, Volume 58, Issue 3, pp 553–578 | Cite as


A Review of its Clinical Potential in Iron Overload in β-Thalassaemia Major and Other Transfusion-Dependent Diseases
Adis Drug Evaluation



Patients with β-thalassaemia and other transfusion-dependent diseases develop iron overload from chronic blood transfusions and require regular iron chelation to prevent potentially fatal iron-related complications. The only iron chelator currently widely available is deferoxamine, which is expensive and requires prolonged subcutaneous infusion 3 to 7 times per week or daily intramuscular injections. Moreover, some patients are unable to tolerate deferoxamine and compliance with the drug is poor in many patients.

Deferiprone is the most extensively studied oral iron chelator to date. Non-comparative clinical studies mostly in patients with β-thalassaemia have demonstrated that deferiprone 75 to 100 mg/kg/day can reduce iron burden in regularly transfused iron-overloaded patients. Serum ferritin levels are generally reduced in patients with very high pretreatment levels and are frequently maintained within an acceptable range in those who are already adequately chelated. Deferiprone is not effective in all patients (some of whom show increases in serum ferritin and/or liver iron content, particularly during long term therapy). This may reflect factors such as suboptimal dosage and/or severe degree of iron overload at baseline in some instances.

Although few long term comparative data are available, deferiprone at the recommended dosage of 75 mg/kg/day appears to be less effective than deferoxamine; however, compliance is superior with deferiprone, which may partly compensate for this. Deferiprone has additive, or possibly synergistic, effects on iron excretion when combined with deferoxamine.

The optimum dosage and long term efficacy of deferiprone, and its effects on survival and progression of iron-related organ damage, remain to be established.

The most important adverse effects in deferiprone-treated patients are arthropathy and neutropenia/agranulocytosis. Other adverse events include gastrointestinal disturbances, ALT elevation, development of antinuclear antibodies and zinc deficiency. With deferiprone, adverse effects occur mostly in heavily iron-loaded patients, whereas with deferoxamine adverse effects occur predominantly when body iron burden is lower.

Conclusion: Deferiprone is the most promising oral iron chelator under development at present. Further studies are required to determine the best way to use this new drug. Although it appears to be less effective than deferoxamine at the recommended dosage and there are concerns regarding its tolerability, it may nevertheless offer a therapeutic alternative in the management of patients unable or unwilling to receive the latter drug. Deferiprone also shows promise as an adjunct to deferoxamine therapy in patients with insufficient response and may prove useful as a maintenance treatment to interpose between treatments.

Pharmacodynamic Properties

Deferiprone is an oral bidentate iron chelator which binds to iron in a 3: 1 ratio. It also binds other metals including aluminium, gallium, copper and zinc, but not calcium or magnesium.

Deferiprone reduces body iron content in iron-overloaded animals and humans. Iron excretion is related to dosage and the degree of iron overload, and occurs largely by the renal route. Deferiprone appears to mobilise iron from both reticuloendothelial and hepatocellular pools, from transferrin, ferritin and haemosiderin and from pathological iron deposits in intact red blood cells from patients with thalassaemia or sickle-cell anaemia.

Depending on concentration, deferiprone has been reported to promote (at low concentrations, in vitro), and conversely to protect against (at high concentrations), oxidative damage caused by oxygen free radicals.

As with deferoxamine, deferiprone inhibits proliferation of several cell lines in vitro and may induce apoptosis. It has also shown myelosuppressive effects in animals and humans. Although in vitro data suggest that deferiprone is markedly less toxic than deferoxamine to bone marrow myeloid progenitors, the clinical relevance of this is unclear, as deferiprone-induced myelosuppression may occur via a reactive metabolite-induced event mediated by the immune system.

Pharmacokinetic Properties

Peak plasma concentrations (Cmax) are reached within approximately 1 hour after oral administration of deferiprone. Food intake reduces the rate, but not the extent, of absorption of the drug. Administration of deferiprone 75 mg/kg/day at 12-hourly intervals produced a Cmax of 34.6 mg/L and area under the plasma concentration-time curve (AUC) of 137.5 mg/L · h in patients with β-thalassaemia. Coadministration of iron (ferrous sulfate 600mg) reduced the AUC by about 20% in healthy volunteers.

It is not clear whether deferiprone induces its own metabolism in vivo. This has been demonstrated in vitro. Trough plasma concentrations of deferiprone decreased during long term treatment with the drug in 1 study, but this was not corroborated by other studies.

The volume of distribution after administration of deferiprone 75 mg/kg/day was 1.55 or 1.73 L/kg at steady state (depending on the dosage schedule) in patients with β-thalassaemia. Deferiprone was found to accumulate (≈3-fold) in thalassaemic, but not normal or sickle, red blood cells in vitro.

