Opioid Allergy Cross-Reactivity: A Retrospective Study Across Three Opioid Classes

IgE-mediated opioid hypersensitivities, or true allergies, are rare and most adverse reactions to opioids can be attributed to side effects or to pseudo-allergies. Given that immune-mediated allergies to opioids are uncommon, literature regarding cross-reactivity among opioid classes are limited. This retrospective study aimed to determine the rates of cross-reactivity and tolerance among patients with previously documented opioid allergy or adverse drug reaction (ADR) across three opioid drug classes (natural, semisynthetic, and synthetic opioids). Patients with documented allergy(s) and/or ADR(s) to opioids were assessed for outcomes of subsequent opioid exposure during any hospital admission at a Veterans Affairs hospital over a 10-year time-period. Veterans were sorted into three cohorts based on the opioid class of the previously documented allergy or ADR. Each cohort had three study arms, one for each class of subsequent opioid exposure. A total of 1507 patients were identified with previously documented allergy or ADR to at least one opioid and at least one subsequent opioid drug exposure. No cross-reactivity among any of the opioid drug classes were found resulting in 100% re-exposure tolerance rates with all study arms. These findings could increase confidence in utilizing opioids in patients with historically documented opioid allergies or ADRs.