l weeks following cessation of therapy. antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. severe colitis may result in death. studies indicate 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. stool cultures for clostridium difficile and stool assay for c. difficile toxin may be helpful diagnostically. 5.2 ultraviolet light and environmental exposure minimize sun exposure including use of tanning beds or sun lamps following drug application. 5.3 concomitant topical medications concomitant topical acne therapy should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. if irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. treatment should be discontinued if the irritation persists.

scaling, itching, burning and stinging. most local skin reactions increased and peaked around week 4 and continually decreased over time reaching near baseline levels by week 12. the percentage of subjects that had symptoms present before treatment, the maximum value recorded during treatment, and the percent with symptoms present at week 12 are shown in table 1. table 1: percent of subjects with local skin reactions. combined results from the two phase 3 trials (n = 773) before treatment (baseline) maximum during treatment end of treatment (week 12) mild mod. mod. = moderate severe mild mod. severe mild mod. severe erythema 22 4 0 25 5 < 1 15 2 0 scaling 8 < 1 0 18 3 0 8 1 0 itching 10 2 0 15 2 0 6 < 1 0 burning 3 < 1 0 8 2 0 2 < 1 0 stinging 2 < 1 0 6 1 0 1 < 1 0 6.2 postmarketing experience 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. anaphylaxis, as well as allergic reactions leading to hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide.

eroxide gel, based on body surface area (bsa) comparisons (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data human data in limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. these data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. animal data animal reproductive/developmental toxicity studies have not been conducted with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide. developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the mrhd for, respectively, based on bsa comparisons) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the mrhd for clindamycin, respectively, based on bsa comparisons) revealed no malformations or embryo-fetal development toxicity. 8.2 lactation risk summary there are no data on the presence of clindamycin or benzoyl peroxide in human milk, the effects on the breastfed child, or the effects on milk production following topical administration. however, clindamycin has been reported to be present in breast milk in small amounts following oral and parenteral administration. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin phosphate and benzoyl peroxide gel and any potential adverse effects on the breastfed child from clindamycin phosphate and benzoyl peroxide gel or from the underlying maternal condition. clinical considerations if used during lactation and clindamycin phosphate and benzoyl peroxide gel is applied to the chest, care should be taken to avoid accidental ingestion by the infant. 8.4 pediatric use safety and effectiveness of clindamycin phosphate and benzoyl peroxide gel in pediatric patients under the age of 12 have not been evaluated. 8.5 geriatric use clinical trials of clindamycin phosphate and benzoyl peroxide gel did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

face area (bsa) comparisons (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data human data in limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. these data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. animal data animal reproductive/developmental toxicity studies have not been conducted with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide. developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the mrhd for, respectively, based on bsa comparisons) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the mrhd for clindamycin, respectively, based on bsa comparisons) revealed no malformations or embryo-fetal development toxicity.

mean auc 0-t was 8.42 ± 6.01 h.ng/ml (n=6). clindamycin plasma concentrations were below loq in all subjects at 24 hours post-dose on the three tested days (day 1, 15, and 30). benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. 12.4 microbiology clindamycin binds to the 50s ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. clindamycin and benzoyl peroxide individually have been shown to havein vitro activity against propionibacterium acnes , an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against p. acnes is not known. p. acnes resistance to clindamycin has been documented. resistance to clindamycin is often associated with resistance to erythromycin.

nt gel formulation containing 1% clindamycin and 5% benzoyl peroxide 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 in a 2-year dermal carcinogenicity study in rats. in an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900, and 3000 mg/kg/day (1.2, 3.6, and 12 times the mrhd for clindamycin and 2.4, 7.2, and 24 times the mrhd for benzoyl peroxide, respectively, based on bsa comparisons) for up to 97 weeks did not cause any increase in tumors. clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. 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. fertility studies have not been performed with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the mrhd for clindamycin, based on bsa comparisons) revealed no effects on fertility or mating ability.

