- 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.
- 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.