The Herpes zoster medicine brivudine (ZOSTEX) inhibits the breakdown of 5-fluoropyrimidines such as 5-fluorouracil (5-FU; 5-FU HEXAL, amongst other generics) and 5-FU prodrugs such as capecitabine (XELODA) and it can therefore lead to a potentially fatal accumulation of 5-FU. Simultaneous use of brivudine even with topical 5-fluoropyrimidine products is absolutely contraindicated. Furthermore, after the Herpes zoster medicine has been taken, an interval of not less than four weeks must be left before treatment with 5-fluoropyrimidines is started (1). However, warnings in the information for healthcare professionals and package leaflet and even on the medicine pack have so far not reliably prevented fatal interactions. In autumn 2008 (data as at 12 Aug.), the Federal Institute for Drugs and Medical Devices (BfArM) overviewed seven such reports with fatal outcomes (2). At the time, we viewed withdrawal from the market as the only sensible response. The BfArM did not consider any additional risk-prevention measures to be necessary (a-t 2008; 39: 88). Now, the brivudine supplier Berlin-Chemie has issued a warning in a Dear Doctor letter (3). Since 2008, the BfArM has recorded a further seven suspected cases from Germany alone. Three of the patients concerned died (4). In the meantime, a further report of a life-threatening interaction between brivudine and capecitabine has also been published in the literature (5).

As Herpes zoster, which brivudine is used to treat, is often triggered by chemotherapeutic agents, the risk of accidental simultaneous use is high and clearly cannot be entirely prevented by warnings. Relevant advantages of brivudine over aciclovir (ZOVIRAX, generics), valaciclovir (VALTREX, generics) and famciclovir (FAMVIR), which lack this risk, have not been proven (a-t 2007; 38: 47).

It is still our view that the withdrawal of brivudine from the market is the only reliable way of preventing fatal interactions with 5-fluoropyrimidines (6), -Ed.

1

Berlin-Chemie: Summary of Product Characteristics: ZOSTEX, as at Oct. 2010

2

BfArM: Letter dated 4. Sept. 2008

3

Berlin-Chemie: Dear Doctor Letter dated 27. Aug. 2012

4

BfArM: Letter dated 5. Juni 2012

5

BAENA-CANADA, J.M. et al.: Nat. Ref. Clin. Oncol. 2010; 7: 55-8

6

atd drug database: evaluation of brivudine, as at Juni 2012