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

Maud Maillard; Matthias Schwab; Michelle Whirl-Carrillo; Ann M Moyer; Guilherme Suarez-Kurtz; Ching-Hon Pui; C Michael Stein; Teri E Klein; Claire Spahn; Sooyeon Kwon; Juanda Leo Hartono; Nanne K de Boer; Tariq Ahmad; Federico Guillermo Antillon-Klussmann; Kelly E Caudle; Motohiro Kato; Allen E J Yeoh; Kjeld Schmiegelow; Jun J Yang

doi:10.1002/cpt.70209

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

Maud Maillard, Matthias Schwab, Michelle Whirl-Carrillo, Ann M Moyer, Guilherme Suarez-Kurtz, Ching-Hon Pui, C Michael Stein, Teri E Klein, Claire Spahn, Sooyeon Kwon, Juanda Leo Hartono, Nanne K de Boer, Tariq Ahmad, Federico Guillermo Antillon-Klussmann, Kelly E Caudle, Motohiro Kato, Allen E J Yeoh, Kjeld Schmiegelow, Jun J Yang

Afdeling for Børn og Unge JMC

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).

Originalsprog	Engelsk
Tidsskrift	Clinical Pharmacology and Therapeutics
ISSN	0009-9236
DOI	https://doi.org/10.1002/cpt.70209
Status	E-pub ahead of print - 31 jan. 2026

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10.1002/cpt.70209Licens: CC BY-NC-ND

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Maillard, M., Schwab, M., Whirl-Carrillo, M., Moyer, A. M., Suarez-Kurtz, G., Pui, C.-H., Stein, C. M., Klein, T. E., Spahn, C., Kwon, S., Hartono, J. L., de Boer, N. K., Ahmad, T., Antillon-Klussmann, F. G., Caudle, K. E., Kato, M., Yeoh, A. E. J., Schmiegelow, K., & Yang, J. J. (2026). Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update. Clinical Pharmacology and Therapeutics. Advance online publication. https://doi.org/10.1002/cpt.70209

Maillard, M, Schwab, M, Whirl-Carrillo, M, Moyer, AM, Suarez-Kurtz, G, Pui, C-H, Stein, CM, Klein, TE, Spahn, C, Kwon, S, Hartono, JL, de Boer, NK, Ahmad, T, Antillon-Klussmann, FG, Caudle, KE, Kato, M, Yeoh, AEJ, Schmiegelow, K & Yang, JJ 2026, 'Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update', Clinical Pharmacology and Therapeutics. https://doi.org/10.1002/cpt.70209

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

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).",

author = "Maud Maillard and Matthias Schwab and Michelle Whirl-Carrillo and Moyer, \{Ann M\} and Guilherme Suarez-Kurtz and Ching-Hon Pui and Stein, \{C Michael\} and Klein, \{Teri E\} and Claire Spahn and Sooyeon Kwon and Hartono, \{Juanda Leo\} and \{de Boer\}, \{Nanne K\} and Tariq Ahmad and Antillon-Klussmann, \{Federico Guillermo\} and Caudle, \{Kelly E\} and Motohiro Kato and Yeoh, \{Allen E J\} and Kjeld Schmiegelow and Yang, \{Jun J\}",

note = "{\textcopyright} 2026 The Author(s). Clinical Pharmacology \& Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.",

year = "2026",

month = jan,

day = "31",

doi = "10.1002/cpt.70209",

language = "English",

journal = "Clinical Pharmacology and Therapeutics",

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T1 - Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes

T2 - 2025 Update

AU - Maillard, Maud

AU - Schwab, Matthias

AU - Whirl-Carrillo, Michelle

AU - Moyer, Ann M

AU - Suarez-Kurtz, Guilherme

AU - Pui, Ching-Hon

AU - Stein, C Michael

AU - Klein, Teri E

AU - Spahn, Claire

AU - Kwon, Sooyeon

AU - Hartono, Juanda Leo

AU - de Boer, Nanne K

AU - Ahmad, Tariq

AU - Antillon-Klussmann, Federico Guillermo

AU - Caudle, Kelly E

AU - Kato, Motohiro

AU - Yeoh, Allen E J

AU - Schmiegelow, Kjeld

AU - Yang, Jun J

PY - 2026/1/31

Y1 - 2026/1/31

N2 - 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).

AB - 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).

UR - https://www.scopus.com/pages/publications/105029175473

U2 - 10.1002/cpt.70209

DO - 10.1002/cpt.70209

M3 - Journal article

C2 - 41618934

SN - 0009-9236

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

ER -

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

Abstract

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