Skip to main content
SpringerLink
Log in

A Risk-Benefit Assessment of Iron-Chelation Therapy

  • Review Articles
  • Risk-Benefit Assessment
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Iron overload caused by lifelong transfusion-dependent anaemias, such as β-thalassaemia major, usually results in lethal cardiac toxicity in the second decade of life if not treated by iron chelation. There is no physiological mechanism for excreting the excess iron accumulated from blood transfusions and, unlike hereditary haemochromatosis, venesection is not an option. Therefore, chelation therapy is the only way to remove excess iron. This must be removed while not depriving cells of the essential iron needed for normal metabolism. Additionally, the iron chelator must prevent iron from participating in the generation of harmful free radicals.

Parenteral chelation therapy with deferoxamine (desferrioxamine) is well established as promoting negative iron balance, reversing cardiac toxicity, and prolonging life expectancy well into the fourth decade of life and, most likely, beyond. Unfortunately, poor compliance with the rigours of parenteral treatment in a minority of patients limits its regular use, resulting in reduced life expectancy in these patients. Use of deferoxamine in excessive dosages may result in growth retardation, sensorineural ototoxicity and ocular toxicity, as well as bone deformities. These effects can be largely avoided if the dosage is adjusted to take account of the degree of iron overload (using the therapeutic index) and if the mean daily dose does not exceed 40 mg/kg. Nevertheless, it is recommended that patients be regularly monitored for such adverse effects.

Deferiprone (L1; CP20) is an orally absorbed bidentate hydroxypyridinone iron chelator that can induce urinary iron excretion, promote negative iron balance and reduce hepatic iron levels in some transfusion-dependent patients, particularly in those who are markedly iron overloaded and have not received regular deferoxamine therapy.

The long term efficacy and toxicity of deferiprone are the subjects of some controversy, and the published results of randomised controlled trials are awaited. Preliminary results suggest that when currently recommended dosages of deferiprone (75 mg/kg/day) are used, hepatic iron settles at levels that still put most patients at an increased risk from iron overload. A number of adverse effects may occur, and require cessation of therapy in up to 30% of patients. These effects include arthritis, nausea and (most seriously) agranulocytosis in 0.6 to 4% of patients. The risk of the latter complication means that frequent white blood cell counts are mandatory for patients taking this drug.

There remains an urgent need to identify an orally active chelator regimen that is as effective as deferoxamine and has an acceptable degree of tolerability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gordeuk VR, Bacon BR, Brittenham GM. Iron overload, causes and consequences. Ann Rev Nutr 1987; 7: 485–508

    Article  CAS  Google Scholar 

  2. Zurlo MG, Stefaano P, Borgna-Pignatti C, et al. Survival and causes of death in thalassaemia major. Lancet 1989; II: 27–30

    Article  Google Scholar 

  3. 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; 331 (9): 567–73

    Article  PubMed  CAS  Google Scholar 

  4. Olivieri N, Brittenham G. Iron-chelating therapy and the treatment of thalassemia. Blood 1997; 89 (3): 739–61

    PubMed  CAS  Google Scholar 

  5. Cohen A, Martin M, Schwartz E. Depletion of excessive iron stores with desferrioxamine. Br J Haematol 1984; 58: 369–73

    Article  PubMed  CAS  Google Scholar 

  6. Aldouri MA, Wonke B, Hoffbrand AV, et al. Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. J Clin Pathol 1987; 40: 1353–9

    Article  PubMed  CAS  Google Scholar 

  7. Olivieri NF. Randomised trial of deferiprone and DFO in thalassaemia major [abstract 2593]. Blood 1996; 88 (10 Suppl. 1): 651a

    Google Scholar 

  8. Crichton RR, Roman F, Roland F. Iron mobilisation from ferritin by chelating agents. J Inorg Biochem 1980; 13: 305–16

    Article  PubMed  CAS  Google Scholar 

  9. Freeman AP, Giles RW, Berdoukas V, et al. Sustained normalisation of cardiac function by chelation therapy in thalassaemia major. Clin Lab Haematol 1989; 11 (4): 299–307

    Article  PubMed  CAS  Google Scholar 

  10. Marcus RE, Davies SC, Bantock HM, et al. Desferrioxamine to improve cardiac function in iron overloaded patients with thalassaemia major. Lancet: 1984; I: 392–3

    Article  Google Scholar 

  11. Gutteridge JMC, Halliwell B. Iron toxicity and oxygen radicals. Baillieres Clin Haematol 1989; 2: 195–256

    Article  PubMed  CAS  Google Scholar 

  12. Hershko C, Graham G, Bates GW, et al. Non-specific serum iron in thalassaemia: an abnormal serum fraction of potential toxicity. Br J Haematol 1978; 40: 255–63

    Article  PubMed  CAS  Google Scholar 

  13. Porter JB, Abeysinghe RD, Marshall L, et al. Kinetics of removal and reappearance of non-transferrin-bound plasma iron with desferrioxamine therapy. Blood 1996; 88 (2): 705–14

    PubMed  CAS  Google Scholar 

  14. Jacobs A. Low molecular weight intracellular iron transport compounds. Blood 1977; 50: 433–9

    PubMed  CAS  Google Scholar 

  15. Pollack S, Weaver J, Zhan H. Intracellular iron. Adv Exp Med Biol 1994; 356: 165–71

    Article  PubMed  CAS  Google Scholar 

  16. Mulligan MM, Althus B, Linder MC. Non-ferritin, non-heme iron pools in rat tissues. Int J Biochem 1986; 18: 791–8

    Article  PubMed  CAS  Google Scholar 

  17. Hider RC, Choudhury R, Rai BL, et al. Design of orally active iron chelators. Acta Haematol 1996; 95: 6–12

    Article  PubMed  CAS  Google Scholar 

  18. Hider RC, Porter JB, Singh S. The design of therapeutically useful iron chelators. In: Bergeron RJ, Brittenham G, editors. The development of iron chelators for clinical use. Boca Raton, F1.: CRC Press, 1994: 353–71

    Google Scholar 

  19. Abeysinghe RD, Roberts PJ, Cooper CE, et al. The environment of the lipoxygenase iron binding site explored with novel hydroxypyridinone iron chelators. J Biol Chem 1996; 271: 7965–72

    Article  PubMed  CAS  Google Scholar 

  20. Cooper C, Lynagh G, Hider RC, et al. Inhibition of ribonucleotide reductase by intracellular iron chelation as monitored by electron paramagnetic resonance. J Biol Chem 1996; 271 (34): 20291–9

    Article  PubMed  CAS  Google Scholar 

  21. Hoyes KP, Hider RC, Porter JB. Cell cycle synchronisation and growth inhibition by 3-hydroxypyridinone iron chelators in leukaemia cell lines. Cancer Res 1992; 52 (17): 4591–9

    PubMed  CAS  Google Scholar 

  22. Porter JB, Lynagh GR, Hider RC. Thymocyte apoptosis: a rapid model for comparative screening of iron chelators: implications for treatment of iron overload in thalassaemia. In: Beuzard Y, Lubin B, Rosa J, editors. Sickle cell disease and thalassaemia: new trends in therapy. Montrouge, France: John Libby Eurotext, 1995; 234: 371–2

    Google Scholar 

  23. Lee P, Mohammed N, Abeysinghe RD, et al. Intravenous infusion pharmacokinetics of desferrioxamine in thalassaemia patients. Drug Metab Dispos 1993; 21 (4): 640–4

    PubMed  CAS  Google Scholar 

  24. Kontoghiorghes GJ, Goddard JG, Bartlett AN, et al. Pharmacokinetic studies in humans with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Clin Pharmacol 1990; 48: 255–61

    CAS  Google Scholar 

  25. Al-Refaie FN, Hershko C, Hoffbrand AV, et al. Results of long-term deferiprone (L1) therapy: a report by the International Study Group on Oral Iron Chelators. Br J Haematol 1995; 91 (1): 224–9

    Article  PubMed  CAS  Google Scholar 

  26. Al-Refaie FN, Sheppard LN, Nortey P, et al. Pharmacokinetics of the oral iron chelator (L1) in patients with iron overload. Br J Haematol 1995; 89: 403–8

    Article  PubMed  CAS  Google Scholar 

  27. Pippard MJ, Johnson DK, Callender ST, et al. Ferrioxamine excretion in iron loaded man. Blood 1982; 60: 288–94

    PubMed  CAS  Google Scholar 

  28. Olivieri NF, Koren G, Herman C, et al. Comparison of oral iron chelator LI and desferrioxamine in iron loaded patients. Lancet 1990; 336: 1275–9

