title: Introduction of higher doses of deferasirox: better efficacy but not effective iron removal from the heart and increased risks of serious toxicities.
abstract: BACKGROUND
  Thousands of iron loaded patients are using deferasirox, who are not aware of the new, fatal and irreversible serious toxic side effects, the need for prophylaxis and the availability of more effective and less toxic chelation therapies.
  
  
  METHODS
  Updating on efficacy issues in relation to the introduction of higher deferasirox doses and comparison to existing chelation therapies. A new maximum dose of 40 mg/kg/day has been introduced for deferasirox in an attempt to achieve negative iron balance in thalassemia and other transfused iron loaded patients. A marginal increase in cardiac iron removal using doses of 30 - 40 mg/kg/day suggests that the rate of iron removal by deferasirox is insufficient by comparison to the deferiprone/deferoxamine combination, where total and rapid clearance of excess cardiac iron and normalization of the body iron stores could be achieved.
  
  
  RESULTS
  Identification of drug interactions and new fatal and permanent toxic side effects of deferasirox and implications on efficacy, toxicity and cost of using higher doses. Deferasirox has been identified to cause fatal gastrointestinal hemorrhages, renal tubulopathy, hepatic and renal failure, alopecia and anaphylactic reactions in addition to previously reported fatal or serious toxic side effects such as agranulocytosis, renal and hepatic toxicity, skin rash and gastric intolerance. Interactions with UDP-glucuronosyl transferase inducers, CYP2C8 and CYP3A4 substrates and drugs affecting enterohepatic recycling are likely to affect deferasirox's efficacy and toxicity. Increased toxicity is expected from the use of higher doses of deferasirox and regular prophylactic monitoring is required to avoid fatal and permanent toxicity incidences. The increased costs from higher doses of deferasirox will mostly affect patients living in the developing countries.
  
  
  CONCLUSIONS
  Only few patients may benefit from the introduction of higher doses of deferasirox. There is a need for introducing more effective prophylactic measures. Safer, more effective and less costly chelation treatments are available using deferiprone, deferoxamine and their combination.
authors.affiliation: Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3, Ammochostou Street, Limassol 3021, Cyprus. kontoghiorghes.g.j@pri.ac.cy
authors.forename: George J
authors.initials: GJ
authors.lastname: Kontoghiorghes
mesh_terms: D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015913:Chelation Therapy / Q000009:adverse effects*; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy; D009206:Myocardium / Q000378:metabolism*; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox