With this new preparation, Sacks et al15 conducted studies to determine whether docosanol 10% cream is efficacious compared with placebo in the topical treatment of episodes of acute herpes simplex labialis. Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of herpes labialis, were randomized to receive either docosanol or polyethylene glycol placebo. Subjects were instructed to initiate therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times a day until healing occurred (ie, the crust fell off spontaneously, or there was no longer evidence of an active lesion) with twice-daily visits. The median time to healing in the 370 docosanol-treated patients was 4.1 days, 18 hours shorter than that observed in the 367 placebo-treated patients (P=.008). The docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P=.002), (2) complete healing of classic lesions (P=.023), and (3) cessation of the ulcer or soft-crust stage of classic lesions (P<.001). Aborted episodes were experienced in 40% of docosanol recipients versus 34% of placebo recipients (P=.109). Adverse experiences with docosanol were mild and similar to those with placebo. The authors concluded that docosanol applied 5 times a day is safe and effective in the treatment of recurrent herpes labialis.15
Because in vitro studies have shown that n-docosanol can enhance the antiviral activity of nucleoside analogs against the replication of herpesviruses, clinical studies of this combination will be of interest.2
Comparative Efficacy of Topical Treatments
McKeough and Spruance14 evaluated the comparative efficacy of penciclovir cream, acyclovir cream, n-docosanol cream, and acyclovir ointment in a guinea pig model of cutaneous HSV-1 disease. The backs of guinea pigs were infected with HSV-1 using a vaccination instrument. Active treatments and corresponding vehicle controls were applied for 3 to 5 days beginning 24 hours after inoculation. After completion of treatment, the animals were killed, and the severity of the infection was assessed from the number of lesions, total lesion area, and lesion virus titer.14
Penciclovir cream effected modest reductions in lesion number (19%), area (38%), and virus titer (88%) compared with its vehicle control, and each of these differences was significantly greater (P<.05) than the reductions effected by acyclovir ointment (0%, 21%, and 75%, respectively). The acyclovir cream effect (reductions of 4%, 28%, and 77%, respectively) was less than that of penciclovir cream, and this difference was confirmed by 2 additional head-to-head experiments. Two experiments with n-docosanol cream failed to show statistically significant differences by any parameter between n-docosanol cream and vehicle control-treated sites or between n-docosanol and untreated infection sites.14
In this model, the efficacy of penciclovir cream was greater than acyclovir cream, acyclovir cream was greater than or equal to acyclovir ointment, and acyclovir ointment was greater than n-docosanol cream. The authors noted that because their model was designed to evaluate compounds that function primarily through antiviral activity, the negative findings with n-docosanol in these studies do not exclude that it might work clinically through other mechanisms.14