Pediatric ondansetron hypersensitivity: Clinical features and a preliminary diagnostic approach

<b>Background:</b> Ondansetron is a common antiemetic that rarely causes hypersensitivity. Skin-prick testing (SPT) and intradermal testing (IDT) may assist in diagnosing ondansetron hypersensitivity; however, their sensitivity, specificity, and optimal concentrations remain unclear. To our knowledge, drug provocation testing (DPT), the criterion standard for diagnosis, has not been previously applied in pediatric cases. <b>Objective:</b> In this study, we aimed to evaluate ondansetron hypersensitivity in children by using a preliminary diagnostic approach that incorporated SPT, IDT, and DPT. <b>Methods:</b> We retrospectively reviewed pediatric patients who were evaluated for suspected ondansetron hypersensitivity between 2019 and 2025. We performed an SPT by using an ondansetron concentration of 2 mg/mL, followed by an IDT with concentrations of 0.02 and 0.2 mg/mL in patients with negative SPT results. In cases of patients with negative skin test results, we conducted DPTs. <b>Results:</b> We included seven pediatric patients ages 3-16 years. All had negative SPT results, which underscores its limited sensitivity. IDT results were positive in three patients with a history of anaphylaxis (one at 0.02 mg/mL, two at 0.2 mg/mL); DPT was not performed in these patients. Among the four with negative skin test results, DPT was performed in three and yielded negative results. We confirmed hypersensitivity in three patients. In another three, no clinical reactivity was observed at the time of DPT, and the diagnosis remained inconclusive in one patient. <b>Conclusion:</b> To our knowledge, this is the first pediatric case series to propose a preliminary diagnostic approach that incorporated DPT in the evaluation of suspected ondansetron hypersensitivity. The findings highlight the limited sensitivity of SPT, emphasize the diagnostic value of IDT, particularly in patients with anaphylaxis, and support the safe applicability of DPT in patients with negative skin test results, with all three DPTs yielding negative results.