Penciclovir

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 )

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 )

WARNINGS AND PRECAUTIONS • Only for topical use of herpes labialis on the lips and face. ( 5 ) 5.1 General Penciclovir Cream, 1% should only be used on herpes labialis on the lips and face. Because no data are available, application to human mucous membranes is not recommended. Particular care should be taken to avoid application in or near the eyes since it may cause irritation. Lesions that do not improve or that worsen on therapy should be evaluated for secondary bacterial infection. The effect of Penciclovir Cream, 1% has not been established in immunocompromised patients.

CONTRAINDICATIONS 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 )

DRUG INTERACTIONS 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.

ADVERSE REACTIONS 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.

Mechanism of Action Penciclovir is an antiviral agent active against alpha herpes viruses [see Microbiology (12.4) ]. Mechanism of Action Penciclovir has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). In cells infected with HSV-1 or HSV-2, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, α-herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Penciclovir triphosphate has an intracellular half-life of 10 hours in HSV-1 and 20 hours in HSV-2 infected cells grown in culture. However, the clinical significance of the intracellular half-life is unknown.