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.

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.

• See full prescribing information for the recommended dosage in adults and pediatrics.
• Patients with severe hepatic impairment: do not exceed a total daily dose of 8 mg.

The most common adverse reactions in adults for the:
• prevention of chemotherapy-induced (greater than or equal to 5%) are: headache, malaise/fatigue, constipation, diarrhea.
• prevention of radiation-induced nausea and vomiting (greater than or equal to 2%) are: headache, constipation, and diarrhea.
• prevention of postoperative nausea and vomiting (greater than or equal to 9%) are: headache and hypoxia.

• Patients known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any components of the formulation.
• Concomitant use of apomorphine.

• Hypersensitivity reactions including anaphylaxis and bronchospasm: Discontinue ZOFRAN if suspected. Monitor and treat promptly per standard of care until signs and symptoms resolve.
• QT interval prolongation and Torsade de Pointes: Avoid in patients with congenital long QT syndrome; monitor with electrocardiograms (ECGs) if concomitant electrolyte abnormalities, cardiac failure or arrhythmias, or use of other QT prolonging drugs.
• Serotonin syndrome: Reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs. If such symptoms occur, discontinue ZOFRAN and initiate supportive treatment. If concomitant use of ZOFRAN with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome. See package insert for complete information.