adapalene/benzoyl peroxide (Rx)

>10%

Stinging/ burning (3-41%)

Dryness (1-41%)

Scaling (1-35%)

Erythema (1-27%)

1-10%

Contact dermatitis (3%)

Application site burning (2%)

Application site irritation (1%)

Skin irritation (1%)

Postmarketing Reports

Allergic contact dermatitis

Blister

Conjunctivitis

Eczema

Eyelid edema

Local skin pain

Pruritus

Rash

Swelling

Skin discoloration

Sunburn

Throat tightness

Hyperpigmentation and hypopigmentation

Contraindications

Hypersensitivity to adapalene, benzoyl peroxide or any of its components

Cautions

Avoid eyes, lips, and mucous membranes

For external use only

Do not apply to abrasions, cuts, eczematous or sunburned skin

Do not wax treated area or apply topical products that may further irritate skin (eg, astringents, abrasive soaps, and cleansers, exfoliants)

Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, reported with use of benzoyl peroxide products; if a serious hypersensitivity reaction occurs, discontinue treatment immediately and initiate appropriate therapy

Avoid exposure to sunlight, including sunlamps, during use; 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 (eg, hat) are recommended when exposure cannot be avoided; weather extremes, such as wind or cold, may be irritating to patients under treatment

Patients with high levels of sun exposure and those with inherent sensitivity to sun should exercise particular caution

Use of sunscreen products and protective apparel, (eg, hat) are recommended when exposure cannot be avoided

Weather extremes, such as wind or cold, may be irritating to patients under treatment

Erythema, scaling, dryness, and stinging/burning may be experienced with use; these are most likely to occur during first four weeks of treatment, are mostly mild to moderate in intensity, and usually lessen with continued use of medication

Irritant and allergic contact dermatitis may occur; depending upon severity of these adverse reactions, patients should be instructed to use a moisturizer, reduce frequency of application, 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 this 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)

Pregnancy

Available pharmacovigilance data 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

Adapalene gel, 0.3%

• 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 maximum recommended human dose (MRHD) of 2 g resulted in fetal skeletal and visceral malformations

Benzoyl peroxide gel, 2.5%

• 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

Lactation

Adapalene gel, 0.3%

• There are no data on presence of adapalene topical gel or its metabolite in human milk, effects on breastfed infant, or effects on milk production; in animal studies, adapalene is present in rat milk with oral administration of the drug
• When a drug is present in animal milk, it is likely that the drug will be present in human milk; it is possible that topical administration of large amounts of adapalene could result in sufficient systemic absorption to produce detectable quantities in human milk

Benzoyl peroxide gel, 2.5%

• 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; any amount of benzoyl peroxide excreted into human milk by a nursing mother would be expected to be rapidly metabolized by tissue and stomach esterases; there are no data on presence of benzoyl peroxide in human milk, its effects on breastfed infant or on milk production
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for therapy and any potential adverse effects on breastfed child from the medication or from the underlying maternal condition.
• To minimize potential exposure to the breastfed infant via breastmilk, use the medication on the smallest area of skin and for shortest duration possible while breastfeeding; advise breastfeeding women not to apply the drug directly to the nipple and areola to avoid direct infant exposure

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Adapalene: Binds to specific retinoic acid nuclear receptors and modulates cellular differentiation, keratinization and inflammatory processes; exact mechanism of action for treatment of acne is unknown

Benzoyl peroxide: Elicits action by releasing active oxygen; effective in vitro against Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones; also elicits a keratolytic and desquamative effect which may also contribute to its efficacy

Pharmacokinetics

Absorption: Benzoyl peroxide absorbed by the skin where it is converted to benzoic acid

Excretion: adapalene (bile), benzoyl peroxide (urine)

Instructions

For topical use only; not for ophthalmic, oral, or intravaginal use

Avoid mucous membranes, eyes, and lips

Apply pea-sized amount for each facial area (eg, chin, forehead, cheek)