Penciclovir cream for herpes simplex labialis

Clinical question Is penciclovir cream effective for the treatment of recurrent herpes labialis?

Background Recurrent herpes labialis is a self-limiting problem in most cases, but may cause considerable pain, disfigurement, and embarrassment. Oral acyclovir has been shown to be an effective treatment in small clinical trials. Additionally, prophylactic therapy with oral acyclovir has been proven effective, but many episodes are mild or not frequent enough to warrant long-term suppressive therapy. A safe, topically administered, and effective therapy is desirable for recurrent infections, since results with topical acyclovir have been disappointing.

Population studied The authors studied immunocompetent men and women at least 18 years of age and in good health who had a history of at least three episodes of herpes labialis per year. Patients who typically ([is greater than] 50% of episodes) experienced classic lesions preceded by prodromal symptoms were included, and patients who frequently ([is greater than] 25% of episodes) experienced false prodromes or aborted lesions were excluded.

Study design and validity A total of 2209 patients were randomly assigned to receive either 1% penciclovir cream or vehicle control cream. Subjects were instructed to apply medication within 1 hour of the first sign or symptom of a cold sore recurrence and then every 2 hours while awake for 4 consecutive days. Patients returned for evaluation within 24 hours of initiation of therapy and continued daily clinic visits until all crusts were gone, then every other day until skin returned to normal. Swabs from lesions were collected to evaluate duration of viral shedding. Patients were trained to recognize stages of lesions and were asked to make diary entries four times daily to record pain level and stage at initiation of therapy and with each application. Initiation of therapy during the prodrome or erythema stage was considered early, while therapy begun during the papule stage or later was considered late.

Outcomes measured The primary outcome measured in the study was lesion healing determined by time to loss of lesion crust and the proportion of patients who had lost lesions by days 6, 7, and 8. Secondary outcomes measured included resolution of lesion pain and cessation of viral shedding. All outcomes were analyzed according to early or late initiation of therapy. An intent-to-treat analysis was performed on all patient groups who applied study medication at least once.

Results Of the 2209 randomized, 1573 patients initiated therapy for recurrence during the 15-month study period. Patient-reported healing was faster in the penciclovir group compared with placebo (4.8 vs 5.5 days, P [is less than] .001). Resolution occurred more rapidly in the penciclovir group regardless of whether medication was applied in the early or late stage. The proportion of patients who healed by days 6, 7, and 8 was significantly greater in the penciclovir group (P [is less than] .001). The penciclovir group reported relief of pain 0.6 days faster than placebo regardless of whether treatment was initiated early or late (P [is less than] .001). There was no overall difference in the isolation of virus from patients in either treatment group. If therapy was initiated early, however, penciclovir-treated patients ceased shedding virus faster than patients treated with placebo.

Recommendations for clinical practice Topical 1% penciclovir cream applied every 2 hours while awake reduced the time to healing of sores, relief of pain, and cessation of viral shedding in patients with an episode of recurrent herpes labialis. Benefit was also demonstrated in patients who applied the cream after sores were already clinically evident. Although these reductions were statistically significant, they may not remain clinically significant when cost and compliance issues are taken into account. Eighty-two percent of patients applied the medication at least six times daily in this study, a percentage unlikely to be attained in actual clinical practice. A 5-day course of generic oral acyclovir (400 mg three times a day) costs around $15, while a small 2-g tube of penciclovir (Denavir) costs approximately $27. It is unlikely that topical penciclovir offers any significant clinical advantages over currently accepted therapies for recurrent herpes labialis.