When is high-dose intravenous iron repletion needed? Assessing new treatment options

David Gozzard, David Gozzard

Abstract

High doses of intravenous iron have a role in the treatment of a number of clinical situations associated with iron deficiency, iron deficiency anemia, and blood loss. In the presence of functioning erythropoiesis, iron supplementation alone may be adequate to replenish iron stores and restore blood loss. Where hormone replacement with an erythropoiesis-stimulating agent is required, iron adequacy will optimize treatment. Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. The literature indicates that high doses of iron are required, with levels of 1500 mg in nondialysis-dependent chronic kidney disease and up to 3600 mg in inflammatory bowel disease. New formulations of intravenous iron have recently been introduced that allow clinicians to administer high doses of iron in a single administration. Ferumoxytol is available in the US, has a maximum dose of 510 mg iron in a single administration, but is limited to use in chronic kidney disease. Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indications. The latest introduction is iron isomaltoside 1000. Again, a test dose is not required, and it can be delivered rapidly as an infusion (in an hour), allowing even higher doses of iron to be administered in a single infusion, ie, 20 mg/kg body weight with no ceiling. This will allow clinicians to achieve high-dose repletion more frequently as a single administration. Treatment options for iron repletion have taken a major leap forward in the past two years, especially to meet the demand for high doses given as a single administration.

Keywords: erythropoiesis; high dose; intravenous iron; iron deficiency; iron deficiency anemia; iron isomaltoside 1000; single dose.

