Medication Summary

The goals of pharmacotherapy in cases of transfusion-induced iron overload are to protect tissues from damage caused by iron, decrease plasma and cytosolic levels of reactive labile iron to normal, and rid the body of all excess iron, thereby preserving organ function.^[13] Three iron-chelating agents are available: deferoxamine, deferasirox, and deferiprone.

Class Summary

Chelating agents help reduce iron levels in the body by promoting the excretion of chelated iron.

Deferoxamine (Desferal mesylate)

View full drug information

The drug is siderophore (iron-binder) derived from the bacterium Streptomyces pilosus.

It is usually administered as a slow SC infusion through a portable pump. It is freely soluble in water. Approximately 8 mg of iron is bound by 100 mg of deferoxamine, forming a 1:1 hexadentate complex. Its half-life is 20-30 minutes.

Promotes renal and hepatic excretion in urine and bile in feces. Gives urine a red discoloration. Readily chelates iron from ferritin and hemosiderin but not from transferrin. Does not affect iron in the cytochromes or hemoglobin. Most effective when provided to the circulation continuously by infusion. Helps prevent damage to the liver and bone marrow from iron deposition.

May be administered either by IM injection or by slow IV infusion.

The starting dose in individuals without iron-induced cardiac dysfunction is 30 mg/kg daily infused over 8 to 12 hours, five days per week. Dosing an be changed by 5 to 10 mg every three to six months depending on transfusion burden and iron status of the patient.

Does not effectively chelate other trace metals of nutritional importance. Provided in vials containing 500 mg of lyophilized sterile drug. Two mL of sterile water for injection should be added to each vial, bringing the concentration to 250 mg/mL. For IV use, this may be diluted in 0.9% sterile saline, 5% dextrose solution, or Ringer solution.

Deferasirox (Exjade tablets)

View full drug information

Tablets for oral suspension. Oral iron chelation agent that is demonstrated to reduce the liver iron concentration in adults and children who receive repeated RBC transfusions. Binds iron with high affinity in a 2:1 ratio (tridentate complex). Approved to treat chronic iron overload due to multiple blood transfusions.

Treatment initiation is recommended with evidence of chronic iron overload (ie, transfusion of about 100 mL/kg packed RBCs [about 20 U for a 40-kg person] and a serum ferritin level consistently >1000 mcg/L).

The dose for deferasirox is 20 mg/kg/day orally once daily, and then increased by 5 to 10 mg every three to six months based on levels of iron stores.

Deferiprone (Ferriprox)

View full drug information

1,2 dimethyl-3-hydroxypyridine-4-one is a member of a family of hydroxypyridine-4-one (HPO) chelators that requires 3 molecules to fully bind iron (III), each molecule providing 2 coordination sites (bidentate chelation). Half-life is approximately 2 hours. Inactive metabolite is predominantly excreted in urine. It is indicated for adults and children aged 3 years and older with iron overload from transfusion for thalassemia syndromes, sickle cell disease, or other anemias. Available as tablets and oral solution.

