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Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT 15 Genotypes: 2018 Update

2018; Wiley; Volume: 105; Issue: 5 Linguagem: Inglês

10.1002/cpt.1304

ISSN

1532-6535

Autores

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

Tópico(s)

Adolescent and Pediatric Healthcare

Resumo

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 ).

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