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Therapeutics

Famciclovir decreased the duration and symptoms of acute herpes zoster and postherpetic neuralgia

ACP J Club. 1995 Nov-Dec;123:67. doi:10.7326/ACPJC-1995-123-3-067


Source Citation

Tyring S, Barbarash RA, Nahlik JE, et al. and the Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Jul 15;123:89-96.


Abstract

Objective

To determine the safety and effectiveness of famciclovir in acute herpes zoster and postherpetic neuralgia.

Design

Randomized, double-blind, placebo-controlled trial with 5-month follow-up.

Setting

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

Patients

419 immunocompetent patients (mean age, 50 y; 52.7% men) who were ≥ 18 years of age and had clinically confirmed, uncomplicated herpes zoster. Exclusion criteria were zoster rash > 72 hours, complications of herpes zoster, crusts at enrollment, other serious disease, pregnancy, or lactation. Follow-up was 90%.

Intervention

Patients were allocated to oral famciclovir, 500 mg (n = 138); famciclovir, 750 mg (n = 135); or placebo (n = 146) 3 times/d for 7 days. Antiviral or immunomodifying therapy and topical medication were prohibited.

Main Outcome Measures

The primary outcome was time to full crusting of lesions and adverse effects. Secondary outcomes were time to last positive viral culture (duration of viral shedding) and time to resolution of vesicles, ulcers, crusts, acute-phase pain, and postherpetic neuralgia. Hazard ratios (HR) > 1 indicated a faster rate of events (e.g., healing) in patients receiving famciclovir than in those receiving placebo; an HR of 2 indicated that the rate was twice as fast.

Main Results

In an intention-to-treat (n = 419) analysis, compared with patients assigned to placebo, the median time to crusting for patients receiving 750 mg of famciclovir was reduced from 7 to 6 days (HR, 1.4; 95% CI, 1.0 to 1.9). In patients receiving either 500 mg or 750 mg of famciclovir, the median time to resolution of vesicles was reduced from 6 to 5 days (HR, 1.4; CI, 1.1 to 1.9 and HR, 1.7; CI, 1.3 to 2.2, respectively); the median time to resolution of ulcers was reduced from 9 to 7 days (HR, 1.6; CI, 1.1 to 2.2 for both); and the median time to last positive culture was reduced by 1 day (HR, 2.0; CI, 1.4 to 3.0 and HR, 2.3; CI, 1.5 to 3.3, respectively). In patients receiving 500 mg of famciclovir, the median time to resolution of crusts was reduced from 21 to 19 days (HR, 1.3; CI, 1.0 to 1.7). The median time to resolution of postherpetic neuralgia was reduced from 119 to 63 days (HR, 1.7; CI, 1.1 to 2.7) in patients receiving 500 mg of famciclovir and from 119 to 61 days (HR, 1.9; CI, 1.2 to 2.9) in patients receiving 750 mg of famciclovir. The groups did not differ for adverse effects.

Conclusion

Famciclovir decreased the duration and symptoms of acute herpes zoster and postherpetic neuralgia.

Sources of funding: SmithKline Beecham Pharmaceuticals and National Institutes of Health.

For article reprint: Dr. S. Tyring, University of Texas Medical Branch, Route, Galveston, TX 77555, USA. FAX 713-333-2338.


Commentary

Few problems are more vexing for patients and their physicians than postherpetic neuralgia (1). Because this pain syndrome is so difficult to manage with analgesics, various alternative agents have been investigated, including tricyclic antidepressants, topical capsaicin, topical aspirin, intravenous and topical lidocaine, ketamine, narcotics, selective sympathetic or somatic nerve blockades, low-energy laser, and other neurosurgical procedures. Unfortunately, unpleasant side effects, cost, and limited efficacy prevent the routine use of these treatments.

The lack of a satisfactory treatment has spurred the search for effective prevention. Systemic and intralesional corticosteroids have been tried and found wanting. Although the antiviral agent acyclovir speeds the healing of acute herpes zoster, it has little effect on postherpetic neuralgia. Famciclovir has pharmacokinetic properties, such as the markedly increased intracellular half-life of its active metabolite, that make it an attractive alternative to acyclovir.

The study by Tyring and colleagues shows clinically important treatment effects on several parameters of postherpetic neuralgia that have proven elusive in studies of acyclovir. The 3 times/d dosing schedule and the paucity of side effects are likely to improve compliance compared with the 5 times/d dosing of acyclovir. A once- or twice-daily dosing interval should be considered in patients with renal impairment (2). Although the cost-effectiveness of famciclovir is not addressed, the 3.5-month reduction in the duration of postherpetic neuralgia in older persons makes this methodologically rigorous study one that should strongly influence our management of acute herpes zoster.

Jay S. Luxenberg, MD
University of California San Francisco, California, USA