Follow-up

Anderson GJ. Mechanisms of iron loading and toxicity. Am J Hematol. 2007 Dec. 82(12 suppl):1128-31. [QxMD MEDLINE Link].
Takahiro Suzuki, Masao Tomonaga, Yasushi Miyazaki, Shinji Nakao, Kazuma Ohyashiki, Itaru Matsumura, et al. Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes. Int J Hematol. 2008 June 27. 88:6. [Full Text].
Ems T, Huecker MR. Biochemistry, Iron Absorption. Molecular and Cellular Iron Transport. 2019 Jan. 559-96. [QxMD MEDLINE Link]. [Full Text].
Diseases of iron metabolism. The Internet Pathology Laboratory for Medical Education. Available at http://library.med.utah.edu/WebPath/TUTORIAL/IRON/IRON.html. Accessed: December 18, 2019.
Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta. 2006 Jul. 1763(7):700-10. [QxMD MEDLINE Link].
Anderson GJ, Darshan D, Wilkins SJ, Frazer DM. Regulation of systemic iron homeostasis: how the body responds to changes in iron demand. Biometals. 2007 Jun. 20(3-4):665-74. [QxMD MEDLINE Link].
Anderson GJ. Mechanisms of iron loading and toxicity. Am J Hematol. 2007 Dec. 82(12 suppl):1128-31. [QxMD MEDLINE Link].
Hershko C. Iron loading and its clinical implications. Am J Hematol. 2007 Dec. 82(12 suppl):1147-8. [QxMD MEDLINE Link].
Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007 May. 92(5):583-8. [QxMD MEDLINE Link]. [Full Text].
Kohgo Y, Ohtake T, Ikuta K, et al. Iron accumulation in alcoholic liver diseases. Alcohol Clin Exp Res. 2005 Nov. 29(11 suppl):189S-93S. [QxMD MEDLINE Link].
Esposito BP, Breuer W, Sirankapracha P, et al. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood. 2003 Oct 1. 102(7):2670-7. [QxMD MEDLINE Link]. [Full Text].
Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995 Dec. 41(12 pt 2):1819-28. [QxMD MEDLINE Link]. [Full Text].
Thomas D. Coates. Iron overload in transfusion-dependent patients. Hematology Am Soc Hematol Educ Program. 2019 Dec 6. 1:337-344. [QxMD MEDLINE Link].
Ganong WF. Digestion and absorption. Ganong WF, ed. Review of Medical Physiology. 17th ed. East Norwalk, Conn, U: Appleton & Lange; 1995. 441.
Saito H. Storage Iron Turnover from a New Perspective. Acta Haematol. 2019. 141 (4):201-208. [QxMD MEDLINE Link].
Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR. Complications of beta-thalassemia major in North America. Blood. 2004 Jul 1. 104(1):34-9. [QxMD MEDLINE Link]. [Full Text].
Brittenham GM. Iron-chelating therapy for transfusional iron overload. N Engl J Med. 2011 Jan 13. 364(2):146-56. [QxMD MEDLINE Link]. [Full Text].
Takatoku M, Uchiyama T, Okamoto S, et al. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol. 2007 Jun. 78(6):487-94. [QxMD MEDLINE Link].
Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C. Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci. 2005. 1054:445-50. [QxMD MEDLINE Link].
Fung EB, Harmatz P, Milet M, et al. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. Am J Hematol. 2007 Apr. 82(4):255-65. [QxMD MEDLINE Link].
Brown KE, Khan CM, Zimmerman MB, Brunt EM. Hepatic iron overload in blacks and whites: a comparative autopsy study. Am J Gastroenterol. 2003 Jul. 98(7):1594-8. [QxMD MEDLINE Link].
Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Multicentre study on prevalence of endocrine complications in thalassaemia major. Clin Endocrinol (Oxf). 1995 Jun. 42(6):581-6. [QxMD MEDLINE Link].
Milosevic R, Antonijevic N, Jankovic G, Babic D, Colovic M. [Aplastic anemia--clinical characteristics and survival analysis] [Serbian]. Srp Arh Celok Lek. 1998 Jul-Aug. 126(7-8):234-8. [QxMD MEDLINE Link].
Aul C, Gattermann N, Germing U, Runde V, Heyll A. [Myelodysplastic syndromes. The epidemiological and etiological aspects] [German]. Dtsch Med Wochenschr. 1992 Aug 14. 117(33):1223-31. [QxMD MEDLINE Link].
Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994 Sep 1. 331(9):574-8. [QxMD MEDLINE Link]. [Full Text].
Suarez WA, Snyder SA, Berman BB, Brittenham GM, Patel CR. Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography. J Am Soc Echocardiogr. 1998 Oct. 11(10):948-56. [QxMD MEDLINE Link].
Wolfe L, Olivieri N, Sallan D, et al. Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. N Engl J Med. 1985 Jun 20. 312(25):1600-3. [QxMD MEDLINE Link].
Huang YC, Chang JS, Wu KH, Peng CT. Regression of myocardial dysfunction after switching from desferrioxamine to deferiprone therapy in beta-thalassemia major patients. Hemoglobin. 2006. 30(2):229-38. [QxMD MEDLINE Link].
Stoyanova E, Cloutier G, Felfly H, Lemsaddek W, Ah-Son N, Trudel M. Evidence for a novel mechanism independent of myocardial iron in ß-thalassemia cardiac pathogenesis. PLoS One. 2012. 7(12):e52128. [QxMD MEDLINE Link].
Aessopos A, Farmakis D. Pulmonary hypertension in beta-thalassemia. Ann N Y Acad Sci. 2005. 1054:342-9. [QxMD MEDLINE Link].
Piatti G, Allegra L, Fasano V, et al. Lung function in beta-thalassemia patients: a longitudinal study. Acta Haematol. 2006. 116(1):25-9. [QxMD MEDLINE Link].
Jean G, Terzoli S, Mauri R, Borghetti L, Di Palma A, Piga A, et al. Cirrhosis associated with multiple transfusions in thalassaemia. Arch Dis Child. 1984 Jan. 59(1):67-70. [QxMD MEDLINE Link]. [Full Text].
Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci U S A. 2006 Sep 12. 103(37):13612-7. [QxMD MEDLINE Link]. [Full Text].
Moayeri H, Oloomi Z. Prevalence of growth and puberty failure with respect to growth hormone and gonadotropins secretion in beta-thalassemia major. Arch Iran Med. 2006 Oct. 9(4):329-34. [QxMD MEDLINE Link].
He LN, Chen W, Yang Y, Xie YJ, Xiong ZY, Chen DY, et al. Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with β-Thalassemia Major: A Meta-Analysis. Biomed Res Int. 2019. 2019:6573497. [QxMD MEDLINE Link]. [Full Text].
De Sanctis V, Roos M, Gasser T, et al. Impact of long-term iron chelation therapy on growth and endocrine functions in thalassaemia. J Pediatr Endocrinol Metab. 2006 Apr. 19(4):471-80. [QxMD MEDLINE Link].
Chong Gao, Li Li, Baoan Chen, Huihui Song, Jian Cheng, Xiaoping Zhang, et al. Clinical outcomes of transfusion-associated iron overload in patients with refractory chronic anemia. Patient Prefer Adherence. 2014 Apr 22. 8:513-517. [QxMD MEDLINE Link]. [Full Text].
Cantinieaux B, Janssens A, Boelaert JR, et al. Ferritin-associated iron induces neutrophil dysfunction in hemosiderosis. J Lab Clin Med. 1999 Apr. 133(4):353-61. [QxMD MEDLINE Link].
Chirio R, Collignon A, Sabbah L, Lestradet H, Torlotin JC. [Yersinia enterocolitica infections and thalassemia major in children] [French]. Ann Pediatr (Paris). 1989 May. 36(5):308; 311-4. [QxMD MEDLINE Link].
Bergmann TK, Vinding K, Hey H. Multiple hepatic abscesses due to Yersinia enterocolitica infection secondary to primary haemochromatosis. Scand J Gastroenterol. 2001 Aug. 36(8):891-5. [QxMD MEDLINE Link].
Chiu HY, Flynn DM, Hoffbrand AV, Politis D. Infection with Yersinia enterocolitica in patients with iron overload. Br Med J (Clin Res Ed). 1986 Jan 11. 292(6513):97. [QxMD MEDLINE Link].
Karimi M, Jamalian N, Rasekhi A, Kashef S. Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia major patients: fluid surrounding the scaphoid bone: a novel finding, as the possible effect of secondary hemochromatosis. J Pediatr Hematol Oncol. 2007 Jun. 29(6):393-8. [QxMD MEDLINE Link].
Hassan M, Hasan S, Giday S, et al. Hepatitis C virus in sickle cell disease. J Natl Med Assoc. 2003 Oct. 95(10):939-42. [QxMD MEDLINE Link].
Halonen P, Mattila J, Suominen P, et al. Iron overload in children who are treated for acute lymphoblastic leukemia estimated by liver siderosis and serum iron parameters. Pediatrics. 2003 Jan. 111(1):91-6. [QxMD MEDLINE Link]. [Full Text].
Files B, Brambilla D, Kutlar A, et al. Longitudinal changes in ferritin during chronic transfusion: a report from the Stroke Prevention Trial in Sickle Cell Anemia (STOP). J Pediatr Hematol Oncol. 2002 May. 24(4):284-90. [QxMD MEDLINE Link].
Borgna-Pignatti C, Castriota-Scanderbeg A. Methods for evaluating iron stores and efficacy of chelation in transfusional hemosiderosis. Haematologica. 1991 Sep-Oct. 76(5):409-13. [QxMD MEDLINE Link].
Kolnagou A, Economides C, Eracleous E, Kontoghiorghes GJ. Low serum ferritin levels are misleading for detecting cardiac iron overload and increase the risk of cardiomyopathy in thalassemia patients. The importance of cardiac iron overload monitoring using magnetic resonance imaging T2 and T2*. Hemoglobin. 2006. 30(2):219-27. [QxMD MEDLINE Link].
Wood JC. Diagnosis and management of transfusion iron overload: the role of imaging. Am J Hematol. 2007 Dec. 82(12 suppl):1132-5. [QxMD MEDLINE Link].
Jacobs EM, Hendriks JC, van Tits BL, et al. Results of an international round robin for the quantification of serum non-transferrin-bound iron: need for defining standardization and a clinically relevant isoform. Anal Biochem. 2005 Jun 15. 341(2):241-50. [QxMD MEDLINE Link].
Pootrakul P, Breuer W, Sametband M, et al. Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator. Blood. 2004 Sep 1. 104(5):1504-10. [QxMD MEDLINE Link]. [Full Text].
Kemna EH, Tjalsma H, Podust VN, Swinkels DW. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem. 2007 Apr. 53(4):620-8. [QxMD MEDLINE Link]. [Full Text].
Guyader D, Gandon Y, Deugnier Y, et al. Evaluation of computed tomography in the assessment of liver iron overload. A study of 46 cases of idiopathic hemochromatosis. Gastroenterology. 1989 Sep. 97(3):737-43. [QxMD MEDLINE Link].
Howard JM, Ghent CN, Carey LS, Flanagan PR, Valberg LS. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology. 1983 Feb. 84(2):209-15. [QxMD MEDLINE Link].
Bell H, Rostad B, Raknerud N, Try K. [Computer tomography in the detection of hemochromatosis] [Norwegian]. Tidsskr Nor Laegeforen. 1994 Jun 10. 114(15):1697-9. [QxMD MEDLINE Link].
Sheth S. SQUID biosusceptometry in the measurement of hepatic iron. Pediatr Radiol. 2003 Jun. 33(6):373-7. [QxMD MEDLINE Link].
Nielsen P, Kordes U, Fischer R, Engelhardt R, Janka GE. [SQUID-biosusceptometry in iron overloaded patients with hematologic diseases] [German]. Klin Padiatr. 2002 Jul-Aug. 214(4):218-22. [QxMD MEDLINE Link].
Brittenham GM, Badman DG. Noninvasive measurement of iron: report of an NIDDK workshop. Blood. 2003 Jan 1. 101(1):15-9. [QxMD MEDLINE Link]. [Full Text].
Avrin WF, Kumar S. Noninvasive liver-iron measurements with a room-temperature susceptometer. Physiol Meas. 2007 Apr. 28(4):349-61. [QxMD MEDLINE Link].