ing 1% clindamycin and 5% benzoyl peroxide 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 in a 2-year dermal carcinogenicity study in rats. in an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900, and 3000 mg/kg/day (1.2, 3.6, and 12 times the mrhd for clindamycin and 2.4, 7.2, and 24 times the mrhd for benzoyl peroxide, respectively, based on bsa comparisons) for up to 97 weeks did not cause any increase in tumors. clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. 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. fertility studies have not been performed with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the mrhd for clindamycin, based on bsa comparisons) revealed no effects on fertility or mating ability.

d papules (papules must be resolving and may be hyperpigmented, though not pink-red) mild some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions) moderate non-inflammatory lesions predominate, with multiple inflammatory lesions evident: several to many comedones and papules/pustules, and there may or may not be one small nodulocystic lesion severe inflammatory lesions are more apparent, many comedones and papules/pustules, there may or may not be a few nodulocystic lesions very severe highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions the results of trial 1 at week 12 are presented in table 2: table 2: trial 1 results clindamycin phosphate and benzoyl peroxide gel clindamycin gel benzoyl peroxide gel vehicle gel trial 1 n = 399 n = 408 n = 406 n = 201 egss clear or almost clear 115 (29%) 84 (21%) 76 (19%) 29 (14%) 2-grade reduction from baseline 131 (33%) 100 (25%) 96 (24%) 38 (19%) inflammatory lesions: mean absolute change 14.8 12.2 13.0 9.0 mean percent (%) reduction 55.0% 47.1% 49.3% 34.5% non-inflammatory lesions: mean absolute change 22.1 17.9 20.6 13.2 mean percent (%) reduction 45.3% 38.0% 40.2% 28.6% the results of trial 2 at week 12 are presented in table 3: table 3: trial 2 results clindamycin phosphate and benzoyl peroxide gel clindamycin gel benzoyl peroxide gel vehicle gel trial 2 n = 398 n = 404 n = 403 n = 194 egss clear or almost clear 113 (28%) 94 (23%) 94 (23%) 21 (11%) 2-grade reduction from baseline 147 (37%) 114 (28%) 114 (28%) 27 (14%) inflammatory lesions: mean absolute change 13.7 11.3 11.2 5.7 mean percent (%) reduction 54.2% 45.3% 45.7% 23.3% non-inflammatory lesions: mean absolute change 19.0 14.9 15.2 8.3 mean percent (%) reduction 41.2% 34.3% 34.5% 19.2%

