BACKGROUND With the increasing use of low-osmolar contrast media (LOCM), hypersensitivity reactions (HSRs) to LOCM have become more common. Although guidelines for the preventive measure for immediate reactions are well established, evidence-based strategies for nonimmediate HSRs remain limited.

OBJECTIVE To determine effective prophylactic strategies for patients with nonimmediate HSRs to LOCM.

METHODS A retrospective cohort study was conducted at the Seoul National University Hospital, involving 4331 patients with nonimmediate HSRs to LOCM from 2012 to 2022.

RESULTS A total of 694 patients underwent 3634 re-exposures to LOCM; the overall recurrence rate was 3.6% per exposure (13.4% per patient). Logistic regression analysis revealed that switching to an LOCM with a different side chain (adjusted odds ratio [aOR], 0.27; 95% confidence interval [CI]: 0.15-0.53; P < .001) and antihistamine premedication (aOR, 0.47; 95% CI: 0.28-0.77; P = .003) reduced the risk of recurrence. For pruritus, urticaria, or angioedema, switching to an LOCM with a different side chain (aOR, 0.32; 95% CI: 0.13-0.75; P = .009) and antihistamine premedication (aOR, 0.37; 95% CI: 0.19-0.73; P = .004) reduced the risk of recurrence. For maculopapular rash, any LOCM change was beneficial (common side chain: aOR, 0.05; 95% CI: 0.01-0.53; P = .012; different side chain: aOR, 0.15; 95% CI: 0.05-0.47; P = .001), while premedication showed no significant effect.

CONCLUSIONS Prophylactic strategies for nonimmediate HSRs to LOCM should be tailored to clinical presentation: antihistamine premedication and side chain substitution are effective for urticaria or angioedema, whereas a maculopapular rash benefits only from switching to an alternative agent without additional benefit from antihistamine premedication.