Palonosetron — Drug Monograph

Brand names: Aloxi

Drug class: Supportive Care Agent

Mechanism of Action

Second-generation 5-HT3 receptor antagonist with a ~100-fold higher binding affinity for the 5-HT3 receptor compared to first-generation agents (ondansetron, granisetron). Uniquely causes allosteric binding and receptor internalization (not just competitive blockade), contributing to its prolonged effect. Half-life ~40 hours (vs. 3–9 hours for first-generation agents). Effectively prevents both acute and delayed CINV with a single dose.

FDA Indications

• Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy
• Prevention of acute nausea and vomiting associated with highly emetogenic chemotherapy
• Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours

Common Side Effects

• Headache
• Constipation
• Diarrhea
• Dizziness
• Fatigue

Clinical Pearl

Palonosetron is preferred over first-generation 5-HT3 antagonists in ASCO/NCCN guidelines for moderately emetogenic chemotherapy as a single agent (without NK1 antagonist) and is the preferred 5-HT3 backbone when NK1 antagonists are used. Its prolonged half-life (~40 hours) provides coverage for the delayed phase of CINV (24–120 hours post-chemo), which first-generation agents lack. It is available in combination with netupitant as Akynzeo (oral) and fosnetupitant as Akynzeo IV — the only…

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