Optimizing iron delivery in the management of anemia: Patient considerations and the role of ferric carboxymaltose

Drug Design, Development and Therapy

Volumn 8, Issue , 2014, Pages 2463-2473

  Toblli, Jorge Eduardo ^a   Angerosa, Margarita ^a  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

Author keywords

Anemia; Ferric carboxymaltose; Intravenous iron; Iron deficiency

Indexed keywords

ERYTHROPOIETIN; FERRIC CARBOXYMALTOSE; FERRIC GLUCONATE; FERRIC ION; FERRITIN; FERROPORTIN; FERROUS ION; FERROUS SULFATE; FERUMOXYTOL; FIBROBLAST GROWTH FACTOR 23; HEME; HEMOGLOBIN; HEPCIDIN; HIGH MOLECULAR WEIGHT IRON DEXTRAN; IRON; IRON DEXTRAN; IRON ISOMALTOSIDE; IRON SACCHARATE; LOW MOLECULAR WEIGHT IRON DEXTRAN; PHOSPHATE; PLACEBO; TRANSFERRIN; UNCLASSIFIED DRUG; MALTOSE;

ABSENCE OF SIDE EFFECTS; ANEMIA; BARIATRIC SURGERY; CHRONIC KIDNEY DISEASE; COST EFFECTIVENESS ANALYSIS; COST MINIMIZATION ANALYSIS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDICATION; DRUG INFUSION; DRUG MEGADOSE; DRUG SAFETY; DRUG SOLUBILITY; DRUG TISSUE LEVEL; DRUG TOLERABILITY; DRUG TOLERANCE; DRUG TRANSPORT; DRUG UTILIZATION; DRUG WITHDRAWAL; ERYTHROPOIESIS; FATIGUE; FERRITIN BLOOD LEVEL; GASTROINTESTINAL DISEASE; GASTROINTESTINAL SYMPTOM; GYNECOLOGIC DISEASE; HEALTH CARE COST; HEART FAILURE; HEMODIALYSIS; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERTENSION; IMMUNOREACTIVITY; INJECTION SITE BURNING; INJECTION SITE PAIN; IRON ABSORPTION; IRON BLOOD LEVEL; IRON DEFICIENCY ANEMIA; IRON METABOLISM; IRON TRANSPORT; LOW DRUG DOSE; MACROPHAGE; MOLECULAR WEIGHT; NONHUMAN; ORTHOPEDIC SURGERY; PARASITEMIA; PATHOPHYSIOLOGY; PATIENT COMPLIANCE; PHOSPHATE BLOOD LEVEL; PREGNANCY DISORDER; QUALITY OF LIFE; RESTLESS LEGS SYNDROME; REVIEW; SINGLE DRUG DOSE; THROMBOCYTE AGGREGATION; THROMBOCYTE COUNT; THROMBOCYTOSIS; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; ANALOGS AND DERIVATIVES; ANEMIA, IRON-DEFICIENCY; DRUG DELIVERY SYSTEM;

ANEMIA, IRON-DEFICIENCY; DRUG DELIVERY SYSTEMS; FERRIC COMPOUNDS; HUMANS; MALTOSE;

EID: 84916931319     PISSN: None     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S55499     Document Type: Review

References (88)

1. McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009;12(4):444-454.
2. Gaskell H, Derry S, Andrew Moore R, McQuay HJ. Prevalence of anaemia in older persons: systematic review. BMC Geriatr. 2008;8:1.
3. National Institute for Health and Clinical Excellence. Anaemia management in people with chronic kidney disease (CKD). NICE Clinical Guideline [Clinical Guideline 114]; 2011. Available from: http://guidance.nice.org.uk/cg114
4. Stoltzfus RJ. Defining iron-deficiency anemia in public health terms: a time for reflection. J Nutr. 2001;131(2S-2S):565S-567S.
5. von Drygalski A, Adamson JW. Ironing out fatigue. Blood. 2011;118:3191-3192.
6. Goodnough LT. Iron deficiency syndromes and iron-restricted erythropoiesis (CME). Transfusion. 2012;52(7):1584-1592.
7. Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008;88(1):7-15.
8. Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academies Press (US); 2001.
9. Shah YM, Matsubara T, Ito S, Yim SH, Gonzalez FJ. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab. 2009;9(2):152-164.
10. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434(3):365-381.
11. Shayeghi M, Latunde-Dada GO, Oakhill JS, et al. Identification of an intestinal heme transporter. Cell. 2005;122(5):789-801.
12. Quigley JG, Yang Z, Worthington MT, et al. Identification of a human heme exporter that is essential for erythropoiesis. Cell. 2004;118(6):757-766.
13. West AR, Oates PS. Mechanisms of heme iron absorption: current questions and controversies. World J Gastroenterol. 2008;14(26):4101-4110.
14. Abboud S, Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem. 2000;275(26):19906-19912.
15. Loréal O, Cavey T, Bardou-Jacquet E, Guggenbuhl P, Ropert M, Brissot P. Iron, hepcidin, and the metal connection. Front Pharmacol. 2014;5:128.
16. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006;108(12):3730-3735.
17. Fleming RE. Iron and inflammation: cross-talk between pathways regulating hepcidin. J Mol Med. 2008;86(5):491-494.
18. Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M. Iron release from macrophages after erythrophagocytosis is up-regulated by fer roport in 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci U S A. 2005;102(5):1324-1328.
19. Theurl I, Fritsche G, Ludwiczek S, Garimorth K, Bellmann-Weiler R, Weiss G. The macrophage: a cellular factory at the interphase between iron and immunity for the control of infections. Biometals. 2005;18(4):359-367.
20. Potdar AA, Sarkar J, Das NK, et al. Computational modeling and analysis of iron release from macrophages. PLoS Comput Biol. 2014;10(7):e1003701.
21. Bartnikas TB, Andrews NC, Fleming MD. Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice. Blood. 2011;117(2):630-637.
22. Funk F, Ryle P, Canclini C, Neiser S, Geisser P. The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose. Arzneimittelforschung. 2010;60(6a):345-353.
23. Auerbach M, Ballard H. Clinical use of intravenous iron: administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program. 2010;2010(1):338-347.
24. Koskenkorva-Frank TS, Weiss G, Koppenol WH, Burckhardt S. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radic Biol Med. 2013;65:1174-1194.
25. Sohn YS, Ghoti H, Breuer W, et al. The role of endocytic pathways in cellular uptake of plasma non-transferrin iron. Haematologica. 2012; 97(5):670-678.
26. Chao Y, Karmali PP, Simberg D. Role of carbohydrate receptors in the macrophage uptake of dext ran-coated iron oxide nanoparticles. Adv Exp Med Biol. 2012;733:115-123.
27. Neiser S, Wilhelm M, Schwarz K, Funk F, Geisser P, Burckhardt S. Assessment of dextran antigenicity of intravenous iron products by immunodiffusion assay. Port J Nephrol Hypertens. 2011; 25:219-224.
28. Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparat ions. Pharmaceutics. 2011;3(1):12-33.
29. Danielson BG. Structure, chemistry, and pharmacokinetics of intravenous iron agents. J Am Soc Nephrol. 2004;15(suppl 2):S93-S98.
30. Bailie GR, Mason NA, Valaoras TG. Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Hemodial Int. 2010;14(1):47-54.
31. Ohgami RS, Campagna DR, Greer EL, et al. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet. 2005;37(11):1264-1269.
32. Geisser P, Banke-Bochita J. Pharmacokinetics, safety and tolerability of intravenous ferric carboxymaltose: a dose escalation study in volunteers with mild iron-deficiency anaemia. Arzneimittelforschung. 2010;60(6a):362-372.
33. Geisser P, Rumyantsev V. Pharmacodynamics and safety of ferric carboxymaltose: a multiple-dose study in patients with iron-deficiency anaemia secondary to a gastrointestinal disorder. Arzneimittelforschung. 2010;60(6a):373-385.
34. Beshara S, Sörensen J, Lubberink M, et al. Pharmacokinetics and red cell utilization of 52Fe/59Fe-labelled iron polymaltose in anaemic patients using positron emission tomography. Br J Haematol. 2003; 120(5):853-859.
