Therapeutic Drug Monitoring of Chelating Agent Deferoxamine for β-Thalassemia Major Patients


Therapeutic drug monitoring is used to prevent or decrease the risk associated with the toxic effects of medication. This study aims to evaluate the potential advantages of Therapeutic Drug Monitoring (TDM) of subcutaneous Deferoxamine injection and prevention of clinical problems in β-thalassaemia major patients. Patients & Methods: Fifty-four thalassemia patients were allocated into two groups; missing, and not missing deferoxamine dose. TDM of Deferoxamine injection and it clinical outcomes was critically studied under the following subheadings: assessment of the adequacy of Deferoxamine usage, serum peak and trough concentrations of Deferoxamine and ferroxamine with needed pharmacokinetics, cardiac parameters and biomarkers, biochemical and hematological indices, adverse effects/toxicity, urinary assessment of Fe, Zn, selenium, and copper levels, compliance to treatment, dose adjustment in correlation to therapeutic index and life style. Results: Demographic data showed no significant difference. Peak plasma concentrations were 144.83±69 and 43.54±39.16 μg/L, while trough concentrations were 33±26.32 and 31.13±21.58 μg/L of Deferoxamine and ferroxamine, respectively. The elimination rate constant was 0.0237±0.00029 min-1, half-life was 34 min, and distribution volume was 0.93±0.078. Although cardiac parameters showed no significant differences, there were significant differences in CK-MB, and hsCRP levels; troponin I value could not be detected. Biochemical and hematological studies showed significant differences in Ferritin B, urea, SGPT, SGOT, alkaline phosphatase, serum albumin and serum calcium. Assessment of adverse effects/toxicity showed significant differences. The correlation of serum ferritin to therapeutic index, and the life style including Vitamin C and/or E administration were assessed for the compliance to treatment. Conclusion: Therapeutic monitoring of chelation therapy by Deferoxamine in β-thalassemia patients is necessary to ensure effective treatment, compliance, and to avoid adverse side effects and toxicity.

Share and Cite:

R. Ratha and T. Altaei, "Therapeutic Drug Monitoring of Chelating Agent Deferoxamine for β-Thalassemia Major Patients," International Journal of Clinical Medicine, Vol. 4 No. 8, 2013, pp. 331-342. doi: 10.4236/ijcm.2013.48059.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. A. Ghiculescu, “Therapeutic Drug Monitoring: Which Drugs, Why, When and How to Do It,” Therapeutic Drug Monitoring, Vol. 31, No. 2, 2008, p. 2.
[2] A. Cao, G. Giuseppe, M. B. Modell, G. Srchi and C. Vullo, “Management Protocol for the Treatment of Thalassemia Patients in Cooperation with WHO,” Thalassaemia International Federation (TIF), Cyprus, 1992.
[3] J. B. Porter, “Deferoxamine Pharmacokinetics,” Semin-Hematol, Vol. 38, No. 1, 2001, pp. 63-68. doi:10.1053/shem.2001.20145
[4] P. Cianciulli, “Iron Chelation Therapy in Thalassemia Syndromes,” Mediterranean Journal of Hematology and Infectious Diseases, Vol. 1 No. 1, 2009.
[5] J. C. Wood, “Cardiac Iron across Different Transfusion-Dependent Diseases,” Blood Reviews, Vol. 22, No. S2, 2008, pp. S14-S21.
[6] P. Kirk, M. Roughton, J. B. Porter, J. M. Walker, M. A. Tanner, J. Patel, D. Wu, J. Taylor, M. A. Westwood, L. J. Anderson and D. J. Pennell, “Cardiac T2* Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Major,” Circulation, Vol. 120, No. 20, 2009, pp. 1961-1968. doi:10.1161/CIRCULATIONAHA.109.874487
[7] G. Chouliaras, V. Berdoukas, V. Ladis, A. Kattamis, A. Chatziliami, C. Fragodimitri, F. Karabatsos and P. Cianciulli, “Iron Chelation Therapy in Thalassemia Syndromes,” Mediterranean Journal of Hematology and Infectious Diseases, Vol. 1, No. 1, 2011, pp. 2035-3006.
[8] H. Keberle, “The Biochemistry of Desfemoxamine and Its Relation to Iron Metabolism,” Annals of the New York Academy of Sciences, Vol. 1, No. 19, 1964, p. 758.
[9] C. Borgna-Pignatti and A. Cohen, “Evaluation of a New Method of Administration of the Iron Chelating Agent Deferoxamine,” Journal of Pediatrics, Vol. 130, No. 1, 1997, pp. 86-88. doi:10.1016/S0022-3476(97)70314-7
[10] R. Prabhu, V. Prabhu and R. S. Prabhu, “Iron Overload in Beta Thalassemia—A Review,” Journal of Bioscience and Technology, Vol. 1, No. 1, 2009, pp. 20-31.
[11] E. Vichinsky, L. Levine, S. Bhatia, J. Bojanowski, T. Coates and D. Foote, “Standards of Care Guidelines for Thalassemia,” Children’s Hospital & Research Center, Oakland, 2012.
