agonism is not known. 7.3 neuromuscular blocking agents clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. therefore, clindamycin phosphate 1.2% and tretinoin 0.025% gel should be used with caution in patients receiving such agents.

such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. severe colitis may result in death. 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. stool cultures for clostridium difficile and stool assay for c. difficile toxin may be helpful diagnostically. 5.2 ultraviolet light and environmental exposure exposure to sunlight, including sunlamps, should be avoided during the use of clindamycin phosphate 1.2% and tretinoin 0.025% gel, and patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution. daily use of sunscreen products and protective apparel (e.g., a hat) are recommended. weather extremes, such as wind or cold, also may be irritating to patients under treatment with clindamycin phosphate 1.2% and tretinoin 0.025% gel.

to clindamycin phosphate 1.2% and tretinoin 0.025% gel in 1853 patients with acne vulgaris. patients were 12 years and older and were treated once daily for 12 weeks. adverse reactions that were reported in ≥1% of patients treated with clindamycin phosphate 1.2% and tretinoin 0.025% gel were compared to adverse reactions in patients treated with clindamycin phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone: table 1: adverse reactions reported in at least 1% of patients treated with clindamycin phosphate 1.2% and tretinoin 0.025% gel: 12-week studies clindamycin phosphate 1.2% and tretinoin 0.025% gel n=1853 n (%) clindamycin n=1428 n (%) tretinoin n=846 n (%) vehicle n=423 n (%) patients with at least one ar 497 (27) 342 (24) 225 (27) 91 (22) nasopharyngitis 65 (4) 64 (5) 16 (2) 5 (1) pharyngolaryngeal pain 29 (2) 18 (1) 5 (1) 7 (2) dry skin 23 (1) 7 (1) 3 (<1) 0 (0) cough 19 (1) 21 (2) 9 (1) 2 (1) sinusitis 19 (1) 19 (1) 15 (2) 4 (1) note: formulations used in all treatment arms were in the clindamycin phosphate 1.2% and tretinoin 0.025% vehicle gel. cutaneous safety and tolerance evaluations were conducted at each study visit in all of the clinical trials by assessment of erythema, scaling, itching, burning, and stinging: table 2: clindamycin phosphate 1.2% and tretinoin 0.025% gel-treated patients with local skin reactions local reaction baseline n=1835 n (%) end of treatment n=1614 n (%) erythema 636 (35) 416 (26) scaling 237 (13) 280 (17) itching 189 (10) 70 (4) burning 38 (2) 56 (4) stinging 33 (2) 27 (2) at each study visit, application site reactions on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe), and the mean scores were calculated for each of the local skin reactions. in studies 1 and 2, 1277 subjects enrolled with moderate to severe acne, 854 subjects treated with clindamycin phosphate 1.2% and tretinoin 0.025% gel and 423 treated with vehicle. analysis over the 12-week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at 2 weeks of therapy, and were slightly higher for the clindamycin phosphate 1.2% and tretinoin 0.025%-treated group, decreasing thereafter. one open-label 12-month safety study for clindamycin phosphate 1.2% and tretinoin 0.025% gel showed a similar adverse reaction profile as seen in the 12-week studies. eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.

agonism is not known. 7.3 neuromuscular blocking agents clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. therefore, clindamycin phosphate 1.2% and tretinoin 0.025% gel should be used with caution in patients receiving such agents.

e. for purposes of comparisons of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of clindamycin phosphate 1.2% and tretinoin 0.025% gel applied daily to a 60 kg person. clindamycin teratology (segment ii) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on body surface area comparison, respectively) revealed no evidence of teratogenicity. tretinoin in oral segment iii studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison). with widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. although no definite pattern of teratogenicity and no causal association have been established from these cases, five of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). the significance of these spontaneous reports in terms of risk to the fetus is not known. dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on body surface area comparison. oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on body surface area comparison. 8.3 nursing mothers it is not known whether clindamycin is excreted in human milk following use of clindamycin phosphate 1.2% and tretinoin 0.025% gel. 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. it is not known whether tretinoin is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when clindamycin phosphate 1.2% and tretinoin 0.025% gel is administered to a nursing woman. 8.4 pediatric use safety and effectiveness of clindamycin phosphate 1.2% and tretinoin 0.025% gel in pediatric patients under the age of 12 have not been established. clinical trials of clindamycin phosphate 1.2% and tretinoin 0.025% gel included patients 12-17 years of age. [see clinical studies (14) .] 8.5 geriatric use clinical studies of clindamycin phosphate 1.2% and tretinoin 0.025% gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of clindamycin phosphate 1.2% and tretinoin 0.025% gel applied daily to a 60 kg person. clindamycin teratology (segment ii) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on body surface area comparison, respectively) revealed no evidence of teratogenicity. tretinoin in oral segment iii studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison). with widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. although no definite pattern of teratogenicity and no causal association have been established from these cases, five of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). the significance of these spontaneous reports in terms of risk to the fetus is not known. dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on body surface area comparison. oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on body surface area comparison.

