ADAPALENE AND BENZOYL PEROXIDE

Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is a white to very pale yellow, opaque gel for topical use containing adapalene 0.3% and benzoyl peroxide 2.5%. Adapalene, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene is (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid). It has the following structural formula: Adapalene: Molecular formula: C 28 H 28 O 3 Molecular weight: 412.5 Benzoyl Peroxide is a highly lipophilic oxidizing agent that localizes in both bacterial and keratinocyte cell membranes. The chemical name for benzoyl peroxide is dibenzoyl peroxide. It has the following structural formula: Benzoyl Peroxide: Molecular formula: C 14 H 10 O 4 Molecular weight: 242.23 Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% contains the following inactive ingredients: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.

Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older. Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is a combination of adapalene, a retinoid, and benzoyl peroxide, and is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older. ( 1 )

• For topical use only. Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is not for oral, ophthalmic, or intravaginal use. • Apply a thin layer of Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% to affected areas of the face and/or trunk once daily after washing. • Use a pea-sized amount for each area of the face (e.g., forehead, chin, each cheek). • Wash hands after application as Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% may bleach hair or colored fabrics. • Avoid the eyes, lips and mucous membranes. • For topical use only • Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is not for oral, ophthalmic, or intravaginal use. ( 2 ) • Apply a thin layer of Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% to affected areas of the face and/or trunk once daily after washing. ( 2 ) • Use a pea-sized amount for each area of the face (e.g., forehead, chin, each cheek). ( 2 ) • Avoid the eyes, lips, and mucous membranes. ( 2 )

Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is contraindicated in patients with a history of hypersensitivity reactions to benzoyl peroxide or any components of the formulation in Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5%. • Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% is contraindicated in patients with a history of hypersensitivity reactions to benzoyl peroxide or any components of the formulation in Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5%. ( 4 )

The most common adverse reactions (incidence ≥1%) are skin irritation, eczema, atopic dermatitis and skin burning sensation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The following adverse reactions are discussed in greater detail elsewhere in the labeling: • Hypersensitivity [see Warnings and Precautions ( 5.1 )] • Skin Irritation/Contact Dermatitis [see Warnings and Precautions ( 5.3 )] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. During the randomized, double-blind, vehicle- and active-controlled clinical trial, 217 subjects were exposed to adapalene and benzoyl peroxide topical gel, 0.3%/2.5%. A total of 197 subjects with acne vulgaris, 12 years and older, were treated once daily for 12 weeks. Adverse reactions reported within 12 weeks of treatment in at least 1% of subjects treated with adapalene and benzoyl peroxide topical gel, 0.3%/2.5% and for which the rate with adapalene and benzoyl peroxide topical gel, 0.3%/2.5% exceeded the rate for the vehicle are presented in Table 1: Table 1. Adverse Reactions Occurring in ≥1% of Subjects with Acne Vulgaris in a 12-week Clinical Trial Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% (N=217) Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% (N=217) Vehicle Gel (N=69) Skin irritation 4% <1% 0% Eczema 1% 0% 0% Dermatitis atopic 1% 0% 0% Skin burning sensation 1% 0% 0% Local tolerability evaluations, presented in Table 2, were conducted at each trial visit in the clinical trial by assessment of erythema, scaling, dryness, and stinging/burning, which peaked at Week 1 of therapy and decreased thereafter. Table 2. Incidence of Local Cutaneous Irritation in 12-week Clinical Trial in Subjects with Acne Vulgaris Maximum Severity During Treatment End of Treatment Severity (Final Score) Moderate Severe Moderate Severe Adapalene and Benzoyl Peroxide Gel, 0.3%/2.5% (N=213) Erythema 20% 1% 4% <1% Scaling 17% 1% 1% <1% Dryness 15% 2% 3% <1% Stinging/burning 19% 6% 1% 1% Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% (N=212) Erythema 15% 1% 2% <1% Scaling 12% <1% 2% 0% Dryness 13% 1% 2% 0% Stinging/burning 14% 9% 3% 0% Vehicle Gel (N=68) Erythema 6% 1% 1% 0% Scaling 6% 0% 1% 0% Dryness 4% 1% 1% 0% Stinging/burning 3% 1% 0% 0% 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of adapalene and benzoyl peroxide topical gel, 0.3%/2.5%. 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. Skin and subcutaneous tissue disorders: sunburn, blister (including vesicles and bullae), pruritus, hyperpigmentation and hypopigmentation.