Deferiprone is metabolised predominantly (>85%) to a glucuronide conjugate that lacks chelating properties. The drug, its conjugate and the deferiprone-iron complex are mainly excreted by the kidney and approximately 80% of a dose is recovered in the urine. Deferiprone is rapidly eliminated, with an elimination half-life (t½β) of approximately 1 to 2.5 hours in patients with β-thalassaemia. The t½β of deferiprone glucuronide was significantly correlated with creatinine clearance and this metabolite was found to accumulate in a patient with renal dysfunction. Although deferiprone is metabolised by the liver, the effects of hepatic impairment on the pharmacokinetics of the drug are yet to be determined.

Therapeutic Potential

Clinical studies, mostly in patients with β-thalassaemia, have demonstrated that deferiprone 75 to 100 mg/kg/day is capable of reducing iron burden in regularly transfused iron-overloaded patients. Factors affecting response to deferiprone appear to include the degree of iron overload and duration, dosage and degree of compliance with therapy.

Serum ferritin levels (an indirect indicator of body iron load) are generally decreased in patients with very high pretreatment levels. In patients who are already adequately chelated at baseline, serum ferritin levels frequently remain stable. However, increases or inadequate decreases in serum ferritin and/or hepatic iron content were seen in some patients, especially after long term treatment. In some instances, this may reflect suboptimal dosage and/or severe degree of iron overload at baseline. Beneficial effects noted in some long term studies include lightening of the skin and decreased serum ALT and non-transferrin-bound iron levels.

It should be noted that long term clinical trials reported to date have generally been noncomparative and conducted in small numbers of patients, who differed greatly with regard to baseline chelation status and underlying disease. Moreover, in many studies, the proportion of patients who were adequately chelated on deferiprone was not reported.

Short term comparative studies have demonstrated that deferiprone ≤75 mg/kg/day is less effective than deferoxamine in increasing iron excretion. However, compliance during clinical use is superior with deferiprone, which may compensate for this to some degree. Few data from long term prospective randomised studies comparing deferiprone with deferoxamine have been reported. In these studies, deferiprone appeared to be slightly less effective than deferoxamine in reducing serum ferritin and less effective in controlling hepatic iron levels.

Preliminary data suggest that deferiprone can be used successfully in combination with deferoxamine, with additive or synergistic effects on urinary iron excretion and substantial reductions in serum ferritin levels being achieved.


The most common adverse events in deferiprone-treated patients have been arthropathy (musculoskeletal stiffness and pain, accompanied by effusion in severe cases) and gastrointestinal disturbances (anorexia, nausea, vomiting). Arthropathy occurred in up to 39% of patients in clinical trials and generally resolves on dosage reduction or drug withdrawal.

The most serious adverse effect associated with deferiprone is severe neutropenia/agranulocytosis (approximately 2% of patients each). This appears to be reversible.

Other adverse events include elevated ALT and immunological abnormalities (development of antinuclear and antihistone antibodies). Deferiprone also promotes increased urinary excretion of zinc, particularly in patients with diabetes mellitus. This may occasionally lead to clinical signs of zinc deficiency (e.g. dry/itchy skin), which respond to zinc supplementation.

Progression of existing liver fibrosis in 5 of a series of 14 patients treated with deferiprone was attributed to the drug, but this conclusion was subsequently questioned on the basis of methodological flaws in the study concerned. Long term follow-up of deferiprone-treated patients by other investigators implicates chronic hepatitis C infection and iron overload, rather than deferiprone, in progression of hepatic fibrosis in transfusional iron-overloaded patients.

Dosage and Administration

The recommended dosage of deferiprone is 25 mg/kg 3 times daily, although some investigators recommend use of dosages up to 100 mg/kg/day and/or twice daily administration. Special monitoring is required in all patients. Particular caution is recommended (with monitoring of renal or hepatic function) when treating patients with impaired renal or hepatic function. Deferiprone is contra-indicated in patients with neutropenia or a history of agranulocytosis or recurrent episodes of neutropenia, those taking drugs known to cause neutropenia, and in pregnant or lactating women. Women of childbearing potential should use contraceptives while taking deferiprone. Weekly monitoring of neutrophil count is recommended and patients should be advised to report immediately any symptoms of infection, such as fever, sore throat or flu-like symptoms.

Deferiprone may interact with concomitantly administered medications containing metallic cations, including aluminium-based antacids.


