Gastroenteritis
Aiya Almogaber, PharmD
New research suggests that giving children with gastroenteritis a short supply of ondansetron after an emergency department (ED) visit can reduce the risk of moderate to severe illness in the days that follow. In a randomized, double-blind trial involving over 1,000 children, those who received ondansetron for use at home were half as likely to experience severe gastroenteritis compared with those given placebo.
Published in the July 17, 2025, issue of NEJM, the study challenges previous concerns about post-discharge ondansetron use and provides evidence that limited, as-needed dosing can improve outcomes without added safety risks. The authors propose that a targeted take-home dosing approach may help bridge the gap between evidence and overall prescribing practice.
“We have been seeing a gradual shift toward the adoption of such an approach,” said Stephen Freedman, MDCM, MSc, from Alberta Children’s Hospital Foundation and lead study author. “Many children with minimal vomiting were receiving multiple doses of ondansetron to take home, despite limited supporting data.”
Freedman noted that this was the first trial to address the issue of multiple doses of ondansetron to be taken at home following ED discharge.
“Prior studies primarily examined its use in the emergency department setting, with limited and inconsistent follow up on post-discharge outcomes,” he said.
Ondansetron’s role after care
Ondansetron is frequently used to treat vomiting when patients, including children, are admitted to the ED with gastroenteritis. Despite conflicting data from earlier trials and observational studies, prescribing rates have remained high. However, its benefit beyond the ED setting has remained unclear.
To clarify the value of ondansetron after discharge, researchers conducted the placebo-controlled trial across six Canadian pediatric EDs. Children aged 6 months to younger than 18 years old with acute gastroenteritis and recent vomiting were randomized to receive up to six doses of oral ondansetron or placebo to use over 48 hours if symptoms persisted. Follow up occurred over 7 days, with the primary endpoint being moderate to severe gastroenteritis, measured by a score of greater than or equal to 9 on a modified Vesikari scale.
Of the 893 participants who completed follow up, moderate to severe gastroenteritis occurred in 5.1% of children who received ondansetron compared with 12.5% in the placebo group—representing an absolute risk reduction of 7.4 percentage points. Though the presence and duration of vomiting were not significantly different, children who received ondansetron had fewer vomiting episodes in the 48 hours following enrollment.
Freedman acknowledged he had reservations about whether a benefit would be observed.
“I believed that most children do not experience a recurrence of vomiting after discharge,” he said.
That suspicion was confirmed. According to Freedman, 70% had no further vomiting and didn’t take any doses. “Still, the benefit among the 30% who did was so significant that it led to a measurable improvement across the entire cohort,” he said.
Rates of return visits, I.V. fluid use, and adverse events were similar between groups. Only 7% of children in either group experienced adverse events, with no significant differences in severity. Among those who took three or more doses, a higher rate of diarrhea was observed in the ondansetron group, but this did not offset the overall benefit in severity scores.
Recommending a new approach
Although 71% of children in the United States receive prescriptions for multiple doses of ondansetron at discharge, the majority never require additional treatment. In this study, only 31.4% of participants vomited after discharge, and the median number of doses was zero.
“The provision of two doses of ondansetron for administration at home is likely sufficient to address ongoing symptoms in nearly all children,” said Freedman. “Our next step is to identify which children are most likely to benefit so we can further refine our recommendations.”
The clinical implications are significant. According to the study, the odds of having a post-enrollment score of 9 or greater on the modified Vesikari scale during the 7 days following discharge were 50% lower in the ondansetron group. This translates to a number needed to treat of 15, meaning ondansetron would need to be given to 15 children to prevent one case of moderate to severe gastroenteritis.
The study findings did not demonstrate any evidence of adverse events, either. ■