Pumping (IV) Iron Linked to Varying Anaphylaxis Risk for Older Adults

While the risk of anaphylaxis after administration of IV iron product was low among older adults, it was more common after certain iron products, researchers found.

The highest adjusted incidence rates for anaphylaxis among Medicare recipients receiving IV iron was 9.8 cases (95% CI 6.2-15.3) per 10,000 first administrations of iron dextran (Dexferrum) and 4.0 (95% CI 2.5-6.6) cases per 10,000 for ferumoxytol (Feraheme), reported Chintan Dave, PharmD, PhD, of Rutgers University in New Brunswick, New Jersey, and colleagues.

Adjusted incidence rates for anaphylaxis per 10,000 administrations of ferric gluconate (Ferrlecit), iron sucrose (Venofer) and ferric carboxymaltose (Injectafer) were much lower (1.5 cases, 95% CI 0.3-6.6, 1.2 cases, 95% CI 0.6-2.5 and 0.8 cases, 95% CI 0.3-2.6, respectively), the authors wrote in Annals of Internal Medicine.

Compared to iron sucrose, adjusted odds ratios for anaphylaxis were 8.3 for iron dextran and 3.4 for ferumoxytol, but did not differ significantly for gluconate or ferric carboxymaltose, they noted.

“Our findings … provide reassuring data with respect to the risk of anaphylaxis with ferric carboxymaltose, which has seen a rapid increase in use following favorable clinical trial data in a variety of clinical indications,” said co-author Soko Setoguchi, MD, DrPH, also of Rutgers University.

The authors noted that because these anaphylactic events are so rare, most clinical trials or meta-analyses are not powered to detect differences between treatments. Thus, their retrospective cohort study used “a target trial emulation approach” within the Medicare fee-for-service database from July 2013 to December 2018.

Participants were Medicare fee-for-service patients, ages 65 and up, with Part D prescription claims and were categorized into five treatment groups by medication.

Overall, 167,925 patients were included in the analysis. The cohort averaged 77-79 years of age, and about two-thirds were women. A large majority (77%-86%) were white. The most common product received was iron sucrose (n=59,755) and ferumoxytol (n=40,778).

Dave’s group noted that users of iron sucrose and ferumoxytol had more chronic kidney disease, likely due to “differences in their approved indication for use.” Interestingly, those with a history of drug allergies were the least likely to receive iron dextran, they added.

Anaphylactic reactions that required hospitalization were only seen among patients using iron dextran or ferumoxytol. Risk of either anaphylaxis or death was higher only for iron dextran (OR 3.2, 95% CI 1.9-5.3), Dave’s team said.

Dave’s team also looked at the adjusted risk when only low-molecular-weight iron dextran was used, during the period after high-molecular-weight iron dextran was withdrawn in 2014. They found the risks were similarly elevated then (OR 8.4, 95% CI 2.8-24.7), albeit with a wide confidence interval.

“Anaphylaxis is just one of many factors to consider when deciding on which IV iron formulation to administer, … such as the clinical indication, number of IV iron administrations required, risk of other adverse reactions and cost,” Dave said.

Limitations to the data included that the case definition of anaphylaxis used encompassed only more serious reactions; milder anaphylactic reactions may have been missed. The study was also limited by its observational design, potential residual confounding, and unknown generalizability to younger patients, as the population here was older.