Siklos

Package leaflet: Information for the user

Siklos 100 mg film-coated tablet, 1,000 mg film-coated tablet

Hydroxycarbamide
Please 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Siklos is and what it is used for

2. What you need to know before taking Siklos

3. How to take Siklos

4. Possible side effects

5. How to store Siklos

6. Contents of the pack and other information

7. What Siklos is and what it is used for

Siklos is used to prevent painful crises, including sudden chest pain, caused by sickle cell anaemia in adults, adolescents, and children over the age of 2 years.
Sickle cell anaemia is an inherited disease affecting red blood cells.
Some red blood cells become abnormal, rigid, and take on a crescent or sickle shape, leading to anaemia.
Sickle-shaped cells become trapped in blood vessels, blocking blood flow. This causes acute painful crises and organ damage.
For the most severe crises, most patients require hospitalisation. Siklos reduces the number of painful crises and the need for hospitalisation related to the disease.
The active substance in Siklos, hydroxycarbamide, is a substance that inhibits the growth and proliferation of certain cells, such as blood cells. These effects lead to a reduction in circulating red and white blood cells and platelets (myelosuppressive effect). In sickle cell anaemia, hydroxycarbamide also helps prevent red blood cells from becoming deformed.

2. What you should know before taking Siklos

Do not take Siklos

• if you are allergic to hydroxycarbamide or to any of the excipients of this medicine (listed in section 6),
• if you have severe liver disease,
• if you have severe kidney disease,
• if you have myelosuppression (you produce a reduced number of red or white blood cells or platelets), as described in section 3 “How to take Siklos, Follow-up of treatment”,
• if you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Siklos

• if you have liver disease,
• if you have kidney disease,
• if you have leg ulcers,
• if you are taking other medicines with myelosuppressive effects (which reduce the number of red and white blood cells or platelets) or if you are undergoing radiotherapy,
• if you know you have vitamin B or folate deficiency.

If you have or have had any of these conditions, inform your doctor. For any questions, please consult your doctor, pharmacist or nurse.
Patients and/or parents or the responsible legal guardian must be able to follow instructions regarding the administration of this medicine, monitoring and care.

Other medicines and Siklos
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Sharing this information is particularly important for:

• certain antiretroviral drugs (which inhibit or destroy retroviruses such as HIV), for example didanosine, stavudine and indinavir (a decrease in white blood cells may occur),
• myelosuppressive drugs (which reduce the production of red and white blood cells or platelets) and radiotherapy,
• certain vaccines,
• continuous glucose monitoring (CGM), used to measure blood glucose (hydroxycarbamide may falsely elevate glucose levels detected by the sensor of some continuous glucose monitoring (CGM) systems, potentially leading to hypoglycemia if these results are relied upon for insulin dosing).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Siklos is not recommended during pregnancy. Contact your doctor immediately if you think you may be pregnant. The use of an effective contraceptive method is strongly recommended.
If you are pregnant or planning a pregnancy while using Siklos, your doctor will discuss with you the potential benefits and risks of continuing treatment with Siklos.
For male patients taking Siklos, if your partner becomes pregnant or plans to become pregnant, your doctor will discuss with her the potential benefits and risks of continuing treatment with Siklos.
The active substance of Siklos passes into human milk. You must not breastfeed during treatment with Siklos.
Hydroxycarbamide may reduce sperm production in male patients during treatment.

Driving and using machines
Some people may experience dizziness while taking Siklos. Do not drive and do not operate tools or machinery if you experience dizziness during treatment with Siklos.

3. How to take Siklos

Take Siklos exactly as prescribed by your doctor. If you have any doubts, consult your doctor or
pharmacist.
Dosage
Your doctor will tell you how much Siklos to take each day and will determine whether the dose is one
whole tablet, half a tablet, or a quarter of a tablet.
The prescribed dose of Siklos should be taken once daily, preferably in the morning before breakfast.
You may take it with a glass of water or with a very small amount of food.
If you are unable to swallow the tablets, they may be crushed immediately before use:

• Place the required dose (preferably broken, if using the Siklos 1,000 mg tablet) into a teaspoon and add water.
• Once the tablet has disintegrated, swallow the contents of the spoon. You may add a drop of fruit juice or mix it with food to mask any possible bitter taste.
• Then drink a glass of water or another beverage.

