Famciclovir reduced lesion healing time in recurrent genital herpes
ACP J Club. 1996 Nov-Dec;125:69. doi:10.7326/ACPJC-1996-125-3-069
Sacks SL, Aoki FY, Diaz-Mitoma F, Sellors J, Shafran SD, for the Canadian Famciclovir Study Group. Patient-initiated, twice-daily oral famciclovir for early recurrent genital herpes. A randomized, double-blind multicenter trial. JAMA. 1996 Jul 3;276:44-9. [PubMed ID: 8667538]
To determine the effectiveness of patient-initiated famciclovir in recurrent genital herpes.
1-year randomized, double-blind, placebo-controlled trial.
15 centers in Canada.
Patients were > 18 years of age (mean age 33 y, 54% women) and had genital herpes with recurrences at least every 4 months, with prodromes in 3 of 4 previous episodes. Exclusion criteria included potential for pregnancy; serious renal, hepatic, cardiac, gastrointestinal, hematologic, or immunologic dysfunction; another genital tract disorder; history of alcohol or drug abuse; or antiviral treatment in the past 2 weeks. Of 692 patients recruited, 467 patients took ≥ 1 dose of the study drug (intention-to-treat sample). 8% of patients withdrew.
Patients were allocated to famciclovir twice daily for 5 days at doses of 125 mg (n = 117), 250 mg (n = 128), or 500 mg (n = 121) or to placebo (n = 101). At enrollment, patients were taught how to take a viral culture at the earliest signs of an outbreak and to start their own treatment. Patients returned to their enrollment site within 12 hours of the start of treatment, twice a day for the 5 treatment days, and then daily until healing was complete.
Main outcome measures
Time to complete healing of all lesions, duration of lesion stage, and time to cessation of viral shedding and resolution of symptoms.
Complete healing of lesions occurred more rapidly in patients who received famciclovir than in those who received placebo. Compared with a median of 4.8 days to complete healing with placebo, 125 mg of famciclovir achieved healing in 3.8 days (hazard ratio [HR] 1.7, 95% CI 1.3 to 2.3, P < 0.001); 250 mg of famciclovir in 3.7 days (HR 1.7, CI 1.3 to 2.3, P < 0.001); and 500 mg of famciclovir in 4.1 days (HR 1.7, CI 1.2 to 2.3, P < 0.01). HRs for median time to cessation of viral shedding were 2.6 for 125 mg, 3.3 for 250 mg, and 4.2 for 500 mg (P < 0.001 for all doses compared with placebo). Times to loss of vesicles, ulcers, crusts, edema, and all symptoms were faster in famciclovir recipients than in placebo recipients; HRs ranged from 1.4 to 2.0. The famciclovir groups did not differ for lesion healing, healing stages, or symptoms. 12 patients withdrew because of adverse events: 10 in the famciclovir groups and 2 in the placebo group. The groups did not differ for adverse events or withdrawals.
Famciclovir therapy, initiated by the patient at the onset of symptoms, reduced the time to lesion healing and the duration of lesion symptoms in patients with recurrent genital herpes.
Source of funding: SmithKline Beecham Pharmaceuticals.
For article reprint: Dr. S.L. Sacks, Viridae Clinical Sciences, Inc, 1134 Burrard Street, Vancouver, British Columbia V6Z 1Y8, Canada. FAX 604-689-5153.
Sacks and colleagues convincingly showed that oral famciclovir given early in the course of an episode of genital herpes reduced the time to resolution of symptoms and cessation of viral shedding. Early treatment was achieved by having patients initiate treatment within 6 hours of the first signs of a symptomatic episode. Confidence in the results is increased by the faultless design of the randomization and follow-up and because both objective (cessation of viral shedding) and subjective (resolution of symptoms) end points were improved by the treatment. The study, however, lacks a measure of subjective severity. Although the median duration of symptoms was decreased by < 1 day, it is difficult to determine whether the pain of patients with severe symptoms was alleviated.
Was it ethical to compare famciclovir with placebo when another treatment (acyclovir) exists for episodes of genital herpes? Probably yes: The affliction is not associated with mortality or severe morbidity even if not treated, and acyclovir is not very effective for treating a single episode.
The emphasis in this and another study (1) is on prompt treatment, and patient-initiated treatment is the best way to achieve this. Judging by the present results, patients accurately predicted the onset of a culture-positive episode, but I wonder whether they will do as well in usual clinical settings. Side ef- fects of famciclovir are minimal (2). Developing resistance may be the main drawback of using antiviral agents. Only anecdotal reports of resistance to acyclovir in herpes viruses isolated from immunocompetent patients have been published, but resistance in immunocompromised hosts is increasing (3).
For the patient with severe recurrent episodes of genital herpes, treatment with famciclovir should be considered.
Leonard Leibovici, MD
Rabin Medical CenterPetah-Tiqva, Israel