Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of 5-HT3 Receptor Antagonists: 2026 Update

Creator(s)

• Claire Moore
• Melissa S. Bourque
• Andreas Halman
• José A G Agúndez
• Cynthia A. Prows
• Keiko Hikino
• Matthias Schwab
• Carolyn J. Oxencis
• Dharmisha Chauhan
• Meta H M Diekstra
• Susie E. Long
• Gillian C. Bell
• Andrea Gaedigk, Children's Mercy Kansas CityFollow
• Michelle Whirl-Carrillo
• Teri E. Klein
• Kelly E. Caudle
• Rachel Conyers

Document Type

Article

Publication Date

8-2026

Identifier

DOI: 10.1002/cpt.70291; PMCID: PMC13339002

Abstract

5-hydroxytryptamine type 3 (5-HT₃) receptor antagonists are used to treat nausea and vomiting and in the prevention of chemotherapy-induced, radiation-induced, and postoperative nausea and vomiting. Most of the 5-HT₃ receptor antagonists (i.e., ondansetron, tropisetron, dolasetron, palonosetron, and ramosetron) are metabolized by CYP2D6, but the extent of CYP2D6 involvement varies. CYP2D6 genetic variation can influence the metabolism of these medications, particularly ondansetron and tropisetron, thereby affecting drug efficacy. This guideline is an update to the 2016 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron and includes updated information on CYP2D6 genetic testing and evidence tables. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for 5-HT3 receptor antagonists based on CYP2D6 genotype, particularly where genetic variation is associated with reduced drug efficacy (updates at https://www.clinpgx.org/guideline/PA166251457).

Journal Title

Clinical pharmacology and therapeutics

Volume

120

Issue

2

First Page

387

Last Page

393

MeSH Keywords

Humans; Cytochrome P-450 CYP2D6; Serotonin 5-HT3 Receptor Antagonists; Genotype; Pharmacogenetics; Antiemetics; Nausea; Vomiting; Pharmacogenomic Testing

PubMed ID

41979467

Keywords

Cytochrome P-450 CYP2D6; Serotonin 5-HT3 Receptor Antagonists; Genotype; Pharmacogenetics; Antiemetics; Nausea; Vomiting; Pharmacogenomic Testing

Comments

Grants and funding

• U24 HG013077/HG/NHGRI NIH HHS/United States

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Publisher's Link: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.70291

Recommended Citation

Moore C, Bourque MS, Halman A, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of 5-HT3 Receptor Antagonists: 2026 Update. Clin Pharmacol Ther. 2026;120(2):387-393. doi:10.1002/cpt.70291