Ghugre NR, Enriquez CM, Gonzalez I, et al. MRI detects myocardial iron in the human heart. Magn Reson Med. 2006 Sep. 56(3):681-6. [QxMD MEDLINE Link].
Westwood MA, Firmin DN, Gildo M, et al. Intercentre reproducibility of magnetic resonance T2* measurements of myocardial iron in thalassaemia. Int J Cardiovasc Imaging. 2005 Oct. 21(5):531-8. [QxMD MEDLINE Link].
Sherif M. Badawy, Robert I. Liem, Cynthia K. Rigsby, Richard J. Labotka, R. Andrew DeFreitas, and Alexis A. Thompson. Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease. British Journal of Hematology. 2016 Aug 10. 175:705-713.
Sparacia G, Midiri M, D'Angelo P, Lagalla R. Magnetic resonance imaging of the pituitary gland in patients with secondary hypogonadism due to transfusional hemochromatosis. MAGMA. 1999 May. 8(2):87-90. [QxMD MEDLINE Link].
Sparacia G, Iaia A, Banco A, D'Angelo P, Lagalla R. Transfusional hemochromatosis: quantitative relation of MR imaging pituitary signal intensity reduction to hypogonadotropic hypogonadism. Radiology. 2000 Jun. 215(3):818-23. [QxMD MEDLINE Link]. [Full Text].
Karimi M, Jamalian N, Rasekhi A, Kashef S. Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia major patients: fluid surrounding the scaphoid bone: a novel finding, as the possible effect of secondary hemochromatosis. J Pediatr Hematol Oncol. 2007 Jun. 29(6):393-8. [QxMD MEDLINE Link].
Papakonstantinou O, Ladis V, Kostaridou S, et al. The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. Eur Radiol. 2007 Jun. 17(6):1535-43. [QxMD MEDLINE Link].
Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005 Aug 15. 106(4):1460-5. [QxMD MEDLINE Link]. [Full Text].
Gandon Y, Olivié D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004 Jan 31. 363(9406):357-62. [QxMD MEDLINE Link].
Jensen PD, Heickendorff L, Carlson I, et al. Expression of CD2 and activation markers on blood T-helper cell subsets in patients with transfusional iron overload. Transfus Med. 2001 Feb. 11(1):21-30. [QxMD MEDLINE Link].
Delaporta P, Kattamis A, Apostolakou F, Boiu S, Bartzeliotou A, Tsoukas E, et al. Correlation of NT-proBNP levels and cardiac iron concentration in patients with transfusion-dependent thalassemia major. Blood Cells Mol Dis. 2013 Jan. 50(1):20-4. [QxMD MEDLINE Link].
Angelucci E, Brittenham GM, McLaren CE, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med. 2000 Aug 3. 343(5):327-31. [QxMD MEDLINE Link]. [Full Text].
Butensky E, Fischer R, Hudes M, et al. Variability in hepatic iron concentration in percutaneous needle biopsy specimens from patients with transfusional hemosiderosis. Am J Clin Pathol. 2005 Jan. 123(1):146-52. [QxMD MEDLINE Link].
Harmatz P, Butensky E, Quirolo K, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood. 2000 Jul 1. 96(1):76-9. [QxMD MEDLINE Link]. [Full Text].
Tobkes AI, Nord HJ. Liver biopsy: review of methodology and complications. Dig Dis. 1995 Sep-Oct. 13(5):267-74. [QxMD MEDLINE Link].
Fitchett DH, Coltart DJ, Littler WA, et al. Cardiac involvement in secondary haemochromatosis: a catheter biopsy study and analysis of myocardium. Cardiovasc Res. 1980 Dec. 14(12):719-24. [QxMD MEDLINE Link].
Thakerngpol K, Fucharoen S, Boonyaphipat P, et al. Liver injury due to iron overload in thalassemia: histopathologic and ultrastructural studies. Biometals. 1996 Apr. 9(2):177-83. [QxMD MEDLINE Link].
