Dermatology World June 2011 : Page 14

BRIEF SUMMARY DUAC ® Topical Gel (clindamycin, 1% -benzoyl peroxide, 5%) The following is a brief summary only; see full prescribing information for complete product information. For Dermatological Use Only. Not for Ophthalmic Uyse. Rx Only INDICATIONS AND USAGE DUAC Topical Gel is indicated for the topical treatment of inflammatory acne vulgaris. DUAC Topical Gel has not been demonstrated to have any additional benefit when compared to benzoyl peroxide alone in the same vehicle when used for the treatment of non-inflammatory acne. CONTRAINDICATIONS DUAC 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, pseudomembranous colitis, or antibiotic-associated colitis. 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 AND STOOL ASSAY FOR Clostridium difficileu 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 Clostridium difficilpe colitis. PRECAUTIONS 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. Information for Patients: Patients using DUAC Topical Gel should receive the following information and instructions: 1. 2. 3. 4. DUAC 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. This medication should not be used for any disorder other than that for which it was prescriybed. Patients should not use any other topical acne preparation unless otherwise directed byy their physician. Patients should report any signs of local adverse reactions to their physician. Patients who develop allergic symptoms such as severe swelling or shortness of breath should discontinue use and contact their physician immediately. DUAC Topical Gel may bleach hair or colored fabric. DUAC Topical Gel can be stored at room temperature up to 25°C (77°F) for up to 2 months. Do not freeze. Keep tube tightly closed. Keep out of the reach of small children. Discard any unused product after 2 months. Before applying DUAC Topical Gel to affected areas, wash the skin gently, rinse with warm water, and pat dry. Excessive or prolonged exposure to sunlight should be limited. To minimize exposure to sunlight, a hat or other clothing should be worn. ©2011 Stiefel Laboratories, Inc. All rights reserved. Printed in USA. DUA063R0 March 2011 Carcinogenesis, Mutagenesis, Impairment of Fertility: Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered twice per week induced squamous cell skin tumors in transgenic TgAC mice in a study using 20 weeks of topical treatment. The clinical significance of this is unknown. In a 2-year dermal carcinogenicity study in mice, treatment with DUAC Topical Gel at doses up to 8000 mg/kg/day (16 times the highest recommended adult human dose of 2.5 g DUAC Topical Gel, based on mg/m 2 ) did not cause an increase in skin tumors. However, topical treatment with another formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, or 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In a 52-week photocarcinogenicity study in hairless mice (40 weeks of treatment followed by 12 weeks of observation), the median time to onset of skin tumor formation decreased and the number of tumors per mouse increased relative to controls following chronic concurrent topical treatment with DUAC Topical Gel and exposure to ultraviolet radiation. Genotoxicity studies were not conducted with DUAC Topical Gel. Clindamycin phosphate was not genotoxic in Salmonella typhimuripum or in a rat micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in Salmonella typhimuripum tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with DUAC 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 DUAC Topical Gel, based on mg/m 2 ) revealed no effects on fertility or mating ability. Pregnancy: Teratogenic Effects: Pregnancy Category C: Animal reproduction studies have not been conducted with DUAC Topical Gel or benzoyl peroxide. It is also not known whether DUAC Topical Gel can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. DUAC Topical Gel should be given to a pregnant woman only if clearly needed. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (240 and 120 times the amount of clindamycin 2 in the highest recomymended adult human doyse based on mg/m , 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/m 2 , respectively) revealed no evidence of teratogenicity. Nursing Women: It is not known whether DUAC Topical Gel is secreted into 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. ADVERSE REACTIONS During clinical trials, all patients were graded for facial erythema, peeling, burning, and dryness on the following scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. The percentage of patients that had symptoms present before treatment (at baseline) and during treatment were as follows: Local reactions witLh use of DUAC TopiLcal Gel % of patients usinLg DUAC Topical GelL with symptom presLent Combined results fLrom 5 studies (n =L 397) Before Treatment (Baseline) During Treatment Mild Moderate Severe Mild Moderate Severe Erythema 28% 3% 0 26% 5% 0 Peeling Burning Dryness 6% 3% 6% <1% <1% <1% 0 0 0 17% 5% 15% 2% <1% 1% 0 0 0 5. 6. 7. 8. (Percentages derived by # subjects with symptom score/# enrolled DUAC Topical Gel subjects, n = 397). Anaphylaxis, as well as allergic reactions leading to hospitalization, has been reported in post-marketing use with DUAC Topical Gel. 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. ©2010 Stiefel Laboratories, Inc. DUA:2BRS January 2011

Stiefel, A GSK Company

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