    Article  PubMed  CAS  Google Scholar 

  29. Singh S, Epemolu RO, Dobbin PS, et al. Urinary metabolic profile in man and rat of 1,2-dimethyl and 1,2-diethyl substituted 3-hydroxypyridin-4-ones. Drug Metab Dispos 1992; 20 (2): 256–61

    PubMed  CAS  Google Scholar 

  30. Porter JB, Hider RC, Huehns ER. The development of iron-chelating drugs. Baillieres Clin Haematol 1989; 2: 257–92

    Article  PubMed  CAS  Google Scholar 

  31. Singh S, Hider RC, Porter JB. Separation and identification of desferrioxamine and its iron chelating metabolites by high-performance liquid chromatography and fast atom bombardment mass spectrometry. Anal Biochem 1990; 187: 1–8

    Article  Google Scholar 

  32. Hershko C, Cook JD, Finch CA. Storage iron kinetics. III: Study of desferrioxamine action by selective radioiron labels of RE and parenchymal cells. J Lab Clin Med 1973; 81: 876–86

    PubMed  CAS  Google Scholar 

  33. Hershko C, Rachmilewitz EA. Mechanism of desferrioxamine-induced iron excretion in thalassaemia. Br J Haematol 1979; 42: 125–32

    Article  PubMed  CAS  Google Scholar 

  34. Hershko C, Grady RW, Cerami RW. Mechanism of iron chelation in the hypertransfused rat: definition of two alternative pathways of iron mobilisation. J Lab Clin Med 1978; 92: 144–51

    PubMed  CAS  Google Scholar 

  35. Pippard MJ. Desferrioxamine-induced iron excretion in humans. Baillieres Clin Haematol 1989; 2 (2): 323–43

    Article  PubMed  CAS  Google Scholar 

  36. Saito K, Nishisato T, Grasso JA, et al. Interaction of transferrin with iron loaded rat peritoneal macrophages. Br J Haematol 1986; 62: 275–86

    Article  PubMed  CAS  Google Scholar 

  37. Andriani M, Nordio M, Saporiti E. Estimation of statistical moments for desferrioxamine and its iron and aluminium chelates: contribution to optimisation of therapy in uraemic patients. Nephron 1996; 72: 218–24

    Article  PubMed  CAS  Google Scholar 

  38. Sephton-Smith R. Iron excretion in thalassaemia major after administration of chelating agents. BMJ 1962; 2: 1577–80

    Article  Google Scholar 

  39. Barry M, Flynn DM, Letsky EA, et al. Long term chelation therapy in thalassaemia: effect on liver iron concentration, liver histology and clinical progress. BMJ 1974; 2: 16–20

    Article  PubMed  CAS  Google Scholar 

  40. Propper RD, Shurin SB, Nathan DG. Reassessment of the use of desferrioxamine B in iron overload. N Engl J Med 1976; 294: 1421–3

    Article  PubMed  CAS  Google Scholar 

  41. Pippard MJ, Callender ST, Weatherall DJ. Intensive iron-chelation with desferrioxamine in iron-loading anaemias. Clin Sci Molecul Med 1978; 54: 99–106

    CAS  Google Scholar 

  42. Nienhuis A. Vitamin C and Iron. N Engl J Med 1981; 304 (3): 170–1

    Article  PubMed  CAS  Google Scholar 

  43. Pippard MJ, Letsky EA, Callender ST, et al. Prevention of iron loading in transfusion-dependent thalassemia. Lancet 1978; 1: 1179–81

    Google Scholar 

  44. Modell CB, Beck J. Long term desferrioxamine therapy in thalassaemia. Ann NY Acad Sci 1974; 232: 201–10

    Article  PubMed  CAS  Google Scholar 

  45. Olivieri NF. Long term follow up of body iron in patients with thalassaemia major during therapy with the orally active iron chelator deferiprone (L1) [abstract 1229]. Blood 1996; 10: 310a

    Google Scholar 

  46. Kontoghiorghes GJ, Aldouri MA, Hoffbrand AV, et al. Effective chelation of iron in β thalassaemia with the oral chelator 1,2,dimethyl-3-hydroxypyridin-4-one. BMJ 1987; 295: 1509–12