Telfer PT, Prestcott E, Holden S, et al. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol. 2000 Sep. 110(4):971-7. [QxMD MEDLINE Link].
Porter JB. Concepts and goals in the management of transfusional iron overload. Am J Hematol. 2007 Dec. 82(12 suppl):1136-9. [QxMD MEDLINE Link].
Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct. 89(10):1187-93. [QxMD MEDLINE Link]. [Full Text].
Buja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med. 1971 Aug. 51(2):209-21. [QxMD MEDLINE Link].
Jensen PD, Jensen FT, Christensen T, et al. Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. Blood. 2003 Jun 1. 101(11):4632-9. [QxMD MEDLINE Link]. [Full Text].
Porter JB, Shah FT. Iron overload in thalassemia and related conditions: therapeutic goals and assessment of response to chelation therapies. Hematol Oncol Clin North Am. 2010. 24:1109. [QxMD MEDLINE Link].
Wang CJ, Kavanagh PL, Little AA, Holliman JB, Sprinz PG. Quality-of-care indicators for children with sickle cell disease. Pediatrics. 2011. 128:484. [QxMD MEDLINE Link]. [Full Text].
Cappellini MD, Bejaoui M, Agaoglu L, et al. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia. Clin Ther. 2007 May. 29(5):909-17. [QxMD MEDLINE Link].
Barry M, Flynn DM, Letsky EA, Risdon RA. Long-term chelation therapy in thalassaemia major: effect on liver iron concentration, liver histology, and clinical progress. Br Med J. 1974 Apr 6. 2(5909):16-20. [QxMD MEDLINE Link]. [Full Text].
Modell B, Letsky EA, Flynn DM, Peto R, Weatherall DJ. Survival and desferrioxamine in thalassaemia major. Br Med J (Clin Res Ed). 1982 Apr 10. 284(6322):1081-4. [QxMD MEDLINE Link]. [Full Text].
Brittenham GM, Griffith PM, Nienhuis AW, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med. 1994 Sep 1. 331(9):567-73. [QxMD MEDLINE Link]. [Full Text].
Kushner, James P., Porter, John P., Olivieri, Nancy F. Secondary Iron Overload. Hematology Am Soc Hematol Educ Program. 2001 Jan 1. 1:47-61. [Full Text].
Homan Kang, Murui Han, Jie Xue, Yoonji Baek, JuOae Chang, Shuang Hu, et al. Renal clearable nanochelators for iron overload therapy. Nat Commun. 2019 Nov 13. 10:5134. [QxMD MEDLINE Link]. [Full Text].
Yan Wang, Zhi Liu, Tien-Min Lin, Shaurya Chanana, and May P. Xiong. Nanogel-DFO Conjugates as a Model to Investigate Pharmacokinetics, Biodistribution, and Iron Chelation In Vivo. Int J Pharm. 2018 Mar 1. 538:79-86. [QxMD MEDLINE Link]. [Full Text].
Ferriprox (deferiprone) [package insert]. Cary, NC: Chiesi USA. April 2021. Available at [Full Text].
Tanner MA, Galanello R, Dessi C, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. 2007 Apr 10. 115(14):1876-84. [QxMD MEDLINE Link]. [Full Text].
Filosa A, Vitrano A, Rigano P, Calvaruso G, Barone R, Capra M, et al. Long-term treatment with deferiprone enhances left ventricular ejection function when compared to deferoxamine in patients with thalassemia major. Blood Cells Mol Dis. 2013 Aug. 51(2):85-8. [QxMD MEDLINE Link].
Sharma R, Anand R, Chandra J, Seth A, Pemde H, Singh V. Distal ulnar changes in children with thalassemia and deferiprone related arthropathy. Pediatr Blood Cancer. 2013 Dec. 60(12):1957-62. [QxMD MEDLINE Link].
Osborne RH, De Abreu Lourenço R, Dalton A, et al. Quality of life related to oral versus subcutaneous iron chelation: a time trade-off study. Value Health. 2007 Nov-Dec. 10(6):451-6. [QxMD MEDLINE Link].
Delea TE, Sofrygin O, Thomas SK, et al. Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective. Pharmacoeconomics. 2007. 25(4):329-42. [QxMD MEDLINE Link].
