Adapalene And Benzoyl Peroxide - Adapalene And Benzoyl Peroxide gel

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.

• 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.

Each gram of adapalene and benzoyl peroxide gel, USP contains 3 mg (0.3%) adapalene, USP and 25 mg (2.5%) benzoyl peroxide, USP in a white to very pale yellow opaque gel. Adapalene and benzoyl peroxide gel, USP is available in pumps containing 45 g or 60 g.

Available pharmacovigilance data with adapalene and benzoyl peroxide gel use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with the combination gel.

Available data from clinical trials with adapalene gel 0.3% use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of adapalene to pregnant rats and rabbits during organogenesis at dose exposures 41 and 81 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 2 g resulted in fetal skeletal and visceral malformations

The systemic exposure of benzoyl peroxide is unknown. Based on published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Hence, maternal use is not expected to result in fetal exposure of the drug.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

No malformations were observed in rats treated with oral adapalene doses of 0.15 mg/kg/day to 5 mg/kg/day, up to 8 times the MRHD of 2 grams of adapalene and benzoyl peroxide gel based on a mg/m² comparison. However, malformations were observed in rats and rabbits when treated with oral doses of ≥ 25 mg/kg/day adapalene (41 and 81 times the MRHD, respectively, based on a mg/m² comparison). Findings included cleft palate, microphthalmia, encephalocele, and skeletal abnormalities in rats and umbilical hernia, exophthalmos, and kidney and skeletal abnormalities in rabbits.

Dermal adapalene embryofetal development studies in rats and rabbits at doses up to 6 mg/kg/day (9.7 and 19.5 times the MRHD, respectively, based on a mg/m² comparison) exhibited no fetotoxicity and only minimal increases in skeletal variations (supernumerary ribs in both species and delayed ossification in rabbits).

• Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with the use of benzoyl peroxide products. (
  5.1 Hypersensitivity

  Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with the use of benzoyl peroxide products. If a serious hypersensitivity reaction occurs, discontinue adapalene and benzoyl peroxide gel immediately and initiate appropriate therapy.
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• Photosensitivity:
  Avoid exposure to sunlight and sunlamps. Wear broad spectrum sunscreen and protective clothing when sun exposure cannot be avoided. (
  5.2 Photosensitivity

  Avoid exposure to sunlight, including sunlamps, during the use of adapalene and benzoyl peroxide gel. Patients with high levels of sun exposure and those with inherent sensitivity to sun should exercise particular caution. Use of broad spectrum sunscreen products and protective apparel (e.g., hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with adapalene and benzoyl peroxide gel.
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• Skin Irritation:
  Erythema, scaling, dryness, stinging/burning, irritant and allergic contact dermatitis may occur with use of adapalene and benzoyl peroxide gel and may necessitate discontinuation. (
  5.3 Skin Irritation/Contact Dermatitis

  Erythema, scaling, dryness and stinging/burning may be experienced with use of adapalene and benzoyl peroxide gel. These are most likely to occur during the first four weeks of treatment, are mostly mild to moderate in intensity and usually lessen with continued use of the medication. Irritant and allergic contact dermatitis may occur. Depending upon the severity of these adverse reactions, patients should be instructed to use a moisturizer, reduce the frequency of the application of adapalene and benzoyl peroxide gel or discontinue use. The product should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of "waxing" as a depilatory method should be avoided on skin treated with adapalene and benzoyl peroxide gel.

  Avoid concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices or limes).
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