and 4-oxo-13-cis-retinoic acid, ranged from 1.0 to 1.4 ng/ml and from 1.6 to 6.5 ng/ml, respectively. plasma concentrations for clindamycin generally did not exceed 3.5 ng/ml, with the exception of one subject whose plasma concentration reached 13.1 ng/ml. 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 has 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 clindamycin phosphate 1.2% and tretinoin 0.025% gel. p. acnes resistance to clindamycin has been documented. resistance to clindamycin is often associated with resistance to erythromycin.

in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 290 times the amount of clindamycin delivered from the recommended clinical dose for clindamycin phosphate 1.2% and tretinoin 0.025% gel, based on body surface area comparison) revealed no effects on fertility or mating ability. tretinoin in two independent studies with long-term topical application of tretinoin in mice, carcinogenicity was not observed. in both studies, tretinoin was administered topically (0.025% or 0.1%) three times per week for up to 2 years. no carcinogenicity was observed with maximum effects of dermal amyloidosis in the basal layer of the skin. tretinoin has been shown to enhance photo co-carcinogenicity in properly performed specific studies, employing concurrent or intercurrent exposure to the drug and uv radiation. the contribution of clindamycin to that effect is unknown. although the significance of these studies to humans is not clear, patients should minimize exposure to sun. the genotoxic potential of tretinoin was evaluated in an in vitro ames salmonella reversion test and an in vitro chromosomal aberration assay in chinese hamster ovary cells. both tests were negative. in oral segment 1 studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).

h up to 300 mg/kg/day of clindamycin (approximately 290 times the amount of clindamycin delivered from the recommended clinical dose for clindamycin phosphate 1.2% and tretinoin 0.025% gel, based on body surface area comparison) revealed no effects on fertility or mating ability. tretinoin in two independent studies with long-term topical application of tretinoin in mice, carcinogenicity was not observed. in both studies, tretinoin was administered topically (0.025% or 0.1%) three times per week for up to 2 years. no carcinogenicity was observed with maximum effects of dermal amyloidosis in the basal layer of the skin. tretinoin has been shown to enhance photo co-carcinogenicity in properly performed specific studies, employing concurrent or intercurrent exposure to the drug and uv radiation. the contribution of clindamycin to that effect is unknown. although the significance of these studies to humans is not clear, patients should minimize exposure to sun. the genotoxic potential of tretinoin was evaluated in an in vitro ames salmonella reversion test and an in vitro chromosomal aberration assay in chinese hamster ovary cells. both tests were negative. in oral segment 1 studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).

scription clear normal, clear skin with no evidence of acne vulgaris almost clear rare non-inflammatory lesions present, with rare non-inflamed 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 nodulo-cystic 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 in study 1, a total of 1252 patients were enrolled, and in study 2, a total of 1288 patients were enrolled. the combined results are presented in table 3. table 3: efficacy results at week 12 in studies 1 and 2 clindamycin phosphate 1.2% and tretinoin 0.025% gel n=845 clindamycin n=426 tretinoin n=846 vehicle n=423 evaluator’s global severity: n (%) patients achieving success success was defined as cleared or almost cleared at week 12. 180 (21%) 70 (16%) 122 (14%) 34 (8%) inflammatory lesion count (% reduction from baseline) mean 48% 42% 39% 26% non-inflammatory lesion count (% reduction from baseline) mean 36% 27% 31% 16% total lesion count (% reduction from baseline) mean 41% 34% 34% 20% in study 3, clindamycin phosphate 1.2% and tretinoin 0.025% gel was compared to clindamycin gel in a total of 2010 patients with moderate or severe acne vulgaris (see table 3 ). as with studies 1 and 2, the co-primary endpoints were mean percent reduction in lesion counts (inflammatory, non-inflammatory and total) and the egs score. in study 3, success on the egs score was assessed by the percentage of subjects who had at least 2 grades of improvement from baseline to week 12. table 4: efficacy results at week 12 in study 3 clindamycin phosphate 1.2% and tretinoin 0.025% gel n=1008 clindamycin n=1002 evaluator’s global severity: n (%) patients achieving success success was defined as at least a 2-grade improvement at week 12 from baseline. 415 (41%) 345 (34%) inflammatory lesion count (% reduction from baseline) mean 61% 55% non-inflammatory lesion count (% reduction from baseline) mean 50% 41% total lesion count (% reduction from baseline) mean 54% 47%

in the event a patient treated with clindamycin phosphate 1.2% and tretinoin 0.025% gel experiences severe diarrhea or gastrointestinal discomfort, clindamycin phosphate 1.2% and tretinoin 0.025% gel should be discontinued and a physician should be contacted. 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 © 2020 bausch health companies inc. or its affiliates 9704800

