Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

Mary V. Relling; Matthias Schwab; Michelle Whirl-Carrillo; Guilherme Suarez-Kurtz; Ching Hon Pui; Charles M. Stein; Ann M. Moyer; William E. Evans; Teri E. Klein; Federico Guillermo Antillon-Klussmann; Kelly E. Caudle; Motohiro Kato; Allen E.J. Yeoh; Kjeld Schmiegelow; Jun J. Yang

doi:10.1002/cpt.1304

Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

Mary V. Relling, Matthias Schwab, Michelle Whirl-Carrillo, Guilherme Suarez-Kurtz, Ching Hon Pui, Charles M. Stein, Ann M. Moyer, William E. Evans, Teri E. Klein, Federico Guillermo Antillon-Klussmann, Kelly E. Caudle, Motohiro Kato, Allen E.J. Yeoh, Kjeld Schmiegelow, Jun J. Yang

Medical Genetics

Research output: Contribution to journal › Article › peer-review

132 Scopus citations

Abstract

Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).

Original language	English (US)
Pages (from-to)	1095-1105
Number of pages	11
Journal	Clinical pharmacology and therapeutics
Volume	105
Issue number	5
DOIs	https://doi.org/10.1002/cpt.1304
State	Published - May 2019

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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Relling, M. V., Schwab, M., Whirl-Carrillo, M., Suarez-Kurtz, G., Pui, C. H., Stein, C. M., Moyer, A. M., Evans, W. E., Klein, T. E., Antillon-Klussmann, F. G., Caudle, K. E., Kato, M., Yeoh, A. E. J., Schmiegelow, K., & Yang, J. J. (2019). Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clinical pharmacology and therapeutics, 105(5), 1095-1105. https://doi.org/10.1002/cpt.1304

Relling, MV, Schwab, M, Whirl-Carrillo, M, Suarez-Kurtz, G, Pui, CH, Stein, CM, Moyer, AM, Evans, WE, Klein, TE, Antillon-Klussmann, FG, Caudle, KE, Kato, M, Yeoh, AEJ, Schmiegelow, K & Yang, JJ 2019, 'Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update', Clinical pharmacology and therapeutics, vol. 105, no. 5, pp. 1095-1105. https://doi.org/10.1002/cpt.1304

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title = "Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update",

abstract = "Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).",

author = "Relling, {Mary V.} and Matthias Schwab and Michelle Whirl-Carrillo and Guilherme Suarez-Kurtz and Pui, {Ching Hon} and Stein, {Charles M.} and Moyer, {Ann M.} and Evans, {William E.} and Klein, {Teri E.} 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 = "Publisher Copyright: {\textcopyright} 2018 The Authors Clinical Pharmacology & Therapeutics {\textcopyright} 2018 American Society for Clinical Pharmacology and Therapeutics",

year = "2019",

month = may,

doi = "10.1002/cpt.1304",

language = "English (US)",

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AU - Suarez-Kurtz, Guilherme

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AU - Stein, Charles M.

AU - Moyer, Ann M.

AU - Evans, William E.

AU - Klein, Teri E.

AU - Antillon-Klussmann, Federico Guillermo

AU - Caudle, Kelly E.

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AU - Yeoh, Allen E.J.

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Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

Abstract

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