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 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

16 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 languageEnglish (US)
Pages (from-to)1095-1105
Number of pages11
JournalClinical pharmacology and therapeutics
Volume105
Issue number5
DOIs
StatePublished - May 1 2019

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thiopurine methyltransferase
Pharmacogenetics
Genotype
Guidelines
Alleles
Thioguanine
6-Mercaptopurine
Azathioprine
Hispanic Americans
Nucleotides
Enzymes
Genes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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

In: Clinical pharmacology and therapeutics, Vol. 105, No. 5, 01.05.2019, p. 1095-1105.

Research output: Contribution to journalArticle

Relling, MV, Schwab, M, Whirl-Carrillo, M, Suarez-Kurtz, G, Pui, CH, Stein, CM, Moyer, A, 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
Relling, Mary V. ; Schwab, Matthias ; Whirl-Carrillo, Michelle ; Suarez-Kurtz, Guilherme ; Pui, Ching Hon ; Stein, Charles M. ; Moyer, Ann ; Evans, William E. ; Klein, Teri E. ; Antillon-Klussmann, Federico Guillermo ; Caudle, Kelly E. ; Kato, Motohiro ; Yeoh, Allen E.J. ; Schmiegelow, Kjeld ; Yang, Jun J. / Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes : 2018 Update. In: Clinical pharmacology and therapeutics. 2019 ; Vol. 105, No. 5. pp. 1095-1105.
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