Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Addmedica, 37 rue de Caumartin, 75009 Paris, France, Phone: +33 1 72 69 01 86, Fax: +33 1 73 72 94 13, E-mail: contact@addmedica.com
Siklos is indicated for the prevention of recurrent painful vaso-occlusive crises including acute chest syndrome in adults, adolescents and children older than 2 years suffering from symptomatic Sickle Cell Syndrome (see section 5.1).
Treatment with Siklos should be initiated by a physician experienced in the management of Sickle Cell Syndrome.
The posology should be based on the patient’s body weight (b.w.).
The starting dose of hydroxycarbamide is 15 mg/kg b.w. and the usual dose is between 15 and 30 mg/kg b.w./day.
As long as the patient responds to therapy either clinically or haematologically (e.g. increase of haemoglobin F (HbF), Mean Corpuscular Volume (MCV), neutrophil count) the dose of Siklos should be maintained.
In case of non-response (re-occurrence of crises or no decrease in crisis rate) the daily dose may be increased by steps of 2.5 to 5 mg/kg b.w./day using the most appropriate strength.
Under exceptional circumstances a maximum dose of 35 mg/kg b.w./day might be justified under close haematological monitoring (see section 4.4). In the event a patient does still not respond when treated with the maximum dose of hydroxycarbamide (35 mg/kg b.w./day) over three to six months, permanent discontinuation of Siklos should be considered.
If blood counts are within the toxic range Siklos should be temporarily discontinued until blood counts recover. Haematologic recovery usually occurs within two weeks. Treatment may then be reinstituted at a reduced dose. The dose of Siklos may then be increased again under close haematological monitoring. A dose producing haematological toxicity should not be tried more than two times.
The toxic range may be characterised by the following results of blood tests:
Neutrophils <2,000/mm³
Platelets <80,000/mm³
Haemoglobin <4.5 g/dl
Reticulocytes <80,000/mm³ if the haemoglobin concentration <9 g/dl
Long-term data on the continued use of hydroxycarbamide in patients with Sickle Cell Syndrome are available in children and adolescents, with a follow-up of 12 years in children and adolescents and over 13 years in adults. It is currently unknown how long patients should be treated with Siklos. The duration of treatment is the responsibility of the treating physician and should be based on the clinical and haematological status of the individual patient.
Because of the rarity of long term data on treatment with hydroxycarbamide in children less than 2 years of age, dose regimens have not been established and thus, in this population, the treatment with hydroxycarbamide is not recommended.
As renal excretion is a main pathway of elimination, dose reduction of Siklos should be considered in patients with renal impairment. In patients with a creatinine clearance ≤60 ml/min the initial Siklos dose should be decreased by 50%. Close monitoring of blood parameters is advised in these patients. Siklos must not be administered to patients with severe renal impairment (creatinine clearance <30 ml/min) (see sections 4.3, 4.4 and 5.2).
There are no data that support specific dose adjustments in patients with hepatic impairment. Close monitoring of blood parameters is advised in these patients. Due to safety considerations, Siklos is contraindicated in patients with severe hepatic impairment (see sections 4.3 and 4.4).
Conforming to the individual dose, the tablet or the half or quarter of the tablet should be taken once daily, preferably in the morning before breakfast and, where necessary, with a glass of water or a very small amount of food.
For patients who are not able to swallow the tablets, these can be disintegrated immediately before use in a small quantity of water in a teaspoon. Adding a drop of syrup or mixing with food can mask a possible bitter taste.
Acute mucocutaneous toxicity has been reported in patients receiving hydroxycarbamide at doses several times above the therapeutic dose. Soreness, violet erythema, oedema on palms and soles followed by scaling of hand and feet, severe generalised hyperpigmentation of the skin and stomatitis have been observed.
In patients with Sickle Cell Syndrome, neutropenia was reported in isolated cases of hydroxycarbamide overdose (1.43 times and 8.57 times of the maximum recommended dose of 35 mg/kg b.w./day). It is recommended that blood counts are monitored for several weeks after overdose since recovery may be delayed.
Treatment of overdose consists of gastric lavage, followed by symptomatic treatment and control of bone marrow function.
3 years.
In-use: Unused broken tablets must be replaced in the bottle and must be used within three months.
Store below 30°C.
High density polyethylene (HDPE) bottle with polypropylene child-resistant closure with a dessicant unit.
Siklos 100 mg film-coated tablets: Pack sizes of 60, 90 or 120 tablets.
Not all pack sizes may be marketed.
Siklos 1000 mg film-coated tablets: Pack size of 30 tablets.
Siklos is a medicinal product that must be handled with care. People who are not taking Siklos and in particular pregnant women should avoid being in contact with hydroxycarbamide. Anyone handling Siklos should wash their hands before and after contact with the tablets. Any unused product or waste material should be disposed of in accordance with local requirements.
In case the prescribed dose requires breaking the tablet in halves or quarters, this should be done out of the reach of food. Powder eventually spilled from the broken tablet should be wiped up with a damp disposable towel, which must be discarded.
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