35. Breymann C, Gliga F, Bejenariu C, Strizhova N. Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia. Int J Gynaecol Obstet. 2008; 101(1):67-73.
36. Kalantar-Zadeh K, Lee GH, Miller JE, et al. Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients. Am J Kidney Dis. 2009;53(5):823-834.
37. Covic A, Mircescu G. The safety and efficacy of intravenous ferric carboxymaltose in anaemic patients undergoing haemodialysis: a multi-centre, open-label, clinical study. Nephrol Dial Transplant. 2010;25(8):2722-2730.
38. 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(4):953-964.
39. Onken JE, Bregman DB, Harrington RA, et al. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrol Dial Transplant. 2014;29(4):833-842.
40. 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(5):1599-1607.
41. Macdougall IC, Bock AH, Carrera F, 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 anemia. Nephrol Dial Transplant. 2014;29(11):2075-2084.
42. Grimmelt AC, Cohen CD, Fehr T, Serra AL, Wuethrich RP. Safety and tolerability of ferric carboxymaltose (FCM) for treatment of iron deficiency in patients with chronic kidney disease and in kidney transplant recipients. Clin Nephrol. 2009;71(2):125-129.
43. Anker SD, Comin Colet J, Filippatos G, et al; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436-2448.
44. Van Craenenbroeck EM, Conraads VM, Greenlaw N, et al. The effect of intravenous ferric carboxymaltose on red cell distribution width: a subanalysis of the FAIR-HF study. Eur J Heart Fail. 2013; 15(7):756-762.
45. Filippatos G, Farmakis D, Colet JC, et al. Intravenous ferric carboxymaltose in iron-deficient chronic heart failure patients with and without anaemia: a subanalysis of the FAIR-HF trial. Eur J Heart Fail. 2013; 15(11):1267-1276.
46. Gutzwiller FS, Pfeil AM, Comin-Colet J, et al. Determinants of quality of life of patients with heart failure and iron deficiency treated with ferric carboxymaltose: FAIR-HF sub-analysis. Int J Cardiol. 2013; 168(4):3878-3883.
47. Comin-Colet J, Lainscak M, Dickstein K, et al. The effect of intravenous ferric carboxymaltose on health-related quality of life in patients with chronic heart failure and iron deficiency: a subanalysis of the FAIR-HF study. Eur Heart J. 2013;34(1):30-38.
48. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al; for the CONFIRM-HF Investigators. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2014.
49. Kulnigg S, Stoinov S, Simanenkov V, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol. 2008;103(5):1182-1192.
50. Befrits R, Wikman O, Blomquist L, et al. Anemia and iron deficiency in inflammatory bowel disease: an open, prospective, observational study on diagnosis, treatment with ferric carboxymaltose and quality of life. Scand J Gastroenterol. 2013;48(9):1027-1032.
51. Kulnigg-Dabsch S, Schmid W, Howaldt S, et al. Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial. Inflamm Bowel Dis. 2013;19(8):1609-1616.
52. Evstatiev R, Marteau P, Iqbal T, et al; FERGI Study Group. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology. 2011; 141(3):846-853.
53. Evstatiev R, Alexeeva O, Bokemeyer B, et al; FERGI Study Group. Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(3):269-277.
54. Reim D, Kim YW, Nam BH, et al. FAIRY: a randomized controlled patient-blind phase III study to compare the efficacy and safety of intravenous ferric carboxymaltose (Ferinject®) to placebo in patients with acute isovolemic anemia after gastrectomy-study protocol for a randomized controlled trial. Trials. 2014;15:111.
55. Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion. 2009;49(12):2719-2728.
56. Herfs R, Fleitmann L, Kocsis I. Treatment of Iron deficiency with or without anaemia with intravenous ferric carboxymaltose in gynaecological practices-a non-interventional study. Geburtshilfe Frauenheilkd. 2014;74(1):81-88.
57. Christoph P, Schuller C, Studer H, Irion O, De Tejada BM, Surbek D. Intravenous iron treatment in pregnancy: comparison of high-dose ferric carboxymaltose vs iron sucrose. J Perinat Med. 2012; 40(5):469-474.
58. Froessler B, Collingwood J, Hody NA, Dekker G. Intravenous ferric carboxymaltose for anaemia in pregnancy. BMC Pregnancy Childbirth. 2014;14:115.
59. Van Wyck DB, Martens MG, Seid MH, Baker JB, Mangione A. Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial. Obstet Gynecol. 2007;110(2 pt 1):267-278.
60. Seid MH, Derman RJ, Baker JB, Banach W, Goldberg C, Rogers R. Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial. Am J Obstet Gynecol. 2008;199(4):435.e1-435.e7.
61. Pfenniger A, Schuller C, Christoph P, Surbek D. Safety and efficacy of high-dose intravenous iron carboxymaltose vs iron sucrose for treatment of postpartum anemia. J Perinat Med. 2012;40(4):397-402.
62. Keeler BD, Simpson JA, Ng S, et al. The feasibility and clinical efficacy of intravenous iron administration for preoperative anaemia in patients with colorectal cancer. Colorectal Dis. 2014;16(10):794-800.
