Aug
2010

Use of parenteral iron products and serious anaphylactic-type reactions.

Wysowski DK, Swartz L, Borders-Hemphill BV, Goulding MR, Dormitzer C
Am J Hematol 2010;85(9):650-654.
NATA Rating :
Review by : M. Muoz
NATA Review

In this paper, the authors report on the use of four parenteral iron products: ferric gluconate, iron sucrose, low-molecular-weight iron dextran (LMWID) and high-molecular-weight iron dextran (HMWID). They also analyze anaphylactic-type reactions and deaths recorded in the IMS Health database, the FDA\’s Adverse Event Reporting System (AERS) database, death certificate data, and emergency department visit databases.

The projected number of eaches (single vials or syringes) of parenteral iron sold in the U.S. increased from about 12.6 million in 2002 to over
16.8 million in 2007 (33.5% increase). From initial marketing to mid-2007, 87 deaths and 412 life-threatening adverse events were recorded by AERS, while only 53 deaths were recorded in death certificate data between 1979 and 2006, and 62 patients attended emergency departments for adverse reaction to IV iron (with no deaths) between 2003 and 2008. As neither the number of patients receiving IV or the number of eaches, nor iron preparation brand names were consistently recorded, the authors conclude that is difficult to determine which product has the highest risk based on these data.

This conclusion is in disagreement with analysis of data from the United States Food and Drug Administration (FDA) on adjusted rate adverse drugs events (ADEs) per 100 mg dose attributed to the provision of these four formulations of intravenous iron during 20012003. In this report, the total number of reported parenteral iron-related ADEs was 1141 amongst approximately 30 million doses administered (approx. 38 ADEs per million), with 11 deaths (7 iron dextran, 3 iron gluconate, 1 iron sucrose).1 Relative to LMWID, total and life-threatening ADEs were significantly more frequent among recipients of HMWID and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per 106 doses for iron sucrose, sodium ferric gluconate complex, LMWID and HMWID, respectively, whereas absolute rates of death were 0.11, 0.25, 0.75, and 0.78 per 106 doses, respectively. Again, it is not clear whether all deaths due LMWID were correctly attributed.

Therefore, it seems that, with the exception of HMWID (increased rates of severe side effects and deaths), the acute safety differences among IV iron products are small when given at the recommended doses, although comparator trials are needed. The authors recommend that, to help differentiate risk among the parenteral iron products, the brand name of the product should always be provided on medical records, death certificates, and adverse drug reaction reports.

– Manuel Muoz

Reference

1. Chertow GM, Mason PD, Vaaga-Nilsen O, Ahlmn J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 2006;21:378-82.