Clinical use, therapeutic aspects and future potential of deferiprone in thalassemia and other conditions of iron and other metal toxicity

The therapeutic aspects and future prospects of the new iron chelating drug deferiprone are reviewed, with an emphasis on its clinical use in thalasse mia and other conditions of iron overload, imbalance and toxicity, as well as its possible use in other metal toxicity conditions. Orally administered deferiprone appears to be as effective as subcutaneous deferoxamine in the removal of iron in transfused iron loaded patients, with an equivalent the rapeutic index profile in both animals and humans. Only about 10% of patien ts requiring iron chelation therapy worldwide receive deferoxamine mainly b ecause of its high cost, toxicity and low compliance with subcutaneous admi nistration. Deferiprone has been used by over 6000 patients in 40 countries worldwide, in some cases daily for more than 10 years, with very promising results. Doses of 50-120 mg/kg/day are effective in bringing patients to n egative iron balance. Deferiprone increases urinary iron excretion, decreas es serum ferritin levels and reduces liver iron in the majority of chronica lly transfused iron loaded patients. All of the toxic side effects of defer iprone are considered reversible and manageable, and include agranulocytosi s, musculoskeletal and joint pains, gastrointestinal complaints and zinc de ficiency. In general, the incidence of toxic side effects could be reduced by using lower doses or combination therapy with deferoxamine. The suggesti on that deferiprone therapy may cause liver fibrosis has not been confirmed . New therapeutic protocols for maximizing the efficacy and minimizing the toxicity of deferiprone are being considered based on new findings in relat ion to its metal chelation, pharmacological, toxicological and metabolic pr operties. (C) 2001 Prous Science. All rights reserved.