Adis International Limited Serum Ferritin Iron Overload Deferoxamine Serum Ferritin Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997 Feb 1; 89: 739–61PubMedGoogle Scholar
  2. 2.
    Porter JB. A risk-benefit assessment of iron-chelation therapy. Drug Saf 1997 Dec; 17(6): 407–21PubMedCrossRefGoogle Scholar
  3. 3.
    Hoffbrand AV, Wonke B. Iron chelation therapy. J Intern Med Suppl 1997; 740: 37–41Google Scholar
  4. 4.
    Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol 1996; 95: 26–36PubMedCrossRefGoogle Scholar
  5. 5.
    Kattamis CA, Kattamis AC. Management of thalassemias: growth and development, hormone substitution, vitamin supplementation, and vaccination. Semin Hematol 1995 Oct; 32: 269–79PubMedGoogle Scholar
  6. 6.
    Giardina PJ, Grady RW. Chelation therapy in β-thalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 1995 Oct; 32: 304–12PubMedGoogle Scholar
  7. 7.
    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: 1353–9PubMedCrossRefGoogle Scholar
  8. 8.
    Mosby’s complete drug reference. Physicians GenRx. 7th ed. Louis (Mo): Mosby-Year Book 1997Google Scholar
  9. 9.
    British National Formulary. 37th ed. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 1999Google Scholar
  10. 10.
    Porter JB, Huehns ER. The toxic effects of desferrioxamine. Baillieres Clin Haematol 1989; 2(2): 459–74PubMedCrossRefGoogle Scholar
  11. 11.
    Hoffbrand AV. Oral iron chelation. Semin Hematol 1996 Jan; 33: 1–8PubMedGoogle Scholar
  12. 12.
    Elorriaga R, Fernández Martín JL, Menéndez Fraga P, et al. Aluminium removal: short- and long-term preliminary results with L1 in rats. Drugs Today 1992; 28 Suppl. A: 177–82Google Scholar
  13. 13.
    Canteros-Piccotto MA, Fernández-Martin JL, Cannata-Ortiz MJ, et al. Effectiveness of deferiprone (L1) releasing the aluminium bound to plasma proteins in chronic renal failure. Nephrol Dial Transplant 1996 Jul; 11: 1488–9PubMedCrossRefGoogle Scholar
  14. 14.
    Kontoghiorghes GJ, Barr J, Baillod RA. Aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Drugs Today 1992; 28 Suppl. A: 183–7Google Scholar
  15. 15.
    Kontoghiorghes GJ, Barr J, Baillod RA. Studies of aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Arzneimittel Forschung 1994 Apr; 44: 522–6PubMedGoogle Scholar
  16. 16.
    Sheppard LN, Kontoghiorghes GJ. Competition between deferiprone, desferrioxamine and other chelators for iron and the effect of other metals. Arzneimittel Forschung 1993 Jun; 43: 659–63PubMedGoogle Scholar
  17. 17.
    Eybl V, Svihovcová P, Koutensky J, et al. Interaction of L1, L1NAII and deferoxamine with gallium in vivo. Drugs Today 1992; 28 Suppl. A: 173–5Google Scholar
  18. 18.
    Al-Refaie FN, Hoffbrand AV. Oral iron chelation therapy. Rec Adv Haematol 1993; 7: 185–216Google Scholar
  19. 19.
    Al-Refaie FN, Sheppard LN, Nortey P, et al. Pharmacokinetics of the oral chelator deferiprone (L1) in patients with iron overload. Br J Haematol 1995 Feb; 89: 403–8PubMedCrossRefGoogle Scholar
  20. 20.
    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 Ther 1990 Sep; 48: 255–61PubMedCrossRefGoogle Scholar
  21. 21.
    Bergeron RJ, Streiff RR, Wiegand J, et al. Acomparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine. Blood 1992 Apr 1; 79: 1882–90. [letter]PubMedGoogle Scholar
  22. 22.
    Venkataram S, Rahman YE. Studies of an oral iron chelator: 1,2-dimethyl-3-hydroxy-pyrid-4-one. I. Iron excretion in rats: development of a new rapid microwave method for iron analysis in faeces [see comments]. Br J Haematol 1990 Jun; 75: 274–7PubMedCrossRefGoogle Scholar
  23. 23.
    Fassos FF, Berkovitch M, Daneman N, et al. Efficacy of deferiprone in the treatment of acute iron intoxication in rats. J Toxicol Clin Toxicol 1996 May; 34: 279–87PubMedCrossRefGoogle Scholar
  24. 24.
    Hung O, Manoach S, Howland MA, et al. Deferiprone for acute iron poisoning [abstract]. J Toxicol Clin Toxicol 1997 Aug; 35: 565CrossRefGoogle Scholar
  25. 25.
    Kontoghiorghes GJ, Aldouri MA, Sheppard L, et al. 1,2-Dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet 1987 Jun 6; I: 1294–5CrossRefGoogle Scholar
  26. 26.
    Kontoghiorghes GJ, Aldouri MA, Hoffbrand AV, et al. Effective chelation of iron in β thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Br Med J Clin Res Ed 1987 Dec 12; 295: 1509–12PubMedCrossRefGoogle Scholar
