Introduction: In highly emetogenic chemotherapy, the recommended dose of the serotonin-receptor antagonist ondansetron (5mg/m2 q8h) may be insufficient to prevent chemotherapy-induced nausea and vomiting. In adults, ondansetron-loading doses (OLD) of 32mg are safe. We aimed to evaluate in children the safety of an OLD of 16mg/m2 (top, 24mg) i.v., followed by two doses of 5mg/m2 q8h. Materials and methods: This retrospective single-center study included all pediatric oncology patients having received ≥1 OLD between 2002 and 2005. Adverse events (AE) definitely, probably, or possibly related to OLD were studied, excluding AE not or unlikely related to the OLD. Associations between potential predictors and at least moderate AE were analyzed by mixed logistic regression. Results: Of 167 patients treated with chemotherapy, 37 (22%) received 543 OLD. The most common AE were hypotension, fatigue, injection site reaction, headache, hot flashes/flushes, and dizziness. At least mild AE were described in 139 OLD (26%), at least moderate AE in 23 (4.2%), and severe AE in 5 (0.9%; exact 95% confidence interval [CI], 0.4-2.1). Life-threatening or lethal AE were not observed (0.0%; 0.0-0.6). At least moderate AE were significantly more frequent in female patients (odds ratio [OR] 3.5; 95% CI 1.4-8.8; p = 0.010), after erroneously given second OLD (17.0; 1.9-154; p = 0.012) and higher 24h cumulative surface corrected dose (1.26 per mg/m2; 1.06-1.51; p = 0.009). OLD given to infants below 2years were not associated with more frequent AE. Conclusions: Ondansetron-loading doses of 16mg/m2 (top, 24mg) i.v. seem to be safe in infants, children, and adolescent