phosphate 1.2% and tretinoin 0.025% gel may harm your unborn baby. • if you are breastfeeding. clindamycin phosphate 1.2% and tretinoin 0.025% gel may pass through your milk and may harm your baby. • about all the medicines and skin products you use: • clindamycin phosphate 1.2% and tretinoin 0.025% gel should not be used with erythromycin-containing products. • avoid medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and skin products that contain alcohol, astringents, spices or lime. these products may cause increased skin irritation if used with clindamycin phosphate 1.2% and tretinoin 0.025% gel. how should i use clindamycin phosphate 1.2% and tretinoin 0.025% gel? use clindamycin phosphate 1.2% and tretinoin 0.025% gel exactly as prescribed. it may take some time for you to see improvement of your acne with clindamycin phosphate 1.2% and tretinoin 0.025% gel. your doctor will tell you how long to use clindamycin phosphate 1.2% and tretinoin 0.025% gel. at bedtime: • wash your face gently with a mild soap and warm water. • pat the skin dry. • apply a pea-size amount of clindamycin phosphate 1.2% and tretinoin 0.025% gel to your fingertip and spread it over your face. gently, smooth it into your skin. do not get clindamycin phosphate 1.2% and tretinoin 0.025% gel in your eyes or mouth, on your lips, on the corners of your nose, or on open wounds. in the morning: • apply a sunscreen and reapply during the day as needed. • do not apply clindamycin phosphate 1.2% and tretinoin 0.025% gel more than once a day. • do not use too much clindamycin phosphate 1.2% and tretinoin 0.025% gel. too much clindamycin phosphate 1.2% and tretinoin 0.025% gel may irritate your skin. • do not wash your face more than 2 to 3 times a day. washing your face too often or scrubbing it may make your acne worse. avoid: • excessive exposure to the sun, cold, and wind. weather extremes can dry and burn the skin. always use a sunscreen on clindamycin phosphate 1.2% and tretinoin 0.025% gel treated skin, even on cloudy days. use other protective clothing such as a hat when you are in the sun. • the use of sunlamps and tanning booths. if your face becomes sunburned, stop clindamycin phosphate 1.2% and tretinoin 0.025% gel until your skin has healed. what are possible side effects with clindamycin phosphate 1.2% and tretinoin 0.025% gel? • skin irritation. clindamycin phosphate 1.2% and tretinoin 0.025% gel may cause skin irritation such as dryness, redness, peeling, burning, or stinging. stop clindamycin phosphate 1.2% and tretinoin 0.025% gel and call your doctor if your skin becomes very red, swollen, blistered, or crusted. • change in skin color. clindamycin phosphate 1.2% and tretinoin 0.025% gel may cause a temporary skin color change (lighter or darker). • colitis. this occurs rarely. stop clindamycin phosphate 1.2% and tretinoin 0.025% gel and call your doctor if you develop severe watery diarrhea, or bloody diarrhea. talk to your doctor about any side effect that bothers you or that does not go away. these are not all the side effects with clindamycin phosphate 1.2% and tretinoin 0.025% gel. ask your doctor or pharmacist for more information. how should i store clindamycin phosphate 1.2% and tretinoin 0.025% gel? • store clindamycin phosphate 1.2% and tretinoin 0.025% gel at room temperature, 59° to 86°f (15° to 30°c). do not freeze. • keep clindamycin phosphate 1.2% and tretinoin 0.025% gel away from heat and light. • keep the tube tightly closed. • keep clindamycin phosphate 1.2% and tretinoin 0.025% gel and all medicines out of reach of children. general information about clindamycin phosphate 1.2% and tretinoin 0.025% gel medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. do not use clindamycin phosphate 1.2% and tretinoin 0.025% gel for a condition for which it was not prescribed. do not give clindamycin phosphate 1.2% and tretinoin 0.025% gel to other people, even if they have the same symptoms you have. it may harm them. this leaflet summarizes the most important information about clindamycin phosphate 1.2% and tretinoin 0.025% gel. if you would like more information, talk with your doctor. you can also ask your pharmacist or doctor for information about clindamycin phosphate 1.2% and tretinoin 0.025% gel that is written for healthcare professionals. if you have questions about clindamycin phosphate 1.2% and tretinoin 0.025% gel you can also call: 1-800-321-4576 (this is a toll-free number) between 10:00 a.m. and 4:00 p.m. eastern time, monday through friday. what are the ingredients in clindamycin phosphate 1.2% and tretinoin 0.025% gel? active ingredients: clindamycin phosphate 1.2% and tretinoin 0.025% inactive ingredients: butylated hydroxytoluene nf, carbomer 981 nf, citric acid usp, edetate disodium usp, glycerin usp, methylparaben nf, polysorbate 80 nf, propylparaben nf, purified water usp and tromethamine usp. 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 © 2020 bausch health companies inc. or its affiliates 9704800 revised: 04/2020