title: Safety of deferasirox: a retrospective cohort study on the risks of gastrointestinal, liver and renal events.
abstract: BACKGROUND
  Deferasirox (DFX) is an effective and well-tolerated oral iron chelator elevating the adherence to iron chelating therapy among patients with iron overload. However, the US Food and Drug Administration issued a warning about the potential adverse events associated with DFX in 2010.
  
  
  METHODS
  To examine the risks of gastrointestinal (GI) bleeding, acute liver necrosis, and acute renal failure among DFX users compared with desferrioxamine (DFO) users in a real-world setting, first-time users of DFX or DFO between 2005 and 2008 in Taiwan's National Health Insurance database were observed in this population-based retrospective cohort study. The risks of different adverse events were individually analyzed by Cox proportional hazards models and adjusted by age, sex, concomitant medications, and prior medical conditions.
  
  
  RESULTS
  Deferasirox users had the highest incidence rates of GI bleeding (2.03 per 10 000 patient-days), acute liver necrosis (0.26 per 10 000 patient-days) and acute renal failure (1.45 per 10 000 patient-days) compared with other iron chelator users. Compared with DFO users, DFX users were not associated with the risk of GI bleeding (adjusted HR 1.03, 95% CI 0.61-1.74, p = 0.90) and the risk of acute liver necrosis (adjusted HR 2.13, 95% CI 0.49-9.33, p = 0.32). The association between DFX use and acute renal failure was found to be statistically significant (HR 2.18, 95% CI 1.18-4.02, p = 0.01; adjusted HR 2.41, 95% CI 1.27-4.58, p = 0.01).
  
  
  CONCLUSIONS
  In this study, we found statistically significant higher risk of acute renal failure and non-statistically significant higher risk of GI bleeding and acute liver necrosis associated with DFX use. More researches are warranted to evaluate the association between DFX use and potential adverse events.
authors.affiliation: Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan; Center for Health and Welfare Policy Research, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Weng-Foung
authors.initials: WF
authors.lastname: Huang
authors.forename: Hsin-Chun
authors.initials: HC
authors.lastname: Chou
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Tsai
authors.forename: Fei-Yuan
authors.initials: FY
authors.lastname: Hsiao
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D000077588:Deferasirox; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D015994:Incidence; D007502:Iron Chelating Agents / Q000009:adverse effects* / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013624:Taiwan / Q000453:epidemiology; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox
keywords: acute liver necrosis; acute renal failure; deferasirox; desferrioxamine; gastrointestinal bleeding; iron chelator; pharmacoepidemiology