Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

Abstract

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 [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/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.

Challenges of Iron Chelation in Thalassemic Children

“…It is rapidly absorbed from the gastrointestinal tract, reaching a maximum plasma concentration 1.5-4 h post dose. The drug is metabolized in the liver and, to a lesser extent, excreted in the urine [36]. According to the DFX pharmacokinetic profile, chelation activity over a 24 h period is provided after once-daily oral administration, while the long-lasting DFX presence in plasma provides efficient protection against the effects of circulating non-transferrin-bound iron [34].…”

Deferasirox film‐coated tablet‐associated ulcerative colitis: An emerging pattern in thalassemia patients?

“…On the other end, the overall duration of chronic therapy does not seem to protect or exacerbate the effect. As already mentioned elsewhere, 13,14 personalized titration would be therefore crucial to balance DFX efficacy and safety. (4) Increased faecal calprotectin was observed in all cases and prompted more specific tests which eventually recognized the presence of GI alterations.…”