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CLINICAL PHARMACOLOGY Mechanism of Action Mechanism of action in acne vulgaris is unknown. [See Microbiology] Pharmacodynamics Pharmacodynamics of EVOCLIN Foam is unknown. Pharmacokinetics In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of EVOCLIN Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for EVOCLIN Foam than for the clindamycin gel, 1%. Following multiple applications of EVOCLIN Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5. Microbiology No microbiology studies were conducted in the clinical trials with this product. Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with EVOCLIN Foam. P. acnes resistance to clindamycin has been documented. Inducible Clindamycin Resistance The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing. Cross Resistance Resistance to clindamycin is often associated with resistance to erythromycin. Clinical Studies In one multicenter, randomized, double-blind, vehicle-controlled clinical trial, subjects with mild to moderate acne vulgaris used EVOCLIN Foam or the vehicle Foam once daily for twelve weeks. Treatment response, defined as the proportion of subjects clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in Table 2. Table 2: Efficacy Results at Week 12 Efficacy Parameters EVOCLIN Foam N=386 Vehicle Foam N=127 Treatment response (ISGA) 31% 18%* Percent reduction in lesion counts Inflammatory Lesions 49% 35%* Noninflammatory Lesions 38% 27%* Total Lesions 43% 31%* * P<0.05

CLINICAL PHARMACOLOGY Mechanism of Action Clindamycin is an antibacterial drug [see Microbiology] Pharmacokinetics Following a single intravaginal application of Clindesse (clindamycin phosphate) cream to 20 healthy women, the mean (range) AUC0-inf and Cmax estimates were 175 (38.6 to 541) ng/mL·hr and 6.6 (0.8 to 39) ng/mL, respectively. The mean Cmax of clindamycin for Clindesse (clindamycin phosphate) was approximately 0.3%, 0.1%, and 7.6% of that observed after the administration of a 150 mg Cleocin oral capsule (2.5 mcg/mL), a 600 mg Cleocin intravenous injection (10.9 mcg/mL), and a single dose of 100 mg of Cleocin Vaginal Cream (86.5 ng/mL), respectively. The peak serum concentration of clindamycin was attained approximately 20 hours post dosing for Clindesse (clindamycin phosphate) . Microbiology Mechanism of Action Clindamycin inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation. Although clindamycin phosphate is inactive in vitro , in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Activity In Vitro Clindamycin is an antibacterial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis: Bacteroides spp. Gardnerella vaginalis Mobiluncus spp. Mycoplasma hominis Peptostreptococcus spp. Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens has not been defined. Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis [see Clinical Studies]. Clinical Studies Two clinical studies were conducted to evaluate the efficacy of Clindesse (clindamycin phosphate) for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was defined by the presence of a homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a “fishy” amine odor when mixed with a 10% KOH solution, and (c) contains clue cells on microscopic examination. Gram's stain results consistent with a diagnosis of bacterial vaginosis include (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells. In a randomized, double-blind, placebo-controlled, clinical study involving 144 non-pregnant female patients aged 18 to 64 with a baseline Nugent score ≥ 4, Clindesse (clindamycin phosphate) demonstrated statistically significantly higher cure rates over placebo as measured by therapeutic cure, clinical cure, and Nugent score cure (Table 2) assessed at 21-30 days after administration of the drug. Therapeutic cure was a composite endpoint which required both clinical cure and Nugent score cure. Clinical cure required normal vaginal discharge, vaginal pH < 4.7, < 20% clue cells on wet mount preparation, and negative “whiff” test (detection of amine odor on addition of 10% KOH solution to sample of the vaginal discharge). A Nugent score of 0-3 was considered a Nugent score cure. The Nugent scoring is based on microscopic examination of the Gram's stained vaginal smears for quantification of specific bacterial morphotypes. Cure rates were consistently higher for Clindesse (clindamycin phosphate) compared to placebo for the following demographic subsets: age, race, height, weight, sexual behavior, and recalcitrant infection status. Table 2: Efficacy of Clindesse (clindamycin phosphate) for Treatment of Bacterial Vaginosis in a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Outcome Clindesse N=78 Placebo N=66 Treatment Difference† (%) [97.5% Confidence Interval] % Cure % Cure Therapeutic Cure 29.5 3.0 26.5 [14.0, 39.0] Clinical Cure 41.0 19.7 21.3 [4.7, 38.0] Nugent Score Cure 44.9 6.1 38.8 [24.6, 53.1] N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4) †Treatment difference = Clindesse (clindamycin phosphate) minus placebo cure rates In a second controlled clinical study involving 432 patients aged 18 to 78 with a baseline Nugent score of ≥ 4, 221 women self-administered a single dose of Clindesse (clindamycin phosphate) , and 211 women self-administered a single daily dose of a formulation of clindamycin vaginal cream for 7 days. A single dose of Clindesse (clindamycin phosphate) was shown to be similar to 7 daily doses of the clindamycin vaginal cream for treatment of bacterial vaginosis as measured by therapeutic cure, clinical cure or Nugent score cure assessed at 21-30 days after administration of the drug in the modified intent-to-treat population (Table 3) and for the per protocol population (Table 4). The study endpoints were identical to those described above for the placebo-controlled study. Statistical analyses did not reveal any significant differences when controlling for the following demographic variables: age, race, height, weight, sexual behavior, and recalcitrant infection status. The cure rates reported in the clinical studies with Clindesse (clindamycin phosphate) were based on resolution of 4 out of 4 Amsel criteria and a Nugent score of < 4, while the criteria for cure in previous clinical studies with the clindamycin vaginal cream were based solely on resolution of 2 out of 4 Amsel criteria, resulting in higher reported rates of cure for bacterial vaginosis. Table 3: Efficacy of Clindesse (clindamycin phosphate) in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Modified-Intent-to-Treat Outcome Clindesse Single Dose N=221 Clindamycin Vaginal Cream (7 doses) N=211 Treatment Difference† (%) [95% Confidence Interval] % Cure % Cure Therapeutic Cure 33.0 37.0 -3.9 [-12.9, 5.1] Clinical Cure 53.4 54.0 -0.6 [-10.0, 8.8] Nugent Score Cure 45.7 49.3 -3.6 [-13.1, 5.8] †Treatment difference = Clindesse (clindamycin phosphate) minus clindamycin vaginal cream cure rates N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4) Table 4: Efficacy of Clindesse (clindamycin phosphate) in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Per Protocol Outcome Clindesse Single Dose N=126 Clindamycin Vaginal Cream (7 doses) N=125 Treatment Difference† (%) [95% Confidence Interval] % Cure % Cure Therapeutic Cure 42.1 45.6 -3.5 [-15.8, 8.7] Clinical Cure 64.3 63.2 1.1 [-10.8, 13.0] Nugent Score Cure 56.5‡ 57.7‡ -1.3 [-13.6, 11.1] † Treatment difference = Clindesse (clindamycin phosphate) minus clindamycin vaginal cream cure rates N = number of patients in treatment group (per protocol population defined as all subjects included in the modified intent-to-treat population who completed the study without significant protocol violation) ‡ Four subjects (2 from each treatment group) did not have complete Nugent scores and were not included in the Nugent Score cure analysis

