ADAPALENE AND BENZOYL PEROXIDE

Adapalene and benzoyl peroxide gel 0.3%/2.5% is a white to very pale yellow opaque gel for topical use containing adapalene, USP 0.3% and benzoyl peroxide 2.5%. Adapalene USP, 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 Hydrous benzoyl peroxide, USP 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 gel, USP contains the following inactive ingredients: acrylamide/sodium acryloyldimethyl taurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water and sorbitan monooleate. Image Image

Adapalene and benzoyl peroxide gel is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older. Adapalene and benzoyl peroxide gel, 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 gel is not for oral, ophthalmic, or intravaginal use. Apply a thin layer of adapalene and benzoyl peroxide gel 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 gel may bleach hair or colored fabrics. Avoid the eyes, lips and mucous membranes. For topical use only Adapalene and benzoyl peroxide gel is not for oral, ophthalmic or intravaginal use. ( 2 ) Apply a thin layer of adapalene and benzoyl peroxide gel 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 gel is contraindicated in patients with a history of hypersensitivity reactions to benzoyl peroxide or any components of the formulation in adapalene and benzoyl peroxide gel. Adapalene and benzoyl peroxide gel is contraindicated in patients with a history of hypersensitivity reactions to benzoyl peroxide or any components of the formulation in adapalene and benzoyl peroxide gel. ( 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 Viona Pharmaceuticals Inc. at 1-888-304-5011 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 gel. 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 gel and for which the rate with adapalene and benzoyl peroxide gel 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 Gel, 0.3%/2.5% (N=217) Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% (N=217) Vehicle (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 (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 gel. 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.