Advances in Iron Chelation Therapy: Towards A New Oral Formulation

Document Type : original article

Authors

1 Assistant professor, Department of pediatrics, Faculty of medicine, Urmia University of Medical Sciences, urmia, Iran.

2 Medical student, Urmia University of Medical Sciences, Urmia, Iran.

Abstract

Background: Patients with thalassemia major require regular monthly blood transfusion and excess iron from multiple blood transfusion deposits in different organs of the body, causing different organ damages. Cardiac iron overload is the main cause of death in patients with thalassemia major.
Method: The aim of this study was to determine the effectiveness of Deferasirox (Nanojade) produced in Iran for the first time as a medicine in reducing iron overload of chronic blood transfusion in patients with Beta-thalassemia major. This is a pre-post quasi-experimental study that was performed on patients with thalassemia major involved in lifelong regular monthly blood transfusions. In this study, based on the existing protocols, injectable and dissolving iron chelating regimes were changed to a new generation of deferasirox oral tablets. To determine the effect of Nanojade, the mean level of the last three serum ferritin levels, before changing chelation, was compared with the serum ferritin levels after starting Nanojade. In the course of treatment, the possible side effects of Nanojade in various organs were monitored regularly.
Results: The mean age of the patients was 16 years (ranging between 3 and 39 years). None of the patients had renal failure, elevated creatinine, or proteinuria with Nanojade. The most important side effect was elevated liver enzyme levels. The mean starting dose of Nanojade was 19.86± 5.78 mg/kg and the mean of the last dose was 23.41 ± 5.49 mg/kg. There was a statistically significant difference between the amount of ferritin at baseline with the serum ferritin of 6 and 18 months after chelation with Nanojade (P = 0.001).
Conclusion: chelation with Nano Jade had less renal and hepatic side effects; and all of the patients had good compliance and significant reduction in the serum ferritin level in comparison to the results of other studies regarding the similar foreign deferasirox products.

Keywords

References

  1. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011 Sep 29; 118 (13):3479-88. doi: 10.1182/blood-2010-08-300335
  2. Akay A, Dragomir A, Yardimci A, Canatan D, Yesil Ipek A, Pogue BW. A data-mining approach for investigating social and economic geographical dynamics of beta-thalassemia's spread. IEEE Tran INF Technol Biomed. 2009 Sep; 13(5):774-80. doi: 10.1109/TITB.2009.2020062.
  3. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood. 1997 Feb 1; 89(3):739-61. Erratum in: Blood 1997 Apr 1; 89(7):2621.
  4. Lorey FW, Arnopp J, Cunningham GC. Distribution of hemoglobinopathy variants by ethnicity in a multiethnic state. Genet Epidemiol. 1996; 13(5):501-12. doi: 10.1002/(SICI)1098-2272(1996)13:5<501::AID-GEPI6>3.0.CO;2-4.
  5. Haghshenas M, Zamani J. [Thalassemia]. 1st ed. Shiraz: Shiraz University of Medical Sciences Publishing Center, 1997 (Book in Persian).
  6. Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, 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. doi: 10.1161/CIRCULATIONAHA.106.648790. Epub 2007 Mar 19.
  7. Lekawanvijit S, Chattipakorn N. Iron overload thalassemia cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol. 2009 Apr; 25(4):213-8. doi: 10.1016/s0828-282x(09)70064-9.
  8. Borgna-Pignatti C, Rigoletto's, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct; 89(10):1187-93.
  9. Bergeron RJ, Brittenham GM. The development of iron chelators for clinical use. CRC Press; 1993 Dec 6.
  10. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007 Sep; 13(9):1096-101. doi: 10.1038/nm1629. Epub 2007 Aug 26.
  11. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999 Dec 23; 341(26):1986-95. doi: 10.1056/NEJM199912233412607. Erratum in: N Engl J Med 2000 Feb 3; 342(5):364.
  12. Takpradit C, Viprakasit V, Narkbunnam N, Vathana N, Phuket K, Pojthanakul B, Sanpakit K, Bua Boonnam J. Using of deferasirox and deferoxamine in refractory iron overload thalassemia. Pediatr Int. 2021 Apr; 63(4):404-409. doi: 10.1111/ped.14444.13
  13. Neufeld EJ. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood. 2006 May 1; 107(9):3436-41. doi: 10.1182/blood-2006-02-002394.
  14. SMITH RS. Iron excretion in thalassaemia major after administration of chelating agents. Br Med J. 1962 Dec 15; 2(5319):1577-80. doi: 10.1136/bmj.2.5319.1577.
  15. Anderson LJ, Wonke B, Prescott E, Holden S, Walker JM, Pennell DJ. Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet. 2002 Aug 17; 360(9332):516-20. doi: 10.1016/s0140-6736(02)09740-4.
  16. Kontoghiorghes GJ, Eracleous E, Economides C, Colnago Aa. Advances in iron overload therapies. Prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and their combinations. Curr Med Chem. 2005; 12(23):2663-81. doi: 10.2174/092986705774463003.
  17. 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):329-47. doi: 10.1080/03630260600642674.
  18. Goldberg SL, Giardina PJ, Chirnomas D, Esposito J, Paley C, Vichinsky E. The palatability and tolerability of deferasirox taken with different beverages or foods. Pediatr Blood Cancer. 2013 Sep; 60(9):1507-12. doi: 10.1002/pbc.24561. Epub 2013 Apr 23.
  19. Waldmeier F, Bruin GJ, Glaenzel U, Hazell K, Sechaud R, Warrington S, Porter JB. Pharmacokinetics, metabolism, and disposition of deferasirox in beta-thalassemic patients with transfusion-dependent iron overload who are at pharmacokinetic steady state. Drug Metab Dispos. 2010 May; 38(5):808-16. doi: 10.1124/dmd.109.030833. Epub 2010 Jan 22.
  20. Chalmers AW, Shammo JM. Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions. Ther Clin Risk Manag. 2016 Feb 15; 12:201-8. doi: 10.2147/TCRM.S82449.
  21. Shah NR. Advances in iron chelation therapy: transitioning to a new oral formulation. Drugs Context. 2017 Jun 16; 6:212502. doi: 10.7573/dic.212502.
  22. Cappellini MD, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A. Guidelines for the Clinical Management of Thalassaemia [Internet]. 2nd Revised ed. Nicosia (CY): Thalassaemia International Federation; 2008. PMID: 24308075.
  23. Cheng WY, Said Q, Hao Y, Xiao Y, Vekeman F, Bobbili P, Duh MS, Nandal S, Blinder M. Adherence to iron chelation therapy in patients who switched from deferasirox dispersible tablets to deferasirox film-coated tablets. Curr Med Res Opin. 2018 Nov; 34(11):1959-1966. doi: 10.1080/03007995.2018.1470500. Epub 2018 Jun 4. Erratum in: Curr Med Res Opin. 2019 Mar; 35(3):559.
  24. Tartaglione, I., Origa, R., Kattamis, A. et al. Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study. Exp Hematol Oncol 9, 20 (2020). https://doi.org/10.1186/s40164-020-00174-2
  25. Taher AT, Origa R, Perrotta S, Kourakina, Ruffo GB, Kattamis A, et al. New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study. AmJ Hematol. 2017 May; 92(5):420-428.doi: 10.1002/ajh.24668. Epub 2017 Feb 18.
Journal of Pediatric Perspectives
Volume 10, Issue 7
July 2022
Pages 16387-16395

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