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 (C₁₈H₃₄C_lN₂O₈PS). The structural formula for clindamycin is represented below:

Clindamycin phosphate has 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.

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.

Compounding Instructions

Prior to dispensing, tap the vial until powder flows freely. Add indicated amount of purified water to the vial (to the mark) and immediately shake to completely dissolve clindamycin. If needed, add additional purified water to bring level up to the mark. Add the solution in the vial to the gel and stir until homogenous in appearance (1 to 1½ minutes). For the 50 gram pump only, reassemble jar with pump dispenser. BenzaClin Topical Gel (as reconstituted) can be stored at room temperature up to 25°C (77°F) for 3 months. Place a 3 month expiration date on the label immediately following mixing.

Store at room temperature up to 25ºC (77ºF) {See USP}.

Do not freeze. Keep tightly closed. Keep out of the reach of children.

US Patents 5,446,028; 5,767,098; 6,013,637
Prescribing Information as of August 2006.
Dermik Laboratories., a business of sanofi-aventis U.S. LLC Bridgewater, NJ 08807
Country of Origin: Canada
©2006 sanofi-aventis U.S. LLC
FDA rev date: 5/23/2007

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.

No information provided.

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.

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 nonsusceptible 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 vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.

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 tumor 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 BenzaClin Topical 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 BenzaClin Topical 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 BenzaClin Topical Gel, based on mg/m2) was statistically significantly higher than that in the sham- and vehicle-controls.

Genotoxicity studies were not conducted with BenzaClin Topical Gel. Clindamycin phosphate was not genotoxic in Salmonella typhimurium or 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. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with BenzaClin Topical Gel or 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 BenzaClin Topical Gel, based on mg/m2) revealed no effects on fertility or mating ability.

Pregnancy: Teratogenic Effects: Pregnancy Category C:

Animal reproductive/developmental toxicity studies have not been conducted with BenzaClin Topical 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/m², 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/m², respectively) revealed no evidence of teratogenicity.

There are no well-controlled trials in pregnant women treated with BenzaClin Topical Gel. It also is not known whether BenzaClin Topical Gel can cause fetal harm when administered to a pregnant woman.

Nursing Women:

It is not known whether BenzaClin Topical Gel is 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.

No information provided.

BenzaClin Topical Gel is contraindicated in those individuals who have shown hypersensitivity to any of its components or to lincomycin. It is also contraindicated in those having a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.

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.

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. Non-medicated 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.

Patients using BenzaClin Topical Gel should receive the following information and instructions:

1. BenzaClin Topical Gel is 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 BenzaClin Topical 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 should report any signs of local adverse reactions to their physician.
6. BenzaClin Topical Gel may bleach hair or colored fabric.
7. BenzaClin Topical Gel can 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 BenzaClin Topical Gel to affected areas wash the skin gently, then rinse with warm water and pat dry.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CLINDAMYCIN/BENZOYL PEROXIDE - TOPICAL

(klin-duh-MY sin/BEN-zoh-ill per-OX-ide)

COMMON BRAND NAME(S): Benzaclin, Duac

USES: This combination medication is used to treat a certain type of acne (inflammatory acne vulgaris). It helps to decrease the number of acne pimples. Clindamycin is an antibiotic that stops the growth of acne-causing bacteria. Benzoyl peroxide can also stop the growth of bacteria as well as reduce oil production in the skin, helping keep your pores open.

HOW TO USE: Before using this medication, wash the affected skin gently with mild, non-medicated cleanser, rinse with warm water, and pat dry. Apply a thin layer of this medication to the affected areas of the skin as directed by your doctor. Be careful to avoid your eyes, mouth, inside your nose, and any areas of broken skin. Wash your hands after each use.

It may take up to 6 weeks to see a decrease in acne and up to 12 weeks to see the full benefit of the medication.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Dry skin, redness, burning, itching, or skin peeling may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

You can use skin moisturizing creams or lotions to help reduce many of the side effects listed above.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may be absorbed into your bloodstream and very rarely cause a severe intestinal condition (pseudomembranous colitis) due to resistant bacteria. This condition may occur weeks after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to benzoyl peroxide; or to clindamycin; or to lincomycin; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: intestinal disorders (e.g., regional enteritis, ulcerative colitis, antibiotic-associated colitis, pseudomembranous colitis).

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

This medication may bleach hair or colored fabric. Avoid contact with hair or clothing.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug may pass into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other acne medications used on the skin (e.g., products that contain erythromycin).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If swallowing/overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Different brands/strengths of this medication may have different storage requirements. Read the package labeling or ask your pharmacist for the storage requirements for the product you are using. Protect from light and moisture. Keep the container tightly closed, and do not store in the bathroom. This medication is good for a limited time after you receive it. Discard any unused medication by the expiration date your pharmacist provides.

Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.