CPIC 2013

The fluoropyrimidines are the mainstay chemotherapeutic agents for the treatment of many types of cancers. Detoxifying metabolism of fluoropyrimidines requires dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene), and reduced or absent activity of this enzyme can result in severe, and sometimes fatal, toxicity. We summarize evidence from the published literature supporting this association and provide dosing recommendations for fluoropyrimidines based on DPYD genotype (updates at http://www.pharmgkb.org). The purpose of this guideline is to provide information to allow the interpretation of clinical dihydropyrimidine dehydrogenase (DPYD) genotype tests so that the results can be used to guide dosing of fluoropyrimidines (5-fluorouracil, capecitabine, and tegafur). Detailed guidelines for use of fluoropyrimidines, their clinical pharmacology (see ref. 1 for review), and analyses of the cost-effectiveness are beyond the scope of this article. The Clinical Pharmacogenetics Implementation Consortium guidelines consider the situation of patients for whom genotype data are already available.