Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

Sci Rep. 2021 Jun 15;11(1):12581. doi: 10.1038/s41598-021-91983-w.

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.

MeSH terms

  • Adult
  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / epidemiology
  • Anemia / pathology
  • Chelation Therapy / trends
  • Deferasirox / administration & dosage*
  • Deferasirox / pharmacokinetics
  • Female
  • Ferritins / blood
  • Humans
  • Iron / blood
  • Iron / metabolism
  • Iron Chelating Agents / administration & dosage
  • Iron Chelating Agents / pharmacokinetics
  • Iron Overload / blood
  • Iron Overload / drug therapy*
  • Iron Overload / epidemiology
  • Iron Overload / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thalassemia / blood
  • Thalassemia / drug therapy*
  • Thalassemia / epidemiology
  • Thalassemia / pathology

Substances

  • Iron Chelating Agents
  • Ferritins
  • Iron
  • Deferasirox