OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Deferoxamine	138-14-7	C25-H48-N6-O8.C-H4-O3-S

ANNOTATED BIBLIOGRAPHY

References updated: 27 December 2017

• 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 does not discuss deferoxamine).
• 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).
• Gratadour P, Fouque D, Chevalier P, Vial T, Chossegros P, Laville M, Labeeuw M, et al. [Acute hepatitis induced by deferoxamine in a patient under chronic hemodialysis]. Therapie 1992; 47: 555. French. [PubMed: 1301648]

  (65 year old man with chronic renal failure on hemodialysis developed fatigue 6 weeks after starting deferoxamine infusions three times weekly during hemodialysis [ALT 656 U/L, GGT 153 U/L, bilirubin 11.5 mg/dL, prothrombin index 21%], which resolved within 3 weeks of stopping the infusions).
• Silliman CC, Peterson VM, Mellman DL, Dixon DJ, Hambidge KM, Lane PA. Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: a randomized, double-blind study of the dose-response relationship. J Lab Clin Med 1993; 122: 48-54. [PubMed: 8320490]

  (In a pilot study of different doses of intravenous deferoxamine in 6 patients with sickle cell disease and iron overload, therapy for up to 3 months led to improvement in liver function and "no toxicity was encountered").
• Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, Burt AD, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med 1998; 339: 417-23. [PubMed: 9700174]

  (Among 19 patients with thalassemia major and iron overload who were treated with deferiprone for an average of 4.6 years, repeat liver biopsies showed progression of fibrosis in 5 of 14 patients with available liver histology; in contrast, no progression of histologic fibrosis was found in 12 separately studied subjects who had been treated with deferoxamine infusions).
• Franchini M, Gandini G, de Gironcoli M, Vassanelli A, Borgna-Pignatti C, Aprili G. Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood 2000; 95: 2776-9. [PubMed: 10779420]

  (Among 27 patients with various forms of iron overload treated with either subcutaneous or bolus intravenous deferoxamine, iron excretion was similar by both methods and was well tolerated and effective in lowering serum ferritin in 26 patients who continued bolus therapy; no mention of ALT elevations or hepatotoxicity).
• Taher A, Sheikh-Taha M, Koussa S, Inati A, Neeman R, Mourad F. Comparison between deferoxamine and deferiprone (L1) in iron-loaded thalassemia patients. Eur J Haematol 2001; 67: 30-4. [PubMed: 11553264]

  (Comparison of 16 patients on oral deferiprone and 40 on subcutaneous deferoxamine therapy for thalassemia major and iron overload, AST elevations [≥2 times ULN, but transient in all] occurred in in 13 [81%] on deferiprone, but apparently none on deferoxamine).
• Franchini M, Gandini G, Veneri D, Aprili G. Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload: an update. Blood 2004; 103: 747-8. [PubMed: 14702291]

  (Further follow up of patients on bolus deferoxamine therapy found that most patients eventually returned to the subcutaneous route because of poor tolerance [infusion reactions and pain]; no mention of ALT elevations or hepatotoxicity).
• 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: 16352812]

  (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).
• 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. [PMC free article: PMC1974786] [PubMed: 17233848]

  (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).
• 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: 23946212]

  (Among 203 patients with sickle cell disease and iron overload treated with deferasirox or deferoxamine for 6 months, after which all were given deferasirox for 2 more years, ALT increases occurred in 9 [6%] which were ≥5 times ULN in 2 [1.5%] of deferasirox- vs none of deferoxamine treated subjects).
• 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. [PMC free article: PMC3871701] [PubMed: 24376563]

  (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).
• 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; 23: 1176-82. [PubMed: 24946110]

  (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).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, none of which were chelating agents such as deferoxamine, deferiprone or deferasirox).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, no case was attributed to deferoxamine or deferiprone, but 1 was due to deferasirox, a 54 year old woman with hemochromatosis who developed ALT elevations [rising from 25 to 305 U/L] without symptoms or jaundice a month after starting deferasirox that resolved rapidly with stopping and recurred upon restarting).
• Calvaruso G, Vitrano A, Di Maggio R, Ballas S, Steinberg MH, Rigano P, Sacco M, et al.; The Investigators of the Multicenter Randomized Clinical Trial of Deferiprone versus Deferoxamine in Sickle-Cell-Disease. Deferiprone versus deferoxamine in sickle cell disease: results from a 5-year long-term Italian multi-center randomized clinical trial. Blood Cells Mol Dis 2014; 53: 265-71. [PubMed: 24814618]

  (Among 60 patients with sickle cell anemia and iron overload treated with deferiprone or deferoxamine for up to 5 years, serum ferritin levels decreased in both groups to a similar extent, and "liver damage" [increase twice the normal value] occurred in 10% of deferiprone, but none of deferoxamine treated subjects).
• Botzenhardt S, Li N, Chan EW, Sing CW, Wong IC, Neubert A. Safety profiles of iron chelators in young patients with haemoglobinopathies. Eur J Haematol 2017; 98: 198-217. [PubMed: 27893170]

  (Review of literature on safety of iron chelators in young patients reported "increased liver enzymes" in 4% of subjects on deferoxamine, 6% on deferprone and 20% on deferasirox; no mention of clinically apparent liver injury).