Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [C-max: 99.5 (FCT) and 69.7 (DT) mu Mol/L; AUC: 1278 (FCT) and 846 (DT), P<0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose-response correlation [Spearman r (dose-serum ferritin variation): - 0.54, P<0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P<0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.

Automated summary

Deferasirox (DFX) is the newest chelator used to treat iron overload in iron-loading anemias, with Film-Coated Tablets (FCT) showing higher bioavailability and superior scalability compared to Dispersible Tablets (DT). FCT exhibited a significant dose-response correlation for serum ferritin variation, while both formulations showed an increased risk of renal impairment that was reversible under monitoring, indicating the effectiveness and safety of DFX for tailoring treatment.