Deferasirox for transfusion-related iron overload: A clinical review

Background: Iron is an essential element involved in energy production, mitochondrial respiration, and DNA synthesis in the body. Excess iron forms insoluble complexes that are deposited in, and cause damage to, internal organs. Diseases such as beta-thalassemia and myelodysplastic syndrome that require frequent blood transfusions can result in excess iron in the body. The traditional therapy for iron overload is overnight infusion of deferoxamine multiple nights per week. Deferasirox is a new once-daily oral agent for iron overload that was approved by the US Food and Drug Administration in November 2005. Objective: The objective of this article was to review available data on deferasirox in the treatment of iron overload, including its mechanism of action, pharmacokinetics, clinical efficacy, and tolerability. Methods: MEDLINE, Iowa Drug Information Service, and International Pharmaceutical Abstracts were searched for English-language articles published before February 2007. Terms used in the search included deferasirox, Exjade, ICL 670, beta-thalassemia, and iron overload. Human clinical trials were included in the review; meeting abstracts were excluded from the review of clinical studies. Results: The literature search identified 5 Phase I/II studies and I Phase III study of deferasirox in pediattic and adult populations. In the Phase I/II trials, which focused primarily on pharmacokinetics and the safety profile, deferasirox was relatively well tolerated. Adverse events were primarily gastrointestinal disruptions and skin rash (8%), which usually resolved with continued therapy. The Phase III study was a multinational, randomized, open-label noninferiority comparison of the effect of deferasirox 5 to 30 mg/kg PO once daily and deferoxamine 20 to 60 mg/kg SC per day, 5 days per week, on reducing liver iron concentrations over I year in 586 patients with beta-thalassemia and transfusion-related iron overload. The 2 agents had similar efficacy, although deferasirox was associated with a higher incidence of adverse effects. Conclusions: Deferasirox is the first oral agent for the treatment of iron overload in the United States. It appears to be effective and well tolerated. However, its long-term efficacy and safety remain to be established.