Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by chemotherapy, radiation therapy, migraines, or surgery.

[17] A large multi-center cohort study found no association between ondansetron exposure and fetal risk compared to other antiemetics.

[19] Trials in emergency department settings support the use of ondansetron to abort vomiting episodes associated with gastroenteritis and dehydration.

[22] In a study of patients diagnosed as having IBS with diarrhea (IBS-D), ondansetron showed statistically significant effects on stool consistency, frequency, urgency and bloating, but not on pain scores.

[6] Three open non-comparative studies have been conducted to assess the safety and efficacy of ondansetron in children receiving a variety of chemotherapy regimens.

[8] Use of ondansetron has been associated with prolongation of the QT interval, which can lead to a potentially fatal heart rhythm known as torsades de pointes.

Although this may happen in any person with any formulation, the risk is most salient with the injectable (intravenous) form of the drug and increases with dose.

People are cautioned to seek immediate medical care if symptoms such as irregular heartbeat/palpitations, shortness of breath, dizziness, or fainting occur while taking ondansetron.

The 5-HT3 receptors are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema in the medulla.

Serotonin is released by the enterochromaffin cells of the small intestine in response to chemotherapeutic agents and may stimulate vagal afferents (via 5-HT3 receptors) to initiate the vomiting reflex.

[31] However, the R–ondansetron enantiomer was 7.9 times more potent as an antagonist of serotonin and 2-methyl-5-hydroxytryptamine (2-methylserotonin) when tested on the longitudinal smooth muscle from guinea pig ileum.

[35] A study of 141 human patients given 4 or 8 mg of intravenous ondansetron for the prevention of post-operative nausea and vomiting also found that R and S–ondansetron have different pharmacokinetic properties.

CYP2D6 was found to be more important for the elimination of S–ondansetron, whereas CYP3A5 genotype had no impact on S–ondansetron plasma levels, measured 3 hours after drug administration.

[40] By this final year of its patent (2006), Zofran had become the 20th highest-selling brand-name drug in the United States, with sales of US$1.3 billion in the first 9 months of 2006 (80% from the US).

[42] In December 2012, the FDA announced that the 32 mg, single intravenous (IV) dose of ondansetron was being withdrawn from U.S. market because of the potential for serious cardiac issues from prolonged QT interval.

The number needed to treat (NNT) to prevent vomiting within 24 hours was 9.5, with 95% confidence interval 6.9 to 15, in the 16 nonduplicated reports.