CLINICAL PHARMACOLOGY Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered to 6 healthy female volunteers for 7 days, approximately 5% (range 0.6% to 11%) of the administered dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 18 ng/mL (range 4 to 47 ng/mL) and on day 7 it averaged 25 ng/mL (range 6 to 61 ng/mL). These peak concentrations were attained approximately 10 hours post-dosing (range 4-24 hours). Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered for 7 consecutive days to 5 women with bacterial vaginosis, absorption was slower and less variable than that observed in healthy females. Approximately 5% (range 2% to 8%) of the dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 13 ng/mL (range 6 to 34 ng/mL) and on day 7 it averaged 16 ng/mL (range 7 to 26 ng/mL). These peak concentrations were attained approximately 14 hours post-dosing (range 4-24 hours). There was little or no systemic accumulation of clindamycin after repeated vaginal dosing of clindamycin phosphate vaginal cream 2%. The systemic half-life was 1.5 to 2.6 hours. Microbiology Clindamycin inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis. (See INDICATIONS AND USAGE.) Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens, Gardnerella vaginalis, Mobiluncus spp., or Mycoplasma hominis, has not been defined. Nonetheless, clindamycin is an antimicrobial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis: Bacteroides spp. Mycoplasma hominis Peptostreptococcus spp. Gardnerella vaginalis Mobiluncus spp. Clinical Studies In two clinical studies involving 674 evaluable non-pregnant women with bacterial vaginosis comparing clindamycin phosphate vaginal cream 2% for 3 or 7 days, the clinical cure rates, determined at 1 month posttherapy, ranged from 72% to 81% for the 3-day treatment and 84% to 86% for the 7-day treatment. Clindamycin Phosphate 3 Day Clindamycin Phosphate 7 Day U.S. Study 94/131 72% 110/128 86% European Study 161/199 81% 181/216 84% In a clinical study involving 249 evaluable pregnant patients in the second and third trimester treated for 7 days, the clinical cure rate, determined at 1 month posttherapy, was 60% (77/129) in the clindamycin arm and 9% (11/120) for the vehicle arm. The determination of clinical cure was based on the absence of a "fishy" amine odor when the vaginal discharge was mixed with a 10% KOH solution and the absence of clue cells on microscopic examination.

