Adverse and hypersensitivity reactions after intravascular administration of nonionic iodine-based contrast media: Do agent-specific differences inform contrast agent selection?

To evaluate clinical evidence regarding acute adverse drug reactions (ADR) and hypersensitivity reactions (HR) associated with currently available nonionic intravascular iodine-based contrast media (ICMs) and to assess the clinical implications for ICM selection and switching strategies. A narrative review was conducted following a comprehensive literature search of PubMed, Embase, Emcare, Web of Science, and the Cochrane Library (2010–present). Original studies, systematic reviews, and meta-analyses reporting agent-specific ADR, HR, cross-reactivity, or outcomes after ICM switching were included. Data were synthesised descriptively using median rates and interquartile ranges. Overall ADR frequencies did not directly mirror HR patterns, highlighting distinct underlying pathophysiological mechanisms. Overall acute ADR rates remained below 1% for most nonionic ICM, with severe events occurring in < 0.02% of administrations. The median HR incidence was 0.71%, with severe reactions comprising approximately 3% of all HR. Although trends suggested differences among individual agents, particularly after stratification by reaction severity, findings were inconsistent across studies and meta-analyses. Iobitridol, iohexol, and ioversol generally showed favourable overall safety profiles, whereas iomeprol and iodixanol more frequently ranked higher in ADR or HR rates. However, geographical bias, differences in ICM utilisation, market share variations, methodological heterogeneity, and other confounding factors limited direct comparisons. While modern nonionic ICMs exhibit an excellent overall safety profile, our findings reveal trends that may inform culprit-based agent switching and personalised ICM selection to improve safety in high-risk patients. Nonetheless, substantial methodological heterogeneity and observational confounding prevent drawing definitive conclusions about the superiority of any single agent. Question Do nonionic ICM differ in adverse and HR rates, and can these differences guide empirical contrast agent switching ? Findings Reaction rates suggest potential agent-specific variations, but methodological heterogeneity and confounding prevent conclusions regarding comparative safety among individual contrast agents . Relevance statement Individualised contrast selection and agent change are valuable clinical strategies to minimise recurrent reactions in high-risk patients, alongside careful documentation and consideration of immunogenetic factors .