title: Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload.
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.
authors.affiliation: Department of Internal Medicine, Haematology-Oncology Division, American University of Beirut, Medical Centre, Beirut, Lebanon. ataher@aub.edu.lb
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
authors.forename: Maria D
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lawniczek
authors.forename: Joan
authors.initials: J
authors.lastname: Clark
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000628:therapy*; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D000077588:Deferasirox; D004334:Drug Administration Schedule; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D003404:Creatinine; D000077588:Deferasirox