Penciclovir

1 INDICATIONS AND USAGE Penciclovir cream 1% is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age or older. Penciclovir cream 1% is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and pediatric patients 12 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply penciclovir cream 1% every 2 hours during waking hours for a period of 4 days. Start treatment as early as possible (i.e., during the prodrome or when lesions appear). Apply penciclovir cream 1% every 2 hours during waking hours for a period of 4 days. ( 2 ) Start treatment as early as possible (i.e., during the prodrome or when lesions appear). ( 2 )

6 ADVERSE REACTIONS One or more local skin reactions were reported by 3% of the subjects treated with penciclovir and 4% of placebo-treated patients. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In two double-blind, placebo-controlled trials, 1,516 patients were treated with penciclovir cream and 1,541 with placebo. One or more local adverse reactions were reported by 3% of the patients treated with penciclovir cream and 4% of placebo-treated patients. The rates of reported local adverse reactions are shown in Table 1. TABLE 1: Local Adverse Reactions Reported in Phase III Trials Penciclovir N=1,516 % Placebo N=1,541 % Application site reaction Hypesthesia/Local anesthesia Taste perversion Rash (erythematous) 1 <1 <1 <1 2 <1 <1 <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. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of penciclovir. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following events have been identified from worldwide postmarketing use of penciclovir 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 penciclovir. General : Headache, oral/pharyngeal edema, parosmia. Skin : Aggravated condition, decreased therapeutic response, local edema, pain, paresthesia, pruritus, skin discoloration, and urticaria.

12.3 Pharmacokinetics Measurable penciclovir concentrations were not detected in plasma or urine of healthy male volunteers (n=12) following single or repeat application of the 1% cream at a dose of 180 mg penciclovir daily (approximately 67 times the estimated usual clinical dose). Pediatric Patients: The systemic absorption of penciclovir following topical administration has not been evaluated in patients <18 years of age.