Arzneimittelforschung 2010; 60(6): 399-412
DOI: 10.1055/s-0031-1296304
Ferric Carboxymaltose
Editio Cantor Verlag Aulendorf (Germany)

The efficacy and safety of current intravenous iron preparations for the management of iron-deficiency anaemia: a review

Wajeh Y Qunibi
Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center, San Antonio, Texas, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)

Abstract

Iron-deficiency anaemia (IDA) is a major health problem worldwide, but responds well to iron supplementation. New approaches are leading to more effective management of this condition.

Iron deficiency (ID) is usually suspected in at-risk patients with declining haemoglobin (Hb) levels and then confirmed by measuring serum ferritin levels and transferrin saturation. However, regular monitoring of these iron indicators and other laboratory parameters in susceptible individuals may lead to early recognition of falling iron stores and facilitate pre-emptive therapeutic intervention before anaemia develops.

Patients with ID are commonly prescribed oral iron preparations because of convenience and low cost. However, the efficacy of these agents is limited by their reduced absorption rate and gastrointestinal side-effects. Alternatively, treatment of IDA in patients requiring erythropoiesis-stimulating agents (ESAs) is more predictably achieved by use of intravenous (i.v.) iron. Unfortunately, the development of serious adverse events (SAEs) from high molecular-weight iron dextran has led to reluctance to use i. v. iron in the treatment of IDA. Similarly, but to a much lesser extent, low molecular-weight iron dextran is associated with a number of SAEs, including allergic or anaphylactic reactions. The introduction of second-generation i.v. iron formulations, including iron sucrose and ferric gluconate, was clearly an improvement over i. v. iron dextran. These formulations proved to be effective in the management of IDA and are not associated with the serious allergic reactions encountered with i. v. iron dextran. For these reasons, use of these preparations became more widespread in the treatment of IDA across a wide range of clinical conditions. An important advantage of i. v. iron over oral iron is that it may bypass hepcidin actions by directly loading transferrin and making iron available to macrophages.

Despite a reduction in the short-term risks, there is still concern about the potential for long-term toxicity of i. v. iron use (e. g. atherosclerosis development, infection and increased mortality). The association of atherosclerosis with iron overload remains unclear. Alternatively, the relative risk for mortality or hospitalization from infection in patients undergoing haemodialysis (HD) who received i. v. iron was shown not to be higher than that observed in the overall HD population. Indeed, doses of i. v. iron up to 400 mg/month were associated with improved patient survival.

Second-generation i.v. iron formulations are more frequently used for treating IDA than i. v. iron-dextran in patients with various chronic conditions including those with chronic kidney disease. In the latter, IDA should be corrected before initiation of ESA therapy, as iron deficiency can lead to hyporesponsiveness to ESA. However, a major limitation of the second-generation i. v. iron agents is that they cannot be administered in large doses and the typical 1000 mg therapy requires several clinic visits. Thus, there is a need for an i. v. iron agent that can be safely administered in a single dose of 1000 mg of iron and therefore requires less frequent clinic visits. This limitation has now been overcome with the introduction of newer i. v. iron preparations.

Ferric carboxymaltose offers effective and rapid correction of IDA by overcoming the limitations observed with previous i. v. iron preparations. This agent has been shown to be effective and well tolerated in a number of randomized controlled trials in a variety of chronic conditions.

