DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20161483

Safety of deferasirox as an oral iron chelator in thalassemic children

Shikha Jaiswal, Rajesh Hishikar, Basant Maheshwari, Onkar Khandwal, Raka Sheohare

Abstract


Background: Thalassemia major patients require frequent blood transfusion leading to iron overload. Iron overload is characterized by excessive iron deposition and consequent injury and dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their coexisting medical conditions. Current prospective, observational study is done to assess the safety of deferasirox as an oral iron chelator, with specific reference to rise in serum creatinine level, alanine aminotransferase level (SGPT), urine albumin level in 50 multi-transfused thalassemia major children receiving deferasirox (DFX) therapy at registered thalassemia society Raipur, India.

Methods: DFX was administered in an initial dose of 20 mg/kg/day and increased to a maximum of 40 mg/kg/day. Serum creatinine, alanine aminotransferase level (SGPT), urine albumin level were estimated in pretransfusion samples at time of registration and at 3 monthly intervals (4 times). The primary end point of the study was completion of 12 months of therapy (January 2013 to December 2013).

Results: Prior to DFX therapy the mean serum creatinine, SGPT, urine albumin of all cases were 0.4617 mg/dl, 20.78 U/L and nil respectively. After 12 months of DFX therapy of mean dose 38 mg/kg/day, the mean serum creatinine was. 0.4624 mg/dL. SGPT was 20.81 U/L, and urine albumin was nil.

Conclusions: Deferasirox monotherapy has a good safety profile and effectively chelates total body iron.  


Keywords


Deferasirox, Iron chelation, Management, Thalassemia

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References


John CW. Diagnosis and management of transfusion iron overload; the role of imaging. Am J Hematol. 2007;82(12):1132-5.

Hershko CM, Link GM, Konijn AM, Cabantchik ZI. Iron chelation therapy. Curr Hematol Rep. 2005;4:110-1.

Cohen AR, Galanello R, Piga A. Safety and effectiveness of long-term therapy with the oral iron chelatordeferiprone. Blood. 2003;102:1583-7.

EMEA: Deferiprone Summary of Product Characteristics. 2006. Available at http://www.ferriprox.com. Accesssed 19 March 2016.

Hoffbrand AV, Cohen A, Hershko C. Role of deferiprone in chelation therapy for transfusional iron overload. Blood. 2003;102:17-24.

Vichinsky E, Onyekwere O, Porter J. A randomized comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. 2007;136:501-8.

Cappellini MD, Cohen A, Piga A. A phase III study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood. 2006;107:3455-62.

Cazzola M, Gattermann N, Greenberg P. ICL670, a once-daily iron chelator, is effective and well tolerated in patients with myelodysplastic syndrome (MDS) and iron overload. Haematologica. 2005;90(2):306.

Daar S, Taher A, Pathare A. Deferasirox (Exjade, ICL670) provides 24 hour protection from labile plasma iron (LPI), in iron overloaded beta-thalassaemia patients previously chelated with mono- or combination therapy. Haematologica. 2006;91(1):31.

Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol. 2005;18:277-87.

Taher A, Jefri A, Elalfy MS, Al Zir K, Daar S, Rofail D, et al. Improved treatment satisfaction and convenience with Deferasirox in iron-overloaded patients with β thalassemia results from the escalator trial. Acta Haematol. 2010;123:220-5.

EXJADE, (Deferasirox). NDA 21-882 / S-002. (INTERNET). [Revised; 2007]. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021882s002lbl. Accessed 19 April 2016.

Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood. 1997;89(3):739-61.

Ehlers KH, Giardina PJ, Lesser ML, Engle MA, Hilgartner MW. Prolonged survival in patients with β-thalassemia major treated with deferoxamine. J Pediatr. 1991;118(4):540-5.

Hershko C. Oral iron chelators: new opportunities and new dilemmas. Haematologica. 2006;91:1307-12.

Modell B, Khan M, Darlison M. Survival in β thalassaemia major in the UK: data from the UK thalassaemia register. Lancet. 2000;355:2051-2.

Zurlo MG, Stefano DP, Borgna PC, Palma DA, Piga A, Melevendi C, Gregorio DF. Survival and causes of death in thalassaemia major. Lancet. 1989;2:27-30.

Merchant R, Ahmed J, Krishnan P, Jankharia B. Efficacy and safety of deferasirox for reducing total body and cardiac iron in thalassemia. Indian Pedia. 2012;49:281-5.

Cappellini MD, Bejaoui M, Agaoglu L, Canatan D, Capra M, Cohen A et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major. Blood. J Hematol. 2011;118:884-93.