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^*

^*Corresponding author for this work

Department of Clinical Medicine

130 Citations (Scopus)

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
Journal	Clinical Pharmacology and Therapeutics
Volume	105
Issue number	5
Pages (from-to)	1095-1105
Number of pages	11
ISSN	0009-9236
DOIs	https://doi.org/10.1002/cpt.1304
Publication status	Published - 2019

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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

Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes : 2018 Update. / Relling, Mary V.; Schwab, Matthias; Whirl-Carrillo, Michelle et al.

In: Clinical Pharmacology and Therapeutics, Vol. 105, No. 5, 2019, p. 1095-1105.

Research output: Contribution to journal › Journal article › Research › peer-review

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.}",

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AU - Relling, Mary V.

AU - Schwab, Matthias

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AU - Suarez-Kurtz, Guilherme

AU - Pui, Ching Hon

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.

AU - Kato, Motohiro

AU - Yeoh, Allen E.J.

AU - Schmiegelow, Kjeld

AU - Yang, Jun J.

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AB - 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).

U2 - 10.1002/cpt.1304

DO - 10.1002/cpt.1304

M3 - Journal article

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JF - Clinical Pharmacology and Therapeutics

IS - 5

ER -

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

Abstract

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