 
  • References

  • 1 Huch R, Schaefer R. Iron deficiency anaemia. (2nd ed) Stuttgart: George Thieme Verlag; 2009
  • 2 Adamson JW, Eschbach JW. Erythropoietin for end-stage renal disease. N Engl J Med. 1998; 339: 625-7
  • 3 Ludwig H, Van BS, Barrett-Lee P, Birgegård G, Bokemeyer C, Gascón P et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer. 2004; 40: 2293-306
  • 4 Shord SS, Hamilton Jr. JM, Cuellar S. Parenteral iron with erythropoiesis-stimulating agents for chemotherapy-induced anemia. J Oncol Pharm Pract. 2008; 14: 5-22
  • 5 Wexler D, Silverberg D, Blum M, Sheps D, Keren G, Wollman Y et al. Anaemia as a contributor to morbidity and mortality in congestive heart failure. Nephrol Dial Transplant. 2005; 20 (Suppl 7) vii11-15
  • 6 Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut. 2004; 53: 1190-7
  • 7 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
  • 8 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
  • 9 Beris P, Munoz M, Garcia-Erce JA, Thomas D, Maniatis A, Van der Linden P. Perioperative anaemia management: consensus statement on the role of intravenous iron. Br J Anaesth. 2008; 100: 599-604
  • 10 World Health Organization Iron Deficiency Anaemia. Assessment, Prevention, and Control. A guide for programme managers Geneva: World Health Organization; 2001
  • 11 World Health Organization Worldwide prevalence of anaemia 1993–2005. WHO Global Database on Anaemia Geneva: World Health Organization; 2008
  • 12 Alleyne M, Horne MK, Miller JL. Individualized treatment for iron-deficiency anemia in adults. Am J Med. 2008; 121: 943-8
  • 13 Thomas L, Franck S, Messinger M, Linssen J, Thome M, Thomas C. Reticulocyte hemoglobin measurement –comparison of two methods in the diagnosis of iron-restricted erythropoiesis. Clin Chem Lab Med. 2005; 43: 1193-202
  • 14 Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003; 102: 783-8
  • 15 Andrews NC. Anemia of inflammation: the cytokine-hepcidin link. J Clin Invest. 2004; 113: 1251-3
  • 16 Fishbane S, Pollack S, Feldman HI, Joffe MM. Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988–2004. Clin J Am Soc Nephrol. 2009; 4: 57-61
  • 17 National Kidney Foundation NKF/K/DOQI Clinical practice guidelines for anaemia of chronic kidney disease. III. Iron support New York: National Kidney Foundation; 2000
  • 18 Nurko S. Anemia in chronic kidney disease: causes, diagnosis, treatment. Cleve Clin J Med. 2006; 73: 289-97
  • 19 Valderrabano F, Horl WH, Macdougall IC, Rossert J, Rutkowski B, Wauters JP. PRE-dialysis survey on anaemia management. Nephrol Dial Transplant. 2003; 18: 89-100
  • 20 Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999; 55: 1899-911
  • 21 Hoën B, Paul-Dauphin A, Hestin D, Kessler M. EPIBAC-DIAL: a multicenter prospective study of risk factors for bacteremia in clinical hemodialysis patients. J Am Soc Nephrol. 1998; 9: 869-76
  • 22 James MT, Laupland KB, Tonelli M, Manns BJ, Culleton BF, Hemmelgarn BR. Risk of bloodstream infection in patients with chronic kidney disease not treated with dialysis. Arch Intern Med. 2008; 168: 2333-9
  • 23 Gotloib L, Silverberg D, Fudin R, Shostak A. Iron deficiency is a common cause of anemia in chronic kidney disease and can often be corrected with intravenous iron. J Nephrol. 2006; 19: 161-7
  • 24 Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohn’s disease. Aliment Pharmacol Ther. 2006; 24: 1507-23
  • 25 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
  • 26 Anand I, McMurray JJV, Whitmore J, Warren M, McCamish MA, Burton PJB. Anemia and its relationship to clinical outcomes in heart failure. Circulation. 2004; 110: 149-54
