Arzneimittelforschung 2010; 60(6): 386-398
DOI: 10.1055/s-0031-1296303
Ferric Carboxymaltose
Editio Cantor Verlag Aulendorf (Germany)

Efficacy and safety of ferric carboxymaltose in correcting iron-deficiency anemia: a review of randomized controlled trials across different indications

George R Bailie
Albany Nephrology Pharmacy (ANephRx) Group, Albany, New York, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)


Ferric carboxymaltose (FCM, Ferinject®) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD).

In most trials, patients received either FCM doses of ≤ 1000 mg, administered intravenously (i. v.) over ≤ 15 min. or oral ferrous sulfate (FeSulf) 325 mg (65 mg iron), three times daily (t.i.d.), or 304 mg (100 mg iron), twice daily (b.i.d.). In one trial, patients on HD received 200 mg i. v. of either FCM or iron sucrose (ISC), two-to-three times weekly. In a pilot study in patients with CHF and CKD, patients received 200 mg of FCM by push injection compared with 200 mg of ISC slow injection. FCM was usually administered until the patient’s calculated total iron replacement dose was achieved.

Treatment with FCM improved indices of anemia (hemoglobin [Hb], ferritin and transferrin saturation [TSAT] values). In patients on HD with IDA secondary to CKD, FCM demonstrated comparable efficacy to ISC in achieving an increase in Hb. In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. Patients with PPA receiving FCM compared with those receiving oral iron achieved an Hb rise ≥ 2.0 g/dl earlier (7 days compared with 14 days; p < 0.001), were more likely to achieve an Hb rise ≥ 3.0 g/dl at any time beginning at day 14 (86.3% compared with 60.4%; p < 0.001), and achieve an Hb > 12.0 g/dl at the end of the study (Day 42; 90.5% compared with 68.6%, p < 0.01). Serum ferritin increased in the i. v. FCM treatment group, but not in the oral iron group. Differences between groups were significant at each study interval. TSAT increased significantly at every interval in both groups; however, FCM-treated patients showed higher TSAT at each interval after the first week. FCM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB. FCM also improved quality of life as well as functional symptoms and exercise capacity in patients with CHF. Safety data from more than 3000 patients showed that FCM was well tolerated. No safety concerns have been identified in breastfed infants of mothers receiving FCM. FCM is, therefore, an effective and well-tolerated option in the treatment of IDA.

  • References

  • 1 Crichton RR, Danielson BG, Geisser P. Iron Therapy –with special emphasis on intravenous administration. 4th ed. Bremen: UNI-Med; 2008
  • 2 Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC 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: 1182-92
  • 3 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: 67-73
  • 4 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: 435-7
  • 5 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: 267-78
  • 6 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: 2719-28
  • 7 Qunibi W, Martinez CO, Smith M, Benjamin J, Dinh Q Efficacy and safety of IV ferric carboxymaltose (FCM) compared to oral iron in anemic patients with non-dialysis-dependent CKD. Poster presented at the XLV ERA-EDTA Congress, May 10–13 2008, Stockholm, Sweden. Poster MO018
  • 8 Schaefer RM, Khasabov NN, Todorov NG, Evenepoel P Intravenous ferric carboxymaltose or iron sucrose to treat iron deficiency anaemia in haemodialysis patients. Poster presented at the XLV ERA-EDTA Congress, May 10–13 2008, Stockholm, Sweden. Poster MP375
  • 9 Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H et al. the FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009; 361: 3436-48
  • 10 Bailie GR, Mason NA, Valaoras TG. Safety and tolerability of intranveous ferric carboxymaltose in patients with iron deficiency anemia. Hemodial Int. 2010; 14: 48-54
  • 11 Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohn’s disease. Aliment Pharmacol Ther. 2006; 24: 1507-23
  • 12 Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut. 2004; 53: 1190-7
  • 13 Gasche C, Berstad A, Befrits R, Beglinger C, Dignass A, Erichsen K et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis. 2007; 13: 1545-53
  • 14 Schroder O, Mickisch O, Seidler U, de Weerth A, Dignass AU, Herfarth H et al. Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease–a randomized, controlled, open-label, multicenter study. Am J Gastroenterol. 2005; 100: 2503-9
  • 15 Ganzoni AM. [Intravenous iron-dextran: therapeutic and experimental possibilities]. Schweiz Med Wochenschr. 1970; 100: 301-3
  • 16 de Silva AD, Mylonaki M, Rampton DS. Oral iron therapy in inflammatory bowel disease: usage, tolerance, and efficacy. Inflamm Bowel Dis. 2003; 9: 316-20
  • 17 Beard JL, Hendricks MK, Perez EM, Murray-Kolb LE, Berg A, Vernon-Feagans L et al. Maternal iron deficiency anemia affects postpartum emotions and cognition. J Nutr. 2005; 135: 267-72
  • 18 Bodnar LM, Cogswell ME, McDonald T. Have we forgotten the significance of postpartum iron deficiency? Am J Obstet Gynecol. 2005; 193: 36-44
  • 19 Ware JE, Kosinski M, Dewey JE. How to Score Version 2 of the SF-36 Health Survey. 3rd ed Lincoln: Quality Metric Inc; 2001
  • 20 Portenoy RK. Fatigue measurement. Interactive textbook of symptom research Bethesda: National Institutes of Health; 2006
  • 21 Morrison J, Patel ST, Watson W, Zaidi QR, Mangione A, Goss TF. Assessment of the prevalence and impact of anemia on women hospitalized for gynecologic conditions associated with heavy uterine bleeding. J Reprod Med. 2008; 53: 323-30
  • 22 Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health. 2007; 10: 183-94
  • 23 Leaf DE, Goldfarb DS. Interpretation and review of health-related quality of life data in CKD patients receiving treatment for anemia. Kidney Int. 2009; 75: 15-24
  • 24 Foley RN, Curtis BM, Parfrey PS. Erythropoietin therapy, hemoglobin targets, and quality of life in healthy hemodialysis patients: a randomized trial. Clin J Am Soc Nephrol. 2009; 4: 726-33
  • 25 Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 2000; 35: 1737-44
  • 26 Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur Heart J. 2008; 29: 2388-442
  • 27 Haas JD, Brownlie T IV Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr. 2001; 131: 676S-688S
  • 28 Dallman PR. Iron deficiency: does it matter?. J Intern Med. 1989; 226: 367-72
  • 29 Davies KJ, Maguire JJ, Brooks GA, Dallman PR, Packer L. Muscle mitochondrial bioenergetics, oxygen supply, and work capacity during dietary iron deficiency and repletion. Am J Physiol. 1982; 242: E418-27
  • 30 Satija P, Ondo WG. Restless legs syndrome: pathophysiology, diagnosis and treatment. CNS Drugs. 2008; 22: 497-518
  • 31 Anker SD, Colet JC, Filippatos G et al FAIR-HF committees and investigators. Rationale and design of Ferinject assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebocontrolled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail. 2009; 11: 1084-91
  • 32 Moreno F Sanz-Guajardo D, López-Gómez JM, Jofre R, Valderrábano F. Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients. Spanish Cooperative Renal Patients Quality of Life Study Group of the Spanish Society of Nephrology. J Am Soc Nephrol. 2000; 11: 335-42
  • 33 Fishbane S, Maesaka JK. Iron management in end-stage renal disease. Am J Kidney Dis. 1997; 29: 319-33
  • 34 Kerr PG. Renal anaemia: recent developments, innovative approaches and future directions for improved management. Nephrology (Carlton). 2006; 11: 542-8
  • 35 Royal College of Physicians (London). National Collaborating Centre for Chronic Conditions. Anaemia management in chronic kidney disease: national clinical guideline for management in adults and children. Available from: Last accessed: 19 November 2009.
  • 36 KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target Am J Kidney Dis. 2007; 50: 471-530
  • 37 Covic A, Mircescu G Safety and efficacy of intravenous (i. v.) ferric carboxymaltose (FCM) in anaemia haemodialysis (HD) patients: a multicenter, open-label clinical study. Poster presented at the 42nd American Society of Nephrology, San Diego, CA: SA-PO2419.
  • 38 Qunibi W, Dinh Q, Benjamin J Safety and tolerability profile of ferric carboxymaltose (FCM): data from the FCM clinical program. Poster presented at the XLV ERA-EDTA Congress, May 10–13 2008, Stockholm, Sweden. Abstract book ERA-EDTA 2008. Poster MP383
  • 39 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
  • 40 Arutyunov GP, Bylova NA, Ivleva AK, Kobalava ZD. The safety of intravenous ferric carboxymaltose versus intravenous iron sucrose in patients with chronic heart failure and chronic kidney disease with iron deficiency. Heart Failure Congress, Nice, France, 30 May-2 Jun, 2009. Abstract 60293.
  • 41 Faich GA. Adverse-drug-reaction monitoring. N Engl J Med. 1986; 314: 1589-92
  • 42 Faich GA, Lawson DH, Tilson HH, Walker A. Clinical trials are not enough. Clin Res Drug Dev. 2009; 1: 75-8