Hypersensitivity and anaphylactic reaction rates reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database varied significantly among intravenous (IV) iron products, however, ferric carboxymaltose was found to be associated with the lowest rates of reporting and downstream medical costs per adverse event (AE), according to the findings of a recent analysis published in Drug Safety.

The comparative study aimed to analyze AEs as well as estimate the associated medical costs for 4 IV iron preparations (iron dextran, iron sucrose, ferumoxytol, and ferric carboxymaltose) used to correct iron deficiency anemia. The study authors extracted cases of hypersensitivity reactions and anaphylaxis/ anaphylactic shock associated with the 4 IV iron preparations that were spontaneously reported to the FAERS database between January 1, 2014, and December 31, 2019.

“The reporting odds ratio lower bound 90% confidence interval (ROR05) >1 and cases ≥5 defined a likely signal for a drug–adverse event association,” the authors explained. Data from the Agency for Healthcare Research and Quality/Healthcare Cost and Utilization Project 2016 was used to estimate AE-associated medical costs.

Results of the study revealed ferumoxytol to have the highest ROR05 value (5.00) and greatest proportion of associated deaths (7.1%) while ferric carboxymaltose had the lowest ROR05 value (3.03) and lowest proportion of associated deaths (0.2%). ROR05 values for iron dextran and iron sucrose were reported to be 4.35 and 3.94, respectively, and the proportions of associated deaths associated with these agents were 5.3% and 2.4%, respectively.

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The study authors also reported the ROR05 for cases/deaths for anaphylaxis/anaphylactic shock to be 39.32/13.4% for ferumoxytol, 37.80/4.5% for iron dextran, 17.60/4.7% for iron sucrose and 8.77/no deaths for ferric carboxymaltose. Findings of the analysis also showed iron dextran was associated with the highest downstream medical costs per AE ($8615), while ferric carboxymaltose was associated with the lowest ($1832). Downstream medical costs per AE for ferumoxytol and iron sucrose were reported to be $8164 and $4212, respectively. 

“We found that although all the IV iron formulations we considered had signals for likely drug–AE associations based on ROR05 for hypersensitivity reactions and anaphylaxis, signals were highest for ferumoxytol and iron dextran, intermediate for iron sucrose, and lowest for ferric carboxymaltose,” the authors wrote. This pattern was also observed when analyzing hospitalization and deaths associated with anaphylaxis or hypersensitivity reactions as well as downstream direct medical costs due to AEs. “Results of this real-world analysis of FAERS data suggest that reporting rates of anaphylaxis and other hypersensitivity reactions among patients requiring an IV iron preparation are lowest with ferric carboxymaltose,” they added.

Disclosure: Multiple authors declared conflicts of interest. Please refer to the original article for a full list of disclosures.


  1. Trumbo H, Kaluza K, Numan S, Goodnough LT. Frequency and associated costs of anaphylaxis and hypersensitivity‑related adverse events for intravenous iron products in the USA: An analysis using the US Food and Drug Administration Adverse Event Reporting System. Drug Saf. 25 November, 2020. doi: 10.1007/s40264-020-01022-2.