  • 27 Nieminen MS, Bohm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G et al. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J. 2005; 26: 384-416
  • 28 European Society of Cardiology; Heart Failure Association of the ESC (HFA); European Society of Intensive Care Medicine (ESICM) Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ. 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. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008; 29: 2388-442
  • 29 Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004; 292: 344-50
  • 30 Tang WH, Tong W, Jain A, Francis GS, Harris CM, Young JB. Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure. J Am Coll Cardiol. 2008; 51: 569-76
  • 31 Wexler D, Silverberg D, Sheps D, Blum M, Keren G, Iaina A et al. Prevalence of anemia in patients admitted to hospital with a primary diagnosis of congestive heart failure. Int J Cardiol. 2004; 96: 79-87
  • 32 Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol. 2006; 48: 2485-9
  • 33 de Silva R, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol. 2006; 98: 391-8
  • 34 Tang YD, Katz SD. Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation. 2006; 113: 2454-61
  • 35 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
  • 36 World Health Organization Pregnancy, childbirth, postpartum and newborn care: A guide for essential practice. Geneva: World Health Organization; 2006
  • 37 Bodnar LM, Cogswell ME, McDonald T. Have we forgotten the significance of postpartum iron deficiency?. Am J Obstet Gynecol. 2005; 193: 36-44
  • 38 Broche DE, Gay C, Armand-Branger S, Grangeasse L, Terzibachian JJ. [Acute postpartum anaemia. Clinical practice and interest of intravenous iron]. Gynecol Obstet Fertil. 2004; 32: 613-9
  • 39 Lebrecht A, Haberlin F, Eberhard J. [Anemia in Puerperium; parenteral iron substitution renders erythropoietin therapy dispensable]. Geburtshilfe Frauenheilkd. 1995; 55: 167-70
  • 40 Bergström S. Infection-related morbidities in the mother, fetus and neonate. J Nutr. 2003; 133: 1656S-60S
  • 41 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
  • 42 Corwin EJ, Murray-Kolb LE, Beard JL. Low hemoglobin level is a risk factor for postpartum depression. J Nutr. 2003; 133: 4139-42
  • 43 Prentice A. Medical management of menorrhagia. West J Med. 2000; 172: 253-5
  • 44 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
  • 45 Crichton RR, Danielson BG, Geisser P. Iron Therapy –with special emphasis on intravenous administration. 4th ed Bremen: UNI-Med; 2008
  • 46 Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckardt KU et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant. 2004; 19: iil-47
  • 47 Clark SF. Iron deficiency anemia. Nutr Clin Pract. 2008; 23: 128-41
  • 48 Alexander M, Kewalramani R, Agodoa I, Globe D. Association of anemia correction with health related quality of life in patients not on dialysis. Curr Med Res Opin. 2007; 23: 2997-3008
  • 49 Hayat A. Safety issues with intravenous iron products in the management of anemia in chronic kidney disease. Clin Med Res. 2008; 6: 93-102
  • 50 Cella D. Factors influencing quality of life in cancer patients: anemia and fatigue. Semin Oncol. 1998; 25: 43-6
  • 51 Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ et al. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol. 1997; 34: 4-12
  • 52 Cucino C, Sonnenberg A. Cause of death in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2001; 7: 250-5
  • 53 Pagourelias ED, Koumaras C, Kakafika AI, Tziomalos K, Zorou PG, Athyros VG et al. Cardiorenal anemia syndrome: do erythropoietin and iron therapy have a place in the treatment of heart failure?. Angiology. 2009; 60: 74-81