[12] A. Cao and O. R. Galanello, “Beta-Thalassemia,” Genetics in Medicine, Vol. 12, No. 2, 2013, pp. 61-76. doi:10.1097/GIM.0b013e3181cd68ed
[13] J. C. Wood, “Cardiac Complications in Thalassemia Major,” Hemoglobin, Vol. 33, No. S1, 2009, pp. S81-S86. doi:10.3109/03630260903347526
[14] J. B. Porter and F. T. Shah, “Iron Overload in Thalassemia and Related Conditions: Therapeutic Goals and Assessment of Response to Chelation Therapies,” Hematology/Oncology Clinics of North America, Vol. 24, No. 6, 2010, pp. 1109-1130. doi:10.1016/j.hoc.2010.08.015
[15] J. S. Kang and M. H. Lee, “Overview of Therapeutic Drug Monitoring,” Korean Journal of Internal Medicine, Vol. 24, No. 1, 2009, pp. 1-10. doi:10.3904/kjim.2009.24.1.1
[16] E. Dunn, “Therapeutic Drug Monitoring,” Feature, Vol. 16, No. 2, 2009, pp. 5-6.
[17] K. Sakha, M. Samadi and A. Rezamand, “Cardiac Involvement of Major Thalassemia and Evaluation of Total Serum Creatine Kinase and Creatine Kinase-MB Isoenzyme and Cardiac Troponin I in These Patients,” Pakistan Journal of Biological Sciences, Vol. 11, No. 7, 2008, pp. 1059-1062. doi:10.3923/pjbs.2008.1059.1062
[18] M. A. Tanner, R. Galanello, C. Dessi, G. C. Smith, M. A. Westwood, A. Agus, 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, Vol. 115, No. 14, 2007, pp. 1876-1884. doi:10.1161/CIRCULATIONAHA.106.648790
[19] T. Cogliandro, G. Derchi, L. Mancuso, M. C. Mayer, B. Pannone, A. Pepe, et al., “Guideline Recommendations for Heart Complications in Thalassemia Major,” Journal of Cardiovascular Medicine (Hagerstown), Vol. 9, No. 5, 2008, pp. 515-25. doi:10.2459/JCM.0b013e3282f20847
[20] J. Caddel, “Metabolic and Nutritional Disease and Disease in Tropics. Moss and Adams Heart Disease in Infants, Children and Adolescents,” 6th Edition, Lippincott, Williams and Wilkins, Philadelphia, 2000, pp. 1266-1267.
[21] D. Defour, J. Lott and J. Henry, “Clinical Enzymology. Clinical Diagnosis and Management by Laboratory Methods,” 20th Edition, Saunders, Philadelphia, 2001, pp. 296-303.
[22] A. Aessopos, V. Berdoukas and M. Tsironi, “The Heart in Transfusion Dependent Homozygous Thalassemia Today Prediction, Prevention and Management,” European Journal of Haematology, Vol. 80, No. 2, 2008, pp. 93-106.
[23] N. Rifai and P. Ridker, “High-Sensitivity C-Reactive Protein: A Novel and Promising Marker of Coronary Heart Disease,” Clinical Chemistry, Vol. 47, No. 3, 2001, pp. 403-411.
[24] R. McPherson, J. Frohlich, G. Fodor and J. Genest, “Canadian Cardiovascular Society Position Statement—Recommendations for the Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease,” Canadian Journal of Cardiology, Vol. 22, No. 11, 2006, pp. 913-927. doi:10.1016/S0828-282X(06)70310-5
[25] A. Sachdeva, R. Misra and S. Yadav, “Desferal in Thalassemia,” In: A. Sachdeva, M. R. Lokeshwar and N. Shah, Eds., Hemoglobinopathies, Jaypee Publications, New Delhi, 2006, pp. 148-156.
[26] P. Tirgar and T. Desai, “Investigation into Beneficial Effects of Triticum aestivum (Wheat Grass) in Iron Overloads Complications,” Pharmacologyonline, Vol. 2, 2011, pp. 900-920.
[27] Z. Younus, Y. Alhially and A. DallalBashi, “Evaluation of Conventional Renal Function Tests in β-Thalassemia Major Patients in Nineveh Province,” Tikrit Journal of Pharmaceutical Sciences, Vol. 8, No. 1, 2012, pp. 6-14.
[28] M. Mohkam, B. S. Shamsian, A. Gharib, S. Nariman and M. T. Arzanian, “Early Markers of Renal Dysfunction in Patients with Beta-Thalassemia Major,” Pediatric Nephrology, Vol. 23, No. 6, 2008, pp. 971-976. doi:10.1007/s00467-008-0753-x
[29] A. Kassab-Chekira, S. Laradia, S. Ferchichia, A. Haj Khelila, M. Fekib, F. Amric, H. Selmid, M. Bejaouie and A. di Mileda, “Oxidant, Antioxidant Status and Metabolic Data in Patients with Beta-Thalassemia,” Clinica Chimica Acta, Vol. 338, No. 1-2, 2003, pp. 79-86. doi:10.1016/j.cccn.2003.07.010
[30] C. B. Modell, “The Pathophysiology of Beta-Thalassaemia Major,” Journal of Clinical Pathology. Supplement (Royal College of Pathologists), Vol. 8, 1974, pp. 12-18.
