Benzaclin

BENZACLIN- clindamycin phosphate and benzoyl peroxide gel
Bausch Health US LLC

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

For Dermatological Use Only — Not for Ophthalmic Use

*Reconstitute Before Dispensing*

DESCRIPTION

BenzaClin^® Topical Gel 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 CIN₂ O₈ PS. 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).

BenzaClin Topical Gel also contains benzoyl peroxide for topical use.Chemically benzoyl peroxide is C₁₄ H₁₀ O₄ . It has the following structural formula:

Benzoyl peroxide has a molecular weight of 242.23.

Each gram of BenzaClin Topical Gel contains, as dispensed, 10 mg (1%) clindamycin as phosphate and 50 mg (5%) benzoyl peroxide in a base of carbomer, sodium hydroxide, dioctyl sodium sulfosuccinate, and purified water.

CLINICAL PHARMACOLOGY

An in vitro percutaneous penetration study comparing BenzaClin Topical Gel 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 BenzaClin Topical Gel 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 BenzaClin

Topical Gel was studied in male and female patients (n=13) with acne vulgaris. BenzaClin

Topical Gel (~2 g) 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 (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(0-12 h) 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 BenzaClin Topical 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 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 BenzaClin, 210 used benzoyl peroxide, 168 used clindamycin, and 166 used vehicle. BenzaClin 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. Nonmedicated make-up could be applied at one hour after the BenzaClin 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
BenzaClinn=120	Benzoyl peroxiden=120	Clindamycinn=120	Vehiclen=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
BenzaClinn=95	Benzoyl peroxiden=95	Clindamycinn=49	Vehiclen=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 BenzaClin group showed greater overall improvement than the benzoyl peroxide, clindamycin and vehicle groups as rated by the investigator.