Taher AT, Temraz S, Cappellini MD. Deferasirox for the treatment of iron overload in non-transfusion-dependent thalassemia. Expert Rev Hematol. 2013 Oct. 6(5):495-509. [QxMD MEDLINE Link].
Porter JB, Elalfy MS, Taher AT, Aydinok Y, Chan LL, Lee SH, et al. Efficacy and safety of deferasirox at low and high iron burdens: results from the EPIC magnetic resonance imaging substudy. Ann Hematol. 2013 Jan. 92(2):211-9. [QxMD MEDLINE Link]. [Full Text].
Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, et al. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. 2007 Feb. 136(3):501-8. [QxMD MEDLINE Link]. [Full Text].
Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006 May 1. 107(9):3455-62. [QxMD MEDLINE Link]. [Full Text].
Piga A, Galanello R, Forni GL, et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica. 2006 Jul. 91(7):873-80. [QxMD MEDLINE Link]. [Full Text].
Poggi M, Sorrentino F, Pugliese P, Smacchia MP, Daniele C, Equitani F, et al. Longitudinal changes of endocrine and bone disease in adults with β-thalassemia major receiving different iron chelators over 5 years. Ann Hematol. 2016 Apr. 95 (5):757-63. [QxMD MEDLINE Link].
Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006 May 1. 107(9):3455-62. [QxMD MEDLINE Link].
Vichinsky E, Torres M, Minniti CP, Barrette S, Habr D, Zhang Y. Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: two-year results including pharmacokinetics and concomitant hydroxyurea. Am J Hematol. 2013 Dec. 88(12):1068-73. [QxMD MEDLINE Link].
Meerpohl JJ, Antes G, Rücker G, Fleeman N, Motschall E, Niemeyer CM, et al. Deferasirox for managing iron overload in people with thalassaemia. Cochrane Database Syst Rev. 2012 Feb 15. 2:CD007476. [QxMD MEDLINE Link].
Naderi M, Sadeghi-Bojd S, Valeshabad AK, Jahantigh A, Alizadeh S, Dorgalaleh A, et al. A prospective study of tubular dysfunction in pediatric patients with Beta thalassemia major receiving deferasirox. Pediatr Hematol Oncol. 2013 Nov. 30(8):748-54. [QxMD MEDLINE Link].
Dubourg L, Laurain C, Ranchin B, Pondarré C, Hadj-Aïssa A, Sigaudo-Roussel D, et al. Deferasirox-induced renal impairment in children: an increasing concern for pediatricians. Pediatr Nephrol. 2012 Nov. 27(11):2115-22. [QxMD MEDLINE Link].
Lee JW, Kang HJ, Choi JY, Kim NH, Jang MK, Yeo CW, et al. Pharmacogenetic study of deferasirox, an iron chelating agent. PLoS One. 2013. 8(5):e64114. [QxMD MEDLINE Link]. [Full Text].
Yoshikawa T, Hara T, Araki H, Tsurumi H, Oyama M, Moriwaki H. First report of drug-induced esophagitis by deferasirox. Int J Hematol. 2012 Jun. 95(6):689-91. [QxMD MEDLINE Link].
Franchini M, Gandini G, Veneri D, et al. Efficacy and safety of phlebotomy to reduce transfusional iron overload in adult, long-term survivors of acute leukemia. Transfusion. 2004 Jun. 44(6):833-7. [QxMD MEDLINE Link].
Temraz S, Santini V, Musallam K, Taher A. Iron overload and chelation therapy in myelodysplastic syndromes. Crit Rev Oncol Hematol. 2014 Jan 24. [QxMD MEDLINE Link].
Breccia M, Alimena G. Efficacy and safety of deferasirox in myelodysplastic syndromes. Ann Hematol. 2013 Jul. 92(7):863-70. [QxMD MEDLINE Link].
Nolte F, Höchsmann B, Giagounidis A, Lübbert M, Platzbecker U, Haase D. Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral Deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload. Ann Hematol. 2013 Jan. 92(2):191-8. [QxMD MEDLINE Link].
