Label: CLINDAMYCIN AND BENZOYL PEROXIDE kit

Topical Gel: clindamycin (1%) as clindamycin phosphate, benzoyl peroxide (5%)

For Dermatological Use Only - Not for Ophthalmic Use

*Reconstitute Before Dispensing*

Clindamycin and benzoyl peroxide topical gel, 1%/5% contains clindamycin phosphate, (7(S)-chloro-7-deoxylincomycin-2-phosphate). Clindamycin phosphate is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin.

Chemically, clindamycin phosphate is (C18H34ClN2O8PS). The structural formula for clindamycin is represented below:

Clindamycin phosphate has a molecular weight of 504.97 and its chemical name is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido) - 1-thio-L- threo-alpha-D-galacto-octopyranoside 2-(dihydrogen phosphate).

Clindamycin and benzoyl peroxide topical gel, 1%/5% also contains benzoyl peroxide, for topical use.

Chemically, benzoyl peroxide is (C14H10O4). It has the following structural formula:

Benzoyl peroxide has a molecular weight of 242.23.

Each gram of clindamycin and benzoyl peroxide topical gel, 1%/5% contains, as dispensed, 10 mg (1%) clindamycin as phosphate and 50 mg (5%) benzoyl peroxide in a base of carbomer homopolymer type C, sodium hydroxide, dioctyl sodium sulfosuccinate, and purified water.

An in vitro percutaneous penetration study comparing clindamycin and benzoyl peroxide topical gel, 1%/5% and topical 1% clindamycin gel alone, demonstrated there was no statistical difference in penetration between the two drugs. Mean systemic bioavailability of topical clindamycin in clindamycin and benzoyl peroxide topical gel, 1%/5% is suggested to be less than 1%.

Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. Less than 2% of the dose enters systemic circulation as benzoic acid. It is suggested that the lipophilic nature of benzoyl peroxide acts to concentrate the compound into the lipid-rich sebaceous follicle.

In two adequate and well controlled clinical studies of 758 patients, 214 used clindamycin and benzoyl peroxide topical gel, 1%/5%, 210 used benzoyl peroxide, 168 used clindamycin, and 166 used vehicle. Clindamycin and benzoyl peroxide topical gel, 1%/5% applied twice daily for 10 weeks was significantly more effective than vehicle in the treatment of moderate to moderately severe facial acne vulgaris. Patients were evaluated and acne lesions counted at each clinical visit; weeks 2, 4, 6, 8 and 10. The primary efficacy measures were the lesion counts and the investigator’s global assessment evaluated at week 10. Patients were instructed to wash the face with a mild soap, using only the hands. Fifteen minutes after the face was thoroughly dry, application was made to the entire face. Non-medicated make-up could be applied at one hour after the clindamycin and benzoyl peroxide topical gel, 1%/5% application. If a moisturizer was required, the patients were provided a moisturizer to be used as needed. Patients were instructed to avoid sun exposure. Percent reductions in lesion counts after treatment for 10 weeks in these two studies are shown below:

The clindamycin and benzoyl peroxide topical gel, 1%/5% group showed greater overall improvement than the benzoyl peroxide, clindamycin and vehicle groups as rated by the investigator.

Clindamycin and benzoyl peroxide topical gel, 1%/5% is indicated for the topical treatment of acne vulgaris.

Clindamycin and benzoyl peroxide topical gel, 1%/5% is contraindicated in those individuals who have shown hypersensitivity to any of its components or to lincomycin. It is also contraindicated in those having a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.

ORALLY AND PARENTERALLY ADMINISTERED CLINDAMYCIN HAS BEEN ASSOCIATED WITH SEVERE COLITIS WHICH MAY RESULT IN PATIENT DEATH. USE OF THE TOPICAL FORMULATION OF CLINDAMYCIN RESULTS IN ABSORPTION OF THE ANTIBIOTIC FROM THE SKIN SURFACE. DIARRHEA, BLOODY DIARRHEA, AND COLITIS (INCLUDING PSEUDOMEMBRANOUS COLITIS) HAVE BEEN REPORTED WITH THE USE OF TOPICAL AND SYSTEMIC CLINDAMYCIN. STUDIES INDICATE A TOXIN(S) PRODUCED BY CLOSTRIDIA IS ONE PRIMARY CAUSE OF ANTIBIOTIC-ASSOCIATED COLITIS. THE COLITIS IS USUALLY CHARACTERIZED BY SEVERE PERSISTENT DIARRHEA AND SEVERE ABDOMINAL CRAMPS AND MAY BE ASSOCIATED WITH THE PASSAGE OF BLOOD AND MUCUS. ENDOSCOPIC EXAMINATION MAY REVEAL PSEUDOMEMBRANOUS COLITIS. STOOL CULTURE FOR Clostridium Difficile AND STOOL ASSAY FOR C. difficile TOXIN MAY BE HELPFUL DIAGNOSTICALLY. WHEN SIGNIFICANT DIARRHEA OCCURS, THE DRUG SHOULD BE DISCONTINUED. LARGE BOWEL ENDOSCOPY SHOULD BE CONSIDERED TO ESTABLISH A DEFINITIVE DIAGNOSIS IN CASES OF SEVERE DIARRHEA. ANTIPERISTALTIC AGENTS SUCH AS OPIATES AND DIPHENOXYLATE WITH ATROPINE MAY PROLONG AND/OR WORSEN THE CONDITION. DIARRHEA, COLITIS, AND PSEUDOMEMBRANOUS COLITIS HAVE BEEN OBSERVED TO BEGIN UP TO SEVERAL WEEKS FOLLOWING CESSATION OF ORAL AND PARENTERAL THERAPY WITH CLINDAMYCIN.

Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

During clinical trials, the most frequently reported adverse event in the clindamycin and benzoyl peroxide topical gel, 1%/5% treatment group was dry skin (12%). The Table below lists local adverse events reported by at least 1% of patients in the clindamycin and benzoyl peroxide topical gel, 1%/5% and vehicle groups.

The actual incidence of dry skin might have been greater were it not for the use of a moisturizer in these studies.

Anaphylaxis, as well as allergic reactions leading to hospitalization, have been reported during post-marketing use of clindamycin/benzoyl peroxide products. 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.

Clindamycin and benzoyl peroxide topical gel, 1%/5% should be applied twice daily, morning and evening, or as directed by a physician, to affected areas after the skin is gently washed, rinsed with warm water and patted dry.

Prior to dispensing, tap the vial until powder flows freely. Add indicated amount of purified water to the vial (to the mark) and immediately shake to completely dissolve clindamycin. If needed, add additional purified water to bring level up to the mark. Add the solution in the vial to the gel and stir until homogenous in appearance (1 to 1½ minutes). For the 35 and 50 gram pumps only, reassemble jar with pump dispenser. Clindamycin and benzoyl peroxide topical gel, 1%/5% (as reconstituted) can be stored at room temperature up to 25°C (77°F) for 3 months. Place a 3 month expiration date on the label immediately following mixing.

Store at room temperature up to 25ºC (77ºF) {See USP}.

Do not freeze. Keep tightly closed.

Keep out of the reach of children.

Rx Only

Manufactured By Padagis

Yeruham, Israel

Distributed By PadagisTM

Allegan, MI 49010

www.padagis.com

Rev 03-22

8R500 RC J6

Rx Only

Clindamycin and Benzoyl Peroxide Topical Gel, 1%/5%

For Topical Use Only

Reconstitute with clindamycin phosphate vial

One 35g Pump (after reconstitution)

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