EMA recommends DPD testing before treatment with IV fluorouracil

  • European Medicines Agency
  • 13 Mar 2020

  • curated by Pavankumar Kamat
  • Univadis Clinical Summaries
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • The European Medicines Agency (EMA) has recommended that patients with cancer should be tested for lack of dihydropyrimidine dehydrogenase (DPD) before initiating treatment with intravenous (IV) fluorouracil.
  • The recommendation also applies to capecitabine and tegafur, which are prodrugs of fluorouracil.

Why this matters

  • Complete DPD deficiency increases the risk for severe and life-threatening side effects of fluorouracil.

Key points

  • EMA's Pharmacovigilance Risk Assessment Committee (PRAC) notes that the percentage of DPD deficiency is low in the white population (8% with low levels and 0.5% with complete absence).
  • Although IV fluorouracil, capecitabine, and tegafur are completely contraindicated in patients with a known complete DPD deficiency, a lower starting dose may be used in those with a partial deficiency.
  • PRAC recommends that testing can be performed by measuring blood levels of uracil, a metabolite of DPD, or by identification of specific DPD gene mutations associated with severe side effects.
  • Regular monitoring of fluorouracil blood levels is warranted for patients receiving continuous infusions of the drug.
  • Testing has been excluded for the antifungal flucytosine which is also converted to fluorouracil following administration, so as to avoid treatment delays.
  • Testing is also not required for patients treated with topical fluorouracil.