Adapalene And Benzoyl Peroxide

1 INDICATIONS AND USAGE Adapalene and benzoyl peroxide topical 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 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 )

2 DOSAGE AND ADMINISTRATION For topical use only. Adapalene and benzoyl peroxide topical gel is not for oral, ophthalmic, or intravaginal use. Apply a thin layer of adapalene and benzoyl peroxide topical 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 topical gel may bleach hair or colored fabrics. Avoid the eyes, lips and mucous membranes. For topical use only Adapalene and benzoyl peroxide topical gel is not for oral, ophthalmic or intravaginal use. ( 2 ) Apply a thin layer of adapalene and benzoyl peroxide topical 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 )

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥1%) are skin irritation, eczema, atopic dermatitis and skin burning sensation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 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. 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 and for which the rate with adapalene and benzoyl peroxide topical 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 Adapalene and Benzoyl Peroxide Topical Gel, 0.3%/2.5% Benzoyl Peroxide Gel, 0.1%/2.5% Vehicle (N=217) (N=217) (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 End of Treatment Severity During Treatment (Final Score) Moderate Severe Moderate Severe Adapalene and Benzoyl Peroxide Topical 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 topical 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.

12.3 Pharmacokinetics A pharmacokinetic trial was conducted in 26 adult and adolescent subjects (12 to 33 years of age) with severe acne vulgaris who were treated with once-daily applications during a 4-week period with, on average, 2.3 grams/day (range 1.6 to 3.1 grams/day) of adapalene and benzoyl peroxide topical gel applied as a thin layer to the face, shoulders, upper chest and upper back. After a 4-week treatment, 16 subjects (62%) had quantifiable adapalene plasma concentrations above the limit of quantification of 0.1 ng/mL, with a mean C max of 0.16 ± 0.08 ng/mL and a mean AUC 0-24hr of 2.49 ± 1.21 ng.h/mL. The most exposed subject had adapalene C max and AUC 0-24hr of 0.35 ng/mL and 6.41 ng.h/mL, respectively. Excretion of adapalene appears to be primarily by the biliary route. Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine. Drug Interactions No formal drug-drug interaction studies were conducted with adapalene and benzoyl peroxide topical gel.