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Rigshospitalet - a part of Copenhagen University Hospital
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Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

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  • 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
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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
JournalClinical Pharmacology and Therapeutics
Volume105
Issue number5
Pages (from-to)1095-1105
Number of pages11
ISSN0009-9236
DOIs
Publication statusPublished - 2019

ID: 59083943