Handling
Siklos is a cytotoxic medicinal product and must be handled with care.
All individuals who are not taking Siklos, particularly pregnant women, must avoid direct contact with tablet residues during division. Wash your hands before and after handling the tablets.
If the prescribed dose requires dividing the tablet into halves or quarters, this should be done away from food. The powder generated during tablet division should be wiped up with absorbent paper, which must then be disposed of properly. For storage of divided tablets, see section 5 “How to store Siklos”.
Treatment follow-up
Your doctor will inform you of how long you should continue taking Siklos.
During treatment with Siklos, you will undergo regular blood tests and examinations to monitor the function of your liver and kidneys. Depending on your prescribed dose, these tests may be performed once a month or every two months.
Based on the results of these tests, your doctor may adjust your dose of Siklos.
If you take more Siklos than you should
If you take more Siklos than prescribed or if the medicine has been ingested by a child, seek immediate medical advice from your doctor or the nearest hospital, as urgent medical intervention may be required. The most common symptoms of Siklos overdose include:

• Skin redness,
• Irritation (pain upon touch) and swelling of the palms of the hands and soles of the feet, followed by peeling of the skin on hands and feet,
• Intense skin pigmentation (localized discoloration),
• Irritation or swelling inside the mouth.

If you forget to take Siklos
Do not take a double dose to make up for the missed tablet. Continue taking the medicine at the next scheduled time, as prescribed by your doctor.
If you stop taking Siklos
Do not stop treatment unless advised by your doctor.
If you have any questions about the use of Siklos, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Siklos can cause side effects, although not everyone experiences them.
Contact your doctor immediately if you experience any of the following serious side effects:

• Severe infection,
• Weakness and/or pale appearance,
• Unexplained bruising (blood collecting under the skin) or bleeding,
• Unusual headache,
• Difficulty breathing.

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

• Fever or chills,
• Nausea or general malaise,
• Skin rash accompanied by itching,
• Ulcers or sores on the legs,
• Open sores (open skin infections),
• Disorientation (confusion) and dizziness.

DETAILS OF THE SIDE EFFECTS
Very common side effects (may affect more than 1 in 10 people):
Reduced number of blood cells (myelosuppression), increased size of red blood cells.
Absence or low number of sperm in semen (azoospermia or oligospermia). Siklos may therefore reduce male fertility.

Common side effects (may affect up to 1 in 10 people):
Reduced number of red blood cells (anaemia), low platelet count, headache, skin reactions, inflammation or ulcers in the mouth (oral mucositis).

Uncommon side effects (may affect up to 1 in 100 people):
Dizziness, nausea, skin rash with itching, nail pigmentation (melanonychia), and hair loss.

Rare side effects (may affect up to 1 in 1,000 people):
Ulcers on the legs and altered liver function.

Very rare side effects (may affect up to 1 in 10,000 people) or frequency not known (frequency cannot be estimated from the available data):
Skin inflammation causing red, scaly patches, sometimes accompanied by joint pain.
Isolated cases of malignant blood disorders (leukaemia), skin cancer in elderly patients, bleeding, gastrointestinal disorders, vomiting, dry skin, fever, absence of menstrual periods (amenorrhoea), and increased body weight.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system detailed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Siklos

Keep this medicine out of the sight and reach of children.
Do not use Siklos after the expiry date stated on the bottle and the carton following Exp.:.
Store this medicine below 30 °C.
Any broken tablets not used must be kept in the bottle and used within three months.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Siklos contains

• The active substance is hydroxycarbamide. Each Siklos 100 mg film-coated tablet contains 100 mg of hydroxycarbamide. Each Siklos 1 000 mg film-coated tablet contains 1 000 mg of hydroxycarbamide.
• The excipients are: sodium stearyl fumarate, silicified microcrystalline cellulose, and butylated methacrylate copolymer.

