Denavir

1 INDICATIONS AND USAGE DENAVIR 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. DENAVIR ® is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and pediatric patients12 years of age and older.

Apply DENAVIR 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 DENAVIR 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).

5 WARNINGS AND PRECAUTIONS • Only for topical use of herpes labialis on the lips and face.

5.1General

DENAVIR 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 DENAVIR has not been established in immunocompromised patients.

4 CONTRAINDICATIONS DENAVIR 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.

8.1Pregnancy Risk Summary

DENAVIR is not absorbed systemically following topical administration and maternal use is not expected to result in fetal exposure to the drug.

6 ADVERSE REACTIONS • One or more local skin reactions were reported by 3% of the subjects treated with DENAVIR and 4% of placebo-treated patients. To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 DENAVIR (penciclovir cream) and 1,541 with placebo. One or more local adverse reactions were reported by 3% of the patients treated with DENAVIR 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.

6.2Post-Marketing Experience The

following adverse reactions have been identified during post-approval use of DENAVIR. 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 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. General: Headache, oral/pharyngeal edema, parosmia.

Skin: Aggravated condition, decreased therapeutic response, local edema, pain, paresthesia, pruritus, skin discoloration, and urticaria.