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Area of Science:

  • Pharmacogenomics
  • Clinical Chemistry
  • Translational Medicine

Background:

  • Germline variants in the DPYD gene impact the safety of fluoropyrimidine drugs by affecting dihydropyrimidine dehydrogenase (DPD) enzyme activity.
  • DPD is crucial for the metabolism of fluoropyrimidines, and deficiency can lead to severe toxicities.
  • Global adoption of DPYD genetic testing varies, necessitating standardized implementation strategies.

Purpose of the Study:

  • To provide practical recommendations for implementing DPYD-guided fluoropyrimidine dosing.
  • To outline best practices for integrating DPYD genotyping into patient care workflows.
  • To address challenges and facilitate the safe use of fluoropyrimidines.

Main Methods:

  • Adapted the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework.
  • Reviewed clinical evidence, regulatory guidance, and stakeholder engagement strategies.
  • Detailed logistics, clinical decision support tools, and sustainable workflow development.

Main Results:

  • The EPIS framework provides a structured approach to DPYD testing implementation.
  • Key considerations include evidence, regulations, stakeholder buy-in, logistics, and decision support.
  • Patient counseling and educational resources are vital for successful integration.

Conclusions:

  • Integrating DPYD genetic testing into clinical practice is essential for safe fluoropyrimidine prescribing.
  • Standardized implementation strategies can mitigate severe fluoropyrimidine-induced toxicities.
  • This guide supports the development of scalable and sustainable DPYD genotype-integrated workflows.