Adapalene and Benzoyl Peroxide

ADAPALENE AND BENZOYL PEROXIDE- adapalene and benzoyl peroxide gel
Prasco Laboratories

1 INDICATIONS AND USAGE

Adapalene and Benzoyl Peroxide gel is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

2 DOSAGE AND ADMINISTRATION

For topical use only; Adapalene and Benzoyl Peroxide gel is not for oral, ophthalmic, or intravaginal use.

Apply a thin film 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). Avoid the eyes, lips and mucous membranes.

3 DOSAGE FORMS AND STRENGTHS

Each gram of Adapalene and Benzoyl Peroxide gel contains 1 mg (0.1%) adapalene and 25 mg (2.5%) benzoyl peroxide in a white to very pale yellow, opaque, aqueous based gel.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be minimized 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 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.

5.2 Local Cutaneous Reactions

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).

6 ADVERSE REACTIONS

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 gel. 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 gel and those reported in subjects treated with the vehicle gel 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

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.

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 gel or with the vehicle gel once daily for 12 weeks. Overall, the safety profile of Adapalene and Benzoyl Peroxide gel 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 adverse 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 gel: 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.

7 DRUG INTERACTIONS

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 drug-drug interaction studies were conducted with Adapalene and Benzoyl Peroxide gel.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C. There are no well-controlled trials in pregnant women treated with Adapalene and Benzoyl Peroxide gel. Animal reproduction studies have not been conducted with the combination gel or benzoyl peroxide. Furthermore, such studies are not always predictive of human response; therefore, Adapalene and Benzoyl Peroxide gel should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

No teratogenic effects were observed in rats treated with oral doses of 0.15 to 5.0 mg adapalene/kg/day, up to 25 times (mg/m² /day) the maximum recommended human dose (MRHD) of 2 grams of Adapalene and Benzoyl Peroxide gel. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of ≥ 25 mg adapalene/kg/day representing 123 and 246 times MRHD, respectively. Findings included cleft palate, microphthalmia, encephalocele and skeletal abnormalities in rats; and umbilical hernia, exophthalmos and kidney and skeletal abnormalities in rabbits.

Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day [25-59 times (mg/m²) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.

8.3 Nursing Mothers

It is not known whether adapalene or benzoyl peroxide is excreted in human milk following use of Adapalene and Benzoyl Peroxide gel. Because many drugs are excreted in human milk, caution should be exercised when Adapalene and Benzoyl Peroxide gel is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Adapalene and Benzoyl Peroxide gel in pediatric patients under the age of 9 have not been established.

8.5 Geriatric Use

Clinical studies of Adapalene and Benzoyl Peroxide gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.