Physicochemical characterization of ferric carboxymaltose brands in India: relevance to anemia management in chronic kidney disease

Abhishek Tandayam; Tarun Singh; P. Venkatesh; Snehal Sameer Muchhala; Bhavesh P. Kotak

doi:10.18203/2319-2003.ijbcp20252568

Authors

Abhishek Tandayam Department of Medical Affairs, Dr Reddy’s Laboratories, 7-1, 27, Ameerpet Road, Leelanagar, Ameerpet, Hyderabad, Telangana, India
Tarun Singh Department of Injectables Formulation R and D, Dr Reddy’s Laboratories Ltd., SCM-GDC Office, Bachupally, S. No. 42,45, Quthbullapur, 46 and 54, Bachupally, Hyderabad, Telangana, India
P. Venkatesh Department of Injectables Analytical R and D, Dr Reddy’s Laboratories Ltd., SCM-GDC Office, Bachupally, S. No. 42,45, Quthbullapur, 46 and 54, Bachupally, Hyderabad, Telangana
Snehal Sameer Muchhala Department of Medical Affairs, Dr Reddy’s Laboratories, 7-1, 27, Ameerpet Road, Leelanagar, Ameerpet, Hyderabad, Telangana, India
Bhavesh P. Kotak Department of Medical Affairs, Dr Reddy’s Laboratories, 7-1, 27, Ameerpet Road, Leelanagar, Ameerpet, Hyderabad, Telangana, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20252568

Keywords:

Anemia, Bioequivalence, Chronic kidney disease, Ferric carboxymaltose, Physicochemical properties

Abstract

Background: Ferric carboxymaltose (FCM) is widely used in the management of anemia associated with chronic kidney disease. The therapeutic efficacy and long-term safety of FCM related to free iron mediated toxicity can be influenced by its physicochemical properties. This study aimed to compare physicochemical properties across various FCM brands available in India.

Methods: Samples of FCM from 6 different manufacturers were procured including Dr. Reddy’s FCM brand injection Irny and subjected to a series of laboratory tests. Key quality attributes like carbohydrate content, molecular weight, etc. were analysed using validated methodologies and compared with USFDA reference-listed drug (RLD) Injectafer.

Results: The carbohydrate content of Dr. Reddy’s injection Irny (8.78%) was comparable to USFDA RLD (8.2%), whereas other brands showed variability ranging from 4.38% to 10.56%. Molecular weight of Irny (2.74 lakh) was also in line with USFDA RLD (2.94 lakh), with other brands mostly exhibiting lower molecular weights. Zeta potential of injection Irny (0.17 mV) closely matched that of USFDA RLD (1.25 mV), while other brands showed more negative values ranging from -0.70 mV to -27 mV. Degradation kinetics (T75 value) of injection Irny (19.14 minutes) were similar to USFDA RLD (18.34 minutes), while other brands demonstrated longer degradation times (21 to 52 minutes).

Conclusions: Study highlighted notable variability in physicochemical properties of different FCM brands. Dr. Reddy’s injection Irny closely aligns with the USFDA RLD Injectafer quality attributes, suggesting comparable potential clinical outcomes and long-term safety. The observed differences among other brands may influence their bioequivalence and long-term safety.

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References

Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382(9888):260-72. DOI: https://doi.org/10.1016/S0140-6736(13)60687-X

Singh AK, Farag YM, Mittal BV, Subramanian KK, Reddy SR, Acharya VN, et al. Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (screening and early evaluation of kidney disease) study. BMC Nephrol. 2013;14:114. DOI: https://doi.org/10.1186/1471-2369-14-114

Stauffer ME, Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS One. 2014,9(1):e84943. DOI: https://doi.org/10.1371/journal.pone.0084943

Muniyandi D, Shanmugam N, Ramanathan K, Vijayaraghavan B, Padmanabhan G. Prevalence of iron deficiency anemia among chronic kidney disease patients in Kaveri Delta region, Tamil Nadu, India. J Adv Med Med Res. 2016,15(11):1-6. DOI: https://doi.org/10.9734/BJMMR/2016/25711

Li Y, Shi H, Wang WM, Peng A, Jiang GR, Zhang JY, et al. Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: first multicenter, cross-sectional study. Medicine. 2016;95(24):e3872. DOI: https://doi.org/10.1097/MD.0000000000003872

Zaawari A, Tejaswini KL, Davina GD, Singanaveni A. Prevalence of anemia among chronic kidney disease patients in India: a single-centre study. Int J Basic Clin Pharmacol. 2022,11:404-9. DOI: https://doi.org/10.18203/2319-2003.ijbcp20222135

Odeyemi A, Oladimeji OM, Ajibare AO, Iyayi AA, Oladimeji AB, Ojo OT, et al. Impact of anemia on the quality of life of chronic kidney disease patients: a single institution experience. West Afr J Med. 2023;40(11):1253-61.

Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. The impact of anemia on cardiomyopathy, morbidity, and mortality in end-stage renal disease. Am J Kidney Dis. 1996;28:53-61. DOI: https://doi.org/10.1016/S0272-6386(96)90130-4

Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631-4. DOI: https://doi.org/10.1681/ASN.2011111078

Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am J Kidney Dis. 2018;71(3):423-35. DOI: https://doi.org/10.1053/j.ajkd.2017.09.026

Hain D, Bednarski D, Cahill M, Dix A, Foote B, Haras MS, et al. Iron-deficiency anemia in CKD: a narrative review for the kidney care team. Kidney Med. 2023;5(8):100677. DOI: https://doi.org/10.1016/j.xkme.2023.100677

Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012,2:279-335.

Lyseng-Williamson KA, Keating GM. Ferric carboxymaltose: a review of its use in iron-deficiency anaemia. Drugs. 2009;69:739-56. DOI: https://doi.org/10.2165/00003495-200969060-00007

Vikrant S, Parashar A. The safety and efficacy of high dose ferric carboxymaltose in patients with chronic kidney disease: a single center study. Indian J Nephrol. 2015;25(4):213-21. DOI: https://doi.org/10.4103/0971-4065.144421

Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, et al; FIND-CKD Study Investigators. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant. 2014;29(11):2075-84. DOI: https://doi.org/10.1093/ndt/gfu201

Tagboto S, Cropper L, Turner J, Pugh-Clarke K. The efficacy of a single dose of intravenous ferric carboxymaltose (Ferinject) on anaemia in a pre-dialysis population of chronic kidney disease patients. J Ren Care. 2009;35(1):18-23. DOI: https://doi.org/10.1111/j.1755-6686.2009.00075.x

Qunibi WY, Martinez C, Smith M, Benjamin J, Mangione A, Roger SD. A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients. Nephrol Dial Transplant. 2011;26:1599-607. DOI: https://doi.org/10.1093/ndt/gfq613

Charytan C, Bernardo MV, Koch TA, Butcher A, Morris D, Bregman DB. Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney disease: a randomized, active-controlled, multi-center study. Nephrol Dial Transplant. 2013;28:953-64. DOI: https://doi.org/10.1093/ndt/gfs528

Zou P, Tyner K, Raw A, Lee S. Physicochemical characterization of iron carbohydrate colloid drug products. AAPS J. 2017;19(5):1359-76. DOI: https://doi.org/10.1208/s12248-017-0126-0

Funk F, Flühmann B, Barton AE. Criticality of surface characteristics of intravenous iron-carbohydrate nanoparticle complexes: implications for pharmacokinetics and pharmacodynamics. Int J Mol Sci. 2022;23(4):2140. DOI: https://doi.org/10.3390/ijms23042140

Bossart J, Rippl A, Barton Alston AE, Flühmann B, Digigow R, Buljan M, et al. Uncovering the dynamics of cellular responses induced by iron-carbohydrate complexes in human macrophages using quantitative proteomics and phosphoproteomics. Biomed Pharmacother. 2023;166:115404. DOI: https://doi.org/10.1016/j.biopha.2023.115404

Verhoef JJF, de Groot AM, van Moorsel M, Ritsema J, Beztsinna N, Maas C, et al. Iron nanomedicines induce Toll-like receptor activation, cytokine production and complement activation. Biomaterials. 2017;119:68-77. DOI: https://doi.org/10.1016/j.biomaterials.2016.11.025

Neiser S, Rentsch D, Dippon U, Kappler A, Weidler PG, Göttlicher J, et al. Physico-chemical properties of the new generation i.v. iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose. Biometals. 2015;28(4):615-35. DOI: https://doi.org/10.1007/s10534-015-9845-9

Nissim J. Intravenous administration of iron. Lancet. 1947;250:49-51. DOI: https://doi.org/10.1016/S0140-6736(47)90053-6

Nissim JA, Robson JM. Preparation and standardization of saccharated iron oxide for intra venous administration. Lancet. 1949;1:686-9. DOI: https://doi.org/10.1016/S0140-6736(49)91958-3

Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011;3(1):12-33. DOI: https://doi.org/10.3390/pharmaceutics3010012

Geisser P, Baer M, Schaub E. Structure/histotoxicity relationship of parental iron preparations. Arzneimittelforschung. 1992;42(12):1439-52.

Danielson BG. Structure, chemistry, and pharmacokinetics of intravenous iron agents. J Am Soc Nephrol. 2004;15(2):S93-8.

Ernsting MJ, Murakami M, Roy A, Li SD. Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J Control Rel. 2013;172(3):782-94. DOI: https://doi.org/10.1016/j.jconrel.2013.09.013

Jahn MR, Andreasen HB, Fütterer S, Nawroth T, Schünemann V, Kolb U, et al. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm. 2011;78(3):480-91. DOI: https://doi.org/10.1016/j.ejpb.2011.03.016

Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems- a review (part 1). Trop J Pharm Res. 2013;12(2):255-64. DOI: https://doi.org/10.4314/tjpr.v12i2.19

Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems- a review (part 2). Trop J Pharm Res. 2013;12(2):265-73. DOI: https://doi.org/10.4314/tjpr.v12i2.20

Toblli JE, Angerosa M. Optimizing iron delivery in the management of anemia: patient considerations and the role of ferric carboxymaltose. Drug Des Devel Ther. 2014;8:2475-91. DOI: https://doi.org/10.2147/DDDT.S55499