[31] A. Mahyar, “The Preventive Role of Zinc from Communicable and Non-Communicable Diseases in Children,” NCD Malaysia, Vol. 4, No. 2, 2005, pp. 21-26.
[32] B. Aziz, M. Al-Kataan and W. Ali, “Lipid Peroxidation and Antioxidant Status in β-Thalassemic Patients: Effect of Iron Overload,” Iraqi Journal of Pharmaceutical Sciences, Vol. 18, No. 2, 2009, pp. 25-32.
[33] M. A. Livrea, L. Tesoriere, A. M. Pintaudi, A. Calabrese, A. Maggio, H. J. Freisleben, D. D’Arpa, R. D’Anna and A. Bongiorno, “Oxidative Stress and Antioxidant Status in Beta-Thalassemia Major: Iron Overload and Depletion of Lipid Soluble Antioxidants,” Blood, Vol. 88, No. 9, 1996, pp. 3608-3614.
[34] R. Wirawan, S. Setiawan and D. Gatot, “Peripheral Blood and Hemoglobin Electrophoresis Pattern in Beta Thalassemia Major Patients Receiving Repeated Blood Transfusion,” Medical Journal of Indonesia, Vol. 13, 2004, pp. 8-16.
[35] S. B. McKenzie, “Nonmalignant Granulocyte and Monocyte Disorders,” In: S. B. McKenzie, Ed., Textbook of Hematology, 2nd Edition, Williams & Wilkins, Baltimore, 1996, pp. 275-280.
[36] A. Tantway, M. El Kholy, T. Moustafa and H. Elsedfy, “Bone Mineral Density and Calcium Metabolism in Adolescent with Beta Thalassemia Major,” Pediatric Endocrinology Reviews, Vol. 6, Suppl. 1, 2008, pp. 132-135.
[37] J. C. Barton, “Chelation Therapy for Iron Overloads,” Current Gastroenterology Reports, Vol. 9, 2007, pp. 74-82. doi:10.1007/s11894-008-0024-9
[38] Pharmaceutical Manufacturing Factory of Desferrioxamine (DESFERAL)? Novartis, “Australia Prescribing Information,” 2011.
[39] A. Dubey, S. Kumar, P. Choudhury, B. Talukdar and R. Puri, “Desferrioxamine Induced Urinary Iron Excretion in Thalassemia,” Indian Pediatrics, Vol. 30, No. 6, 1993, pp. 775-778.
[40] S. De Virgilis, F. Frau and G. Sanna, “Iron Elimination Following Intravenous Desferrioxamine Infusion in Patients with Thalassemia Major,” Pediatric Hematology-Oncology, Vol. 2, No. 1, 1985, pp. 47-48.
[41] M. R. Summers, A. Jacobs, D. Tudway, P. Perera and C. Ricketts, “Studies in Desferrioxamine and Ferrioxamine Metabolism in Normal and Iron-Loaded Subjects,” British Journal of Haematology, Vol. 42, No. 4, 1979, pp. 547-555. doi:10.1111/j.1365-2141.1979.tb01167.x
[42] A. Prasad, “Clinical, Biochemical and Nutritional Spectrum of Zinc Deficiency in Human Subjects: An Update,” Nutrition Reviews, Vol. 41, No. 7, 1983, pp. 197-208. doi:10.1111/j.1753-4887.1983.tb07155.x
[43] Z. A. Karciogluo, “Zinc in the Eye,” Survey of Ophthalmology, Vol. 27, No. 2, 1982, pp. 114-122. doi:10.1016/0039-6257(82)90195-3
[44] S. C. Davies, R. E. Marcus, J. L. Hungerford, M. H. Miller, G. B. Arden and E. R. Huehns, “Ocular Toxicity of High Dose Intravenous Desferrioxamine,” The Lancet, Vol. 322, No. 8343, 1983, pp. 181-184. doi:10.1016/S0140-6736(83)90170-8
[45] R. Galanello and R. O. Galanello, “Beta-Thalassemia,” Orphanet Journal of Rare Diseases, Vol. 5, 2010, p. 11. doi:10.1186/1750-1172-5-11
[46] J. Kushner, J. Porter and N. Olivieri, “Secondary Iron Overload,” American society for Hematology, 2011, pp. 47-61.
[47] R. Robins-Browne and J. Prpic, “Effects of Iron and Desferrioxamine on Infections with Yersinia Enterocolitica,” Infection and Immunity, Vol. 47, No. 3, 1985, pp. 774-779.
[48] M. C. Stuart, M. Kouimtzi and S. R. Hill, “WHO Model Formulary,” World Health Organization, Geneva, 2009.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.