Other safety alerts
|
| |
| The United Kingdom: Flucytosine (Ancotil): new contraindication in patients with DPD deficiency |
| |
Medicines and Healthcare products Regulatory Agency (MHRA) announces that a new contraindication for patients with complete dihydropyrimidine dehydrogenase (DPD) deficiency has been introduced, although pre-testing of DPD status before flucytosine treatment is not required.
Flucytosine is an antifungal drug authorised to treat systemic yeast and fungal infections. It is typically used in combination with amphotericin to treat cryptococcal meningitis, severe systemic candidiasis, and other long-standing fungal infections. Flucytosine is a 5-fluorouracil prodrug, and systemic exposure of 5-fluorouracil has been observed in patients treated with flucytosine.
Following a European review of fluorouracil and related medicines, treatment with flucytosine is now contraindicated in patients with known complete DPD deficiency. A letter has been sent to healthcare professionals to inform of this new contraindication. In order to avoid a delay in starting antimycotic therapy, testing for DPD deficiency is not required before treatment with flucytosine. However, determination of DPD activity should be considered when there is a confirmed or suspected drug toxicity. In case of suspected drug toxicity, consideration should be given to stopping treatment with flucytosine.
DPD activity is rate limiting in the catabolism of 5-fluorouracil. Patients with DPD deficiency who are treated with systemic 5-fluorouracil or its prodrugs are therefore at increased risk of toxicity, including, for example, stomatitis, diarrhoea, mucosal inflammation, neutropenia, and neurotoxicity.
Patients with known complete DPD deficiency are at higher risk of developing life-threatening toxicity and must not be treated with flucytosine. In patients with partial DPD deficiency, the risk of severe drug toxicity is increased, with the level of toxicity correlating with the extent of DPD deficiency.
The majority of data on the frequency of DPD deficiency are in Caucasian people. The European review considered that complete DPD deficiency is rare (0.01–0.5% of Caucasian people). Partial DPD deficiency is estimated to affect 3–9% of Caucasian people.
Advice for healthcare professionals:
- Flucytosine should not be used in patients with known complete DPD deficiency due to the risk of life-threatening toxicity.
- Patients with a partial DPD deficiency are also at increased risk of severe toxicity.
- Do not delay antimycotic therapy with flucytosine for pre-treatment testing of DPD deficiency; however, consider determination of DPD activity if drug toxicity is confirmed or suspected.
- In cases of drug toxicity, consider stopping treatment with flucytosine.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/flucytosine-ancotil-new-contraindication-in-patients-with-dpd-deficiency
In Hong Kong, there is no registered pharmaceutical product containing flucytosine. Related news was previously issued by European Medicines Agency, and was posted on the Drug Office website since 18 Mar 2019, with the latest update posted on 2 May 2020. Letters to inform local healthcare professionals of the risk of severe side effects associated with the use of fluorouracil and related medicines (including flucytosine) in patients with dihydropyrimidine dehydrogenase deficiency were issued by the DH on 18 Mar 2019.
Ends/Friday, Oct 23, 2020
Issued at HKT 16:00
|
| |
|
