Ethical issues and risk/benefit assessment of iron chelation therapy: Advances with deferiprone/deferoxamine combinations and concerns about the safety, efficacy and costs of deferasirox

Hemoglobin

Volumn 32, Issue 1-2, 2008, Pages 1-15

  Kontoghiorghes, George J ^a  

^a Postgraduate Research Institute of Science Technology Environment and Medicine Limassol   (Cyprus)

Author keywords

Agranulocytosis; Chelation therapy; Deferasirox (DFRA); Deferiprone (L1); Deferoxamine (DFO); Thalassemia; Toxicity; Transfusional iron overload

Indexed keywords

DEFERASIROX; DEFERIPRONE; DEFEROXAMINE;

AGRANULOCYTOSIS; ARTHRALGIA; CHELATION THERAPY; CLINICAL TRIAL; CONFERENCE PAPER; COPPER DEFICIENCY; CYPRUS; CYTOPENIA; DEVELOPING COUNTRY; DRUG COST; DRUG EFFICACY; DRUG INDUSTRY; DRUG SAFETY; ERYTHROCYTE TRANSFUSION; EUROPEAN UNION; EYE TOXICITY; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL SYMPTOM; HEPATITIS; HUMAN; INFECTION; IRON CHELATION; KIDNEY FAILURE; LIVER FAILURE; LIVER TOXICITY; MORTALITY; MUCORMYCOSIS; MUSCULOSKELETAL PAIN; NAUSEA; NEUTROPENIA; RASH; RISK ASSESSMENT; SURVIVAL RATE; THALASSEMIA; THROMBOCYTOPENIA; YERSINIOSIS; ZINC DEFICIENCY;

BENZOIC ACIDS; CHELATION THERAPY; DEFEROXAMINE; DRUG APPROVAL; DRUG THERAPY, COMBINATION; HUMANS; IRON; IRON CHELATING AGENTS; IRON OVERLOAD; PYRIDONES; RISK ASSESSMENT; SIDEROPHORES; THALASSEMIA; TRIAZOLES;

EID: 39349086377     PISSN: 03630269     EISSN: 1532432X     Source Type: Journal    
DOI: 10.1080/03630260701726533     Document Type: Conference Paper

References (33)