    Article  PubMed  CAS  Google Scholar 

  47. Olivieri NF, Cameron RG, Brittenham GM. Exacerbation of hepatic fibrosis in patients with thalassemia major receiving the orally active chelator deferiprone (L1). Proceedings of the International Conference on HIV and Iron: 1997 Mar 14–15: Brugge, poster PB2

  48. Modell B, Letsky EA, Flynn DM, et al. Survival and desferrioxamine in thalassaemia major. BMJ 1982; 284: 1081–4

    Article  PubMed  CAS  Google Scholar 

  49. Gabutti V, Piga A. Results of long term chelation therapy. Acta Haematol 1996; 95: 26–36

    Article  PubMed  CAS  Google Scholar 

  50. Davies SC, Marcus RE, Hungerford JL, et al. Ocular toxicity of high-dose intravenous desferrioxamine. Lancet 1983; II: 181–4

    Article  Google Scholar 

  51. De Virgillis S, Congia M, Frau F, et al. Desferrioxamine-induced growth retardation in patients with thalassaemia major. J Paediatr 1988; 4: 661–9

    Article  Google Scholar 

  52. Piga A, Luzzatto L, Capalbo P, et al. High dose desferrioxamine as a cause of growth failure in thalassaemic patients. Eur J Haematol 1988; 40: 380–1

    Article  PubMed  CAS  Google Scholar 

  53. Araujo A, Kosaryan M, MacDowell A, et al. A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload. Br J Haematol 1996; 93 (4): 835–7

    Article  PubMed  CAS  Google Scholar 

  54. Porter JB, Jaswon MS, Huehns ER, et al. Desferrioxamine ototoxicity: evaluation of risk factors in thalassaemic patients and guidelines for safe dosage. Br J Haematol 1989; 73: 403–9

    Article  PubMed  CAS  Google Scholar 

  55. Cohen AR, Mizanin J, Schwartz E. Rapid removal of excessive iron with daily high dose intravenous chelation therapy. J Pediatr 1987; 115: 151–5

    Google Scholar 

  56. Porter JB, Faherty AM. 12 years experience of intravenous desferrioxamine using indwelling intravenous devices in thalassaemia [abstract 334]. Br J Haematol 1996; 93 Suppl. 1:86

    Google Scholar 

  57. Borgna-Pignatti C, Cohen A. Evaluation of a new method of administration of the iron chelating agent deferoxamine. J Pediatr 1997; 130(1): 86–8

    Article  PubMed  CAS  Google Scholar 

  58. Jensen P, Heickendorff L, Pedersen B, et al. The effect of iron chelyation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996; 94 (2): 288–99

    Article  PubMed  CAS  Google Scholar 

  59. Alberti D, Piga A, Porter J, et al. Preliminary results of single s.c. bolus injections of the new depot formulation of desferrioxamine in thalassemia major patients [abstract]. Proceedings of 8th International Conference on Oral Iron Chelation. 1997 Sep 19–21: Corfu, 48

  60. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994; 331 (9): 574–8

    Article  PubMed  CAS  Google Scholar 

  61. Porter JB, Huehns ER. The toxic effects of desferrioxamine. Baillieres Clin Haematol 1989; 2: 459–74

    Article  PubMed  CAS  Google Scholar 

  62. Modell B. Advances in the use of iron-chelating agents for the treatment of iron overload. Prog Haematol 1979; 11: 267–312

    CAS  Google Scholar 

  63. Agarwal MB, Gupte SS, Viswanathan D, et al. Long term assessment of efficacy and safety of L1, an oral iron chelator in transfusion dependent thalassaemia. Br J Haematol 1992; 82: 460–6

    Article  PubMed  CAS  Google Scholar 

  64. Walker JA, Sherman RA, Eisinger RP. Thrombocytopenia associated with intravenous desferrioxamine. Am J Kid Dis 1985; 6: 254–6

    PubMed  CAS  Google Scholar 

  65. Hoffbrand AV, Bartlett AN, Veys PA, et al. Agranulocytosis and thrombocytopenia in patient with Blackfan-Diamond anaemia during oral chelator trial [letter]. Lancet 1989; II: 457

