Label: CLINDAMYCIN AND BENZOYL PEROXIDE gel

Pharmacokinetics:

The pharmacokinetics (plasma and urine) of clindamycin from Clindamycin and Benzoyl Peroxide Gelwas studied in male and female patients (n=13) with acne vulgaris. Clindamycin and Benzoyl Peroxide Gel(~2g) was applied topically to the face and back twice daily for four and a half (4.5) days. Quantifiable (>LOQ=1 ng/mL) clindamycin plasma concentrations were obtained in six of thirteen subjects (46.2%) on Day 1 and twelve of thirteen subjects (92.3%) on Day 5. Peak plasma concentrations (C max) of clindamycin ranged from 1.47 ng/mL to 2.77 ng/mL on Day 1 and 1.43 ng/mL to 7.18 ng/mL on Day 5. The AUC (0 to 12h)ranged from 2.74 ng.h/mL to 12.86 ng.h/mL on Day 1 and 11.4 ng.h/mL to 69.7 ng.h/mL on Day 5.

The amount of clindamycin excreted in the urine during the 12 hour dosing interval increased from a mean (SD) of 5745 (3130) ng on Day 1 to 12069 (7660) ng on Day 5. The mean % (SD) of the administered dose that was excreted in the urine ranged from 0.03% (0.02) to 0.08% (0.04).

A comparison of the single (Day 1) and multiple (Day 5) dose plasma and urinary concentrations of clindamycin indicates that there is accumulation of clindamycin following multiple dosing of Clindamycin and Benzoyl Peroxide Gel. The degree of accumulation calculated from the plasma and urinary excretion data was ~2-fold.

Microbiology:

The clindamycin and benzoyl peroxide components individually have been shown to have in vitroactivity against Propionibacterium acnesan organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acneswas not examined in clinical trials with this product.

General:

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 non-susceptible 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 vitrostudies have shown antagonism between these two antimicrobials. The clinical significance of this in vitroantagonism is not known.

Information for Patients:

Patients using Clindamycin and Benzoyl Peroxide Gelshould receive the following information and instructions:

1. Clindamycin and Benzoyl Peroxide Gelis to be used as directed by the physician. It is for external use only. Avoid contact with eyes, and inside the nose, mouth, and all mucous membranes, as this product may be irritating.

2. This medication should not be used for any disorder other than that for which it was prescribed.

3. Patients should not use any other topical acne preparation unless otherwise directed by physician.

4. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using clindamycin and benzoyl peroxide gel. To minimize exposure to sunlight, a wide-brimmed hat or other protective clothing should be worn, and a sunscreen with SPF 15 rating or higher should be used.

5. Patients who develop allergic symptoms such as severe swelling or shortness of breath should discontinue Clindamycin and Benzoyl Peroxide Geland contact their physician immediately. In addition, patients should report any signs of local adverse reactions to their physician.

6. Clindamycin and Benzoyl Peroxide Gelmay bleach hair or colored fabric.

7. Clindamycin and Benzoyl Peroxide Gelcan be stored at room temperature up to 25°C (77°F) for 3 months. Do not freeze. Discard any unused product after 3 months.

8. Before applying Clindamycin and Benzoyl Peroxide Gelto affected areas wash the skin gently, then rinse with warm water and pat dry.

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Carcinogenesis, Mutagenesis, Impairment of Fertility:

Benzoyl peroxide 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 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 and benzoyl peroxide gel with exposure to ultraviolet radiation (40 weeks of treatment followed by 12 weeks of observation).

In a 2-year dermal carcinogenicity study in rats, treatment with clindamycin and benzoyl peroxide gel at doses of 100, 500 and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats. The incidence of keratoacanthoma at the treated site of males treated with 2000 mg/kg/day (8 times the highest recommended adult human dose of 2.5 g clindamycin and benzoyl peroxide gel based on mg/m 2) was statistically significantly higher than that in the sham- and vehicle-controls.

Genotoxicity studies were not conducted with clindamycin and benzoyl peroxide gel. Clindamycin phosphate was not genotoxic in Salmonella typhimuriumor in a rat micronucleus test. Clindamycin phosphate sulfoxide, an oxidative degradation product of clindamycin phosphate and benzoyl peroxide, was not clastogenic in a mouse micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimuriumtests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with Clindamycin and Benzoyl Peroxide Gelor benzoyl peroxide 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 g clindamycin and benzoyl peroxide gel, based on mg/m 2) revealed no effects on fertility or mating ability.

Pregnancy:

Teratogenic Effects: Pregnancy Category C:

Animal reproductive/developmental toxicity studies have not been conducted with clindamycin and benzoyl peroxide gel or benzoyl peroxide. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m 2, respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg/m 2, respectively) revealed no evidence of teratogenicity.

There are no well-controlled trials in pregnant women treated with Clindamycin and Benzoyl Peroxide Gel. It also is not known whether Clindamycin and Benzoyl Peroxide Gelcan cause fetal harm when administered to a pregnant woman.

Nursing Women:

It is not known whether Clindamycin and Benzoyl Peroxide Gelis excreted in human milk after topical application. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established.