“Can you write me a prescription for Zofran?”

You are in the middle of a busy ED shift. Your acute gastroenteritis patient has passed their PO challenge with flying colors after one dose of Zofran. Parents are thrilled and want to have this magical cure at home – so as you are reviewing discharge instructions, they ask “can you send us home with some Zofran please?” 

Do you agree to send the prescription? If yes, how many doses – one? two? ten??? This has long been a gray area in pediatric emergency medicine, and in my own training, I’ve seen wide variation among attendings. That variability isn’t surprising – until now, there simply hasn’t been strong evidence to guide what we should (or shouldn’t) be prescribing.

Now, thanks to a new multicenter, double-blind RCT published in the New England Journal of Medicine, we finally have data to guide this decision. 

The authors of this study conducted a multicenter, double-blind, placebo-controlled RCT across six Canadian pediatric EDs. They enrolled 1030 children (6 months–<18 years) with acute gastroenteritis and ≥3 vomiting episodes in the preceding 24 hours. All had received an initial ondansetron dose in the ED and successfully completed a PO challenge. 

The families were then discharged with six as-needed doses of either ondansetron solution (0.15 mg/kg) or placebo to be used over the next 48 hours, if there was recurrence of emesis.

Key results:

• Primary outcome: Moderate-to-severe gastroenteritis (modified Vesikari ≥9 within 7 days)
  • Ondansetron: 5.1% vs Placebo: 12.5%
  • Adjusted OR: 0.50 (95% CI, 0.40–0.60) → NNT ≈ 15.
• Vomiting: Fewer episodes within 48 hours (rate ratio 0.76) in the patients who received ondansetron.
• Health care use: Trend toward fewer unscheduled visits (9.3% vs 13.2%) and fewer repeat ED visits (5.9% vs 9.2%).
• Safety: Adverse events comparable (7.0% vs 7.1%); mild increase in diarrhea in those receiving ≥3 doses, no arrhythmias or masking of alternate diagnoses observed.

Clinical implications:

In this multicenter RCT, children discharged with as-needed ondansetron had half the risk of developing moderate-to-severe gastroenteritis and experienced fewer episodes of emesis in the first 48 hours after discharge, suggesting real symptom control for those who did continue to have emesis after discharge. The unscheduled visits and repeat ED presentation were trending towards being lower in the group of patients discharged with ondansetron, though these findings were not statistically significant (but think about whether they are clinically significant to you). Importantly, adverse events were comparable between groups, so you can decrease your worry about whether you are going to cause an arrhythmia if you discharge your patient home with Zofran. 

Bottom line: A short supply of ondansetron for home use after an ED visit appears to be both effective and safe.

So next time you get asked “Can you write me a prescription for Zofran please,” what will your response be? Are you changing your practice based on this study? 

Reference:

Freedman, Stephen B., et al. “Multidose ondansetron after emergency visits in children with gastroenteritis.” New England Journal of Medicine, vol. 393, no. 3, 17 July 2025, pp. 255–266.

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