Breccia M, Finsinger P, Loglisci G, Federico V, Santopietro M, Colafigli G. Deferasirox treatment for myelodysplastic syndromes: "real-life" efficacy and safety in a single-institution patient population. Ann Hematol. 2012 Sep. 91(9):1345-9. [QxMD MEDLINE Link].
Lee SE, Yahng SA, Cho BS, Eom KS, Kim YJ, Lee S. Improvement in hematopoiesis after iron chelation therapy with deferasirox in patients with aplastic anemia. Acta Haematol. 2013. 129(2):72-7. [QxMD MEDLINE Link].
Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, Habr D, et al. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial. Blood. 2010 Oct 7. 116(14):2448-54. [QxMD MEDLINE Link].
Detry O, Defechereux T, Honore P, et al. [Combined liver and heart transplantation in a patient with thalassemia major] [French]. Rev Med Liege. 1997 Aug. 52(8):532-4. [QxMD MEDLINE Link].
Sardi B. High-dose vitamin C and iron overload. Ann Intern Med. 2004 May 18. 140(10):846; author reply 846-7. [QxMD MEDLINE Link].
Fan FS. Iron deficiency anemia due to excessive green tea drinking. Clin Case Rep. 2016 Nov. 4 (11):1053-1056. [QxMD MEDLINE Link]. [Full Text].
Porter JB, Davis BA. Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. Best Pract Res Clin Haematol. 2002 Jun. 15(2):329-68. [QxMD MEDLINE Link].
Savulescu J. Thalassaemia major: the murky story of deferiprone. BMJ. 2004 Feb 14. 328(7436):358-9. [QxMD MEDLINE Link]. [Full Text].
Olivieri NF, Brittenham GM, McLaren CE, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med. 1998 Aug 13. 339(7):417-23. [QxMD MEDLINE Link]. [Full Text].
Wanless IR, Sweeney G, Dhillon AP, et al. Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia. Blood. 2002 Sep 1. 100(5):1566-9. [QxMD MEDLINE Link]. [Full Text].
Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005 Aug 15. 106(4):1460-5. [QxMD MEDLINE Link].
Delea TE, Hagiwara M, Thomas SK, et al. Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States. Am J Hematol. 2008 Apr. 83(4):263-70. [QxMD MEDLINE Link].
Rose C. [Post transfusionnal iron overload] [French]. Rev Prat. 2006 Dec 15. 56(19):2141-5. [QxMD MEDLINE Link].
Tsang E, Leitch HA. Can iron overload in patients with lower-risk myelodysplastic syndromes be reduced using erythropoiesis-stimulating agents?. Ann Hematol. 2016 Jan. 95 (1):73-8. [QxMD MEDLINE Link].
Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998 Jul 2. 339(1):5-11. [QxMD MEDLINE Link]. [Full Text].
Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005 Dec 29. 353(26):2769-78. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Complications of iron overload as manifested in various organs in the body
Iron absorption

of 2

Author

Geneva E Guarin, MD, MBA Resident Physician, Department of Internal Medicine, Einstein Medical Center Philadelphia

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Gerald L Logue, MD Professor of Medicine, Head of the Division of Hematology, Vice Chairman for Education, Department of Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Gerald L Logue, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American College of Physicians, American Society of Hematology, American Federation for Clinical Research

Disclosure: Nothing to disclose.

Sections Transfusion-Induced Iron Overload
Overview
Presentation
- History
- Physical
- Causes
- Complications
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Media Gallery
References

Transfusion-Induced Iron Overload Medication

Medication Summary

Chelating Agents