Differences in Hypersensitivity Reactions to Iodinated Contrast Media: Analysis of the US Food and Drug Administration Adverse Event Reporting System Database

Abstract

Background: A comparative hypersensitivity risk profile of frequently used iodinated contrast media (ICM) may be required for their safer use.

Objective: To explore the association between hypersensitivity reactions (HSRs) and specific ICM and characterize the spectrum of ICM-related HSRs.

Methods: We performed a disproportionality analysis and proportionality test to assess the safety profile of ICM-related HSRs and compare the frequency ratio of specific HSRs in diverse age, sex, and country subgroups. We used reports downloaded from the US Food and Drug Administration Adverse Event Reporting System and data on the national use of individual ICM for this analysis.

Results: A total of 11,343,365 adverse event reports were collected from the first quarter of 2013 to the first quarter of 2021, among which 5,432 cases were identified as ICM-induced HSRs. All of the studied ICMs were associated with overreporting frequencies of HSRs, in which iomeprol showed the highest reporting odds ratio (ROR) of 24.75 (95% CI, 19.61-31.24). Iopromide (ROR = 22.29; 95% CI, 20.18-24.62) and ioversol (ROR = 20.85; 95% CI, 18.54-23.44) were more likely to cause angioedema than other ICMs, particularly in the group aged 45 to 64 years. Iomeprol was associated with the largest disproportionality for severe cutaneous adverse reactions (ROR = 127.90; 95% CI, 103.32-159.88), whereas iodixanol exhibited maximal incidence when total use cases were considered. Regarding anaphylactic shock, iopamidol presented the highest disproportionality (ROR = 31.11; 95% CI, 27.15-35.65), especially in males or seniors aged greater than 65 years, whereas iopromide resulted in the maximum frequency in China and the United States.

Conclusions: Different ICMs exhibited diverse profiles regarding HSRs, which could be further affected by age, sex, or geographic area. Prospective studies are required for patient safety.

Keywords: Anaphylactic shock; Angioedema; Drug allergy; FAERS; ICM; SCARS.