Medline ® Abstracts for References 9,15

OBJECTIVE: To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia.

DESIGN: A randomized, double-blind, placebo-controlled, multicenter trial.

SETTING: 36 centers in the United States, Canada, and Australia.

PATIENTS: 419 immunocompetent adults with uncomplicated herpes zoster.

INTERVENTION: Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days.

MEASUREMENTS: Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study.

RESULTS: Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months.

CONCLUSIONS: Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.

Herpes zoster is a serious medical problem, not only because of the discomfort associated with the acute rash, but also because of the potential for post-herpetic neuralgia. Acyclovir is currently the antiviral drug of choice for the treatment of herpes zoster. Efforts are underway to develop new drugs that have improved activity against varicella-zoster virus as well as more favorable pharmacokinetic properties. The goal of these efforts is to develop an orally administered antiviral drug that will accelerate the events of cutaneous healing as well as reduce the frequency and severity of post-herpetic neuralgia. Investigational drugs currently under evaluation include valaciclovir and famciclovir, the prodrugs of acyclovir and penciclovir, respectively. Two new uracil derivatives, sorivudine and BW882C87, with increased anti-varicella-zoster virus activity in vitro are also being studied.