  • 54 Al-Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001; 38: 955-62
  • 55 Atkinson LS, Baxley EG. Postpartum fatigue. Am Fam Physician. 1994; 50: 113-8
  • 56 Paterson JA, Davis J, Gregory M, Holt SJ, Pachulski A, Stamford DE et al. A study on the effects of low haemoglobin on postnatal women. Midwifery. 1994; 10: 77-86
  • 57 Perez EM, Hendricks MK, Beard JL, Murray-Kolb LE, Berg A, Tomlinson M et al. Mother-infant interactions and infant development are altered by maternal iron deficiency anemia. J Nutr. 2005; 135: 850-5
  • 58 Coyne D. Iron indices: what do they really mean?. Kidney Int Suppl.. 2006; S4-8
  • 59 Kalantar-Zadeh K, Streja E, Miller JE, Nissenson AR. Intravenous iron versus erythropoiesis-stimulating agents: friends or foes in treating chronic kidney disease anemia?. Adv Chronic Kidney Dis. 2009; 16: 143-51
  • 60 Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol. 2006; 1 (Suppl 1) S4-S8
  • 61 Fishbane S, Mittal SK, Maesaka JK. Beneficial effects of iron therapy in renal failure patients on hemodialysis. Kidney Int Suppl. 1999; 69: S67-70
  • 62 Toblli JE, Brignoli R. Iron(III)-hydroxide polymaltose complex in iron deficiency anemia/review and meta-analysis. Arzneimittelforschung. 2007; 57 (6a) 431-8
  • 63 Burckhardt-Herold S, Klotz J, Funk F, Büchi R, Petrig-Schaffland J, Geisser P. Interactions between iron(III)-hydroxide polymaltose complex and commonly used drugs/simulations and in vitro studies. Arzneimittelforschung. 2007; 57 (6a) 360-9
  • 64 Legssyer R, Geisser P, McArdle H, Crichton RR, Ward RJ. Comparison of injectable iron complexes in their ability to iron load tissues and to induce oxidative stress. Biometals. 2003; 16: 425-33
  • 65 Berenbaum MC, Child KJ, Davis B, Sharpe HM, Tomich EG. Animal and human studies on ferrous fumarate, an oral hematinic. Blood. 1960; 15: 540-50
  • 66 Eschbach JW. Iron requirements in erythropoietin therapy. Best Pract Res Clin Haematol. 2005; 18: 347-61
  • 67 Rozen-Zvi B, Gafter-Gvili A, Paul M, Leibovici L, Shpilberg O, Gafter U. Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis. Am J Kidney Dis. 2008; 52: 897-906
  • 68 Auerbach M. Clinical experience with intravenous iron. Transfus Altern Transfus Med. 2007; 9: 26-30
  • 69 Auerbach M, Coyne D, Ballard H. Intravenous iron: from anathema to standard of care. Am J Hematol. 2008; 83: 580-8
  • 70 Qunibi W, Martinez CO, Smith M, Benjamin J, Dinh Q. A randomized controlled trial comparing IV ferric carboxymaltose (FCM) to oral iron in anemic patients with non-dialysis-dependent CKD. Poster presented at the 40th Annual Meeting of the American Society of Nephrology, 31 Oct–5 Nov 2007, San Francisco, CA, USA. ASN SU-PO1030
  • 71 Halpin D, Ackland P, Agrawal S, Anderson C, Bradley R, Dunn R et al. Anaemia management in chronic kidney disease. National Clinical Guideline for management in adults and children London: Royal College of Physicians; 2006
  • 72 Hotta T, Ogawa H, Saito A, Ito A. Iron balance following recombinant human erythropoietin therapy for anemia associated with chronic renal failure. Int J Hematol. 1991; 54: 195-200
  • 73 Auerbach M, Ballard H. Intravenous iron in oncology. J Natl Compr Canc Netw. 2008; 6: 585-92
  • 74 Hedenus M, Birgegard G, Nasman P, Ahlberg L, Karlsson T, Lauri B et al. Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study. Leukemia. 2007; 21: 627-32
  • 75 KDOQ I National Kidney Foundation KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis. 2006; 47: S11-145
  • 76 Horl WH. Iron therapy for renal anemia: how much needed, how much harmful?. Pediatr Nephrol. 2007; 22: 480-9
  • 77 Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist. 2007; 12: 231-42
