Presented by: Antonio Volpi. Department of Public Health, University of Rome ‘Tor Vergata’, Italy.

Brivudin or BVDU [(E)-5-(2-bromovinyl)-2¢-deoxyuridine] is a thymidine analogue selectively activated by varicella zoster virus (VZV) thymidine kinase and thymidylate kinase in infected cells, where it accumulates as the phosphorylated compound and is not able to leave the cell. Brivudin triphosphate specifically inhibits VZV replication by acting as a substrate for the viral DNA polymerase at nanomolar concentrations. The plasma half-life of brivudin in humans is about 16 h, which warrants only one administration a day. It does not need dose adjustments for renal or liver impairment. The only known drawback is the longterm inhibition of the enzyme dihydropyrimidine dehydrogenase, which participates in the degradation of 5-fluorouracil (5-FU). Administration of 5-FU or derivatives within 4 weeks of brivudin treatment can leave patients at risk of severe or lethal complications.

There have been a number of randomized clinical trials of brivudin in the treatment of herpes zoster. A comparison of brivudin 125 mg/day once daily and aciclovir 800 mg five times a day, initiated within 48 h of lesion onset, both for 7 days, demonstrated that brivudin was more effective than aciclovir in terminating vesicle formation (15.3 h vs 18.8 h; P=0.022). Pain occurring or persisting after rash healing (postherpetic neuralgia; PHN) was significantly lower in brivudin recipients (32.7%) than in the aciclovir group (43.5%; P=0.006). A multi-centre, prospective, double-blind, randomized trial of 2027 patients showed that brivudin (125 mg once daily) is as effective as famciclovir (250 mg, three times daily) in rash healing and preventing PHN. Once-daily brivudin is an effective therapy of herpes zoster and favours adherence by patients.