  27. 27.
    Agarwal MB, Gupte SS, Viswanathan C, et al. Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial. Br J Haematol 1992 Oct; 82: 460–6PubMedCrossRefGoogle Scholar
  28. 28.
    Fassos FF, Klein J, Fernandes D, et al. Urinary iron excretion depends on the mode of administration of the oral iron chelator 1,2-dimethyl-3-hydoxypyrid-4-one in patients with homozygous β-thalassemia. Clin Pharmacol Ther 1994 Jan; 55: 70–5PubMedCrossRefGoogle Scholar
  29. 29.
    Fassos FF, Klein J, Fernandes D, et al. The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels. Int J Clin Pharmacol Ther 1996 Jul; 34: 288–92PubMedGoogle Scholar
  30. 30.
    Matsui D, Klein J, Hermann C, et al. Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia. Clin Pharmacol Ther 1991 Sep; 50: 294–8PubMedCrossRefGoogle Scholar
  31. 31.
    Hornstein M, Sautjeaurostoker C, Peduzzi J, et al. Oxacillin-hydrolyzing beta-lactamase involved in resistance to imipenem in Acinetobacter baumannii. FEMS Microbiol Lett 1997 Aug 15; 153: 333–9PubMedCrossRefGoogle Scholar
  32. 32.
    Stobie S, Tyberg J, Matsui D, et al. Comparison of the pharmacokinetics of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in healthy volunteers, with and without co-administration of ferrous sulfate, to thalassemia patients. Int J Clin Pharmacol Ther Toxicol 1993 Dec; 31: 602–5PubMedGoogle Scholar
  33. 33.
    Zevin S, Link G, Grady RW, et al. Origin and fate of iron mobilized by the 3-hydroxypyridin-4-one oral chelators: studies in hypertransfused rats by selective radioiron probes of reticuloendothelial and hepatocellular iron stores. Blood 1992 Jan 1; 79: 248–53PubMedGoogle Scholar
  34. 34.
    Nielsen P, Fürtjes M, Dresow B, et al. The iron-decorporating effect of L1 in normal and TMH-ferrocene iron-loaded rats and in one patient with post-transfusional siderosis as judged by 59FE-labelling technique. Drugs Today 1992; 28 Suppl. A: 45–53Google Scholar
  35. 35.
    Kontoghiorghes GJ, Sheppard L, Chambers S. New synthetic approach and iron chelation studies of l-alkyl-2-methyl-3-hydroxypyrid-4-ones. Arzneimittel Forschung 1987; 37: 1099–102PubMedGoogle Scholar
  36. 36.
    Kontoghiorghes GJ, Chambers S, Hoffbrand AV. Comparative study of iron mobilization from haemosiderin, ferritin and iron(III) precipitates by chelators. Biochem J 1987 Jan 1; 241: 87–92PubMedGoogle Scholar
  37. 37.
    Shalev O, Repka T, Goldfarb A, et al. Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo. Blood 1995 Sep 1; 86: 2008–13PubMedGoogle Scholar
  38. 38.
    De Franceschi L, Shalev O, Piga A, et al. Deferiprone therapy in homozygous human β-thalassaemia removes erythrocyte membrane free iron and reduces KCl cotransport activity. J Lab Clin Med 1999; 133: 64–9PubMedCrossRefGoogle Scholar
  39. 39.
    Diav-Citrin O, Koren G. Oral iron chelation with deferiprone. Pediatr Clin North Am 1997 Feb; 44: 235–47PubMedCrossRefGoogle Scholar
  40. 40.
    van der Kraaij AM, van Eijk HG, Koster JF. Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3. Circulation 1989 Jul; 80: 158–64PubMedCrossRefGoogle Scholar
  41. 41.
    Motekitis RJ, Martell AE. Stabilization of the iron (III) chelates of 1,2-dimethyl-3-hydroxypyrid-4-ones and related ligands. Inorg Chim Acta 1991; 183: 71–80CrossRefGoogle Scholar
  42. 42.
    Cragg L, Hebbel RP, Solovey A, et al. The iron chelator L1 potentiates iron-mediated oxidative DNA damage [abstract]. Blood 1996 Nov 15; 88 (10 Suppl. 1, Pt 1):646Google Scholar
  43. 43.
    Matthews AJ, Vercellotti GM, Menchaca HJ, et al. Iron and atherosclerosis: inhibition by the iron chelator deferiprone (11). J Surg Res 1997 Nov; 73: 35–40PubMedCrossRefGoogle Scholar
  44. 44.
    Shalev O, Choong S, Goldfarb A, et al. Deferiprone (L1) attenuates methemoglobin formation in metabolically stressed normal (N) and β-thalassemic (T) RBC [abstract]. Blood 1998; 92 (Suppl. 1 Pt 1): 529aGoogle Scholar
  45. 45.
    Browne PV, Shalev O, Choong S, et al. Amelioration of red cell pathobiology and hemolysis in murine thalassemia via deferiprone-mediated removal of red blood cell membrane iron [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 482aGoogle Scholar
  46. 46.
    Korkina LG, Afanas’ev IB, Deeva IB, et al. Free radical status of blood of patients with iron overload: the effect of chelating treatment. Drugs Today 1992; 28 Suppl. A: 137–41Google Scholar
  47. 47.
    Naves DML, Elorrianga R, Canteros A, et al. Effect of desferrioxamine and deferiprone (L1) on the proliferation of MG-63 bone cells and on phosphatase alkaline activity. Nephrol Dial Transplant 1998; 13 Suppl. 3: 23–8CrossRefGoogle Scholar
  48. 48.
    Blatt J, Taylor SR, Kontoghiorghes GJ. Comparison of activity of deferoxamine with that of oral iron chelators against human neuroblastoma cell lines. Cancer Res 1989 Jun 1; 49: 2925–7PubMedGoogle Scholar
  49. 49.
    Hileti D, Panayiotidis P, Hoffbrand AV. Iron chelators induce apoptosis in proliferating cells. Br J Haematol 1995 Jan; 89: 181–7PubMedCrossRefGoogle Scholar
  50. 50.
    Cunningham JM, Al-Refaie FN, Hunter AE, et al. Differential toxicity of α-keto hydroxypyridine iron chelators and desferrioxamine to human haemopoietic precursors in vitro. Eur J Haematol 1994 Mar; 52: 176–9PubMedCrossRefGoogle Scholar
  51. 51.
    Al-Refaie FN, Wilkes S, Wonke B, et al. The effect of deferiprone (L1) and desferrioxamine on myelopoiesis using a liquid culture system. Br J Haematol 1994 May; 87: 196–8CrossRefGoogle Scholar
  52. 52.
    Loebstein R, Diav-Citrin O, Atanackovic G, et al. Deferiprone-induced agranulocytosis: a critical review of five rechallenged cases. Clin Drug Invest 1997 Jun; 13: 345–9CrossRefGoogle Scholar
  53. 53.
    Berdoukas V, Bentley P, Frost H, et al. Toxicity of oral iron chelator L1. Lancet 1993 Apr 24; 341: 1088PubMedCrossRefGoogle Scholar
  54. 54.
    Porter JB, Hoyes KP, Abeysinghe RD, et al. Future of oral iron chelator deferiprone (L1). Lancet 1991; 341: 1480Google Scholar
  55. 55.
    Link G, Pinson A, Hershko C. Ability of the orally effective iron chelators dimethyl- and diethyl-hydroxypyrid-4-one and of deferoxamine to restore sarcolemmal thiolic enzyme activity in iron-loaded heart cells. Blood 1994 May 1; 83: 2692–7PubMedGoogle Scholar
  56. 56.
    Pope E, Berkovitch M, Klein J, et al. Salivary measurement of deferiprone concentrations and correlation with serum levels. Ther Drug Monit 1997 Feb; 19: 95–7PubMedCrossRefGoogle Scholar
  57. 57.
    Diav-Citrin O, Atanackovic G, Loebstein R, et al. An investigation into variability in the response to deferiprone in patients with thalassemia major. Ther Drug Monit 1999; 21: 74–81PubMedCrossRefGoogle Scholar
  58. 58.
    Hileti D, Shalev O, Telfer PT, et al. L1 (deferiprone) accumulates within thalassaemic but not normal or sickle red blood cells [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 483aGoogle Scholar
  59. 59.
    Hileti D, Ward RJ, Peters TJ, et al. Pharmacokinetics, tissue distribution and cell uptake of 14C-labelled oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in the rat [abstract]. Br J Haematol 1995; 89 Suppl. 1: 87CrossRefGoogle Scholar
  60. 60.
    Singh S, Epemolu RO, Dobbin PS, et al. Urinary metabolic profiles in human and rat of 1,2-dimethyl- and 1,2-diethylsubstituted 3-hydroxypyridin-4-ones. Drug Metab Dispos 1992 Mar–Apr; 20: 256–61PubMedGoogle Scholar
  61. 61.
    Al-Refaie FN, Wonke B, Hoffbrand AV, et al. Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. Blood 1992 Aug 1; 80: 593–9PubMedGoogle Scholar
  62. 62.
    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 Sep; 91: 224–9PubMedCrossRefGoogle Scholar
  63. 63.
    Hoffbrand AV, Al-Refaie F, Davis B, et al. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood 1998 Jan 1; 91: 295–300PubMedGoogle Scholar
  64. 64.
    Kersten MJ, Lange R, Smeets MEP, et al. Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann Hematol 1996 Nov; 73: 247–52PubMedCrossRefGoogle Scholar
  65. 65.
    Longo F, Fischer R, Engelhardt R, et al. Iron balance in thalassemia patients treated with deferiprone [abstract]. Blood 1998; 92 (10 Suppl. 1, Pt 1): 325aGoogle Scholar
  66. 66.
    Mazza P, Amurri B, Lazzari G, et al. Oral iron chelating therapy. A single center interim report on deferiprone (L1) in thalassaemia. Haematologica 1998; 83: 496–501PubMedGoogle Scholar
  67. 67.
    Olivieri NF, Brittenham GM, Matsui D, et al. Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med 1995 Apr 6; 332: 918–22PubMedCrossRefGoogle Scholar