  • 78 Bokemeyer C, Aapro MS, Courdi A, Foubert J, Link H, Os-terborg A et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer. 2007; 43: 258-70
  • 79 Bastit L, Vandebroek A, Altintas S, Gaede B, Pintér T, Suto TS et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol. 2008; 26: 1611-8
  • 80 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
  • 81 Nemeth E, Turtte MS, Powelson J, Vaughn MB, Donovan A, Ward DM et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004; 306: 2090-3
  • 82 Gasche C. Anemia in IBD: the overlooked villain. Inflamm Bowel Dis. 2000; 6: 142-50
  • 83 Toblli JE, Lombrana A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007; 50: 1657-65
  • 84 Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observerblinded trial. J Am Coll Cardiol. 2008; 51: 103-12
  • 85 Munoz M, Breymann C, Garcia-Erce JA, Gomez-Ramirez S, Comin J, Bisbe E. Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion. Vox Sang. 2008; 94: 172-83
  • 86 Hallberg L, Ryttinger L, Solvell L. Side-effects of oral iron therapy. A double-blind study of different iron compounds in tablet form. Acta Med Scand Suppl. 1966; 459: 3-10
  • 87 Breymann C, Gliga F, Bejenariu C, Strizhova N. Comparative efficacy and safety of intravenous ferric carboxymal-tose in the treatment of postpartum iron deficiency anemia. Int J Gynaecol Obstet. 2008; 101: 67-73
  • 88 Hamstra RD, Block MH, Schocket AL. Intravenous iron dextran in clinical medicine. JAMA. 1980; 243: 1726-31
  • 89 Fletes R, Lazarus JM, Gage J, Chertow GM. Suspected iron dextran-related adverse drug events in hemodialysis patients. Am J Kidney Dis. 2001; 37: 743-9
  • 90 American Regent Inc. Dexferrum Summary of Product Characteristics. New York; 2009.
  • 91 Pharmacosmos A/S. CosmoFer Summary of Product Characteristics. Holbaek; 2009.
  • 92 Watson Pharmaceuticals, Inc. INFeD Prescribing Information. Corona; 2009.
  • 93 Sanofi-Aventis. Ferrlecit Summary of Product Characteristics. Bridgewater; 2010.
  • 94 Vifor Pharma Ltd. Venofer Summary of Product Characteristics. St. Gallen; 2009.
  • 95 Vifor Pharma Ltd, UK. Ferinject Summary of Product Characteristics. Surrey; 2010.
  • 96 AMAG Pharmacueticals Inc. Feraheme Prescribing Information. Lexington; 2009
  • 97 Bailie GR. Breaking new ground in intravenous iron therapy. Eur Haematol Touch Briefings. 2008; 58-60
  • 98 Van Wyck DB. Labile iron: manifestations and clinical implications. J Am Soc Nephrol. 2004; 15 (Suppl 2) S107-11
  • 99 Horl WH, Macdougal IC, Rossert J, Schaefer R. OPTA therapy with iron and erythropoiesis stimulating agents in chronic kidney disease. Nephrol Dial Transplant. 2007; 22 (Suppl 3) ii2-6
  • 100 Auerbach M, Ballard H, Glaspy J. Clinical update: intravenous iron for anaemia. Lancet. 2007; 369: 1502-4
  • 101 Bhandal N, Russell R. Intravenous versus oral iron therapy for postpartum anaemia. BJOG. 2006; 113: 1248-52
  • 102 Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmen J. On the relative safety of parenteral iron formulations. Nephrol Dial Transplant. 2004; 19: 1571-5
  • 103 Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmen J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant. 2006; 21: 378-82
  • 104 Kalantar-Zadeh K, Regidor DL, McAllister CJ, Michael B, Warnock DG. Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol. 2005; 16: 3070-80
  • 105 Bailie GR, Clarke JA, Lance CE, Lane PL. Hypersensitivity reactions and deaths associated with intravenous iron preparations. Nephrol Dial Transplant. 2005; 20: 1443-9
  • 106 Auerbach M, Al Talib K. Low-molecular weight iron dextran and iron sucrose have similar comparative safety profiles in chronic kidney disease. Kidney Int. 2008; 73: 528-30
