PENCICLOVIR

Penciclovir cream, 1% contains penciclovir, an antiviral agent active against herpes viruses. Penciclovir cream, 1% is available for topical administration as a 1% white to off-white homogenous cream. Each gram of penciclovir cream, 1% contains 10 mg of penciclovir and the following inactive ingredients: cetostearyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water and white petrolatum. Chemically, penciclovir is known as 9-[4-hydroxy-3-(hydroxymethyl)butyl] guanine. Its molecular formula is C 10 H 15 N 5 O 3 ; its molecular weight is 253.26. It is a synthetic acyclic guanine derivative and has the following structure: Figure 1: Structural Formula of Penciclovir Penciclovir is a white or off-white crystalline powder. At 20°C it has a solubility of 0.25 mg/mL in methanol, 1.67 mg/mL in propylene glycol, and 1.25 mg/mL in water. In aqueous buffer (pH 2) the solubility is 6.04 mg/mL. Penciclovir is not hygroscopic. Its partition coefficient in n-octanol/water is 0.03. Structural Formula

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)

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)

Penciclovir cream, 1% is contraindicated in patients with known hypersensitivity to the product or any of its components. Contraindicated in patients with known hypersensitivity to the product or any of its components. (4)

One or more local skin reactions were reported by 3% of the subjects treated with penciclovir cream, 1% and 4% of placebo-treated patients. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 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, 1% and 1,541 with placebo. One or more local adverse reactions were reported by 3% of the patients treated with penciclovir cream, 1% 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 1 2 Hypesthesia/Local anesthesia <1 <1 Taste perversion <1 <1 Rash (erythematous) <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 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of penciclovir cream, 1%. 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 post-marketing use of penciclovir cream, 1% 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 cream, 1%. General: Headache, oral/pharyngeal edema, parosmia. Skin: Aggravated condition, decreased therapeutic response, local edema, pain, paresthesia, pruritus, skin discoloration, and urticaria.

No drug interaction studies have been performed with penciclovir cream, 1%. Due to minimal systemic absorption of penciclovir cream, 1%, systemic drug interactions are unlikely.