  68. 68.
    Taher A, Chamoun S, Koussa S, et al. Efficacy and tolerance of the oral iron chelator, deferiprone, in thalassemia: the Lebanese experience [in abstract]. Br J Haematol 1998; 102: 55Google Scholar
  69. 69.
    Cohen A, Galanello R, Piga A, et al. A multi-center safety trial of the oral iron chelator deferiprone. Ann N Y Acad Sci 1998; 850: 223–6PubMedCrossRefGoogle Scholar
  70. 70.
    Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous β thalassaemia. N Engl J Med 1994; 331: 554–78CrossRefGoogle Scholar
  71. 71.
    Brittenham GM, Griffith PM, Nienhuis AW, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassaemia major. N Engl J Med 1994 Sep 1; 331: 567–73PubMedCrossRefGoogle Scholar
  72. 72.
    Brittenham GM, Cohen AR, McLaren CE, et al. Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol 1993; 42: 81–5PubMedCrossRefGoogle Scholar
  73. 73.
    Al-Refaie FN, Wickens DG, Wonke B, et al. Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and L1. Br J Haematol 1992 Oct; 82: 431–6PubMedCrossRefGoogle Scholar
  74. 74.
    Olivieri NF, Brittenham GM, McLaren CE, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassaemia major. N Engl J Med 1998; 339: 417–23PubMedCrossRefGoogle Scholar
  75. 75.
    Ambu R, Crisponi G, Sciot R, et al. Uneven hepatic iron and phosphorus distribution in beta-thalassemia. J Hepatol 1995: 544–50Google Scholar
  76. 76.
    Villeneuve J-P, Bilodeau M, Lepage R, et al. Variability in hepatic iron concentration measured from needle-biopsy specimens. J Hepatol 1996 Aug; 25(2): 172–7PubMedCrossRefGoogle Scholar
  77. 77.
    Faa G, Sciot R, Farci AMG, et al. Iron concentration and distribution in the newborn liver. Liver 1994; 14: 193–9PubMedGoogle Scholar
  78. 78.
    Angelucci E, Baronciani D, Lucarelli G. Needle liver biopsy in thalassaemia: analyses of diagnostic accuracy and safety in 1184 consecutive biopsies. Br J Haematol 1995; 89: 757–61PubMedCrossRefGoogle Scholar
  79. 79.
    Brittenham GM, Farrell DE, Harris JW, et al. Magnetic-susceptibility measurement of human iron stores. N Engl J Med 1982; 307: 1671–5PubMedCrossRefGoogle Scholar
  80. 80.
    Nielsen P, Fischer R, Engelhardt R, et al. Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deferiprone. Br J Haematol 1995 Dec; 91: 827–33PubMedCrossRefGoogle Scholar
  81. 81.
    Collins AF, Fassos FF, Stobie S, et al. Iron-balance and dose-response studies of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease. Blood 1994 Apr 15; 83: 2329–33PubMedGoogle Scholar
  82. 82.
    Grady RW, Hilgartner MW, Giardina PJ. Deferiprone: its efficacy relative to that of Desferal [abstract]. Blood 1996 Nov 15; 88 (10 Suppl. 1, Pt 1): 310Google Scholar
  83. 83.
    Grady RW, Giardina PJ. Deferiprone (DFP) and desferal (DFO): are they complementary? 8th International Conference Oral Chelation in the Treatment of Thalassaemia and Other Diseases; 1997 Sep 19–21; CorfuGoogle Scholar
  84. 84.
    Olivieri NF, Koren G, Hermann C, et al. Comparison of oral iron chelator LI and desferrioxamine in iron-loaded patients. Lancet 1990 Nov 24; 336: 1275–9PubMedCrossRefGoogle Scholar
  85. 85.
    Addis A, Loebstein R, Koren G, et al. Meta-analytic review of the clinical effectiveness of oral deferiprone (L1). Eur J Pharmacol 1999; 55: 1–6CrossRefGoogle Scholar
  86. 86.
    Wonke B, Wright C, Hoffbrand AV. Combined therapy with deferiprone and desferrioxamine. Br J Haematol 1998; 103: 361–4PubMedCrossRefGoogle Scholar
  87. 87.
    Olivieri NF, Iron CRG. Randomized trial of deferiprone (L1) and deferoxamine (DFO) in thalassemia major [abstract]. Blood 1996 Nov 15; 88 (10 Suppl. 1, Pt 1): 651Google Scholar
  88. 88.
    Tondury P, Kontoghiorghes GJ, Ridolfi-Luthy A, et al. L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. Br J Haematol 1990 Dec; 76: 550–3PubMedCrossRefGoogle Scholar
  89. 89.
    Olivieri NF, Koren G, Matsui D, et al. Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. Blood 1992 May 15; 79: 2741–8PubMedGoogle Scholar
  90. 90.
    Olivieri NF, Belluzzo N, Muraca M, et al. Evidence of reduction in hepatic, cardiac and pituitary iron stores in patients with thalassaemia major during long-term therapy with the orally active iron chelating agent L 1. American Society of Haematology 36th Annual Meeting; 1994 December 2–6; NashvilleGoogle Scholar
