ADAPALENE AND BENZOYL PEROXIDE 0.1%/2.5% GEL PAD

Adapalene and benzoyl peroxide, 0.1% / 2.5% is a 1.2g gel pad for topical use containing adapalene USP, 0.1% and benzoyl peroxide USP, 2.5%. Adapalene USP, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene, USP is (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid). It has the following structural formula: Adapalene, USP: Molecular formula: C 28 H 28 O 3 Molecular weight: 412.5 Benzoyl Peroxide, USP is a highly lipophilic oxidizing agent that localizes in both bacterial and keratinocyte cell membranes. The chemical name for benzoyl peroxide, USP is dibenzoyl peroxide. It has the following structural formula: Benzoyl Peroxide, USP: Molecular formula: C 14 H 10 O 4 Molecular weight: 242.23 Inactive ingredients: carbomer 980, docusate sodium, edetate disodium, glycerin, poloxamer 182, polysorbate 80, propylene glycol, purified water, sorbitan monooleate and xanthan gum. Adapalene Chemical Structure Benzoyl Peroxide Chemical Structure

Adapalene and benzoyl peroxide gel pad 0.1% / 2.5% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. Adapalene and benzoyl peroxide gel pad 0.1% / 2.5% is a combination of adapalene, a retinoid, and benzoyl peroxide, and is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. ( 1 )

For topical use only; adapalene and benzoyl peroxide gel pad is not for oral, ophthalmic, or intravaginal use. Apply adapalene and benzoyl peroxide gel pad to affected areas of the face and/or trunk once daily after washing. Use pad for area of the face (e.g., forehead, chin, each cheek). Avoid the eyes, lips and mucous membranes. Adapalene and benzoyl peroxide gel pad is not for oral, ophthalmic, or intravaginal use. ( 2 ) Apply adapalene and benzoyl peroxide gel pad to affected areas of the face and/or trunk once daily after washing. Use pad amount for area of the face (e .g., fore head, chin, each cheek). Avoid the eyes, lips and mucous membranes. ( 2 )

None None. ( 4 )

Most commonly reported adverse events (greater than or equal to 1%) in patients treated with adapalene and benzoyl peroxide were dry skin, contact dermatitis, application site burning, application site irritation and skin irritation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Gabar at 1-470-737-9424 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience 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 clinical trials, 1401 subjects were exposed to adapalene and benzoyl peroxide. A total of 1036 subjects with acne vulgaris, 12 years and older, were treated once daily for 12 weeks to 12 months. Related adverse events reported within 12 weeks of treatment and in at least 1% of subjects treated with adapalene and benzoyl peroxide and those reported in subjects treated with the vehicle are presented in Table 1: Table 1. Drug Related Adverse Events Reported in Clinical Trials by At Least 1% of Patients Treated For 12 Weeks System Organ Class/ Preferred Term Adapalene and Benzoyl Peroxide N=564 Vehicle N=489 Subjects with AE (s) 14% 4% Dry Skin 7% 2% Contact dermatitis 3% <1% Application site burning 2% <1% Application site irritation 1% <1% Skin irritation 1% 0% Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials by assessment of erythema, scaling, dryness, burning, and stinging. Table 2. Incidence of Local Cutaneous Irritation in Controlled Clinical Trials (N=553) Treatment Emergent Signs and Symptoms Maximum Severity During Treatment End of Treatment Severity (12 Weeks) Mild Moderate Severe Mild Moderate Severe Erythema 27% 13% 1% 8% 2% 1% Scaling 35% 11% 1% 9% 1% <1% Dryness 41% 13% 1% 10% 2% <1% Stinging/burning 41% 15% 3% 7% 2% 1% Analysis over the 12 week period showed that local tolerability scores for erythema, scaling, dryness, and stinging/burning peaked at Week 1 of therapy and decreased thereafter. During a pediatric clinical trial, 285 children with acne vulgaris, 9 to 11 years of age were treated with adapalene and benzoyl peroxide or with the vehicle once daily for 12 weeks. Overall, the safety profile of adapalene and benzoyl peroxide in these subjects is comparable to the safety profile observed in older subjects 12 years of age and above, both in the nature and frequency of the observed events. Analysis of local tolerability evaluations shows similar incidence of treatment emergent signs and symptoms as in subjects 12 years of age and above, with local tolerability signs and symptoms peaking during the first week and decreasing over time. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of adapalene and benzoyl peroxide: eyelid edema, sunburn, blister, pain of skin, pruritus, swelling face, conjunctivitis, skin discoloration, rash, eczema, throat tightness and allergic contact dermatitis. 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.

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. No formal drugdrug interaction studies were conducted with adapalene and benzoyl peroxide.