63. Malone M, Barish C, He A, Bregman D. Comparative review of the safety and efficacy of ferric carboxymaltose versus standard medical care for the treatment of iron deficiency anemia in bariatric and gastric surgery patients. Obes Surg. 2013;23(9):1413-1420.
64. Bisbe E, García-Erce JA, Díez-Lobo AI, Muñoz M; Anaemia Working Group España. A multicentre comparative study on the efficacy of intravenous ferric carboxymaltose and iron sucrose for correcting preoperative anaemia in patients undergoing major elective surgery. Br J Anaesth. 2011;107(3):477-478.
65. Bisbe E, Moltó L, Arroyo R, Muniesa JM, Tejero M. Randomized trial comparing ferric carboxymaltose vs oral ferrous glycine sulphate for postoperative anaemia after total knee arthroplasty. Br J Anaesth. 2014; 113(3):402-409.
66. Steinmetz T, Tschechne B, Harlin O, et al. Clinical experience with ferric carboxymaltose in the treatment of cancer-and chemotherapy-associated anaemia. Ann Oncol. 2013;24(2):475-482.
67. Rineau E, Chaudet A, Carlier L, Bizot P, Lasocki S. Ferric carboxymaltose increases epoetin-α response and prevents iron deficiency before elective orthopaedic surgery. Br J Anaesth. 2014;113(2):296-298.
68. Schatz U, Arneth B, Siegert G, et al. Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations. Atheroscler Suppl. 2013;14(1):115-122.
69. Allen RP, Adler CH, Du W, Butcher A, Bregman DB, Earley CJ. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med. 2011;12(9):906-913.
70. Hornyak M, Scholz H, Kiemen A, Kassubek J. Investigating the response to intravenous iron in restless legs syndrome: an observational study. Sleep Med. 2012;13(6):732-735.
71. Calvet X, Ruíz MÀ, Dosal A, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency. PLoS One. 2012;7(9):e45604.
72. Bhandari S. Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice. Ther Clin Risk Manag. 2011;7:501-509.
73. Muñoz M, Gómez-Ramírez S, Martín-Montañez E, Naveira E, Seara J, Pavía J. Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study. Blood Transfus. 2014;12(1):40-49.
74. Brock E, Braunhofer P, Troxler J, Schneider H. Budget impact of parenteral iron treatment of iron deficiency: methodological issues raised by using real-life data. Eur J Health Econ. Epub 2014 Dec.
75. Fragoulakis V, Kourlaba G, Goumenos D, Konstantoulakis M, Maniadakis N. Economic evaluation of intravenous iron treatments in the management of anemia patients in Greece. Clinicoecon Outcomes Res. 2012;4: 127-134.
76. Toblli JE, Cao G, Olivieri L, Angerosa M. Comparison of the renal, cardiovascular and hepatic toxicity data of original intravenous iron compounds. Nephrol Dial Transplant. 2010;25(11):3631-3640.
77. Toblli JE, Cao G, Oliveri L, Angerosa M. Assessment of the extent of oxidative stress induced by intravenous ferumoxytol, ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model. Arzneimittelforschung. 2011;61(7):399-410.
78. Toblli JE, Rivas C, Cao G, et al. Ferric carboxymaltose-mediated attenuation of Doxorubicin-induced cardiotoxicity in an iron deficiency rat model. Chemother Res Pract. 2014;2014:570241.
79. Toblli JE, Cao G, Giani JF, Dominici FP, Angerosa M. Nitrosative stress and apoptosis by intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose, and ferric carboxymaltose in a nonclinical model. Drug Res (Stuttg). Epub 2014 Jul 22.
80. Hussain I, Bhoyroo J, Butcher A, Koch TA, He A, Bregman DB. Direct comparison of the safety and efficacy of ferric carboxymaltose versus iron dextran in patients with iron deficiency anemia. Anemia. 2013; 2013:169107.
81. Onken JE, Bregman DB, Harrington RA, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014;54(2):306-315.
82. Prats M, Font R, García C, Cabré C, Jariod M, Vea AM. Effect of ferric carboxymaltose on serum phosphate and C-terminal FGF23 levels in non-dialysis chronic kidney disease patients: post-hoc analysis of a prospective study. BMC Nephrol. 2013;14:167.
83. Gravesen E, Hofman-Bang J, Mace ML, Lewin E, Olgaard K. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats. BMC Nephrol. 2013;14:281.
84. Fell LH, Zawada AM, Rogacev KS, Seiler S, Fliser D, Heine GH. Distinct immunologic effects of different intravenous iron preparations on monocytes. Nephrol Dial Transplant. 2014;29(4):809-822.
85. Maretty L, Sharp RE, Andersson M, Kurtzhals JA. Intravenous ferric carboxymaltose accelerates erythropoietic recovery from experimental malarial anemia. J Infect Dis. 2012;205(7):1173-1177.
86. Malek A. In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta. Arzneimittelforschung. 2010;60(6a):354-361.
87. Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women-PREFER a randomized, placebo-controlled study. PLoS One. 2014;9(4):e94217.
88. Thompson CA. Ferric carboxymaltose approved for iron deficiency anemia. Am J Health Syst Pharm. 2013;70(17):1458.