Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update

Clinical Pharmacology & Therapeutics 2026 Open access

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Authors: M. Maillard, Matthias Schwab, Michelle Whirl-Carrillo, AM Moyer, Guilherme Suarez‐Kurtz, CH Pui, C Michael Stein, Teri E. Klein, Claire Spahn, Sooyeon Kwon, Juanda Leo Hartono, Nanne K de Boer
+7 more Tariq Ahmad, Federico Guillermo Antillon-Klussmann, Kelly E. Caudle, Motohiro Kato, Allen E J Yeoh, K. Schmiegelow, Jun J Yang
DOI: 10.1002/cpt.70209
Cited by: 20
References: 53

Abstract

Thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) are key enzymes that catabolize thiopurines. Decreased or no-function alleles in TPMT and NUDT15 are associated with reduced or no enzyme activity and predictive of pronounced adverse effects, including severe myelosuppression, that may occur among individuals treated with standard doses of thiopurines. Genetic variants in these genes are present in all world populations; however, their frequency varies by ancestry. In this updated guideline, we provide recommendations for adjusting starting doses of mercaptopurine, thioguanine, and azathioprine based on TPMT and NUDT15 genotypes, including for individuals with variants in both genes (updates on www.clinpgx.org).

Fields of Study & Subjects

Acute Lymphoblastic Leukemia research Folate and B Vitamins Research Pregnancy and Medication Impact

Publication details

Journal / source
Clinical Pharmacology & Therapeutics
Publisher
Wiley
Volume
119
Issue
4
Pages
916–927
Publication date
31 January 2026
Language
EN