24,918 © 2020 bausch health companies inc. or its affiliates 9613801

his leaflet for a complete list of ingredients in clindamycin phosphate and benzoyl peroxide gel. • crohn’s disease or ulcerative colitis. • had inflammation of the colon (colitis), or severe diarrhea with past antibiotic use. • talk with your doctor if you are not sure if you have any of the conditions listed above. before using clindamycin phosphate and benzoyl peroxide gel, tell your doctor about all of your medical conditions, including if you: • plan to have surgery. clindamycin phosphate and benzoyl peroxide gel may affect how certain medicines work that may be given during surgery. • are pregnant or plan to become pregnant. it is not known if clindamycin phosphate and benzoyl peroxide gel will harm your unborn baby. • are breastfeeding or plan to breastfeed. it is not known if clindamycin phosphate and benzoyl peroxide gel passes into your breast milk. clindamycin when taken by mouth or by injection has been reported to appear in breast milk. talk to your doctor about the best way to feed your baby during treatment with clindamycin phosphate and benzoyl peroxide gel. tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. clindamycin phosphate and benzoyl peroxide gel may affect the way other medicines work and other medicines may affect how clindamycin phosphate and benzoyl peroxide gel works. • especially tell your doctor if you take medicine by mouth that contains erythromycin or use products on your skin that contain erythromycin. clindamycin phosphate and benzoyl peroxide gel should not be used with products that contain erythromycin. • tell your doctor about any skin products you use. other skin and topical acne products may increase the irritation of your skin when used with clindamycin phosphate and benzoyl peroxide gel. know the medicines you take. keep a list of them and show it to your doctor and pharmacist when you get a new medicine. how should i use clindamycin phosphate and benzoyl peroxide gel? • use clindamycin phosphate and benzoyl peroxide gel exactly as your doctor tells you to use it. see the detailed “instructions for use” for directions about how to apply clindamycin phosphate and benzoyl peroxide gel. • your doctor will tell you how long to use clindamycin phosphate and benzoyl peroxide gel. • apply clindamycin phosphate and benzoyl peroxide gel to your face 1 time each day. what should i avoid while using clindamycin phosphate and benzoyl peroxide gel? • limit your time in sunlight. you should avoid using tanning beds or sunlamps during treatment with clindamycin phosphate and benzoyl peroxide gel. if you have to be in sunlight, wear a wide-brimmed hat or other protective clothing, and use sunscreen to cover the treated areas. • avoid getting clindamycin phosphate and benzoyl peroxide gel in your hair or on colored fabric. clindamycin phosphate and benzoyl peroxide gel may bleach hair or colored fabric. what are possible side effects of clindamycin phosphate and benzoyl peroxide gel? clindamycin phosphate and benzoyl peroxide gel can cause serious side effects including: • inflammation of the colon (colitis). stop using clindamycin phosphate and benzoyl peroxide gel and call your doctor right away if you have severe stomach (abdominal) cramps, watery diarrhea, or bloody diarrhea during treatment, and within several weeks after treatment with clindamycin phosphate and benzoyl peroxide gel. • allergic reactions. stop using clindamycin phosphate and benzoyl peroxide gel, call your doctor and get help right away if you have any of the following symptoms during treatment with clindamycin phosphate and benzoyl peroxide gel: o severe itching o swelling of your face, eyes, lips, tongue or throat o trouble breathing the most common side effects of clindamycin phosphate and benzoyl peroxide gel include application site pain, application site irritation including redness, itching, burning, and stinging. stop using clindamycin phosphate and benzoyl peroxide gel and call your doctor if you have a skin rash or your skin becomes very red, itchy or swollen. talk to your doctor about any side effect that bothers you or that does not go away. these are not all of the possible side effects with clindamycin phosphate and benzoyl peroxide gel. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store clindamycin phosphate and benzoyl peroxide gel? • store clindamycin phosphate and benzoyl peroxide gel at room temperature at or below 77°f (25°c). • do not freeze clindamycin phosphate and benzoyl peroxide gel. • throw away (discard) clindamycin phosphate and benzoyl peroxide gel that has passed the expiration date. • store pump upright. • keep the container tightly closed. keep clindamycin phosphate and benzoyl peroxide gel and all medicines out of the reach of children. general information about the safe and effective use of clindamycin phosphate and benzoyl peroxide gel. medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use clindamycin phosphate and benzoyl peroxide gel for a condition for which it was not prescribed. do not give clindamycin phosphate and benzoyl peroxide gel to other people, even if they have the same condition you have. it may harm them. you can also ask your doctor or pharmacist for information about clindamycin phosphate and benzoyl peroxide gel that is written for healthcare professionals. what are the ingredients in clindamycin phosphate and benzoyl peroxide gel? active ingredients: clindamycin phosphate and benzoyl peroxide inactive ingredients: carbomer 980, potassium hydroxide, propylene glycol, and purified water distributed by: oceanside pharmaceuticals, a division of bausch health us, llc, bridgewater, nj 08807 usa manufactured by: bausch health companies inc., laval, quebec h7l 4a8, canada u.s. patent numbers: 8,288,434; 8,663,699; 8,895,070; 9,078,870; 10,220,049 and 10,624,918 © 2020 bausch health companies inc. or its affiliates for more information about clindamycin phosphate and benzoyl peroxide gel, call 1-800-321-4576. this patient information has been approved by the u.s. food and drug administration. revised: 09/2020 9613801