  • 107 Chandler G, Harchowal J, Macdougall IC. Intraveous iron sucrose: establishing a safe dose. Am J Kid Dis. 2001; 38 (5) 988-91
  • 108 Charytan C, Schwenk MH, Al-Saloum MM, Spinowitz BS. Safety of iron sucrose in hemodialysis patients intolerant to other parenteral iron products. Nephron Clin Pract. 2004; 96: c63-6
  • 109 Reis KA, Guz G, Ozdemir H, Erten Y, Atalay V, Bicik Z et al. Intravenous iron therapy as a possible risk factor for atherosclerosis in end-stage renal disease. Int Heart J. 2005; 46: 255-64
  • 110 Drueke T, Witko-Sarsat V, Massy Z, Descamps-Latscha B, Guerin AP, Marchais SJ et al. Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation. 2002; 106: 2212-7
  • 111 You SA, Wang Q. Ferritin in atherosclerosis. Clin Chim Acta. 2005; 357: 1-16
  • 112 Fishbane S. Review of issues relating to iron and infection. Am J Kid Dis. 1999; 34 (4 Suppl 2) S47-52
  • 113 Payne SM, Wyckoff EE, Murphy ER, Oglesby AG, Boulette ML, Davies NM. Iron and pathogenesis of Shigella: iron acquisition in the intracellular environment. Biometals. 2006; 19 (2) 173-80
  • 114 Besarab A. more than a decade of experience and still no consensus: Controversies in iron therapy. Clin J Am Soc Nephrol. 2006; 1: S1-S3
  • 115 Hoën B, Paul-Dauphin A, Kessler M. Intravenous iron administration does not significantly increase the risk of bacteremia in chronic hemodialysis patients. Clin Nephrol. 2002; 57: 457-61
  • 116 Aronoff GR, Bennett WM, Blumenthal S, Charytan C, Pennell JP, Reed J et al. Iron sucrose in hemodialysis patients: safety of replacement and maintenance regimens. Kidney Int. 2004; 66: 1193-8
  • 117 Scheiber-Mojdehkar B, Lutzky B, Schaufler R, Sturm B, Goldenberg H. Non-transferrin-bound iron in the serum of hemodialysis patients who receive ferric saccharate: no correlation to peroxide generation. J Am Soc Nephrol. 2004; 15: 1648-55
  • 118 Feldman HI, Joffe M, Robinson B, Knauss J, Cizman B, Guo W et al. Administration of parenteral iron and mortality among hemodialysis patients. J Am Soc Nephrol. 2004; 15: 1623-32
  • 119 Geisser P. The pharmacology and safety profile of ferric carboxymaltose (Ferinject): structure/reactivity relationships of iron preparations. Port J Nephrol Hypert. 2009; 23: 11-6
  • 120 Lyseng-Williamson KA, Keating GM. Ferric carboxymaltose: a review of its use in iron-deficiency anaemia. Drugs. 2009; 69: 739-56
  • 121 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: 2436-48
  • 122 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
  • 123 Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JE, Goodnough LT. Ferric Carboxymaltose Study Group. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion. 2009; 49: 2719-28
  • 124 Qunibi W, Quinn D, Benjamin J Safety and tolerability profile of ferric carboxymaltose (FCM), a new high dose intravenous iron, across ten multi-center clinical trials. Poster presented at the XLV ERA-EDTA Congress, May 10–13, 2008, Stockholm, Sweden. MP383
  • 125 Auerbach M. Ferumoxytol as a new, safer, easier-to-administer intravenous iron: yes or no?. Am J Kidney Dis. 2008; 52: 826-9
  • 126 Provenzano R, Schiller B, Rao M, Coyne D, Brenner L, Pereira BJ. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol. 2009; 4: 386-93
  • 127 Spinowitz BS, Kausz AT, Baptista J, Noble SD, Sothinathan R, Bernardo MV et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008; 19: 1599-605
  • 128 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: 907-15
  • 129 Geisser P, Baer M, Schaub E. Structure/histotoxicity relationship of parenteral iron preparations. Arzneimittelforschung. 1992; 42: 1439-52