented in bottles of 30 tablets.

Only some pack sizes may be marketed.

Marketing Authorization 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

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

België/Belgique/Belgien/Lietuva

AddmedicaAddmedica

Tel : +32-(0)2-808 297337 rue de Caumartin

75009 Paris - Prancuzija

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

????????Luxembourg/Luxemburg

AddmedicaAddmedica

37 rue de Caumartin37 rue de Caumartin

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

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

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

Ceská republikaMagyarország

AddmedicaAddmedica

37 rue de Caumartin37 rue de Caumartin

75009 Paris - Francie75009 Párizs - Franciaország

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

DanmarkMalta

AddmedicaAddmedica

37 rue de Caumartin37 rue de Caumartin

75009 Paris - Frankrig75009 Parigi - Franza

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

DeutschlandNederland

AddmedicaAddmedica

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

EestiNorge

AddmedicaAddmedica

37 rue de Caumartin37 rue de Caumartin

75009 Pariis - Prantsusmaa75009 Paris - Frankrike

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

Ελλ?δαÖsterreich

DEMO ABEEAddmedica

Τηλ : +30 210 81 61 80237 rue de Caumartin

75009 Paris - Frankreich

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

Last update of the summary of product characteristics

The detailed information on this medicinal product is available on the website of the European Medicines Agency:: http://www.ema.europa.eu /There are also links to other websites on rare diseases and orphan medicinal products.