EPIDUO gel is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

For topical use only; EPIDUO gel is not for oral, ophthalmic, or intravaginal use.

Apply a thin film of EPIDUO 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.

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

None

Erythema, scaling, dryness, and stinging/burning may be experienced with use of EPIDUO 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 EPIDUO 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 EPIDUO 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).

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 EPIDUO 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 EPIDUO gel and those reported in subjects treated with the vehicle gel are presented in :

Local tolerability evaluations, presented in , 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.

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 EPIDUO gel.

Pregnancy Category C. There are no well-controlled trials in pregnant women treated with EPIDUO 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, EPIDUO 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 (Adapalene) /kg/day, up to 25 times (mg/m/day) the maximum recommended human dose (MRHD) of 2 grams of EPIDUO gel. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of ≥ 25 mg Adapalene (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 (Adapalene) /kg/day [25-59 times (mg/m) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.

EPIDUO (Adapalene (Adapalene) and benzoyle peroxide) gel, 0.1%/2.5% is a white to very pale yellow, opaque gel for topical use containing Adapalene (Adapalene) 0.1%  and benzoyl peroxide 2.5%.

Adapalene (Adapalene) , a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties.  The chemical name for Adapalene (Adapalene) is (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-  naphthoic acid). It has the following structural formula:

Adapalene (Adapalene) :

Benzoyl Peroxide is a highly lipophilic oxidizing agent that localizes in both bacterial and keratinocyte cell membranes.  The chemical name for benzoyl peroxide is dibenzoyl peroxide.  It has the following structural formula:

Benzoyl Peroxide:

EPIDUO gel contains the following inactive ingredients: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.

Adapalene (Adapalene)
Adapalene (Adapalene) binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that Adapalene (Adapalene) is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of Adapalene (Adapalene) for the treatment of acne is unknown.

Benzoyl peroxide
Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects.

A pharmacokinetic study was conducted in 24 subjects with acne vulgaris who were treated once daily for 30 days with 2 grams/day of EPIDUO gel applied to 1000 cm of acne involved skin, (face, chest, and upper back).

Two subjects (20%) had quantifiable Adapalene (Adapalene) plasma concentrations above the limit of quantification (LOQ = 0.1ng/mL). The highest Adapalene (Adapalene) C and AUC was 0.21 ng/mL and 1.99 ng•h/mL, respectively. Excretion of Adapalene (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.

The safety and efficacy of EPIDUO gel applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing EPIDUO gel to the gel vehicle in acne subjects.

Treatment response was defined as the percent of subjects who had a two grade improvement and rated ‘Clear’ and ‘Almost Clear’ at Week 12 based on the Investigator's Global Assessment (IGA) and mean absolute change from baseline at Week 12 in both inflammatory and non-inflammatory lesion counts. An IGA score of 'Clear' corresponded to residual hyperpigmentation  and erythema may be present. An IGA score of ‘Almost Clear’ corresponded to a few scattered comedones and a few small papules.

In Study 1, 517 subjects were randomized to EPIDUO gel, Adapalene (Adapalene) 0.1% in vehicle gel, benzoyl peroxide 2.5% in vehicle gel, or vehicle gel. The median age of these 517 subjects was 15 years old and 60% were males. At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions. The majority of subjects had a baseline IGA score of ‘Moderate’ which corresponded to more than half of the face is involved, many comedones, papules and pustules. The efficacy results at week 12 are presented in .

In Study 2, 1668 subjects were randomized to EPIDUO gel, Adapalene (Adapalene) 0.1% in vehicle gel, benzoyl peroxide 2.5% in vehicle gel, or vehicle gel. The median age of subjects was 16 years old and 49% were males. At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions as well as an Investigator Global Assessment score of ‘Moderate’. The efficacy results at week 12 are presented in .

In both Studies 1 and 2 the treatment effect was smaller in subjects with a small number of baseline lesions than in subjects with a large number of baseline lesions.

EPIDUO (Adapalene (Adapalene) and benzoyl peroxide) gel 0.1% / 2.5% is white to very pale yellow in color and opaque in appearance, and is supplied as follows:

45 gram tube         NDC 0299-5908-4545 gram pump       NDC 0299-5908-25

Storage and handling

Information for Patients

Patient Information EPIDUO® (Ep-E-Do-Oh) (Adapalene (Adapalene) and benzoyl peroxide) gel 0.1%/2.5%

Read this Patient Information leaflet about EPIDUO gel before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your treatment or your medical condition. If you have any questions about EPIDUO gel, talk with your doctor or pharmacist.

Acne vulgaris is a condition in which the skin has blackheads, whiteheads and pimples.

It is not known if EPIDUO gel is safe and effective in children younger than 12 years old.

Especially tell your doctor if you use any other medicine for acne.  Using EPIDUO gel with topical medicines that contain sulfur, resorcinol or salicylic acid may cause skin irritation.

Know the medicines you take.  Keep a list of them to show your doctor and pharmacist when you get a new medicine.

Tell your doctor right away if these side effects continue for longer than 4 weeks or get worse, you may have to stop using EPIDUO gel.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of EPIDUO gel.  For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to GALDERMA LABORATORIES, L.P. at 1-866-735-4137

This Patient Information leaflet summarizes the most important information about EPIDUO gel. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about EPIDUO gel that is written for health professionals.

Revised:  June 2011

Marketed by:GALDERMA LABORATORIES, L.P., Fort Worth, Texas 76177 USAManufactured by:Galderma Production Canada Inc., Baie d’Urfé, QC, H9X 3S4 CanadaMade in Canada.GALDERMA is a registered trademark.XXXXX-X

FOR TOPICAL USE ONLY

NET WT. 45 g

Lot no. and expiration date on crimp.

Marketed by:GALDERMA LABORATORIES, L.P.14501 North Freeway, Fort Worth, TX 76177 USAManufactured by:Galderma Production Canada Inc.Baie d’Urfé, QC, H9X 3S4 CanadaMade in Canada.Galderma is a registered trademark. P51651-0

PUMP

FOR TOPICAL USE ONLY

NET WT. 45 g

See package insert for complete prescribing information.

Marketed by:GALDERMA LABORATORIES, L.P.14501 North Freeway, Fort Worth, TX 76177 USAManufactured by:Galderma Production Canada Inc.Baie d’Urfé, QC, H9X 3S4 CanadaMade in Canada. Galderma is a registered trademark.