Herpes labialis is a common condition characterized by recurrent vesicular eruptions primarily on the lips and perioral skin. Most commonly caused by herpes simplex virus type 1 (HSV-1), this condition can significantly affect quality of life in patients with multiple recurrences, which may cause pain, embarrassment, and psychosocial distress. Oral HSV is the most easily acquired herpesvirus. Approximately 50% of Americans are seropositive for HSV-1 by the time they reach adolescence—by age 50 years, 80% to 90% carry the virus.1 The first part of this series discussed oral antiviral agents in the treatment of herpes labialis. In the second part of this series, we review topical therapeutic agents that are available in the treatment of herpes labialis and its associated symptoms.
Topical Agents For many years, acyclovir ointment was the only topical agent available for herpes labialis. Over the last several years, many new topical therapies have been investigated, and 3 have been approved by the US Food and Drug Administration (FDA). Currently, the 4 approved topical treatments available for herpes labialis include acyclovir ointment and cream (Zovirax®), penciclovir cream (Denavir®), and n-docosanol cream (Abreva®)(Table).
Acyclovir—Acyclovir ointment, which was first brought to market in 1982, is of questionable value in the treatment of recurrent herpes labialis.2 Acyclovir cream, which appears to provide better absorption than the ointment, has been available in many countries outside the United States for more than a decade. To examine more comprehensively the safety and efficacy of this formulation, Spruance et al3 conducted 2 independent, identical, parallel, randomized, double-blind, vehicle-controlled, multicenter clinical trials (N=686 in study 1 and N=699 in study 2). Healthy adults with a history of recurrent herpes labialis were randomized to receive acyclovir cream 5% or vehicle control and asked to self-initiate treatment 5 times a day for 4 days starting within 1 hour of recurrence onset. The mean duration of episodes was significantly decreased in both studies (study 1: 4.3 vs 4.8 days in treated vs placebo, respectively; study 2: 4.6 vs 5.2 days in treated vs placebo, respectively)(P≤.05). In addition, lesion pain was reduced significantly for subjects in both studies, though acyclovir cream did not prevent the development of classic lesions.3
In another study, Biagioni and Lamey4 used infrared thermography to identify the prodromal stage of herpes labialis and treated the active area with acyclovir cream 5 times a day for 5 days. All patients (N=70) were evaluated at 72 hours thermographically and clinically, and localized increase in temperature over the symptomatic area was noted. The development of a clinical herpes lesion was prevented in 46% (32/70) of the patients. In the lesions that did develop (38/70), an 80% reduction in clinical lesion size was observed in 82% (31/38) of the subjects. The remaining 18% (7/38) of patients showed a reduction in healing time.4
In a recent publication, Seth et al5 reported the use of a novel liposomal acyclovir topical gel. In this study, 10 patients with recurrent, mild facial infection were subjected to double-blind clinical evaluation, using a 1% liposomal acyclovir topical gel in a 5% hydroxypropylmethyl cellulose K4M gel base. The efficacy of plain acyclovir gel and liposomal acyclovir gel was compared by application to herpetic lesions 5 times a day for up to 8 weeks. In patients treated with liposomal acyclovir gel, a significant increase in the average percentage improvement of lesion healing was observed after 2 to 3 weeks of therapy (P<.05).5
Topical acyclovir also has been evaluated in combination with a topical steroid. Evans and colleagues6 assessed the efficacy of a combination of acyclovir cream 5% and hydrocortisone cream 1% (ME-609) in treating experimentally UV radiation (UVR)–induced herpes labialis in patients with a history of recurrent herpes labialis. Starting on day 2, 380 subjects were randomized to receive ME-609 or vehicle control 6 times a day for 5 days. Fewer patients in the treatment arm developed delayed classic lesions. Statistically significant reductions in healing time (9.0 vs 10.1 days in treated and placebo groups, respectively; P=.04) and maximum lesion size (43 vs 60 mm in treated and placebo groups, respectively; P=.07) were noted in treated patients compared with patients given placebo. Overall, combination treatment with an antiviral and anti-inflammatory agent led to a reduction in the incidence of classic lesions, healing time, lesion size, and lesion tenderness.6
Penciclovir—Penciclovir, famciclovir’s active metabolite, is FDA approved for episodic treatment of herpes labialis. Topical penciclovir cream 1% applied every 2 hours for 4 days can decrease the duration of lesion healing, pain, and viral shedding, as evidenced by several studies, with some benefit in the early and late stages of lesion development.7-10 Penciclovir interferes with viral replication and significantly limits both the severity and duration of cold sores.