References

    1. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Hematol. 2009;122(2–3):78–86.
    1. Craig R, Mindell J, editors. Health Survey for England 2005: The Health of Older People. Vol. 1. London: TSO; 2007.
    1. De Benoist B, McLean E, Egli I, Cogswell M, editors. Worldwide Prevalence of Anemia 1993–2005: WHO Global Database on Anemia. Geneva: World Health Organisation; 2005.
    1. Besarab A, Amin N, Ahsan M, et al. Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients. J Am Soc Nephrol. 2000;11:530–538.
    1. Melamed N, Ben-Haroush A, Kaplan B, Yogev Y. Iron supplementation in pregnancy – does the preparation matter? Arch Gynecol Obstet. 2007;276(6):601–604.
    1. Lawrence R. Development and comparison of iron dextran products. PDA J Pharm Sci Technol. 1998;52(5):190–197.
    1. Venofer® [Package insert] Surrey, UK: Syner-med Pharmaceutical Products Ltd; 2010.
    1. Cosmofer® [Package insert] Holbaek, Denmark: Pharmacosmos A/S; 2010.
    1. Ferrlecit® [Monograph] Bridgewater, NJ: Sanofi-aventis US LLC; 2010.
    1. Feraheme® [Monograph] Cambridge, MA: AMAG Pharmaceuticals Inc; 2009.
    1. Ferinject® [Package insert] Surrey, UK: Syner-med Pharmaceutical Products Ltd; 2010.
    1. Monofer® [Package insert] Cambridge, MA: AMAG Pharmaceuticals Inc; 2010.
    1. Peebles G, Stanley S. Evaluation of service reconfiguration for managing intravenous iron supplementation in non-hemodialysis patients with chronic renal failure. Journal of Outcomes Research. 2004;8:15–25.
    1. Jenkins A. Using iron dextran to treat iron-deficiency anemia. Hospital Pharmacist. 2005;12(6):224–225.
    1. Auerbach M, Coyne D, Ballard H. Intravenous iron: From anathema to standard of care. Am J Hematol. 2008;83(7):580–588.
    1. Agarwal R. Individualizing decision-making – resurrecting the doctor-patient relationship in the anemia debate. Clin J Am Soc Nephrol. 2010;5(7):1340–1346.
    1. The Renal Association . Clinical Practice Guidelines: Chronic Kidney Disease. Hampshire, UK: The Renal Association; 2010.
    1. Jungers P, Qualim Z, Nguyen-Khoa T, Massey Z, London G. Cardioprotection: An essential component for predialysis chronic renal failure treatment. Nephrologie. 2003;24(2):79–88. French.
    1. Macdougall IC. Iron supplementation in the non-dialysis chronic kidney disease (ND-CKD) patient: Oral or intravenous? Curr Med Res Opin. 2010;26(2):473–482.
    1. Ganzoni AM. Schweiz Med Wochenschr. 1970;100(7):301–303. German. [Intraverous iron-deptran: therapeutic and experimental possibilities]. [German]
    1. Peebles G, Fenwick S. Intravenous iron administration in a short-stay hospital setting. Nurs Stand. 2008;22(48):35–41.
    1. Gasche C, Lomer MCE, Cavill, Weiss G. Iron, anemia, and inflammatory bowel disease. Gut. 2004;53:1190–1197.
    1. Gasche C, Berstad A, Befrits R, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel disease. Inflamm Bowel Dis. 2007;13(12):1545–1553.
    1. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr. 2000;72(1):S257–S264.
    1. National Institute for Health and Clinical Excellence . Antenatal care: Routine Care for the Healthy Pregnant Woman. Clinical Guideline. London, UK: National Institute for Health and Clinical Excellence; 2008.
    1. Bashiri A, Smolin A, Sheiner E, Zelingher J, Mazor M. Maternal rehospitalization after singleton term vaginal delivery. J Matern Fetal Neonatal Med. 2003;14(5):344–348.
    1. Knight M, Callaghan WM, Berg C, et al. Trends in postpartum hemorrhage in high resource countries: A review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth. 2009;9:55.
    1. Royal College of Obstetricians and Gynecologists . National Sentinel Caesarean Section Audit (England, Wales and Northern Ireland) London, UK: Royal College of Obstetricians and Gynecologists Press; 2001.
    1. Breymann C. The use of iron sucrose complex for anemia in pregnancy and the postpartum period. Semin Hematol. 2006;43(Suppl 6):S28–S31.
    1. Bodnar LM, Siega-Riz AM, Miller WC, Cogswell ME, McDonald T. Who should be screened for postpartum anemia? An evaluation of current recommendations. Am J Epidemiol. 2002;156(10):903–912.
    1. Hallak M, Sharon AS, Diukman R, Auslender R, Abramovici H. Supplementing iron intravenously in pregnancy. A way to avoid blood transfusions. J Reprod Med. 1997;42(2):99–103.
    1. Qunibi W, Dinh Q, Benjamin J. Safety and tolerability profile of ferric carboxymaltose (FCM) a new high dose intravenous iron, across ten multi-center trials. J Am Soc Nephrol. 2007;18 SU–PO1029.
    1. Protheroe J. Modern management of menorrhagia. J Fam Plann Reprod Health Care. 2004;30(2):118–122.
    1. Oehler MK, Rees MC. Menorrhagia: An update. Acta Obstet Gynecol Scand. 2003;82(5):405–422.
    1. 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(5):323–330.
    1. Lo L. Modern management of menorrhagia. Hong Kong Practitioner. 1996;18(2):62–66.
    1. Prentice A. Medical management of menorrhagia. BMJ. 1999;319:1343–1345.
    1. National Institute for Health and Clinical Excellence . Heavy Menstrual Bleeding. Clinical Guideline. London, UK: National Institute for Health and Clinical Excellence; 2007.
    1. Kim YH, Chung HH, Kang SB, Kim SC, Kim YT. Safety and usefulness of intravenous iron sucrose in the management of preoperative anemia in patients with menorrhagia: A phase IV, open label, prospective, randomized study. Acta Haematol. 2009;121(1):37–41.
    1. 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.
    1. Bokemeyer C, Aapro MS, Courdi A, et al. European Organisation for Research and Treatment of Cancer (EORTC) Taskforce for the Elderly EORTC guidelines for the use of erythropoietic proteins in anemic patients with cancer. Eur J Cancer. 2004;40(15):2201–2216.
    1. Crawford J, Cella D, Cleeland CS, et al. Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin-alfa therapy. Cancer. 2002;95(4):888–895.
    1. Weiss G. Pathogenesis and treatment of anemia of chronic disease. Blood Rev. 2002;16(2):87–96.
    1. Auerbach M. Should intravenous iron be the standard of care in oncology. J Clin Oncol. 2008;26(10):1579–1581.
    1. Fishbane S, Frei GL, Maesaka J. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis. 1995;26(1):41–46.
    1. Auerbach M, Ballard H, Trout JR, et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy related anemia: A multicenter, open label, randomized trial. J Clin Oncol. 2004;22(7):1301–1307.
    1. Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR, et al. Intravenous ferric gluconate improves response to epoietin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist. 2007;12(2):231–242.
    1. Bastit L, Vandebroek A, Altintas S, et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoietin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol. 2008;26(10):1611–1618.
    1. Pedrazzoli P, Farris A, Del Prete S, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoietin alfa. J Clin Oncol. 2008;26(10):1619–1625.
    1. American Society of Clinical Oncology Important information for physicians about changes affecting the FDA-approved use of erythropoiesis stimulating agents (ESA) Available from: . Accessed Jun 8 2010.
    1. Steensma DP. Is anemia of cancer different from chemotherapy induced anemia? J Clin Oncol. 2008;26(7):1022–1024.
    1. Singh AK, Tang KL, Bamhart H, et al. CHOIR investigators Correction of anemia with epoietin alfa in chronic kidney disease. N Engl J Med. 2006;355(20):2085–2098.
    1. National Institute for Health and Clinical Excellence . London, UK: National Institute for Health and Clinical Excellence; 2008. Erythropoietin analogues for anemia caused by cancer treatment. Technology appraisal guidance.
    1. Aapro MS, Link H. September 2007 Update on EORTC guidelines and anemia management with erythropoiesis-stimulating agents. Oncologist. 2008;13(Suppl 3):33–36.
    1. Steensma DP. New ASH/ASCO guidelines on the use of erythropoiesis-stimulating agents: A chorale amid cacophony. J Support Oncol. 2007;5(10):471–473.
    1. Special Eurobarometer . European Commission; 2006. Health and Food 246/Wave 643 – TNS Opinion and Social.
    1. Portier K, Tolson JK, Roberts SM. Body weight distributions for risk management. (NHANES 1999–2002) Risk Anal. 2007;27(1):11–26.
    1. European Pharmacopoeia – Monograph. Page 1408.
    1. Luitpold Pharmaceuticals Inc Methods and Compositions for Administration of Iron. 19th July 2007. WO2007/081744 A2.
    1. 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.
    1. Wysowski DK, Swartz L, Borders-Hemphill BV, et al. Use of parenteral iron products and serious anaphylactic-type reactions. Am J Hematol. 2010;85(9):650–654.
    1. Chertow GM, Winkelmayer WC. On the relative safety of intravenous iron formulations: New answers, new questions. Am J Hematol. 2010;85(9):643–644.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner