Benzaclin

BenzaClin Topical Gel is indicated for the topical treatment of acne vulgaris.

BenzaClin Topical Gel should be applied twice daily, morning and evening, or as directed by a physician, to affected areas after the skin is gently washed, rinsed with warm water and patted dry.

During clinical trials, the most frequently reported adverse event in the BenzaClin treatment group was dry skin (12%). The table below lists local adverse events reported by at least 1% of patients in the BenzaClin 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 postmarketing 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.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 C18H34CIN2O8PS. 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 C14H10O4. 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.

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.

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:

The BenzaClin group showed greater overall improvement than the benzoyl peroxide, clindamycin and vehicle groups as rated by the investigator.

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 AND STOOL ASSAY FOR C. difficile TOXIN MAY BE HELPFUL DIAGNOSTICALLY. WHEN SIGNIFICANT DIARRHEA OCCURS, THE DRUG SHOULD BE DISCONTINUED. LARGE BOWEL ENDOSCOPY SHOULD BE CONSIDERED TO ESTABLISH A DEFINITIVE DIAGNOSIS IN CASES OF SEVERE DIARRHEA. ANTIPERISTALTIC AGENTS SUCH AS OPIATES AND DIPHENOXYLATE WITH ATROPINE MAY PROLONG AND/OR WORSEN THE CONDITION. DIARRHEA, COLITIS, AND PSEUDOMEMBRANOUS COLITIS HAVE BEEN OBSERVED TO BEGIN UP TO SEVERAL WEEKS FOLLOWING CESSATION OF ORAL AND PARENTERAL THERAPY WITH CLINDAMYCIN.

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 colitis.