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What is Siklos?

Siklos is a medicine containing the active substance hydroxycarbamide, available as tablets (1000 mg).

What is Siklos used for?

Siklos is indicated in the treatment of adult patients and children with sickle cell disease or sickle cell disease (a genetic disease in which red blood cells change shape and become extremely rigid when they are not carrying oxygen). The drug is used to prevent painful vasoocclusive seizures, which are recurrent. There is a vaso-occlusive crisis when the blood vessels are obstructed by the presence of abnormal red blood cells, which thus limit the flow of blood to an organ. Among these episodes there is also acute thoracic syndrome, a life-threatening condition characterized by sudden chest pain, fever, difficulty breathing or traces of fluid in the lungs on the X-ray.

Because the number of patients with sickle cell disease is low, the disease is considered rare and Siklos was designated an "orphan medicine" (a medicine used in rare diseases) on 9 July 2003.

The medicine can only be obtained with a prescription.

How is Siklos used?

Treatment with Siklos should be started by a doctor who has experience in the treatment of sickle cell disease.

Siklos should be taken once a day, preferably in the morning before breakfast. The initial dose is generally 15 mg per kilogram of body weight, rounded to the nearest 250 mg (a quarter tablet). The tablet surface has incisions that allow it to be easily divided into four equal parts. The dosage is adjusted according to the patient's response to treatment; generally the dose is between 15 and 30 mg per kilogram of body weight per day. In exceptional cases doses up to 35 mg per kilogram of body weight per day can be used, provided that the patient's blood is monitored to detect the possible appearance of undesirable effects. In patients who do not respond to this dose or who experience side effects, it may be necessary to stop or stop treatment. In patients with mild or moderate kidney problems the dose of Siklos must be reduced; the drug should not be used in patients with severe liver or kidney problems. The use of Siklos is not recommended in children under the age of 2 years. For more information, see the package leaflet.

How does Siklos work?

The active ingredient in Siklos, hydroxycarbamide, inhibits the growth and reproduction of certain cells such as blood cells. Although its exact mechanism of action in this disease is not known, hydroxycarbamide can reduce the number of cells circulating in the blood and, in patients suffering from sickle cell disease, prevent red blood cells from taking on a different form. This reduces the risk of occlusion of blood vessels.

Hydroxycarbamide, formerly known as hydroxyurea, has been available in the European Union (EU) for several decades for the treatment of other diseases, including some types of cancer.

What studies have been carried out on Siklos?

Since hydroxycarbamide is a well-known substance, already used in other medicines, the company presented data from the scientific literature supporting the administration of Siklos to adults and children suffering from sickle cell disease. In particular, it provided evidence of the effectiveness of Siklos taken from 11 published studies, conducted on 378 children, and from three national information registers on 155 children, treated with Siklos for a maximum period of 7 years. The manufacturer also presented the scientific evidence gathered in a study carried out on 299 adults, in which the effects of Silkos were compared with a placebo (a dummy treatment), as well as the results of other studies involving 430 adults and data coming from from a national register of information on 123 adults treated with Siklos. The studies compared the number of vaso-occlusive seizures before and after treatment with Siklos, defined as any painful episode involving the arms, legs, abdomen, back or chest.

What benefit has Siklos shown during the studies?

Patients treated with Siklos reported fewer vaso-occlusive seizures after treatment with Siklos than at the time before treatment, with a frequency reduction of between 66% and 80% in both children and adults. The frequency of cases of acute chest syndrome is also decreased (25-33%). Finally, there was a reduction in the number of hospital admissions, as well as days spent in hospital. These effects were maintained for up to 7 years. In the study comparing Siklos with placebo in adults, fewer vaso-occlusive seizures were seen in patients taking the medicine (2.5 seizures per year) than in placebo-treated patients (4.5 seizures per year).

What is the risk associated with Siklos?

The most common side effects with Siklos (seen in more than 1 patient in 10) are bone marrow depression, which causes neutropenia (decreased levels of neutrophils, a type of white blood cell), reticulocytopenia (decreased reticulocyte levels, a type of precursor of red blood cells) and macrocytosis (enlargement of red blood cells). Patients taking Siklos must have blood tests before and regularly during treatment, to check the red blood cell count and also to monitor the status of the kidneys and liver. Blood cell counts generally return to normal levels within two weeks after stopping Siklos treatment. For the full list of all side effects reported with Siklos, see the Package Leaflet.

Siklos should not be used in people who may be hypersensitive (allergic) to hydroxycarbamide or any of the other substances. Furthermore, it must not be used by people with severe liver or kidney problems, or with dangerously low blood cell counts. Breast-feeding should be discontinued while taking Siklos.

Why has Siklos been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Siklos' benefits are greater than its risks for the prevention of painful recurrent vaso-occlusive seizures, including acute chest syndrome in pediatric patients and adults with symptomatic sickle cell disease. The Committee therefore recommended that Siklos be given marketing authorization.