    Article  Google Scholar 

  66. Olivieri NF, Buncie JR, Chew E, et al. Visual and auditory neurotoxicity in patients receiving subcutaneous desferrioxamine infusions. N Engl J Med 1986; 314 (14): 869–73

    Article  PubMed  CAS  Google Scholar 

  67. Chiodo A, Alberti P, Sher G, et al. Desferrioxamine ototoxicity in an adult transfusion dependent population. J Otolarangol 1997; 26 (2): 116–22

    CAS  Google Scholar 

  68. Arden GB, Wonke B, Kennedy C, et al. Ocular changes in patients undergoing long term desferrioxamine treatment. Br J Opthalmol 1984; 68: 873–7

    Article  CAS  Google Scholar 

  69. Miller KB, Rosenwasser LJ, Bessette JM, et al. Rapid desensitisation for desferrioxamine anaphylactic reaction [letter]. Lancet 1981; I: 1059

    Article  Google Scholar 

  70. Freedman MH, Grisaru D, Olivieri NF, et al. Pulmonary syndrome in patients with thalassaemia receiving intravenous desferrioxamine infusions. Am J Dis Child 1990; 144:565–569

    PubMed  CAS  Google Scholar 

  71. Koren G, Kochavi Atiya Y, Bentur Y, et al. The effects of subcutaneous deferoxamine administration on renal function in thalassemia major. Int J Hematol 1991; 54 (5): 371–5

    PubMed  CAS  Google Scholar 

  72. Mehta J, Singhal S, Revanker R, et al. Fatal systemic lupus erythematosus in patient taking oral iron chelator L1 [letter]. Lancet 1991; 337: 298

    Article  PubMed  CAS  Google Scholar 

  73. De Sanctis V, Pinamonti A, Di Palma A, et al. Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine. Eur J Pediatr 1996; 155: 368–72

    Article  PubMed  Google Scholar 

  74. Robins-Browne RM, Prpic JK. Desferrioxamine and systemic yersiniosis [letter]. Lancet 1983; II: 1372

    Article  Google Scholar 

  75. Gallant R, Freedman MH, Vellend H, et al. Yersinia sepsis in patients with iron overload treated with desferrioxamine [letter]. N Engl J Med 1986; 314: 1643

    PubMed  CAS  Google Scholar 

  76. Kouides PA, Slapak CA, Rosenwasser LJ, et al. Pneumocystis carinii pneumonia as a complication of desferrioxamine therapy. Br J Haematol 1988; 70: 382–4

    Article  Google Scholar 

  77. Boelaert JR, Verauwe PL, Vandepitte JM. Mucormycosis infections in dialysis patients. Ann Intern Med 1987; 107 (5): 782–3

    PubMed  CAS  Google Scholar 

  78. Bosquet J, Navarro M, Robert G, et al. Rapid desensitisation for desferrioxamine anaphylactoid reaction. Lancet 1983; II: 859–60

    Article  Google Scholar 

  79. Koren G, Bentur Y, Strong D, et al. Acute changes in renal function associated with desferrioxamine therapy. Am J Dis Child 1990; 143(9): 1077–80

    Google Scholar 

  80. Tenenbein M, Kowalski S, Sienko A, et al. Pulmonary toxic effects of continuous desferrioxamine administration in acute iron poisoning. Lancet 1992; 339: 699–701

    Article  PubMed  CAS  Google Scholar 

  81. Blake DR, Winyard P, Lunec J, et al. Cerebral and ocular toxicity induced by desferrioxamine. Q J Med 1985; 56: 345–55

    PubMed  CAS  Google Scholar 

  82. Dickerhoff R. Acute aphasia and loss of vision with desferrioxamine overdose. J Pediatr Hematol Oncol 1987; 9: 287–8

    CAS  Google Scholar 

  83. Lange R, Lameijer W, Roozendaal KL, et al. Pharmaceutical analysis and pharmacokinetics of the oral iron chelator 1,2-dimethyl-3-hydroxypyridi-4-one [abstract]. Proceedings 4th International Conference on Oral Chelation: 1993 Mar 26–29: Limasol, Cyprus, 11

  84. Pippard MJ, Pattanapanyssat K, Tiperkae J, et al. Metabolism of the iron chelates of desferrioxamine and hydroxypyridinones in the rat [abstract]. Proceedings of the European Iron Club: 1989 Aug 28–31: Budapest, 55

