title: Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for patients with transfusion-dependent β-thalassemia.
abstract: BACKGROUND
  Deferasirox is an oral iron-chelating agent taken once-daily by patients with transfusion-dependent iron overload. However, some patients are unresponsive or unable to tolerate once-daily deferasirox. The current study evaluated whether twice-daily deferasirox treatment showed increased efficacy or tolerability in unresponsive or intolerant patients.
  
  
  METHODS
  Patients from two Taiwanese hospitals with transfusion-dependent β-thalassemia, including those who showed increasing serum ferritin levels for six consecutive months, with at least one level >2,500 ng/dl, while treated with >30 mg/kg/day of once-daily deferasirox (unresponsive) or developed deferasirox-related adverse events (AEs) at the dosage required to maintain the iron burden balance (intolerant) and were treated twice-daily with the same total daily dose of deferasirox since 2008, were enrolled in the study and evaluated retrospectively by medical record review.
  
  
  RESULTS
  Eighteen patients were included for analysis. A statistically significant median decrease in serum ferritin levels was detected in the 11 unresponsive patients after 6 months of continuous twice-daily deferasirox treatment. Five out of the seven intolerant patients experienced either no deferasirox-related AEs or less severe AEs. The 12 patients from both groups (11 unresponsive, 1 intolerant) who received continuous twice-daily deferasirox for 6 months showed a mild but significant median increase in serum creatinine levels.
  
  
  CONCLUSIONS
  Twice-daily deferasirox dosing is effective in iron chelation and improves tolerability in transfusion-dependent β-thalassemia patients who are unresponsive to or intolerant of once-daily deferasirox. Future studies with greater patient numbers will be required to confirm the results reported herein.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsiu-Hao
authors.initials: HH
authors.lastname: Chang
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Lu
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liao
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Lin
authors.forename: Yung-Li
authors.initials: YL
authors.lastname: Yang
authors.forename: Dong-Tsamn
authors.initials: DT
authors.lastname: Lin
authors.forename: Shyh-Shin
authors.initials: SS
authors.lastname: Chiou
authors.forename: Shiann-Tarng
authors.initials: ST
authors.lastname: Jou
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.forename: Tai-Tsung
authors.initials: TT
authors.lastname: Chang
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage*; D002648:Child; D000077588:Deferasirox; D004334:Drug Administration Schedule; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D019190:Iron Overload / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D012189:Retrospective Studies; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D000077588:Deferasirox