  91. 91.
    Olivieri NF, Brittenham GM, Armstrong SAM, et al. First prospective randomized trial of the iron chelators deferiprone [L1] and deferoxamine [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 249aGoogle Scholar
  92. 92.
    Tricta F, Dougherty G, Diav-Citrin O, et al. Randomized trial of deferiprone (L1) and deferoxamine (DFO) in thalassemia major [abstract]. 6th International Conference on Thalassemia and the Haemoglobinopathies; 1997 April 5–10; MaltaGoogle Scholar
  93. 93.
    Maggio A, Calabrese A, Capra M, et al. Efficacy of L1 (deferiprone) versus desferrioxamine shown by a randomized multicentric clinical trial [abstract]. 7th International Conference on Thalassaemia and the Haemoglobinopathies; 1999 May 31–June 4; Bangkok, ThailandGoogle Scholar
  94. 94.
    Grady RW, Berdoukas VA, Giardina PJ. Iron chelation: combined therapy could be a better approach [abstract]. Blood 1998; 92 Suppl. 1 Pt 2: 16bGoogle Scholar
  95. 95.
    Matsui D, Hermann C, Klein J, et al. Critical comparison of novel and existing methods of compliance assessment during a clinical trial of an oral iron chelator. J Clin Pharmacol 1994 Sep; 9: 944–9Google Scholar
  96. 96.
    Olivieri NF, Matsui D, Hermann C. Compliance assessed by the Medication Event Monitoring System. Arch Dis Child 1991 Dec; 66: 1399–402PubMedCrossRefGoogle Scholar
  97. 97.
    Tricta F, Piga A, Tricta RM, et al. Electronic monitoring of compliance with deferiprone in thalassemia major patients [abstract]. Br J Haematol 1996 Jun; 93 Suppl. 2: 34–5Google Scholar
  98. 98.
    Olivieri NF, Matsui D, Berkovitch M, et al. Superior effectiveness of the oral iron chelator L1 vs subcutaneous deferoxamine in patients with homozygous beta-thalassemia (HBT): the impact of patient compliance during two years of therapy [abstract]. Blood 1991 Suppl. 1: 344aGoogle Scholar
  99. 99.
    Basran RK, Fassos FF, Shaw D, et al. Assessment of the relative quality of life in patients receiving subcutaneous deferoxamine and the orally active iron chelating agent L1 [abstract]. Blood 1994 Nov 15; 84 Suppl. 1: 261aGoogle Scholar
  100. 100.
    Bartlett AN, Hoffbrand AV, Kontoghiorghes GJ. Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (11). Br J Haematol 1990 Oct; 76: 301–4PubMedCrossRefGoogle Scholar
  101. 101.
    al-Refaie FN, Wonke B, Hoffbrand AV. Arthropathy in thalassaemia patients receiving deferiprone [letter; comment]. Lancet 1994 Jul 23; 344: 262–3PubMedCrossRefGoogle Scholar
  102. 102.
    Berkovitch M, Laxer RM, Inman R, et al. Arthropathy in thalassaemia patients receiving deferiprone. Lancet 1994 Jun 11; 343: 1471–2PubMedCrossRefGoogle Scholar
  103. 103.
    Castriota-Scanderbeg A, Sacco M. Agranulocytosis, arthritis and systemic vasculitis in a patient receiving the oral iron chelator L1 (deferiprone). Br J Haematol 1997 Feb; 96: 254–5PubMedCrossRefGoogle Scholar
  104. 104.
    Al-Refaie FN, Wonke B, Hoffbrand AV. Deferiprone-associated myelotoxicity. Eur J Haematol 1994 Nov; 53: 298–301PubMedCrossRefGoogle Scholar
  105. 105.
    Hoffbrand AV, Bartlett AN, Veys PA, et al. Agranulocytosis and thrombocytopenia in patient with Blackfan-Diamond anaemia during oral chelator trial [letter] [see comments]. Lancet 1989 Aug 19; 2: 457PubMedCrossRefGoogle Scholar
  106. 106.
    Bertola U, Collell M, Piga A, et al. Neutropenia in homozygous β thalassaemia patients on desferrioxamine treatment. 8th International Conference Oral Chelation in the Treatment of Thalassaemia and Other Diseases; 1997 Sep 19–21; CorfuGoogle Scholar
  107. 107.
    Mehta J, Chablani A, Reporter R, et al. Autoantibodies in thalassaemia major: relationship with oral iron chelator L 1. J Assoc Physicians India 1993 Jun; 41: 339–41PubMedGoogle Scholar
  108. 108.
    Mehta J, Singhal S, Mehta BC. Deferiprone in iron overload [letter]. N Engl J Med 1995 Aug 31; 333: 597–8PubMedCrossRefGoogle Scholar
  109. 109.
    Olivieri NF, Matsui D, Liu PP, et al. Oral iron chelation with 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron loaded thalassemia patients. Bone Marrow Transplant 1993; 12 Suppl. 1: 9–11PubMedGoogle Scholar
  110. 110.