  85. Dobbin PS, Hider RC, Hall AD, et al. Synthesis, physicochemical proerties and biological evaluation of N-substituted-2-al-kyl-3-hydroxy-4(iH)-pyridinones. J Med Chem 1993; 36 (17): 2448–58

    Article  PubMed  CAS  Google Scholar 

  86. Cragg L, Hebbel RP, Solovey A, et al. The iron chelator L1 potentiatesiron-mediated oxidative DNA damage [abstract 2573]. Blood 1996; 88 (10 Suppl. 1): 646a

    Google Scholar 

  87. Collins AF, Fassos FF, Stobie S, et al. Iron-balance and doseresponse studies of the oral iron chelator l,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease. Blood 1994; 83 (8): 2329–33

    PubMed  CAS  Google Scholar 

  88. Kontoghiorghes GJ, Sheppard L, Barr J, et al. Iron balance studies with the oral chelator 1,2,dimethyl-3-hydroxypyridin-4-one [abstract]. Br J Haematol 1988; 69: 129

    Google Scholar 

  89. Stefanini S, Chiancone E, Cavallo S, et al. The interaction of hydroxypyridinones with human serum transferrin and ovotransferrin. J Inorg Biochem 1991; 44 (1): 27–37

    Article  PubMed  CAS  Google Scholar 

  90. Kontoghiorghes GJ, Aldouri MA, Sheppard L, et al. 1,2-Di-methyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet 1987; I: 1294–5

    Article  Google Scholar 

  91. Al Refaie FN, Wonke B, Hoffbrand AV, et al. Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyridin-4-one (L1) in thalassemia major. Blood 1992; 80: 593–9

    Google Scholar 

  92. Olivieri NF, Brittenham GM, Matsui D, et al. Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med 1995; 332 (14): 918–22

    Article  PubMed  CAS  Google Scholar 

  93. Hoffbrand AV, Wonke B, Al-Refaie F, et al. Over 3 year follow up of 56 transfusion dependent patients receiving oral iron chelation [abstract 2592]. Blood 1996; 88 (10 Suppl 1): 651a

    Google Scholar 

  94. Callea F, Faa G, Sciot R. Liver histology in thalassemia patients receiving deferiprone [abstract]. 8th International Conference on oral iron chelation: 1997 Sep 19–21: Corfu, 59

  95. Brittenham GM. Development of iron-chelating agents for clinical use. Blood 1992; 80: 569–74

    PubMed  CAS  Google Scholar 

  96. Porter JB, Hoyes KP, Abeysinghe RD, et al. Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4-one iron chelators in overloaded and non-overloaded mice. Blood 1991; 79: 2727–34

    Google Scholar 

  97. Porter JB, Hoyes KP, Abeysinghe R, et al. Animal toxicology of iron chelator L1 [letter]. Lancet 1989; II: 156.

    Article  Google Scholar 

  98. Berdoukas V, Bentley P, Frost H, et al. Toxicity of oral chelator L1 [letter]. Lancet 1993; 341: 1088

    Article  PubMed  CAS  Google Scholar 

  99. Carthew P, Dorman BM, Edwards RE, et al. A unique rodent model for both cardiotoxic and hepatotoxic effects of prolonged iron overload. Lab Invest 1993; 69: 217–22

    PubMed  CAS  Google Scholar 

  100. Hoffbrand AV. Prospects for oral iron chelation. J Lab Clin Med 1994; 21: 86–92

    Google Scholar 

  101. Cohen A. A multicenter safety trial of the oral iron chelator deferiprone [abstract No. 26]. 7th Cooleys Anaemia Symposium: 1997 May 30-Jun 2: Cambridge MA, USA

  102. Mehta J, Chablani A, Reporter R, et al. Autoantibodies in thalassaemia major: relationship with oral iron chelator L1. J Assoc Physicians India 1993; 41 (6): 339–41

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, University College London, 98 Chenies Mews, London, WC1E 6HX, England

    John B. Porter

Authors
  1. John B. Porter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John B. Porter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Porter, J.B. A Risk-Benefit Assessment of Iron-Chelation Therapy. Drug-Safety 17, 407–421 (1997). https://doi.org/10.2165/00002018-199717060-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199717060-00006

Keywords

Search

Navigation