These studies show that 1-day, high-dose valacyclovir therapy at the first symptom of a cold sore is a safe and effective treatment. Both 1- and 2-day valacyclovir regimens provide clinically and statistically significant benefits over placebo in duration of the episode and time to lesion healing. Time to cessation of pain and/or discomfort was also significantly decreased by 1- or 2-day treatment with valacyclovir. The proportion of subjects with prevented and/or blocked cold sore lesions was higher in the valacyclovir-treated groups, although statistical significance was not reached. These two large, well-controlled trials provide evidence that early, high-dose, short-duration antiviral intervention can shorten the clinical course of cold sores and that 2 days of therapy provide no additional benefit over 1 day.
These results support the premise that achieving and maintaining high concentrations of acyclovir in plasma above the HSV-1 99% inhibitory concentration level, during the period of early viral replication, can interrupt the 2 to 3 cycles of viral replication thought to be necessary to produce clinically apparent lesions (18
). The valacyclovir 1-day treatment regimen of 2 g twice daily was expected to provide a peak acyclovir concentration of approximately 8 μg/ml and a concentration-time profile in excess of the 99% inhibitory concentration of 4.21 μg/ml for approximately 5.5 h (~23%) during the first 24-h period (3
). A single-day valacyclovir regimen of 2 g twice daily for 2 doses produces systemic concentrations not clinically achievable with oral acyclovir dosing or topical therapy. Hence, this may explain the inconsistent efficacy results observed in previous clinical trials with oral acyclovir therapy for cold sores (14
). It is presumed, but not proven, that a strong antiviral effect hastens wound resolution by decreasing the extent of keratinocyte destruction, the viral antigen load, and the attendant inflammatory response, which impair reepithelization at the site of infection (1
One-day, two-dose oral valacyclovir constitutes a convenient treatment for herpes labialis in comparison to topical therapies, which typically require frequent applications for multiple days (13
). While direct comparisons between oral and topical therapy have not been conducted, the available data suggest that oral therapy is more effective. Penciclovir 1% cream (Denavir) is indicated for the treatment of cold sores. The clinical studies leading to approval demonstrated that the cream was efficacious in shortening the median healing time of classical cold sore episodes by 0.7 to 1.0 days (13 to 17%) compared to the vehicle controls (13
). Acyclovir 5% cream (Zovirax cream) is also indicated for cold sores and has been shown in two large, well-controlled clinical trials to shorten the duration of classical cold sore episodes by a similar magnitude to that of penciclovir 1% cream (19
). The clinical results reported in the two valacyclovir studies indicate a difference between valacyclovir and placebo-treated patients in mean classical lesion healing time of 1.1 to 1.3 days (18 to 21%) (Table ).
Although the proportion of subjects with prevented and/or blocked cold sore lesions was higher in the valacyclovir-treated groups, statistical significance was not reached. Two studies, one using topical acyclovir cream and one using oral acyclovir, have shown some apparent effect on the prevention of cold sore lesion progression (6
). However, these results have not been reproduced in subsequent studies (14
). The present valacyclovir studies are the two largest, placebo-controlled trials of herpes labialis treatment designed to test the hypothesis that the progression of cold sore lesions could be prevented with oral medication if taken early (i.e., at the first symptoms). Both studies showed similar trends in favor of valacyclovir, and in a combined analysis of these two trials, a statistically significant effect on preventing and/or blocking cold sore lesion development was demonstrated (S. K. Tyring, S. L. Spruance, M. Vargas-Cortes, and M. Schultz, Proc. Summer Session Am. Acad. Dermatol., abstr. 31, 2002).
The magnitude of benefit to the patient that can be achieved by the episodic treatment of herpes labialis is less than the efficacy of prophylactic drug administration. Nevertheless, many patients prefer intermittent to continuous medication. For these individuals, the 1.1- to 1.3-day effect on mean lesion healing time shown in this trial, an 18 to 21% reduction, would be clinically significant to many of them. While considered a minor illness, herpes labialis lesions can be disfiguring and painful during eating or talking and can adversely affect self-image, particularly among teenagers.
These two large trials indicate that valacyclovir therapy, taken at the first symptom of a cold sore, reduces the duration of an episode, the time to lesion healing, and the duration of pain and/or discomfort. The 1-day valacyclovir regimen is a safe and effective treatment of cold sores while also offering the potential advantage of simple and convenient dosing over currently available treatments.