Spruance et al7 conducted a randomized, multicenter, double-blind, placebo-controlled, 2-arm, parallel trial to compare the safety and efficacy of penciclovir cream 1% with vehicle control cream in the treatment of recurrent herpes simplex labialis in immunocompetent patients. Treatment was self-initiated by the patient within the first hour of the first sign or symptom of a recurrence. A total of 2209 patients were enrolled and given study medication, 1573 of whom initiated treatment for a recurrence. Patients applied the medication every 2 hours during waking hours for 4 days. Healing of classic lesions was 0.7 days faster in penciclovir-treated patients compared with placebo-treated patients (median, 4.8 vs 5.5 days; P<.001). Reduction in duration of lesion pain was observed in penciclovir-treated patients compared with placebo-treated patients (median, 3.5 vs 4.1 days; P<.001). Lesion viral shedding also resolved faster in penciclovir-treated patients compared with those who received vehicle control cream (median, 3 vs 3 days; P=.003). Statistically significant reductions in time to healing and pain resolution occurred with topical penciclovir cream when treatment was initiated in the early (prodrome or erythema) stage or late (papule or vesicle) stage of the lesion.7
Boon et al8 evaluated the efficacy and tolerability of penciclovir cream versus placebo control (purified water) in treating sunlight-induced herpes labialis. Healthy patients (mean age, 38.3 years; range, 18–81 years) with a history of sunlight-induced herpes labialis self-initiated treatment with either penciclovir cream (n=266) or purified water (n=275) within one hour of development of the signs and symptoms of a recurrence.
A significant reduction in the time to lesion healing (P<.001), with a reduction in median time of up to 2 days, was noted. There was a significant reduction in maximum lesion area (P=.008), faster resolution of lesion-associated symptoms (P=.026), reduction in pain duration (P≤.040), itching (P≤.032), burning (P≤.028), and tenderness (P≤.026). The daily self-assessment of lesion attributes showed significantly fewer severe or extreme assessments of lesion size (P≤.003), noticeability (P≤.003), amount of scab or crust (P≤.003), raised or swollen area (P≤.040), soreness or tenderness (P≤.043), and overall severity (P≤.001) throughout the study.8
Recently, Raborn et al9 conducted 2 randomized, double-blind, parallel-group clinical trials to compare the efficacy and safety of topical penciclovir cream 1% for recurrent herpes labialis. Of the 4573 immunocompetent patients with a history of recurrent herpes simplex labialis (defined as 3 or more episodes per year) that were enrolled in the study, 3057 patients initiated treatment (1516 with penciclovir cream 1% and 1541 with placebo). Patients were instructed to apply medication 6 times a day for the first day and thereafter every 2 hours during waking hours for 4 consecutive days. In the treatment group, patients lost classic lesions 31% faster than did those in the placebo group and experienced 28% faster resolution of lesion pain. Significant benefits were achieved with penciclovir use whether treatment was initiated in the early stages (P=.001) or later stages (P=.0055) of the recurrence.9
Lin and associates10 compared the efficacy of topical penciclovir cream 1% versus acyclovir cream 3% in the treatment of herpes labialis. In a randomized, double-blind, multicenter trial, 248 patients with a history of herpes labialis were randomly allocated to 1 of the 2 treatment groups (n=124 each) to receive either penciclovir cream 1% or acyclovir cream 3%. Before treatment (day 0) and at every visit (days 3, 5, and 7), signs and symptoms scores were recorded by the same physician. Two hundred twenty-five patients completed the study. No significant differences were noted in efficacy, clinical cure rate, and safety between the 2 groups; however, a trend toward a shorter time to resolution of symptoms, cessation of new blisters, and loss of crust (P≤.008) was noted in penciclovir-treated patients compared with acyclovir-treated patients. In addition, signs and symptoms scores in penciclovir-treated patients were significantly lower than those in the acyclovir-treated patients on days 5 (P<.01) and 7 (P<.05), supporting the finding that topical penciclovir cream 1% is at least as convenient and effective as acyclovir cream 3% in the treatment of herpes labialis.10
A susceptibility program was established by Sarisky et al11 to assess the resistance profile for serial HSV isolates from immunocompetent patients with recurrent herpes labialis. The isolates were obtained throughout a 4-day treatment period with topical penciclovir cream 1% or placebo. Two isolates (2/1035; 0.19%), representing 0.34% of the patients (2/585), were confirmed to be penciclovir resistant. These were highly resistant to penciclovir (50% inhibiting concentration [IC50], >55 µg/mL) and were isolated less than 17 hours after the start of patient-initiated treatment. However, subsequent isolates on days 2 and 3 from the same patients were completely susceptible to penciclovir cream (IC50, <2.0 µg/mL). None of the patients were found to have penciclovir-resistant species at the end of acute treatment, regardless of treatment group. Overall, the prevalence of penciclovir resistance was found to be similar to that of acyclovir resistance (ie, 0.3%) reported in immunocompetent untreated populations.11
N-docosanol—Docosanol is a compound that inhibits herpes virus replication by blocking fusion of the viral envelope with the plasma membrane and can potentially limit both the duration and severity of herpes labialis.2 Presently, docosanol 10% cream is approved by the FDA as an over-the-counter agent for application 5 times a day during episodes of herpes labialis. In one small clinical trial with 63 patients, n-docosanol 10% cream significantly reduced the healing time of patients’ herpes labialis episodes compared with stearic acid–containing placebo cream.12 Application of n-docosanol 10% cream early in the prodrome or erythema stage of a recurrent episode of herpes labialis shortened mean healing time by approximately 3 days compared with late treatment with n-docosanol 10% cream and early or late treatment with the placebo. A subsequent larger study with 846 patients found no benefit.13 Because of a concern that the vehicle may have had a beneficial effect on herpes labialis and masked an effect by n-docosanol, a polyethylene glycol control preparation was created.14