    Olivieri NF, Koren G, Freedman MH, et al. Rarity of systemic lupus erythematosus after oral iron chelator L1 [letter]. Lancet 1991 Apr 13; 337: 924PubMedCrossRefGoogle Scholar
  111. 111.
    Mehta J, Singhal S, Revankar R, et al. Fatal systemic lupus erythematosus in patient taking oral iron chelator L1 [letter]. Lancet 1991 Feb 2; 337: 298PubMedCrossRefGoogle Scholar
  112. 112.
    Loebstein R, Dalal I, Nisbet-Brown E, et al. Immune function in patients with β thalassaemia receiving the orally active iron-chelating agent deferiprone. Br J Haematol 1997 Sep; 98(3): 597–600PubMedCrossRefGoogle Scholar
  113. 113.
    Alrefaie FN, Wonke B, Wickens DG, et al. Zinc concentration in patients with iron overload receiving oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one or desferrioxamine. J Clin Pathol 1994 Jul; 47: 657–60CrossRefGoogle Scholar
  114. 114.
    Erer B, Angelucci E, Lucarelli G. HCV infection in thalassemia before and after BMT. Bone Marrow Transplant 1997; 19 Suppl. 2: 155–7Google Scholar
  115. 115.
    Lai ME, Argiolu F, Balaci L, et al. A prospective study of transfusion associated hepatitis in thalassemic children after the introduction of anti-HCV donor screening. Bone Marrow Transplant 1997; 19 Suppl. 2: 158–9Google Scholar
  116. 116.
    Kowdley KV, Kaplan MM. Iron-chelation therapy with oral deferiprone-toxicity or lack of efficacy? N Engl J Med 1998 Aug 13; 339: 468–9PubMedCrossRefGoogle Scholar
  117. 117.
    Callea F. Iron chelation with oral deferiprone in patients with thalassemia [letter]. N Engl J Med 1998; 339: 1710–1PubMedCrossRefGoogle Scholar
  118. 118.
    Töndury P, Zimmermann A, Nielsen P, et al. Liver iron and fibrosis during long-term treatment with deferiprone in Swiss thalassaemic patients. Br J Haematol 1998 Jun; 101(3):413–5PubMedCrossRefGoogle Scholar
  119. 119.
    Piga A, Facello S, Gaglioti C, et al. No progression of liver fibrosis in thalassemia major during deferiprone or desferrioxamine iron chelation [abstract]. Blood 1998 Nov 15; 92 (10 Suppl. 1, Pt 2): 21bGoogle Scholar
  120. 120.
    Galanello R, De Virgilis S, Agus A, et al. Sequential liver fibrosis grading during deferiprone treatment in patients with thalassaemia major. 9th International Conference on Iron Chelation in the Treatment of Thalassaemia and Other Diseases; 1999 Mar 25–28; HamburgGoogle Scholar
  121. 121.
    Stella M, Pinzello G, Maggio A. Iron chelation with oral deferiprone in patients with thalassemia. N Engl J Med 1998; 339: 1712PubMedGoogle Scholar
  122. 122.
    Marciani MG, Iani C, Desiato MT, et al. Subclinical auditory and visual involvement during oral deferiprone therapy [letter]. Am J Hematol 1996 Feb; 51: 179–80PubMedCrossRefGoogle Scholar
  123. 123.
    Chiesi Farmaceutici. Deferiprone Chiesi Farmaceutici. Summary of product characteristics. Parma, Italy, 1999Google Scholar
  124. 124.
    Piga A, Alberti D, Hassan I, et al. Efficacy of a new formulation of desferrioxamine (CGH 749B) given as a subcutaneous bolus injection in transfusion-dependent beta thalassemic patients. Blood 1997 Suppl. 1: 32aGoogle Scholar
  125. 125.
    Borgna-Pignatti C, Cohen A. Evaluation of a new method of administration of the iron chelating agent deferoxamine. J Pediatr 1997 Jan; 130: 86–8PubMedCrossRefGoogle Scholar
  126. 126.
    Schnebli HP. CGP 72 670: a new potent, orally active iron chelator. Br J Haematol 1998; 102: 280Google Scholar
  127. 127.
    Olivieri NF. Long-term therapy with deferiprone. Acta Haematol 1996; 95(1): 37–48PubMedCrossRefGoogle Scholar
  128. 128.
    Pfannkuch F, Bentley P, Schnebli HP. Future of oral iron chelator deferiprone (L1) [letter]. Lancet 1993 Jun 5; 341: 1480PubMedCrossRefGoogle Scholar
  129. 129.
    Nathan DG. An orally active iron chelator. N Engl J Med 1995 Apr 6; 332: 953–4PubMedCrossRefGoogle Scholar
  130. 130.
    Kontoghiorghes GJ, Bartlett AN, Sheppard L, et al. Oral iron chelation therapy with deferiprone: monitoring of biochemical, drug and iron excretion changes. Arzneimittel Forschung 1995 Jan; 45: 65–9PubMedGoogle Scholar
  131. 131.
    Olivieri NF, Koren G, Matsui D, et al. Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. Drugs Today 1992; 28 Suppl. A: 123–32Google Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

Personalised recommendations