194 - 5-HT3 Receptor Antagonists for Nausea/Vomiting: An In-Depth Drug Class Review

HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

Sean P. Kane, PharmD, BCPS

Health & Fitness, Medicine

4.9 • 650 Ratings

🗓️ 5 December 2025

⏱️ 35 minutes

🔗️ Recording | iTunes | RSS

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Summary

In this episode, we review the pharmacology, indications, adverse effects, and unique drug characteristics of 5-HT3 receptor antagonists such as ondansetron (Zofran) and palonosetron (Aloxi).

Key Concepts

There are four 5-HT3 (serotonin subtype 3) receptor antagonists on the market: ondansetron, granisetron, dolasetron, and palonosetron. These have primarily been studied for acute chemotherapy-induced nausea and vomiting (within 24 hours of chemotherapy administration) and for post-operative nausea and vomiting.
When used for chemotherapy-induced nausea/vomiting, 5-HT3 receptor antagonists are given prior to chemotherapy (usually 30-60 minutes before) on day #1. They are not given on subsequent days because they are not as effective for delayed nausea and vomiting.
Palonosetron has the longest half-life, longer binding affinity to the 5-HT3 receptor, and trends towards having the best efficacy among the 5-HT3 receptor antagonists.
5-HT3 receptor antagonists are associated with QTc prolongation and may cause headache, dizziness, constipation, or diarrhea. Their association with an increased risk of serotonin syndrome is controversial and not supported from a mechanistic perspective.

References

Simino GP, Marra LP, Andrade EI, et al. Efficacy, safety and effectiveness of ondansetron compared to other serotonin-3 receptor antagonists (5-HT3RAs) used to control chemotherapy-induced nausea and vomiting: systematic review and meta-analysis. Expert Rev Clin Pharmacol. 2016;9(9):1183-1194. doi:10.1080/17512433.2016.1190271
Tricco AC, Soobiah C, Blondal E, et al. Comparative efficacy of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis. BMC Med. 2015;13:136. Published 2015 Jun 18. doi:10.1186/s12916-015-0371-y
Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296
Herrstedt J, Clark-Snow R, Ruhlmann CH, et al. 2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting. ESMO Open. 2024;9(2):102195. doi:10.1016/j.esmoop.2023.102195
Rojas-Fernandez CH. Can 5-HT3 Antagonists Really Contribute to Serotonin Toxicity? A Call for Clarity and Pharmacological Law and Order. Drugs Real World Outcomes. 2014;1(1):3-5. doi:10.1007/s40801-014-0004-3
Li WS, van der Velden JM, Ganesh V, et al. Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials. Ann Palliat Med. 2017;6(2):104-117. doi:10.21037/apm.2016.12.01

Transcript

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0:00.0	Welcome to Helix Talk, an educational podcast for healthcare students and providers covering real-life clinical pearls, professional pharmacy topics, and drug therapy discussions.
0:11.0	This podcast is provided by pharmacists and faculty members at Rosal Franklin University College of Pharmacy.
0:17.0	This podcast contains general information for educational purposes only. This is not professional
0:22.4	advice and should not be used in lieu of obtaining advice from a qualified health care provider.
0:27.2	And now on to the show. Welcome to Helix Talk, episode 194. I'm your co-host, Dr. Kane.
0:35.6	And I'm Dr. Patel. And the title of today's episode is 5HT3 receptor antagonists for nausea and vomiting, an in-depth
0:43.3	drug class review.
0:44.3	So similar to some of the drug class review episodes we have in past, Dr. Kane, we're
0:49.3	going to talk about the pharmacology, the indication, the adverse effects, some of the unique characteristics
0:55.0	of agents and how they kind of separate from one another.
0:59.0	I would say that most people have probably heard of on dancetron or zofran.
1:03.0	This is the first 5H2-3 receptor antagonist that made it to the U.S. market.
1:07.0	And that was way back in 1991.
1:09.0	So kind of an older drug class, if you think about it.
1:10.9	Yeah. And I believe we have a few more agents. So they kind of all end in the last letters of
1:17.1	cetron. So we have granocetron, chytrol, we have dolocetron, the anzumet. We have polonocetron,
1:24.4	a loxie. And that was like the latest one in the market.
1:32.4	And that was 2003, so still it's been two decades since the last one, but we're still getting new data on these 5HT3 receptor antagonists, and we'll kind of go through kind of their role
1:37.8	in therapy throughout today's episode.
1:40.6	Before we get there, we have to kind of talk about understanding how the drug works, the drug targets,
1:45.6	and the pathophysiology of nausea and vomiting.
1:49.1	Yeah, and so Dr. King and I teach this topic in the GI series of therapy, and there are quite a few other agents,
	...

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