Correspondence
Intravenous Iron
N Engl J Med 2007; 357:93-94July 5, 2007
- Article
To the Editor:
Before iron was used as an adjunct to erythropoietic stimulatory therapy in patients undergoing hemodialysis, parenteral iron was considered to be dangerous. High-molecular-weight iron dextran (Imferon [Fisons], which is no longer manufactured) was the only product available and was associated with anaphylaxis. Nonetheless, marked improvements in hemoglobin responsiveness1 resulted in the extensive use of high-molecular-weight iron dextran in nephrology. In the mid-1990s, two events changed the prescribing practices of nephrologists. First, high-molecular-weight iron dextran was removed from the market, and subsequently, low-molecular-weight iron dextran (InFed [Watson]) was released. Low-molecular-weight iron dextran was the standard of care for patients with anemia from hemodialysis.1 Shortly thereafter, another high-molecular-weight iron dextran product (DexFerrum [American Regent]) was released for clinical use.
Two new compounds, ferric gluconate (Ferrlecit [Watson]) and iron sucrose (Venofer [American Regent]), were introduced in the late 1990s. These new products were associated with lower rates of serious adverse events than were the previously released products.2 When reported serious adverse events were stratified according to the product,3 virtually all events were due to high-molecular-weight iron dextran; the incidence of acute reactions with each of the other three products, including low-molecular-weight iron dextran, was approximately 1 in 200,000.
In September 1998, the distribution of low-molecular-weight iron dextran was halted by the Food and Drug Administration (FDA) for administrative reasons, leaving high-molecular-weight iron dextran as the only product available (ferric gluconate and iron sucrose had not yet been introduced in the United States). During that time, there was an 1100% increase in reported adverse events from the use of high-molecular-weight iron dextran. Later, low-molecular-weight iron dextran was reintroduced into the market. Since these events, 10 articles have reported a marked increase in the incidence of adverse events in adults and children from the use of the high-molecular-weight product. One article4 urged clinicians not to use high-molecular-weight iron dextran (citing estimated adverse event rates of >25%).
Intravenous iron has also been shown to play a major role in the management of anemia in other medical settings, especially in hematology and oncology.5 Unfortunately, there is widespread ignorance among hematologists, oncologists, and other specialists who use parenteral iron about the relative safety of the products available.
We believe there is inappropriate underuse of intravenous iron in patients with chronic diseases, because practitioners are reluctant to use the products for fear of serious adverse events. This fear is perpetuated by the continued use of high-molecular-weight iron dextran by hospitals that perceive it as a less expensive generic equivalent to the low-molecular-weight product. As a result, the more toxic high-molecular-weight product is often administered when low-molecular-weight iron dextran is actually ordered. We believe that there is ample evidence of the need to abandon the use of high-molecular-weight iron dextran in clinical medicine.
Michael Auerbach, M.D.
Auerbach Hematology and Oncology, Baltimore, MD 21237
mauerbachmd@aol.com George M. Rodgers, M.D.
University of Utah School of Medicine, Salt Lake City, UT 84132Dr. Auerbach reports receiving consulting fees from Watson Pharmaceuticals. No other potential conflict of interest relevant to this letter was reported.
5 References1
Adamson JW ,Eschbach JW . Erythropoietin for end-stage renal disease. N Engl J Med 1998;339:625-627
Full Text | Web of Science | Medline2
Coyne DW ,Adkinson NF ,Nissenson AR , et al. Sodium ferric gluconate complex in hemodialysis patients. II. Adverse reactions in iron dextran-sensitive and dextran-tolerant patients. Kidney Int 2003;63:217-224
CrossRef | Web of Science | Medline3
Chertow GM ,Mason PD ,Vaage-Nilsen O ,Ahlmen J . Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 2006;21:378-382
CrossRef | Web of Science | Medline4
Mamula P ,Piccoli DA ,Peck SN ,Markowitz JE ,Baldassano RN . Total dose intravenous infusion of iron dextran for iron-deficiency anemia in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2002;34:286-290
CrossRef | Web of Science | Medline5
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;22:1301-1307
CrossRef | Web of Science | Medline
- Citing Articles (14)
Citing Articles
1
Susan P. Foy, Vinod Labhasetwar. (2011) Oh the irony: Iron as a cancer cause or cure?. Biomaterials 32:35, 9155-9158
CrossRef2
Huseyin ATALAY, Yalcin SOLAK, Kadir ACAR, Nilgun GOVEC, Suleyman TURK. (2011) Safety profiles of total dose infusion of low-molecular-weight iron dextran and high-dose iron sucrose in renal patients. Hemodialysis International 15:3, 374-378
CrossRef3
Yalcin Solak, Huseyin Atalay, Ibrahim Guney, Kultigin Turkmen, Emine Kaya, Suleyman Turk. (2011) Comparison of Adverse-Event Profiles of Intravenous Low-Molecular-Weight Iron Dextran and Iron Sucrose in Peritoneal Dialysis Patients. Renal Failure 33:3, 307-311
CrossRef4
Lucia Del Vecchio, Francesco Locatelli. 2010. Erythropoietin and Iron Therapy in Patients with Renal Failure. , 357-367.
CrossRef5
J. Tsay, Z. Yang, F. P. Ross, S. Cunningham-Rundles, H. Lin, R. Coleman, P. Mayer-Kuckuk, S. B. Doty, R. W. Grady, P. J. Giardina, A. L. Boskey, M. G. Vogiatzi. (2010) Bone loss caused by iron overload in a murine model: importance of oxidative stress. Blood 116:14, 2582-2589
CrossRef6
A. Khalafallah, A. Dennis, J. Bates, G. Bates, I. K. Robertson, L. Smith, M. J. Ball, D. Seaton, T. Brain, J. E. J. Rasko. (2010) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. Journal of Internal Medicine 268:3, 286-295
CrossRef7
Michael Auerbach. (2010) Finding a safe and effective intravenous iron treatment for restless legs syndrome. Sleep Medicine 11:5, 429-430
CrossRef8
LUCIA DEL VECCHIO, FRANCESCO LOCATELLI. (2010) Erythropoietin and iron therapy in patients with renal failure. Transfusion Alternatives in Transfusion Medicine 11:1, 20-29
CrossRef9
Ajay Singh, Tejas Patel, Joachim Hertel, Marializa Bernardo, Annamaria Kausz, Louis Brenner. (2008) Safety of Ferumoxytol in Patients With Anemia and CKD. American Journal of Kidney Diseases 52:5, 907-915
CrossRef10
Michael Auerbach. (2008) Ferumoxytol as a New, Safer, Easier-to-Administer Intravenous Iron: Yes or No?. American Journal of Kidney Diseases 52:5, 826-829
CrossRef11
Michael Auerbach, Dan Coyne, Harold Ballard. (2008) Intravenous iron: From anathema to standard of care. American Journal of Hematology 83:7, 580-588
CrossRef12
T. J. Littlewood, R. Alikhan. (2008) The use of intravenous iron in patients with cancer-related anaemia. British Journal of Haematology 141:6, 751-756
CrossRef13
M Auerbach, K Al Talib. (2008) Low-molecular weight iron dextran and iron sucrose have similar comparative safety profiles in chronic kidney disease. Kidney International 73:5, 528-530
CrossRef14
Richard A. Sherman. (2007) Briefly noted. Seminars in Dialysis 20:6, 629-630
CrossRef
