Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia

João Ricardo Friedrisch, Rodolfo Delfini Cançado, João Ricardo Friedrisch, Rodolfo Delfini Cançado

Abstract

Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15mg/kg; maximum of 1000mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia.

Keywords: Anemia; Iron-deficiency; Therapeutics.

Copyright © 2015 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

References

    1. de Benoist B., McLean E., Egli I., Cogswell M. World Health Organization; Geneva: 2008. Worldwide prevalence of anaemia 1993–2005: WHO global database on anaemia. 41 p.
    1. Gaskell H., Derry S., Andrew Moore R., McQuay H.J. Prevalence of anaemia in older persons: systematic review. BMC Geriatr. 2008;8:1.
    1. National Institute for Health and Clinical Excellence . National Institute for Health and Clinical Excellence; UK: 2006. Clinical guideline 39: anaemia management in people with chronic kidney disease (CKD) [Internet] Available from: [cited 15.07.14]
    1. Silla L.M., Zelmanowicz A., Mito I., Michalowski M., Hellwing T., Shilling M.A. High prevalence of anemia in children and adult women in an urban population in southern Brazil. PLOS ONE. 2013;8(7):e68805.
    1. Brugnara C., Beris P. Iron therapy. In: Beaumont C., Beris P., Beuzard Y., Brugnara C., editors. Disorders of erythropoiesis, erythrocytes and iron metabolism. European School of Haematology; Paris: 2009. pp. 512–528.
    1. Gisbert J.P., Gomollon F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol. 2008;103(5):1299–1307.
    1. Cook J.D. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol. 2005;18(2):319–332.
    1. Coyne D.W., Auerbach M. Anemia management in chronic kidney disease: intravenous iron steps forward. Am J Hematol. 2010;85(5):311–312.
    1. Muñoz M., Gómez-Ramírez S., García-Erce J.A. Intravenous iron in inflammatory Bowell disease. World J Gastroenterol. 2009;15(37):4666–4674.
    1. Erichsen K., Ulvik R.J., Nysaeter G., Johansen J., Ostborg J., Berstad A. Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scand J Gastroenterol. 2005;40(9):1058–1065.
    1. Gasche C., Waldhoer T., Feichtenschlager T., Male C., Mayer A., Mittermaier C. Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia. Am J Gastroenterol. 2001;96(8):2382–2387.
    1. Gisbert J.P., Bermejo F., Pajares R., Perez-Calle J.L., Rodriguez M., Algaba A. Oral and intravenous iron treatment in inflammatory bowel disease: hematological response and quality of life improvement. Inflamm Bowel Dis. 2009;15(10):1485–1491.
    1. Schroder O., Mickisch O., Seidler U., de Weerth A., Dignass A.U., Herfarth H. 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(11):2503–2509.
    1. Lindgren S., Wikman O., Befrits R., Blom H., Eriksson A., Granno C. Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: a randomized, controlled, evaluator-blind, multicentre study. Scand J Gastroenterol. 2009;44(7):839–845.
    1. Traina F. Deficiência de ferro no paciente submetido à ressecção gástrica ou intestinal: prevalência, causas, repercussões clínicas, abordagem diagnóstica e prevenção. Rev Bras Hematol Hemoter. 2010;32:78–83.
    1. Cançado R.D., Lobo C., Friedrich J.R. Tratamento da anemia ferropriva com ferro por via parenteral. Rev Bras Hematol Hemoter. 2010;32:121–128.
    1. Cançado R.D., Brasil S.A., Noronha T.G., Chiattone C.S. Avaliação da eficácia do uso intravenoso de sacarato de hidróxido de ferro III no tratamento de pacientes adultos com anemia ferropriva. Rev Bras Hematol Hemoter. 2007;29(2):123–129.
    1. Cançado R.D., Brasil S.A., Noronha T.G., Chiattone C.S. O uso intravenoso de sacarato de hidróxido de ferro III em pacientes com anemia ferropriva. Rev Assoc Med Bras. 2005;51(6):323–328.
    1. Fernandes N., Abrita R.R., do Carmo W.B., Carvalho G.H., Silva J.H., Lopes T.M. Impacto do tratamento intravenoso com sacarato de hidróxido de ferro III nos marcadores séricos de deficiência de ferro e na hemoglobina sérica em pacientes com doença renal crônica pré-dialítica. J Bras Nefrol. 2007;29(1):33–37.
    1. Cançado R.D., Muñoz M. Intravenous iron therapy: how far have we come? Rev Bras Hematol Hemoter. 2011;33(6):461–469.
    1. Abensur H. Deficiência de ferro na doença renal crônica. Rev Bras Hematol Hemoter. 2010;32(Suppl. 2):84–88.
    1. Blasco P.G., Levites M.R., Mônaco C. Ferro endovenoso melhora sintomas de pacientes com insuficiência cardíaca que têm deficiência. Diagn Trat. 2010;15(3):125–126.
    1. Fabron Júnior A. Ferro endovenoso no tratamento da anemia ferropriva: seguro e eficaz. Rev Bras Hematol Hemoter. 2007;29(2):106–108.
    1. Lyseng-Williamsom K.A., Keating G.M. Ferric carboxymaltose: a review of its use in iron-deficiency anaemia. Drugs. 2009;69(6):739–756.
    1. Kulnigg S., Stoinov S., Simanenkov V., Dudar L.V., Karnafel W., Garcia L.C. 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.
    1. Anker S.D., Comin Colet J., Filippatos G., Willenheimer R., Dickstein K., Drexler H. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436–2448.
    1. Van Wyck D.B., Mangione A., Morrison J., Hadley P.E., Jehle J.A., Goodnough L.T. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion. 2009;49(12):2719–2728.
    1. Covic A., Mircescu G. The safety and efficacy of intravenous iron carboxymaltose in anaemic patients undergoing haemodialysis: a multi-centre, open-label, clinical study. Nephrol Dial Transplant. 2010;25(8):2722–2730.
    1. Macdougall L., Chappeli J., Chai M.O. Hospital Pharmacy Europe; 2010. Iron supplementation: focus on ferric carboxymaltose [Internet] Available from: [cited 15.07.14]
    1. Jahn M.R., Andreasen H.B., Futterer S., Nawroth T., Schunemann V., Kolb U. 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):480–491.
    1. Singh A., Patel T., Hertel J., Bernardo M., Kausz A., Brenner L. Safety of ferumoxytol in patients with anemia and CKD. Am J Kidney Dis. 2008;52(5):907–915.
    1. Provenzano R., Schiller B., Rao M., Coyne D., Brenner L., Pereira B.J. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol. 2009;4(2):386–393.
    1. Lu M., Cohen M.H., Rieves D., Pazdur R. FDA review of ferumoxytol (Feraheme) for the treatment of iron deficiency anemia in adults with chronic kidney disease. Am J Hematol. 2010;859(5):315–319.
    1. Braile G. Efficacy and safety of ferricarboximaltose in correcting iron deficiency anemia: a review of randomized controlled trials across different indications. Arzneimittelforschung. 2010;60(6a):386–398.
    1. Schaefer R.M., Khasabov N.N., Todorov N.G., Evenepoel P. Intravenous ferric carboxymaltose or iron sucrose to treat iron deficiency anaemia in haemodialysis patients. Poster presented at the XLV ERA-EDTA Congress; Stockholm, Sweden; 2008. (Poster MP375)
    1. Van Wyck D.B., Martens M.G., Seid M.H., Baker J.B., 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.
    1. Bisbe E., Garcia-Erce J.A., Diez-Lobo A.I., Munoz M. 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.
    1. Bregman D.B., Goodnough L.T. Experience with intravenous ferric carboximaltose in patients with iron deficiency anemia. Ther Adv Hematol. 2014;5(2):48–60.
    1. US Food and Drug Administration Center for Drug Evaluation and Research [Internet]. Available from: [cited 15.07.14].
    1. European Medicines Agency New recommendations to manage risk of allergic reactions with intravenous iron-containing medicines [Internet]. Available from: [cited 15.07.14].
    1. Wolf M., Koch T.A., Bregman D.B. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013;28(8):1793–1803.
    1. Schouten B.J., Hunt P.J., Livesey J.H., Frampton C.M., Soule S.G. FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab. 2009;94(7):2332–2337.
    1. Froessler B., Collingwood J., Hodyl N.A., Dekker G. Intravenous ferric carboxymaltose for anaemia in pregnancy. BMC Pregnancy Childbirth. 2014;14:115.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren