Zovirax Topical (Acyclovir Sodium Topical) - Clinical Pharmacology

CLINICAL PHARMACOLOGY

Pharmacokinetics: Adults:    A clinical pharmacology study was performed with ZOVIRAX Cream in adult volunteers to evaluate the percutaneous absorption of acyclovir. In this study, which included 6 male volunteers, the cream was applied to an area of 710 cm² on the backs of the volunteers 5 times daily at intervals of 2 hours for a total of 4 days. The weight of cream applied and urinary excretion of acyclovir were measured daily. Plasma concentration of acyclovir was assayed 1 hour after the final application. The average daily urinary excretion of acyclovir was approximately 0.04% of the daily applied dose. Plasma acyclovir concentrations were below the limit of detection (0.01 µM) in 5 subjects and barely detectable (0.014 µM) in 1 subject. Systemic absorption of acyclovir from ZOVIRAX Cream is minimal in adults.

Pediatric Patients:    The systemic absorption of acyclovir following topical application of cream has not been evaluated in patients <18 years of age.

CLINICAL TRIALS

Adults:    ZOVIRAX Cream was evaluated in 2 double-blind, randomized, placebo (vehicle)-controlled trials for the treatment of recurrent herpes labialis. The average patient had 5 episodes of herpes labialis in the previous 12 months. In the first study, median age was 37 years (range 18 to 81 years), 74% were female, and 94% were Caucasian. In the second study, median age was 38 years (range 18 to 87 years), 73% were female, and 94% were Caucasian. Subjects were instructed to initiate treatment within 1 hour of noticing signs or symptoms and continue treatment for 4 days, with application of study medication 5 times per day. In both studies, the mean duration of the recurrent herpes labialis episode was approximately one-half day shorter in the subjects treated with ZOVIRAX Cream (n = 682) compared with subjects treated with placebo (n = 703) (approximately 4.5 days versus 5 days, respectively). No significant difference was observed between subjects receiving ZOVIRAX Cream or vehicle in the prevention of progression of cold sore lesions.

Pediatric Patients:    An open-label, uncontrolled trial with ZOVIRAX Cream 5% was conducted in 113 patients aged 12 to 17 years with herpes labialis. In this study, therapy was applied using the same dosing regimen as in adults and subjects were followed for adverse events. The safety profile was similar to that observed in adults.