ADVERSE REACTIONS In two double-blind, placebo-controlled trials, 1516 patients were treated with Denavir (penciclovir cream) and 1541 with placebo. The most frequently reported adverse event was headache, which occurred in 5.3% of the patients treated with Denavir and 5.8% of the placebo-treated patients. The rates of reported local adverse reactions are shown in Table 2 below. One or more local adverse reactions were reported by 2.7% of the patients treated with Denavir and 3.9% of placebo-treated patients. Table 2 - Local Adverse Reactions Reported in Phase III Trials Penciclovir n=1516 % Placebo N=1541 % Applications site reaction 1.3 1.8 Hypesthesia/Local anesthesia 0.9 1.4 Taste perversion 0.2 0.3 Pruritus 0.0 0.3 Pain 0.0 0.1 Rash (erythematous) 0.1 0.1 Allergic reaction 0.0 0.1 Two studies, enrolling 108 healthy subjects, were conducted to evaluate the dermal tolerance of 5% penciclovir cream (a 5-fold higher concentration than the commercial formulation) compared to vehicle using repeated occluded patch testing methodology. The 5% penciclovir cream induced mild erythema in approximately one-half of the subjects exposed, an irritancy profile similar to the vehicle control in terms of severity and proportion of subjects with a response. No evidence of sensitization was observed. Post-Marketing Experience The following events have been identified from worldwide post-marketing use of Denavir in treatment of recurrent herpes labialis (cold sores) in adults. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Denavir cream. General: Headache, oral/pharyngeal edema, parosmia. Skin: Application site reactions, aggravated condition, decreased therapeutic response, erythematous rash, local edema, pain, paresthesia, pruritus, skin discoloration and urticaria.