1. Abstract Book. 16th International Conference on Chelation (ICOC) for the Treatment of Thalassemia, Cancer and Other Diseases Related to Metal and Free Radical Imbalance and Toxicity. Limassol, Cyprus. October 25-31, 2006; 1-85.
2. Kontoghiorghes GJ, Eracleous E, Economides Ch, Kolnagou A. Advances in iron overload therapies. Prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NAll and their combinations. Curr Med Chem 2005; 12(23):2663-2681.
3. World Health Organization: community control of hereditary anaemias. WHO Bull 1983; 61(1):63-80.
4. Kontoghiorghes GJ, Neocleous K, Kolnagou A. Benefits and risks of deferiprone in iron overload in thalassemia and other conditions. Comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Saf 2003; 26(8):553-584.
5. Modell B, Khan M, Darlison M. Survival in β-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet, 2000; 355(9220): 2051-2052.
6. Kontoghiorghes GJ, Pattichis K, Neocleous K, Kolnagou A. The design and development of deferiprone (L1) and other iron chelators for clinical use: targeting methods and application prospects. Curr Med Chem 2004; 11(16):2161-2183.
7. Kontoghiorghes GJ. New oral iron-chelating drugs for the treatment of transfusional iron overload and other diseases. Drugs Future 2006; 30(12):1241-1251.
8. Nick H, Acklin P, Lattmann R, Buechlmayer P, Hauffe S, Hauffe S, Schupp J, Alberti D. Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr Med Chem, 2003;10(12):1065-1076.
9. Porter JB. Deferasirox: an effective once-daily orally active iron chelator. Drugs Today (Barc) 2006; 42(10):623-637.
10. Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ, Sechaud R, Krebs-Brown AJ, Anderson JR, Alberti D, Sizer KC, Nathan DG. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2003; 361(9369):1597-1602.
11. Galanello R, Piga A, Alberti D, Rouan MC, Bigler H, Sechaud R. Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to β-thalassemia. J Clin Pharmacol 2003; 43(6):565-572.
12. Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, Files B, Hassell K, Kelly P, Wilson F, Bernaudin F, Forni G L, Okpala I, Ressayre-Djaffer C, Alberti D, Holland J, Marks P, Fung E, Fischer R, Mueller BU, Coates T. The Deferasirox in Sickle Cell Investigators. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol 2007; 136(3):501-508.
13. Anonymous. Exjade (deferasirox) tablets for oral suspension. Prescribing information. Novartis pharmaceutical corporation USA (NDA 21-882). October, 2006; 1-12.
14. Anonymous: Exjade (deferasirox) tablets for oral suspension update. Keeping you informed about changes to the Exjade prescribing information. Novartis Oncology, USA (EXJ-OT-0623-A). November, 2006; 1.
15. Kontoghiorghes GJ. Do we need more iron chelating drugs? Lancet 2003; 362(9382):495-496.
16. Kolnagou A, Kontoghiorghes GJ. Effective combination therapy of deferiprone and deferoxamine for the rapid clearance of excess cardiac iron and the prevention of heart disease in thalassemia. The protocol of the International Committee on Oral Chelators. Hemoglobin 2006; 30(2):239-249.
17. Anderson LJ, Wonke B, Prescott E, Holden S, Walker JM, Pennel DJ. Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in β-thalassaemia. Lancet 2002; 360(9332):516-520.
18. Peng CT, Chow KC, Chen JH, Chiang YP, Lin TY, Tsai CH. Safety monitoring of cardiac and hepatic systems in β-thalassaemia patients with chelating treatment in Taiwan. Eur J Haematol 2003; 70(6):392-397.
19. Kolnagou A, Fessas Ch, Papatryphonas A, Economides Ch, Kontoghiorghes GJ. Prophylactic use of deferiprone (L1) and magnetic resonance imaging T2* or T2 for preventing heart disease in thalassaemia Br J Haematol 2004; 127(3):360-361.
20. Pennel DJ, Berdoukas V, Karagiorga M, Ladis V, Piga A, Aessopos A, Gotsis ED, Tanner MA, Smith GC, Westwood MA, Wonke B, Galanello R. Randomized controlled trial of deferiprone or deferoxamine in β-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006; 107(9):3738-3744.
21. Tsironi M, Deftereos S, Andriopoulos P, Farmakis D, Meletis J, Aessopos A. Reversal of heart failure in thalassemia major by combined chelation therapy: a case report. Eur J Haematol 2005; 74(1):84-85.
22. Tefler P, Goen PG, Christou S, Hadjigavriel M, Kolnagou A, Pangalou E, Pavlides N, Psiloines M, Simamonian K, Skordos G, Sitarou M, Angastiniotis M. Survival of medically treated thalassaemia patients in Cyprus. Trends and risk factors over the period 1980-2004. Haematologica 2006; 91(9):1187-1192.
23. Crapper McLachlan DR, Dalton AJ, Kruck TP, Bell MY, Smith WL, Kalow W, Andrews DF. Intramuscular desferioxamine in patients with Alzheimer's disease. Lancet 1991; 337(8753):1304-1308.
24. Yamamoto RS, Williams GM, Frangel HH, Weisburger JH. 8-Hydroxyquinoline: chronic toxicity and inhibitory effect on the carcinogenicity of N-2-fluorenylacetamide. Toxicol Appl Pharmacol 1971; 19(4):687-98.
25. Kontoghiorghes GJ. Chelators affecting iron absorption in mice. Arzneimittel-Forschung/Drug Res 1990; 40(12):1332-1335.
26. Wood JC, Otto-Duessl M, Gonzalez I, Aguilar MI, Shimada H, Nick H, Nelson M, Moats R. Deferasirox and deferiprone remove cardiac iron in the iron-overloaded gerbil. Transl Res 2006; 148(5):272-280.
27. Shashaty G, Frankewich R, Chakraborti T, Choudary J, Al-Fayoumi S, Kacuba A, Castillo S, Robie-Suh K, Rieves D, Weiss K, Pazdur R. Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis. Oncology (Williston Park) 2006; 20(14):1799-1806.
28. Kontoghiorghes GJ. Deferasirox: uncertain future following renal failure fatalities, agranulocytosis and other toxicities. Expert Opin Drug Saf 2007; 6(3):236-239.
29. Henter JI, Karlen J. Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia. Blood 2007; 109(12):5157-5159.
30. Anonymous. Deferiprone: agranulocytosis and neurological disorders. Prescrire Int 2007;16(88):72.
31. Hohneker JA. Important information about Exjade (deferasirox). Tablets for oral suspension. Changes to the warnings and adverse reactions sections. Novartis pharmaceutical corporation USA. (www.fda.gov) May 14, 2007; 1-4.
32. Kontoghiorghes GJ. Future chelation monotherapy and combination therapy strategies in thalassemia and other conditions. Comparison of deferiprone, deferoxamine, ICL670, GT56-252, L1NAll and starch deferoxamine polymers. Hemoglobin 2006; 30(2):329-347.
33. Kontoghiorghes GJ, Sheppard L. Simple synthesis of the potent iron chelators 1-alkyl-3-hydroxy-2-methylpyrid-4-ones. Inorg Chim Acta 1987; 136:L11-L12.