CLINICAL PHARMACOLOGY Pharmacokinetics In an open label, parallel group study of 24 patients with acne vulgaris, once-daily topical administration of approximately 3-12 grams/day of Clindagel® for five days resulted in peak plasma clindamycin concentrations that were less than 5.5 ng/mL. Following multiple applications of Clindagel® less than 0.04% of the total dose was excreted in the urine. Microbiology Although clindamycin phosphate is inactive in vitro, rapid in vitro hydrolysis converts this compound to clindamycin which has antibacterial activity. Clindamycin inhibits bacteria protein synthesis at the ribosomal level by binding to the 50S ribosomal subunit and affecting the process of peptide chain initiation. In vitro studies indicated that clindamycin inhibited all tested Propionibacterium acnes cultures at a minimum inhibitory concentration (MIC) of 0.4 μg/mL. Crossresistance has been demonstrated between clindamycin and erythromycin. Clinical Studies In one 12-week multicenter, randomized, evaluator-blind, vehicle-controlled, parallel comparison clinical trial in which patients used Clindagel® (clindamycin phosphate topical gel, 1%) once daily or the vehicle gel once daily, in the treatment of acne vulgaris of mild to moderate severity, Clindagel® applied once daily was more effective than the vehicle applied once daily. The mean percent reductions in lesion counts at the end of treatment in this study are shown in the following table: Lesions Clindagel® QD N=162 Vehicle Gel QD N=82 Inflammatory 51% 40%* Noninflammatory 25% 12% * Total 38% 27% * * P < 0.05 There was a trend in the investigator's global assessment of the results which favored Clindagel® QD over the vehicle QD. In a contact sensitization study, four of the 200 subjects appeared to develop suggestive evidence of allergic contact sensitization to Clindagel®. There was no signal for contact sensitization in the clinical trials under normal use conditions.

Find Lowest Prices on EVOCLIN® (clindamycin phosphate) Foam DESCRIPTION EVOCLIN (clindamycin phosphate) Foam contains clindamycin (1%) as clindamycin 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. The chemical name for clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below: Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97 g/mol EVOCLIN Foam contains clindamycin (1%) as clindamycin phosphate, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.

Find Lowest Prices on Clindesse® (clindamycin phosphate) DESCRIPTION Clindamycin phosphate, a lincosamide, 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. The chemical name for clindamycin phosphate 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). It has a molecular weight of 504.96, and the molecular formula is C18H34CIN2O8 PS. The structural formula is represented below: Clindesse is a semi-solid, white cream, which contains clindamycin phosphate, USP, at a concentration equivalent to 20 mg clindamycin base per gram. The cream also contains edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution. Clindesse (clindamycin phosphate) does not comply with the pH test of the USP monograph for clindamycin phosphate vaginal cream.

CLINDAMAX® VAGINAL CREAM (clindamycin phosphate) Vaginal Cream DESCRIPTION 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. The chemical name for clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans-4-propyl-L-2- pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). It has a molecular weight of 504.96, and the molecular formula is C18H34ClN2O8PS. The structural formula is represented below: ClindaMax® Vaginal Cream (clindamycin phosphate vaginal cream USP, 2%), is a semi-solid, white cream, which contains 2% clindamycin phosphate, USP, at a concentration equivalent to 20 mg clindamycin per gram. The pH of the cream is between 3.0 and 6.0. The cream also contains benzyl alcohol, cetostearyl alcohol, cetyl palmitate, mineral oil, polysorbate 60, propylene glycol, sorbitan monostearate, and stearic acid. Each applicatorful of 5 grams of vaginal cream contains approximately 100 mg of clindamycin phosphate.

Find Lowest Prices on Clindagel® (clindamycin phosphate) Topical Gel, 1% DESCRIPTION Clindagel® (clindamycin phosphate gel) topical gel, 1%, a topical antibiotic, contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram in a gel vehicle consisting of carbomer 941, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, and purified water. Chemically, clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7 (S)-chlorosubstitution of the 7 (R)-hydroxyl group of the parent antibiotic, lincomycin, and has the structural formula represented below: The chemical name for clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4- propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-.-D-galacto-octopyranoside 2-(dihydrogen phosphate).

