DEFERIPRONE

Deferiprone therapy should be initiated and maintained by a physician experienced in the treatment of patients with thalassaemia. Posology Deferiprone is usually given as 25mg/kg body weight, orally, three times a day for a total daily dose of 75mg/kg body weight.

Dose per kilogram body weight should be calculated to the nearest half tablet. See table below for recommended doses for body weights at 10kg increments. To obtain a dose of about 75mg/kg/day, use the number of tablets suggested in the following table for the body weight of the patient.

Sample body weights at 10kg increments are listed. 9). Dose adjustment The effect of deferiprone in decreasing the body iron is directly influenced by the dose and the degree of iron overload. After starting deferiprone therapy, it is recommended that serum ferritin concentrations, or other indicators of body iron load, be monitored every two to three months to assess the long-term effectiveness of the chelation regimen in controlling the body iron load.

Dose adjustments should be tailored to the individual patient's response and therapeutic goals (maintenance or reduction of body iron burden). Interruption of therapy with deferiprone should be considered if serum ferritin measurements fall below 500μg/l.

Dose adjustments when used with other iron chelators In patients for whom monotherapy is inadequate, Deferiprone may be used with deferoxamine at the standard dose (75 mg/kg/day) but should not exceed 100 mg/kg/day. In the case of iron-induced heart failure, Deferiprone at 75-100 mg/kg/day should be added to deferoxamine therapy.

The product information of deferoxamine should be consulted. Concurrent use of iron chelators is not recommended in patients whose serum ferritin falls below 500 μg/l due to the risk of excessive iron removal. 2). The safety and pharmacokinetics of deferiprone in patients with end stage renal disease are unknown.

2). The safety and pharmacokinetics of deferiprone in patients with severe hepatic impairment are unknown. Paediatric population There are limited data available on the use of deferiprone in children between 6 and 10 years of age, and no data on deferiprone use in children under 6 years of age.

Method of administration Oral use.

Summary of the safety profile The most common adverse reactions reported during therapy with deferiprone in clinical trials were nausea, vomiting, abdominal pain, and chromaturia, which were reported in more than 10% of patients. 5 x 109/l, which occurred in approximately 1% of patients.

Less severe episodes of neutropenia were reported in approximately 5% of patients.

Tabulated list of adverse reactions Adverse reaction frequencies:

Very common (≥1/10), Common (≥1/100 to <1/10), Not known (cannot be estimated from the available data). 4). Data from pooled clinical studies in patients with systemic iron overload showed that 63% of the episodes of agranulocytosis occurred within the first six months of treatment, 74% within the first year and 26% after one year of therapy.

6 years) and median duration was 10 days in clinical studies. 3% of the reported episodes of agranulocytosis from clinical studies and post-marketing experience. 5 cases per 100 patient-years). This rate should be considered in the context of the underlying elevated incidence of neutropenia in thalassaemia patients, particularly in those with hypersplenism.

Episodes of diarrhoea, mostly mild and transient, have been reported in patients treated with deferiprone. Gastrointestinal effects are more frequent at the beginning of therapy and resolve in most patients within a few weeks without the discontinuation of treatment.

In some patients it may be beneficial to reduce the dose of deferiprone and then scale it back up to the former dose. Arthropathy events, which ranged from mild pain in one or more joints to severe arthritis with effusion and significant disability, have also been reported in patients treated with deferiprone.

Mild arthropathies are generally transient. Increased levels of serum liver enzymes have been reported in some patients taking deferiprone. 4). Some patients experienced progression of fibrosis associated with an increase in iron overload or hepatitis C.

8 ‘Description of selected adverse reactions’). The patient's absolute neutrophil count (ANC) should be monitored every week during the first year of therapy. For patients whose Deferiprone has not been interrupted during the first year of therapy due to any decrease in the neutrophil count, the frequency of ANC monitoring may be extended to the patient’s blood transfusion interval (every 2-4 weeks) after one year of deferiprone therapy.

4 below). In clinical studies, weekly monitoring of the neutrophil count has been effective in identifying cases of neutropenia and agranulocytosis. Agranulocytosis and neutropenia usually resolve upon discontinuation of Deferiprone, but fatal cases of agranulocytosis have been reported.

If the patient develops an infection while on deferiprone, therapy should be immediately interrupted, and an ANC obtained without delay. The neutrophil count should be then monitored more frequently. Patients should be aware to contact their physician if they experience any symptoms indicative of infection (such as fever, sore throat and flu-like symptoms).

Immediately interrupt deferiprone if the patient experiences infection. Suggested management of cases of neutropenia is outlined below. It is recommended that such a management protocol be in place prior to initiating any patient on deferiprone treatment.

Treatment with deferiprone should not be initiated if the patient is neutropenic. 5x109/l. 5x109/l): Instruct the patient to immediately discontinue deferiprone and all other medicinal products with a potential to cause neutropenia. The patient should be advised to limit contact with other individuals in order to reduce the risk of infection.

Obtain a complete blood cell (CBC) count, with a white blood cell (WBC) count, corrected for the presence of nucleated red blood cells, a neutrophil count, and a platelet count immediately upon diagnosing the event and then repeat daily.

1. - History of recurrent episodes of neutropenia. - History of agranulocytosis. 6). 6). 5).