Clindamycin and Benzoyl Peroxide

CLINDAMYCIN AND BENZOYL PEROXIDE-
Perrigo New York Inc

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

For Dermatological Use Only — Not for Ophthalmic Use

*Reconstitute Before Dispensing*

DESCRIPTION

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 (C18 H34 ClN2 O8 PS). The structural formula for clindamycin is represented below:

Chemical Structure
(click image for full-size original)

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 (C14 H10 O4 ). It has the following structural formula:

Chemical Structure

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.

CLINICAL PHARMACOLOGY

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.

Pharmacokinetics:

The pharmacokinetics (plasma and urine) of clindamycin from clindamycin and benzoyl peroxide topical gel, 1%/5% was studied in male and female patients (n=13) with acne vulgaris. Clindamycin and benzoyl peroxide topical gel, 1%/5% (~2g) was applied topically to the face and back twice daily for four and a half (4.5) days. Quantifiable (>LOQ=1ng/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 (Cmax ) 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 (0-12h) 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 topical gel, 1%/5%. 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 vitro activity against Propionibacterium acnes an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with this product.

CLINICAL STUDIES

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:

Study 1

Clindamycin and benzoyl peroxide topical gel, 1%/5%

n=120

Benzoyl peroxide

n=120

Clindamycin

n=120

Vehicle

n=120

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 topical gel, 1%/5%

n=95

Benzoyl peroxide

n=95

Clindamycin

n=49

Vehicle

n=48

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

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