Chemically, clindamycin phosphate is (CHClNOPS). 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).

Chemically, Benzoyl peroxide (Benzoyl peroxide; erythromycin) is (CHO). It has the following structural formula:

Benzoyl peroxide (Benzoyl peroxide; erythromycin) has a molecular weight of 242.23.

Each gram of contains, as dispensed, 10 mg (1%) clindamycin as phosphate and 50 mg (5%) Benzoyl peroxide (Benzoyl peroxide; erythromycin) in a base of carbomer, propylene glycol, potassium hydroxide, and purified water.

An in vitro percutaneous penetration study comparing 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 is suggested to be less than 1%.

Benzoyl peroxide (Benzoyl peroxide; erythromycin) 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 (Benzoyl peroxide; erythromycin) 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 Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5%, 210 used Benzoyl peroxide (Benzoyl peroxide; erythromycin) , 168 used clindamycin, and 166 used vehicle. Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) 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 Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) 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 Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5% group showed greater overall improvement than the Benzoyl peroxide (Benzoyl peroxide; erythromycin) , clindamycin and vehicle groups as rated by the investigator.

Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5%

Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5%

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 colitis.

For dermatological use only; not for ophthalmic use. 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.

The use of antibiotic agents may be associated with the overgrowth of nonsusceptible organisms including fungi. If this occurs, discontinue use of this medication and take appropriate measures.

Avoid contact with eyes and mucous membranes.

Clindamycin and erythromycin containing products should not be used in combination. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this antagonism is not known.

Benzoyl peroxide (Benzoyl peroxide; erythromycin) has been shown to be a tumor promoter and progression agent in a number of animal studies. The clinical significance of this is unknown. Benzoyl peroxide (Benzoyl peroxide; erythromycin) in acetone at doses of 5 and 10 mg administered twice per week induced skin tumors in transgenic Tg.AC mice in a study using 20 weeks of topical treatment.

In a 52 week dermal photocarcinogenicity study in hairless mice, the median time to onset of skin tumor formation was decreased and the number of tumors per mouse increased following chronic concurrent topical administration of Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5% with exposure to ultraviolet radiation (40 weeks of treatment followed by 12 weeks of observation).

Genotoxicity studies were not conducted with Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5%. Clindamycin phosphate was not genotoxic in or in a rat micronucleus test. Clindamycin phosphate sulfoxide, an oxidative degradation product of clindamycin phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) , was not clastogenic in a mouse micronucleus test. Benzoyl peroxide (Benzoyl peroxide; erythromycin) has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with or Benzoyl peroxide (Benzoyl peroxide; erythromycin) to evaluate the effect on fertility. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 grams Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5%, based on mg/m2) revealed no effects on fertility or mating ability.

During clinical trials, the most frequently reported adverse event in the Clindamycin Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) 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 Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) 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 (Benzoyl peroxide; erythromycin) 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 Phosphate and Benzoyl peroxide (Benzoyl peroxide; erythromycin) Gel, 1%/5%

US Patents 5,733,886; 6,117,843

Distributed by: Morgantown, WV 26505

Manufactured by: Buffalo, NY 14213

090068

REVISED JUNE 2009DW-M-CLBZPX:R3