Historically, IV iron administration was associated with frequent infusion reactions when high-molecular-weight iron dextran was utilized. However, such occurrences are infrequent with newer formulations. Nonetheless, it is still unclear how one IV iron formulation currently in use compares with other formulations with respect to their adverse event (AE) profile.

Investigators conducted a multicenter, retrospective cohort study from January 1, 2015, to September 7, 2021, to evaluate the rates of infusion reactions among four commonly used IV iron-repletion strategies (iron sucrose, low-molecular-weight iron dextran, feurmoxytol, and ferric carboxymaltose) and determine how subsequent administration of IV iron was managed in patients with a history of an adverse reaction to the hematinic.

The primary outcome was to determine the overall incidence of AEs and serious AEs (SAEs) among all patients who received at least one dose of IV iron. An AE was defined as the administration of diphenhydramine, epinephrine, famotidine, and/or hydrocortisone within 24 hours of the IV iron infusion. A SAE was described as those involving the use of epinephrine within 24 hours of IV iron administration.

Secondary outcomes included the incidence of AEs in those who received premedication (i.e., diphenhydramine, famotidine, and/or hydrocortisone) within 24 hours preceding the infusion, and in those who received test doses. A subgroup analysis was performed to measure the incidence of AEs in patients with a documented allergy history and in those with a history of infusion-related reactions who received subsequent doses of IV iron; this was further stratified by IV iron formulation and use of premedication.

A total of 35,737 IV iron infusions were administered to 12,237 patients during the 6.5-year period. The mean age of the population was 51 years. Of these patients, 79.1% had a documented allergy to either medication, food allergies, or contact allergies. A breakdown of the IV infusion included 62.4% iron sucrose, 25.2% full-dose iron dextran with or without a test dose, 8.8% ferumoxytol, 3.4% ferric carboxymaltose, and 0.2% an iron dextran test dose only.

The cumulative incidence of infusion-related AEs was 3.9% (1,389 reactions). A further breakdown revealed that 4.3% were due to iron sucrose, 3.8% were due to low-molecular-weight iron dextran with test and full dose, full dose alone or test dose alone, 1.8% from ferumoxytol, and 1.4% associated with ferric carboxymaltose. Although these differences between formulations had a P value of <.001, the study was not specifically designed to compare the rate of AEs between individual formulations.

Epinephrine use was deployed in only two patients, both of whom were administered low-molecular-weight iron dextran. As far as the use of premedication, 2,157 iron infusions (6.0%) were associated with the use of either diphenhydramine (50.3%), famotidine (40.8%), or hydrocortisone (27.8%).

The incidence of AEs among those who received one of the above pretreatment medications was about 23-fold higher than those who did not receive an antiallergenic agent (38.6% vs. 1.7%, P <.001). Having a history of allergies to medication, food allergies, or contact allergies was associated with a significantly higher rate of AEs compared with those without an allergy history (4.2% vs. 3.2%; P <.001).

Among those with a prior infusion reaction who required further iron therapy, 86% received the same iron formulation to which they had the AE; of these, 80% were premedicated. Of the 14% who were switched to a different parenteral iron product, only one-third were premedicated. Retreating with the problematic formulation led to further AEs. Rates of recurrent AEs were significantly higher in the patients who received the same IV iron formulation to which they had had a prior reaction whether they were premedicated (68%) or not premedicated (32%) compared with those who received a different IV iron product and who were pretreated (21%) or who were not premedicated (5%) (P <.001).

The take-home points for pharmacists from this study is that the incidence of infusion reactions associated with IV iron formulations is low at 3.9%. Among these formulations, there is a significantly different comparative rate of infusion-related AEs with low-molecular-weight iron dextran posing a slightly greater risk for serious AEs. Pretreatment with diphenhydramine, famotidine or hydrocortisone appears unnecessary in most cases and may actually increase the risk of AEs.

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