Deferiprone - A review of its clinical potential in iron overload in beta-thalassaemia major and other transfusion-dependent diseases

Patients with beta-thalassaemia and other transfusion-dependent diseases de velop iron overload from chronic blood transfusions and require regular iro n chelation to prevent potentially fatal iron-related complications, The on ly iron chelator currently widely available is deferoxamine, which is expen sive and requires prolonged subcutaneous infusion 3 to 7 times per week or daily intramuscular injections. Moreover. some patients are unable to toler ate deferoxamine and compliance with the drug is poor in many patients. Deferiprone is the most extensively studied oral iron chelator to date. Non comparative clinical studies mostly in patients with beta-thalassaemia have demonstrated that deferiprone 75 to 100 mg/kg/day can reduce iron burden i n regularly transfused iron-overloaded patients, Serum ferritin levels are generally reduced in patients with very high pretreatment levels and are fr equently maintained within an acceptable range in those who are already ade quately chelated. Deferiprone is not effective in all patients (some of who m show increases in serum ferritin and/or liver iron content, particularly during long term therapy), This may reflect factors such as suboptimal dosa ge and/or severe degree of iron overload at baseline in some instances. Although few long term comparative data are available, deferiprone at the r ecommended dosage of 75 mg/kg/day appears to be less effective than deferox amine; however, compliance is superior with deferiprone, which may partly c ompensate for this. Deferiprone has additive, or possibly synergistic, effe cts on iron excretion when combined with deferoxamine, The optimum dosage and long term efficacy of deferiprone, and its effects o n survival and progression of iran-related organ damage, remain to be estab lished. The most important adverse effects in deferiprone-treated patients are arth ropathy and neutropenia/agranulocytosis. Other adverse events include gastr ointestinal disturbances. ALT elevation, development of antinuclear antibod ies and zinc deficiency, With deferiprone, adverse effects occur mostly in heavily iron-loaded patients, whereas with deferoxamine adverse effects occ ur predominantly when body iron burden is lower. Conclusion: Deferiprone is the most premising oral iron chelator under deve lopment at present. Further studies are required to determine the best way to use this new drug. Although it appears to be less effective than deferox amine at the recommended dosage and there are concerns regarding its tolera bility, it may nevertheless offer a therapeutic alternative in the manageme nt of patients unable or unwilling to receive the latter drug. Deferiprone also shows promise as an adjunct to deferoxamine therapy in patients with i nsufficient response and may prove useful as a maintenance treatment to int erpose between treatments.