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Deferasirox is an oral iron chelating agent used to treat chronic iron overload.  Deferasirox has been linked to a low rate of transient serum aminotransferase elevations during therapy and to rare instances of clinically apparent liver injury, which can be severe and even fatal.



Deferasirox (dee fer’ a sir ox) is an orally available iron chelating agent that is selective for ferric iron and binds iron with a high affinity.  Deferasirox binds two iron molecules and is eliminated in the feces after hepatic metabolism by glucuronidation.  Deferasirox also binds zinc and copper, but to a far lower extent than iron.  In clinical trials in patients with transfusion related iron overload, deferasirox lowered both circulating and tissue (cardiac, liver) iron.  Deferasirox was approved for use in the United States in 2005 and current indications are for chronic iron overload due to blood transfusion and in nontransfusion dependent thalassemia syndromes.  Deferasirox is available in tablets of 125, 250 and 500 mg under the brand name Exjade.  The recommended initial dose is 10 to 20 mg/kg daily.  Side effects can include diarrhea, nausea, abdominal pain, headache, dizziness, rash and increases in serum creatinine.  Uncommon, but potentially severe adverse events are renal failure, gastrointestinal bleeding, bone marrow suppression and hypersensitivity reactions including Stevens Johnson syndrome.



In large clinical trials of deferasirox, elevations in serum aminotransferase levels above 5 times the upper limit of normal (ULN) occurred in 6% of patients and led to drug discontinuation in 1% to 2%.  In addition, there have been several single case reports of clinically apparent liver injury arising during deferasirox therapy which was often severe and occasionally fatal.  The onset of acute liver injury ranged from a few days to 8 weeks after starting deferasirox, and the pattern of injury was typically hepatocellular with marked elevations in serum aminotransferase levels.  Immunoallergic and autoimmune features were absent.  Recovery was usually rapid once deferasirox was stopped, but some cases were associated with progressive liver injury and hepatic failure.  Deferasirox has a boxed warning regarding hepatotoxicity and regular monitoring of serum bilirubin and aminotransferase levels is recommended.


Mechanism of Injury

The mechanism of injury accounting for serum enzyme elevations during deferasirox therapy is not known.  Deferasirox is metabolized in the liver largely by glucuronidation and biliary excretion.


Outcome and Management

Serum aminotransferase elevations above 5 times the upper limit of normal (if confirmed) should lead to dose reduction or temporary cessation.  Deferasirox has been implicated in cases of acute liver failure, but not in instances of chronic hepatitis or vanishing bile duct syndrome.  There does not appear to be cross reactivity in risk for hepatic injury between deferasirox and other chelators including deferoxamine or deferiprone.


Drug Class:  Hematological Agents; Chelating Agents, Iron Chelators


Other Drugs in the Subclass, Iron Chelators:  Deferiprone, Deferoxamine


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Deferasirox – Exjade®


Hematological Agents



Product labeling at DailyMed, National Library of Medicine, NIH


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Deferasirox 201530-41-8 C21-H15-N3-O4 Deferasirox structure

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References updated:  06 August 2014

  1. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.  (Review of hepatotoxicity published in 1999 before the availability of deferasirox).

  2. Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013.  (Textbook on hepatotoxicity; iron chelating agents are not discussed).

  3. Byrns MC, Penning TM. Treatment of metal exposure. Environmental toxicology: carcinogens and heavy metals. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1872-6.  (Textbook of pharmacology and therapeutics).

  4. Deferasirox (Exjade): a new iron chelator. Med Lett Drugs Ther 2006; 48 (1233): 35-6. PubMed Citation  (Concise review of the efficacy, safety and costs of deferasirox mentions that it has been associated with serum aminotransferase elevations and several cases of hepatitis).

  5. Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, Aydinok Y, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood 2006; 107: 3455-62. PubMed Citation  (Among 586 patients with beta thalassemia treated with either oral deferasirox or subcutaneous deferoxamine for one year, decreases in liver iron concentrations were similar with the highest doses; side effects of deferasirox included elevations in creatinine in 38% and ALT [ ≥2 times ULN] in two patients).

  6. Galanello R, Piga A, Forni GL, Bertrand Y, Foschini ML, Bordone E, Leoni G, et al. Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with beta-thalassemia major. Haematologica 2006; 91: 1343-51. PubMed Citation  (Among 40 children [ages 2-17 years] with beta thalassemia treated with deferasirox for 48 weeks, liver iron concentrations gradually increased and 5 developed ALT or AST elevations 5 times ULN, which resolved on stopping and did not recur on restarting deferasirox).

  7. Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, Files B, et al.; Deferasirox in Sickle Cell Investigators. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol 2007; 136: 501-8. PubMed Citation  (Among 195 adults with sickle cell disease and iron overload treated with either deferasirox or deferoxamine for 1 year, both groups had similar decreases in liver iron concentration, while ALT elevations ≥5 times ULN occurred in none on deferoxamine vs 5 [4%] on deferasirox, resolving despite continuing therapy in 4, but recurring with reexposure in 1 patient).

  8. Cappellini MD. Long-term efficacy and safety of deferasirox. Blood Rev 2008; 22 Suppl 2: S35-41. PubMed Citation  (Review of the efficacy and safety of deferasirox, mentions that reversible elevations in serum aminotransferase levels occur in some patients).

  9. Taher A, El-Beshlawy A, Elalfy MS, Al Zir K, Daar S, Habr D, Kriemler-Krahn U, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study. Eur J Haematol 2009; 82: 458-65. PubMed Citation  (In an open label study of deferasirox in 237 patients with beta thalassemia and iron overload, ALT elevations occurred in 5.5% of patients, but most resolved without need for discontinuation).

