Management of vomiting in children and young people with gastroenteritis: ondansetron

The updated Cochrane review (Carter and Fedorowicz 2012) included 10 randomised controlled trials (RCTs; n=1479) in children and young people aged 3 months to 13 years. Four of the included RCTs investigated oral ondansetron, 4 RCTs investigated intravenous ondansetron, 1 RCT investigated a dimenhydrinate suppository and 1 investigated oral granisetron.

Dosing regimens varied between the 8 RCTs which investigated ondansetron but most used a weight‑dependent dosage. In most studies a single oral or intravenous dose of ondansetron was given. Oral ondansetron (2 mg to 8 mg depending on weight or age) was given as an orodispersible tablet or a solution, and intravenous ondansetron was mainly given at a dose of 0.15 mg/kg (0.3 mg/kg in 1 study).

Pooled data from 4 RCTs (n=574) found oral ondansetron was more effective than placebo at stopping vomiting based on the proportion of children and young people who stopped vomiting (relative risk [RR] 1.44, 95% confidence interval [CI] 1.29 to 1.61, p<0.00001, number needed to treat [NNT] 4 [95% CI 4 to 6]).

Pooled data from 3 RCTs (n=465) found the proportion of children and young people needing intravenous fluid therapy was lower with oral ondansetron compared with placebo during the emergency department stay (RR 0.41, 95% CI 0.29 to 0.59, p<0.00001, NNT 5 [95% CI 4 to 8]) and up to 72 hours after discharge.

Pooled data from 3 RCTs (n=465) found oral ondansetron reduced the immediate hospital admission rate during the emergency department stay (RR 0.40, 95% CI 0.19 to 0.83, p=0.01) but not hospitalisation up to 72 hours after discharge, compared with placebo.

Pooled data from 3 RCTs (n=186) found intravenous ondansetron was more effective than placebo at stopping vomiting based on the proportion of children and young people who stopped vomiting (RR 2.01, 95% CI 1.49 to 2.71, p<0.00001, NNT 3 [95% CI 3 to 5]).

In 3 of the 4 RCTs that compared oral ondansetron with placebo there was an increase in the number of episodes of diarrhoea (p<0.05). In 1 of the 3 RCTs that compared intravenous ondansetron with placebo, more episodes of diarrhoea were reported in the ondansetron group in the first 24 hours compared with placebo (p=0.013).

The updated Cochrane review (Carter and Fedorowicz 2012) was well‑conducted, but it is limited by the quality of the trials it included. The authors suggest that study design in the included studies was adequate overall but there was an unclear or high risk of bias in some of the domains, which reflects the challenges faced in screening and following up children and young people presenting to emergency departments.

The 8 RCTs included in the updated Cochrane review that investigated ondansetron were conducted mostly in the emergency departments of children's hospitals in the USA, Canada, Turkey, Venezuela, Qatar and Thailand. The findings of these may not be generalisable to UK practice.

The retrospective cohort study of ondansetron use in emergency departments of children's hospitals in the USA (Freedman et al. 2014) found oral ondansetron use increased from a median institutional rate of 0.11% of patient visits in 2002 to 42.2% in 2011. However, this increased use of oral ondansetron was not associated with reductions in the rates of intravenous rehydration (18.7% of children or young people during the low ondansetron use period and 17.8% during the high ondansetron use period) or hospitalisation (6.0% during the low ondansetron use period and 6.7% during the high ondansetron use period).

This study is limited by its observational nature, and also reflects US not UK practice. However, it provides useful data to determine the clinical effectiveness of ondansetron in 'real‑world' conditions.

Ondansetron prolongs the QT interval in a dose‑dependent manner and cases of Torsade de Pointes have been reported in people using ondansetron. Ondansetron should be avoided in people with congenital long QT syndrome and should be used with caution in people who have or may develop prolongation of QTc, such as people with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or people taking other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration (see ondansetron summaries of product characteristics for details). Dose‑dependent QT interval prolongation with ondansetron is discussed in more detail in the July 2013 Drug Safety Update from the MHRA.

Ondansetron tablets are £1.71 for 10×4 mg tablets and £44.05 for 10×8 mg tablets (excluding VAT; Drug Tariff, September 2014).

Ondansetron orodispersible tablets are £35.97 to £37.76 for 10×4 mg tablets and £71.94 to £75.53 for 10×8 mg tablets (excluding VAT; costs taken from the Drug Tariff, September 2014).

Ondansetron 4 mg/5 ml oral solution is £36.82 for 50 ml (excluding VAT; costs taken from the Drug Tariff, September 2014).

Ondansetron (Zofran) 2 mg/ml injection is £29.97 for 5×2 ml (4 mg) ampoules and £59.95 for 5×4 ml (8 mg) ampoules (excluding VAT; costs taken from MIMS September 2014).