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

Research output: Contribution to journalArticle

60 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 languageEnglish (US)
Pages (from-to)1095-1105
Number of pages11
JournalClinical pharmacology and therapeutics
Volume105
Issue number5
DOIs
StatePublished - 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