High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies

Abstract

Oral valacyclovir is better absorbed than oral acyclovir, increasing acyclovir bioavailability three- to fivefold. This provides the opportunity to explore whether high systemic acyclovir concentrations are effective in the treatment of cold sores (herpes labialis). Two randomized, double-blind, placebo-controlled studies were conducted. Subjects were provided with 2 g of valacyclovir twice daily for 1 day (1-day treatment), 2 g of valacyclovir twice daily for 1 day and then 1 g of valacyclovir twice daily for 1 day (2-day treatment), or a matching placebo and instructed to initiate treatment upon the first symptoms of a cold sore. In study 1, the median duration of the episode (primary endpoint) was reduced by 1.0 day (P = 0.001) with 1-day treatment and 0.5 days (P = 0.009) with 2-day treatment compared to placebo. Similarly, the mean duration of the episode was statistically significantly reduced by 1.1 days with 1-day treatment and 0.7 days with 2-day treatment compared to placebo. The proportion of subjects in whom cold sore lesion development was prevented and/or blocked was increased by 6.4% (P = 0.096) with 1-day treatment and 8.5% (P = 0.061) with 2-day treatment compared to placebo. The time to lesion healing and time to cessation of pain and/or discomfort were statistically significantly reduced with valacyclovir compared to placebo. In study 2, results similar to those in study 1 were obtained. AEs were similar across treatment groups. These studies provide evidence supporting a simple, 1-day valacyclovir treatment regimen for cold sores that is safe and effective. The 1-day valacyclovir regimen offers patients a unique and convenient dosing alternative compared to available topical therapies.

Figures

FIG. 1.

Kaplan Meier plots of the duration of vesicular and nonvesicular cold sore episodes showing the proportion of subjects not healed versus the duration of the episode (time in days) for each treatment regimen within each study. Study 1: placebo, n = 292; 1-day valacyclovir treatment, n = 311; 2-day valacyclovir treatment, n = 299. Study 2: placebo, n = 317; 1-day valacyclovir treatment, n = 298; 2-day valacyclovir treatment, n = 339.

FIG. 2.

Plot of the difference in proportion (%) of subjects in whom cold sore lesion development was prevented and/or blocked with 1-day treatment (2 g of valacyclovir twice daily for 1 day) and 2-day treatment (2 g of valacyclovir twice daily for 1 day and then 1 g of valacyclovir twice daily for 1 day) from placebo within each study. 95% CI, 95% confidence interval.

FIG. 3.

Kaplan Meier plots of time to vesicular lesion healing showing proportion of subjects not healed versus duration of lesion healing (time in days) for each treatment regimen within each study. Study 1: placebo, n = 171; 1-day valacyclovir treatment, n = 164; 2-day valacyclovir treatment, n = 142. Study 2: placebo, n = 192; 1-day valacyclovir treatment, n = 161; 2-day valacyclovir treatment, n = 170.