XERESE

XERESE contains acyclovir, a synthetic nucleoside analogue active against herpes viruses, and hydrocortisone, an anti-inflammatory corticosteroid, combined in a cream for topical administration. Each gram of XERESE contains 50 mg (equivalent to 5%, w/w) of acyclovir, 10 mg (equivalent to 1%, w/w) of hydrocortisone and the following inactive ingredients: cetostearyl alcohol, citric acid monohydrate, isopropyl myristate, mineral oil, Poloxamer 188, propylene glycol, purified water, USP, sodium hydroxide, sodium lauryl sulfate, and white petrolatum. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH to approximately pH 5. Acyclovir, 2-Amino-9-[(2-hydroxyethoxy)methyl]-1,9-dihydro-6H-purin-6-one, is a synthetic nucleoside analogue active against herpes viruses. The maximum solubility of acyclovir in water at 37°C is 2.5 mg/mL. The pKa’s of acyclovir are 2.27 and 9.25. Its empirical formula is C 8 H 11 N 5 O 3 . The structural formula is provided in Figure 1: Figure 1: Structural Formula of Acyclovir Hydrocortisone, pregn-4-ene-3,20-dione, 11,17,21-trihydroxy- (11β), is an anti-inflammatory corticosteroid. Its empirical formula is C 21 H 30 O 5 . The structural formula is provided in Figure 2: Figure 2: Structural Formula of Hydrocortisone Structural Formula of Acyclovir Structural Formula of Hydrocortisone

XERESE, a combination of acyclovir, a herpes simplex virus deoxynucleoside analog DNA polymerase inhibitor, and hydrocortisone, a corticosteroid, is indicated for the early treatment of recurrent herpes labialis (cold sores) to reduce the likelihood of ulcerative cold sores and to shorten the lesion healing time in adults and children (6 years of age and older). XERESE, a combination of acyclovir, a herpes simplex virus deoxynucleoside analog DNA polymerase inhibitor, and hydrocortisone, a corticosteroid, is indicated for the early treatment of recurrent herpes labialis (cold sores) to reduce the likelihood of ulcerative cold sores and to shorten the lesion healing time in adults and children (6 years of age and older). (1)

Topically apply XERESE 5 times per day for 5 days. Therapy should be initiated as early as possible after the first signs and symptoms (i.e., during the prodrome or when lesions appear). For each dose, topically apply a quantity of XERESE sufficient to cover the affected area, including the outer margin. Avoid unnecessary rubbing of the affected area to avoid aggravating or transferring the infection. For children 6 years of age and older, the dosage is the same as in adults. Topically apply XERESE 5 times per day for 5 days. Therapy should be initiated as early as possible after the first signs and symptoms (i.e., during the prodrome or when lesions appear). (2)

None. None. (4)

The following most common adverse reactions (<1%) were local skin reactions: Drying or flaking of the skin; burning or tingling, erythema; pigmentation changes; application site reactions including signs and symptoms of inflammation. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Reactions in Clinical Trials Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice. The safety data derived from XERESE clinical trials reflect exposure to XERESE in 1,056 subjects with recurrent herpes labialis treated 5 times daily for 5 days. The most common adverse reactions (<1%) were local skin reactions, and occurred in the area of the application site, including: - Drying or flaking of the skin; burning or tingling following application; erythema; pigmentation changes; application site reaction including signs and symptoms of inflammation. Contact dermatitis following application has been observed when applied under occlusion in dermal safety trials. Where contact sensitivity tests have been conducted, the reactive substances were hydrocortisone or a component of the cream base. A trial enrolling 225 healthy adults was conducted to evaluate the contact sensitization potential of XERESE using repeat insult patch testing methodology. Of 205 evaluable subjects, one confirmed case (0.5%) of sensitization to hydrocortisone and 2 additional cases (1.0%) of possible sensitization to the XERESE base were identified. Additionally, one subject developed a contact allergy in the photosafety study to propylene glycol, one of the inactive ingredients of the cream base. Dermal tolerance was assessed in a 21-day cumulative irritation trial in 36 healthy subjects. XERESE, its cream base and Zovirax ® (acyclovir) Cream 5% all showed a high and cumulative irritation potential under occlusive and semi-occlusive conditions. Photoallergic potential and phototoxicity were assessed in two trials in 50 and 30 healthy volunteers, respectively. No photoallergic or phototoxicity potential was identified for XERESE.

No drug interaction studies have been performed with XERESE. No drug interaction studies have been performed with XERESE. (7)