Description of the appearance of Siklos and contents of the pack
Siklos 100 mg film-coated tablets are oblong, whitish tablets with a score line on both sides. The tablet can be divided into two equal parts. On one side of each half, the letter 'H' is imprinted.
Siklos 100 mg is supplied in plastic bottles containing 60, 90 or 120 tablets.
Siklos 1 000 mg film-coated tablets are capsule-shaped, whitish tablets with three score lines on both faces. The tablet can be divided into four equal parts. On one side of each quarter, the letter "T" is imprinted.
Siklos 1 000 mg is supplied in bottles containing 30 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
THERAVIA
16 Rue Montrosier
92200 Neuilly-sur-Seine
France

Manufacturer
Delpharm Lille
Parc d’Activités Roubaix-Est
22 rue de Toufflers
CS 50070
59452 Lys-lez-Lannoy
France

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
THERAVIA THERAVIA
Tél/Tel: +32(0) 2 808 2973 16 Rue Montrosier
92200 Neuilly-sur-Seine - Prancūzija
Tel: +33 (0)1 72 69 01 86

България Luxembourg/Luxemburg
THERAVIA THERAVIA
16 Rue Montrosier Tél/Tel : +352 27 86 23 29
92200 Neuilly-sur-Seine - Франция
Tel: +33 (0)1 72 69 01 86

Česká republika Magyarország
THERAVIA THERAVIA
16 Rue Montrosier 16 Rue Montrosier
92200 Neuilly-sur-Seine - Francie 92200 Neuilly-sur-Seine - Franciaország
Tel: +33 (0)1 72 69 01 86 Tel: +33 (0)1 72 69 01 86

Danmark Malta
Oresund Pharma ApS THERAVIA
Orient Plads 1 16 Rue Montrosier
2150 Nordhavn 92200 Neuilly-sur-Seine - Franza
Danmark Tel: +33 (0)1 72 69 01 86
Tlf: +45 53 63 39 16

Deutschland Nederland
THERAVIA THERAVIA
Tel : 0800 10 90 001 Tel: +31 (0) 20 208 2161

Eesti Norge
THERAVIA Oresund Pharma ApS
16 Rue Montrosier Orient Plads 1
92200 Neuilly-sur-Seine - Prantsusmaa 2150 Nordhavn
Tel: +33 (0)1 72 69 01 86 Danmark
Tlf: +45 53 63 39 16

Ελλάδα Österreich
DEMO ABEE THERAVIA
Τηλ: +30 210 81 61 802 16 Rue Montrosier
92200 Neuilly-sur-Seine - Frankreich
Tel: +33 (0)1 72 69 01 86

España Polska
Abacus Medicine A/S THERAVIA
Tel: +34 910605214 16 Rue Montrosier
92200 Neuilly-sur-Seine - Francja
Tel: +33 (0)1 72 69 01 86

France Portugal
THERAVIA Abacus Medicine A/S
16 Rue Montrosier Tel: +34 910605214
92200 Neuilly-sur-Seine
Tel: +33 (0)1 72 69 01 86

Hrvatska România
THERAVIA THERAVIA
16 Rue Montrosier 16 Rue Montrosier
92200 Neuilly-sur-Seine 92200 Neuilly-sur-Seine - Franţa
Tel: +33 (0)1 72 69 01 86 Tel: +33 (0)1 72 69 01 86

Ireland Slovenija
THERAVIA THERAVIA
Tel: +353(0)1-9038043 16 Rue Montrosier
92200 Neuilly-sur-Seine - Francija
Tel: +33 (0)1 72 69 01 86

Ísland Slovenská republika
THERAVIA THERAVIA
16 Rue Montrosier 16 Rue Montrosier
92200 Neuilly-sur-Seine - Frakkland 92200 Neuilly-sur-Seine - Francúzsko
Sími: +33 (0)1 72 69 01 86 Tel: +33 (0)1 72 69 01 86

Italia Suomi/Finland
THERAVIA Oresund Pharma ApS
Tel: 800 959 161 Orient Plads 1
2150 Nordhavn
Denmark
Puh/Tel: +45 53 63 39 16

Κύπρος Sverige
The Star Medicines Importers Co Ltd Oresund Pharma ApS
Τηλ: +357 25 37 1056 Orient Plads 1
2150 Nordhavn
Denmark
Tel: +45 53 63 39 16

Latvija
THERAVIA
16 Rue Montrosier
92200 Neuilly-sur-Seine - Francija
Tel: +33 (0)1 72 69 01 86

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.