Mechanism of Action

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex.

Indication

ZOFRAN is a 5-HT3 receptor antagonist indicated for the prevention of:

• Nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2
• Nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy
• Nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen
• Postoperative nausea and/or vomiting