Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload

Br J Haematol. 2009 Dec;147(5):752-9. doi: 10.1111/j.1365-2141.2009.07908.x. Epub 2009 Sep 18.

Abstract

The highest approved dose of deferasirox is currently 30 mg/kg per d in many countries; however, some patients require escalation above 30 mg/kg per d to achieve their therapeutic goals. This retrospective analysis investigated the efficacy (based on change in serum ferritin levels) and safety of deferasirox >30 mg/kg per d in adult and paediatric patients with transfusion-dependent anaemias, including beta-thalassaemia, sickle cell disease and the myelodysplastic syndromes. In total, 264 patients pooled from four clinical trials received doses of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks. In the overall population there was a statistically significant median decrease in serum ferritin of 440 microg/l (P < 0.0001) from pre-dose-escalation to the time-of-analysis; significant decreases were also observed in adult and paediatric patients, as well as beta-thalassaemia patients. The adverse event profile in patients who received deferasirox doses of >30 mg/kg per d was consistent with previously published data. There was no worsening of renal or liver function following dose escalation. Deferasirox >30 mg/kg per d effectively reduced iron burden to levels lower than those achieved prior to dose escalation in patients with transfusion-dependent anaemias. This has important implications for patients who are heavily transfused and may require higher doses to reduce body iron burden.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Anemia / therapy*
  • Benzoates / administration & dosage
  • Benzoates / adverse effects
  • Benzoates / therapeutic use*
  • Child
  • Child, Preschool
  • Creatinine / blood
  • Deferasirox
  • Drug Administration Schedule
  • Female
  • Ferritins / blood
  • Humans
  • Iron Chelating Agents / administration & dosage
  • Iron Chelating Agents / adverse effects
  • Iron Chelating Agents / therapeutic use*
  • Iron Overload / blood
  • Iron Overload / drug therapy*
  • Iron Overload / etiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transfusion Reaction*
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*
  • Young Adult

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Ferritins
  • Creatinine
  • Deferasirox