CLINDAMYCIN AND BENZOYL PEROXIDE- clindamycin and benzoyl peroxide_gel

CLINICAL PHARMACOLOGY
An in vitro Clindamycin and Benzoyl Peroxide Gel Clindamycin and Benzoyl Peroxide Gel 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. The pharmacokinetics (plasma and urine) of clindamycin from Clindamycin and Benzoyl Peroxide Gel Clindamycin and Benzoyl Peroxide Gel max (0 to 12h) 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. 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 clindamycin and benzoyl peroxide components individually have been shown to have in vitro Propionibacterium acnes P.
Pharmacokinetics:
The pharmacokinetics (plasma and urine) of clindamycin from Clindamycin and Benzoyl Peroxide Gel Clindamycin and Benzoyl Peroxide Gel max (0 to 12h) 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
Microbiology:
The clindamycin and benzoyl peroxide components individually have been shown to have in vitro Propionibacterium acnes P. acnes

Clindamycin and Benzoyl Peroxide Gel

Clindamycin and Benzoyl Peroxide Gel

During clinical trials, the most frequently reported adverse event in the clindamycin and benzoyl peroxide gel 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 gel and vehicle groups. Local Adverse Events en dash all causalities in >/= 1% of patients Clindamycin and Benzoyl Peroxide n=420 Vehicle n=168 Application site reaction 13 (3%) 1 (<1%) Dry skin 50 (12%) 10 (6%) Pruritus 8 (2%) 1 (<1%) Peeling 9 (2%) - Erythema 6 (1%) 1 (<1%) Sunburn 5 (1%) - 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 Gel

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 2 There are no well-controlled trials in pregnant women treated with Clindamycin and Benzoyl Peroxide Gel Clindamycin and Benzoyl Peroxide Gel
Nursing Women:
It is not known whether Clindamycin and Benzoyl Peroxide Gel
Pediatric Use:
Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established.

CLINICAL STUDIES
In two adequate and well controlled clinical studies of 758 patients, 214 used clindamycin and benzoyl peroxide gel, 210 used benzoyl peroxide, 168 used clindamycin, and 166 used vehicle. Clindamycin and benzoyl peroxide gel 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 gel 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: Study 1 Clindamycin and Benzoyl Peroxide Benzoyl Peroxide Clindamycin Vehicle Mean percent reduction in inflammatory lesion counts 46% 32% 16% +3% Mean percent reduction in non-inflammatory lesion counts 22% 22% 9% +1% Mean percent reduction in total lesion counts 36% 28% 15% 0.2% Study 2 Clindamycin and Benzoyl Peroxide Benzoyl Peroxide Clindamycin Vehicle Mean percent reduction in inflammatory lesion counts 63% 53% 45% 42% Mean percent reduction in non-inflammatory lesion counts 54% 50% 39% 36% Mean percent reduction in total lesion counts 58% 52% 42% 39% The clindamycin and benzoyl peroxide gel group showed greater overall improvement than the benzoyl peroxide, clindamycin and vehicle groups as rated by the investigator.
WARNINGS
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 C. difficile 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
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 Genotoxicity studies were not conducted with clindamycin and benzoyl peroxide gel. Clindamycin phosphate was not genotoxic in Salmonella typhimurium S. typhimurium Clindamycin and Benzoyl Peroxide Gel 2

REMEDYREPACK INC.

CLINDAMYCIN AND BENZOYL PEROXIDE- clindamycin and benzoyl peroxide_gel Product manual source documgent