  10. Gattermann N, Finelli C, Porta MD, Fenaux P, Ganser A, Guerci-Bresler A, Schmid M, et al.; EPIC study investigators. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study. Leuk Res 2010; 34: 1143-50. PubMed Citation  (Among 341 patients with myelodysplastic syndromes and iron overload treated with deferasirox for up to one year, serum ALT and ferritin levels decreased together; one patient had an increase in ALT levels from 28 U/L before therapy to 568 U/L at day 190, with no information on symptoms, Alk P, bilirubin or long term outcome).

  11. Phatak P, Brissot P, Wurster M, Adams PC, Bonkovsky HL, Gross J, Malfertheiner P, et al. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology 2010; 52: 1671-779. PubMed Citation  (Among 49 patients with hemochromatosis treated with deferasirox for 48 weeks, ALT levels rose ≥3 times ULN in 16% and ≥5 times ULN in 10% of patients, but largely among those who received the highest dose [15 mg/kg/day]).

  12. Aslam N, Mettu P, Marsano-Obando LS, Martin A. Deferasirox induced liver injury in haemochromatosis. J Coll Physicians Surg Pak 2010; 20: 551-3. PubMed Citation  (63 year old woman with hemochromatosis developed fatigue and dark urine one month after starting deferasirox [bilirubin 13.2 mg/dL, ALT 115 U/L, Alk P 395 U/L], improving slowly after stopping).

  13. Imran FS, Phatak P. Deferasirox induced liver injury in haemochromatosis. J Coll Physicians Surg Pak 2011; 21: 718; author reply 718. PubMed Citation  (Letter in response to Aslam [2010] suggesting that the liver injury was due to the high dose used [~20 mg/kg]).

  14. Cappellini MD, Bejaoui M, Agaoglu L, Canatan D, Capra M, Cohen A, Drelichman G, et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood 2011; 118: 884-93. PubMed Citation  (Among 555 patients with thalassemia continued on deferasirox for up to 5 years after participation in a controlled trial [Cappellini 2008], liver iron concentrations decreased in those treated with the higher doses [20 and 30 mg/kg/day] and side effects were less with longer duration of therapy, ALT elevations ≥10 times ULN occurring in 1% of patients, but no mention of clinically apparent liver injury).

  15. Vichinsky E, Bernaudin F, Forni GL, Gardner R, Hassell K, Heeney MM, Inusa B, et al. Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease. Br J Haematol 2011; 154: 387-97. PubMed Citation  (Among 185 patients with sickle cell anemia and iron overload continued on deferasirox for up to 5 years after participation in a controlled trial [Vichinsky 2007], 5 [2.7%] had ALT elevations ≥5 times ULN, 2 more had elevations ≥10 times ULN, and one patient with chronic hepatitis C and cirrhosis underwent liver transplantation).

  16. Sinakos E, Vlachaki E, Tsapas A. Safety of deferasirox in sickle cell disease patients with co-existing liver impairment. Br J Haematol 2012; 157: 505-6; author reply 506-7. PubMed Citation  (Letter in response to Vichinsky [2011] requesting further information on the patient with hepatitis C who died; the authors reply that the patient had anti-HCV, but was HCV RNA negative [suggesting that the liver disease was not due to hepatitis C]).

  17. Vichinsky E, Torres M, Minniti CP, Barrette S, Habr D, Zhang Y, Files B; study CICL670A2201 investigators. Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: two-year results including pharmacokinetics and concomitant hydroxyurea. Am J Hematol 2013; 88: 1068-73. PubMed Citation  (Among 203 patients with sickle cell disease and iron overload treated with deferasirox or deferoxamine for 6 months and then all were given deferasirox for 2 more years, ALT increases occurred in 9 [6%], which were ≥5 times ULN in 2 [1.5%] deferasirox vs none of deferoxamine treated subjects).

  18. Kontoghiorghes GJ. A record number of fatalities in many categories of patients treated with deferasirox: loopholes in regulatory and marketing procedures undermine patient safety and misguide public funds? Author's response. Expert Opin Drug Saf 2013; 12: 794-5. PubMed Citation  (Editorial stating that there were 4113 fatalities among patients being treated with deferasirox in 2012 according to an anonymous postmarketing surveillance source, and that many patients who were being treated did not have iron overload).

  19. Riva A. A record number of fatalities in many categories of patients treated with deferasirox: loopholes in regulatory and marketing procedures undermine patient safety and misguide public funds? Expert Opin Drug Saf 2013; 12: 793-4. PubMed Citation  (Letter in response to Kontoghiorghes [2013] from the sponsor of deferasirox claiming that the editorial had many factual inaccuracies).

  20. Xia S, Zhang W, Huang L, Jiang H. Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials. PLoS One 2013; 8: e82662. PubMed Citation  (Systematic review and metaanalysis of 16 publications comparing iron chelating agents found differences in myocardial content, but not "live iron" concentrations with different therapies and that the combination of deferoxamine and deferiprone had "higher risk" than deferoxamine).

  21. Huang WF, Chou HC, Tsai YW, Hsiao FY. Safety of deferasirox: a retrospective cohort study on the risks of gastrointestinal, liver and renal events. Pharmacoepidemiol Drug Saf 2014 Jun 19. [Epub ahead of print] PubMed Citation  (Retrospective analysis of a Taiwanese health database found that first time users of deferasirox had higher crude rates of acute liver necrosis than those on deferoxamine [2 of 133 vs 21 of 3507 patients: 0.26 vs 0.05 per 10,000 patient-days], yet the differences in rates were not statistically significant).

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  1. PubMed logoRecent References on Deferasirox

  2. Clinical Trials logoTrials on Deferasirox

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