Dihydropyrimidine Dehydrogenase Deficiency and Implementation of Upfront DPYD Genotyping

Clin Pharmacol Ther. 2022 Oct;112(4):791-802. doi: 10.1002/cpt.2667. Epub 2022 Jun 12.


Fluoropyrimidines (FP; 5-fluorouracil, capecitabine, and tegafur) are a commonly prescribed class of antimetabolite chemotherapies, used for various solid organ malignancies in over 2 million patients globally per annum. Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the critical enzyme implicated in FP metabolism. DPYD variant genotypes can result in decreased DPD production, leading to the development of severe toxicities resulting in hospitalization, intensive care admission, and even death. Management of toxicity incurs financial burden on both patients and healthcare systems alike. Upfront DPYD genotyping to identify variant carriers allows an opportunity to identify patients who are at high risk to suffer from serious toxicities and allow prospective dose adjustment of FP treatment. This approach has been shown to reduce patient morbidity, as well as improve the cost-effectiveness of managing FP treatment. Upfront DPYD genotyping has been recently endorsed by several countries in Europe and the United Kingdom. This review summarizes current knowledge about DPD deficiency and upfront DPYD genotyping, including clinical and cost-effectiveness outcomes, with the intent of supporting implementation of an upfront DPYD genotyping service with individualized dose-personalization.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects
  • Dihydropyrimidine Dehydrogenase Deficiency* / drug therapy
  • Dihydropyrimidine Dehydrogenase Deficiency* / genetics
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Dihydrouracil Dehydrogenase (NADP) / metabolism
  • Fluorouracil
  • Genotype
  • Humans
  • Prospective Studies


  • Antimetabolites, Antineoplastic
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil