Pharmacology · 5-HT3 receptor antagonists (setrons)
Palonosetron !
A long-acting 5-HT3 antagonist given by IV before chemotherapy. Its half-life of about 40 hours also covers the delayed phase after moderate chemotherapy.
Updated 2026-11-01
Cryo-EM structure of the mouse 5-HT3A receptor with palonosetron in the serotonin pocket; the human receptor's pocket is closely similar.
Mechanism of action
Palonosetron is a 5-HT3 antagonist with very strong affinity for the receptor and little or no affinity for other receptors. It blocks serotonin's action on vagal afferents in the gut and in the brainstem vomiting centres. Its high affinity and long half-life let a single dose protect against both acute and delayed vomiting after moderately emetogenic chemotherapy.
- Palonosetron binds the 5-HT3 receptor with very high affinity
- Serotonin cannot open the channel on vagal and brainstem neurons
- Its long half-life keeps the block for days
- A single dose covers acute and delayed vomiting after moderate chemotherapy
Pharmacokinetics
- Distribution
- Large volume of distribution; about 62% bound to plasma proteins.
- Metabolism
- Mainly CYP2D6, and to a lesser extent CYP3A4 and CYP1A2; it does not inhibit or induce CYP enzymes.
- Elimination
- By both the kidney and metabolism.
- Half-life
- Mean terminal half-life about 40 hours.
Indications
- Prevention of acute and delayed nausea and vomiting from moderately emetogenic chemotherapy, and of acute nausea and vomiting from highly emetogenic chemotherapy.
- Prevention of post-operative nausea and vomiting for up to 24 hours after surgery.
Adverse effects
Common
- Headache
- Constipation
- Bradycardia and QT prolongation after surgery
Contraindications
- Hypersensitivity to palonosetron
Key interactions
- SSRIs, SNRIs, MAO inhibitors, mirtazapine, fentanyl, lithium, tramadol, IV methylene blue
- Serotonin syndrome; palonosetron is stopped if it appears.
- QT-prolonging drugs
- Possible additive effect on the QT interval.
What is monitored
- Signs of serotonin syndrome when given with serotonergic drugs
- Heart rate and ECG after surgery in at-risk patients
- Bowel function
Administration and safety
- Single IV dose before chemotherapy or before induction of anaesthesia
- Routine post-operative prevention is not used in patients with little expected risk
- The infusion line is flushed with normal saline before and after the dose
Nursing care
- Time the dose before chemotherapy starts
- Explain that one dose protects for several days, so repeat doses are not given on the following days unless prescribed
- Ask about constipation and headache
- Watch for agitation, tremor, sweating or fever with serotonergic drugs
Pregnancy and breastfeeding
There are no data in pregnant women; animal studies showed no effect on embryo-fetal development.
Test yourself
Think of the answer, then tap the question to see it.
What sets palonosetron apart from ondansetron and granisetron?
Very high receptor affinity and a much longer half-life (about 40 hours), so one dose also covers delayed vomiting after moderately emetogenic chemotherapy.
Through which CYP enzyme is palonosetron mainly metabolised?
CYP2D6, with smaller roles for CYP3A4 and CYP1A2.
Which serious drug interaction is shared by all 5-HT3 antagonists?
Serotonin syndrome with serotonergic drugs such as SSRIs, SNRIs, fentanyl or tramadol.
Related drugs
← Back to the class: 5-HT3 receptor antagonists (setrons)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - PALONOSETRON HYDROCHLORIDE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Palonosetron Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 6Y1Z: Mouse serotonin 5HT3 receptor in complex with palonosetron (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.