The Medicines and Healthcare products Regulatory Agency (MHRA) has introduced a new contraindication for the antifungal flucytosine (Ancotil) in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, following a European review of fluorouracil and related medicines.
Flucytosine, a prodrug of 5-fluorouracil used for the treatment of systemic mycoses, may result in life-threatening and severe toxicity in patients with complete and partial DPD deficiency. DPD deficiency is reported to occur more frequently in the Caucasian population. Complete deficiency is rare (0.01-0.5% of Caucasian people), and partial deficiency is estimated to affect 3-9 per cent of Caucasian people.
MHRA recommends that flucytosine should not be used in patients with known complete DPD deficiency. Patients with partial DPD deficiency also have an increased risk of severe drug toxicity, but the level of toxicity correlates with the extent of DPD deficiency.
Pre-treatment testing for DPD deficiency is not warranted to avoid any delay in initiating antimycotic therapy; however, if confirmed or suspected drug toxicity is observed in 5-fluorouracil users, they should be promptly assessed for DPD activity. In case of suspected drug toxicity, clinicians should consider cessation of flucytosine treatment.
This article originally appeared on Univadis, part of the Medscape Professional Network.