INDICATIONS EVOCLIN Foam is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older. DOSAGE AND ADMINISTRATION EVOCLIN Foam is for topical use only, and not for oral, ophthalmic, or intravaginal use. Apply EVOCLIN Foam once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area. If there has been no improvement after 6 to 8 weeks or if the condition becomes worse, treatment should be discontinued. The contents of EVOCLIN Foam are flammable; avoid fire, flame and/or smoking during and immediately following application. HOW SUPPLIED Dosage Forms And Strengths White to off-white thermolabile foam. Each gram of EVOCLIN Foam contains, as dispensed, 12 mg (1.2%) of clindamycin phosphate, equivalent to 10 mg (1%) of clindamycin. EVOCLIN Foam containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is white to off-white in color and thermolabile. It is available in the following sizes: 100 gram aerosol can - NDC 0145-0061-00 50 gram aerosol can - NDC 0145-0061-50 Storage and Handling Store at controlled room temperature between 68°F to 77°F (20°C to 25°C). Flammable. Avoid fire, flame or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C). Keep out of reach of children. Manufactured for: Stiefel Laboratories, Inc. Research Triangle Park, NC 27709. Revised: 1/2012

INDICATIONS Treatment of Bacterial Vaginosis Clindesse (clindamycin phosphate) is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in non-pregnant women. DOSAGE AND ADMINISTRATION The recommended dose is the complete contents of a single pre-filled applicator containing 5 g of Clindesse (clindamycin phosphate) cream administered once intravaginally at any time of the day. Not for ophthalmic, dermal, or oral use. HOW SUPPLIED Dosage Forms And Strengths Clindesse is an intravaginal cream containing clindamycin phosphate 2%. Each pre-filled, single-dose applicator delivers approximately 5 g of cream containing approximately 100 mg of clindamycin. Storage And Handling Clindesse (clindamycin phosphate) Vaginal Cream, 2%, is available in cartons containing one single-dose, pre-filled disposable applicator (NDC 64011-124-08). Each applicator delivers approximately 5 g of vaginal cream containing approximately 100 mg of clindamycin. Store at 20°-25°C (68°-77°F). [See USP Controlled Room Temperature.] Avoid heat above 30°C (86°F). Manufactured by KV Pharmaceutical™ Co. for Ther-Rx™ Corporation. St. Louis, MO 63044. Revised: 12/2010

INDICATIONS ClindaMax® Vaginal Cream, is indicated in the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis). ClindaMax® Vaginal Cream, can be used to treat non-pregnant women and pregnant women during the second and third trimester. (See Clinical Studies.) NOTE: For purposes of this indication, a clinical diagnosis of bacterial vaginosis is usually defined by the presence of a homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains clue cells on microscopic examination. Gram's stain results consistent with a diagnosis of bacterial vaginosis include (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells. Other pathogens commonly associated with vulvovaginitis, e.g., Trichomonas vaginalis, Chlamydia trachomatis, N. gonorrhoeae, Candida albicans, and Herpes simplex virus should be ruled out. DOSAGE AND ADMINISTRATION The recommended dose is one applicatorful of ClindaMax® Vaginal Cream, (5 grams containing approximately 100 mg of clindamycin phosphate) intravaginally, preferably at bedtime, for 3 or 7 consecutive days in non-pregnant patients and for 7 consecutive days in pregnant patients. (See Clinical Studies.) HOW SUPPLIED ClindaMax® Vaginal Cream (clindamycin phosphate vaginal cream USP, 2%) is a white to off-white cream having a slight odor and is supplied as follows: 40 g tube (with 7 disposable applicators) NDC 0462-0277-40 Store at 20° to 25°C (68° to 77° F) [see USP Controlled Room Temperature]. Manufactured by: PharmaDerm®, A division of Nycomed US Inc. Melville, NY 11747 USA. Revised: Oct 2009

INDICATIONS Clindagel® is indicated for topical application in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate. (See CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS). DOSAGE AND ADMINISTRATION Apply a thin film of Clindagel® once daily to the skin where acne lesions appear. Use enough to cover the entire affected area lightly. Keep container tightly closed. HOW SUPPLIED Clindagel® containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is available in the following size: 75 mL bottle - NDC 16781-462-75 Store under controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Do not store in direct sunlight. Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA. by: DPT Laboratories, Ltd., San Antonio, Texas 78215 USA. Revised: Nov 2015

PATIENT INFORMATION EVOCLIN (Ev-o-clin) (clindamycin phosphate) Foam Important: For skin use only. Do not use EVOCLIN Foam in your eyes, mouth or vagina. Read the Patient Information that comes with EVOCLIN Foam before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. What is EVOCLIN Foam? EVOCLIN Foam is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older. It is not known if EVOCLIN Foam is safe and effective in children under 12 years of age. Who should not use EVOCLIN Foam? Do not use EVOCLIN Foam if you: have Crohn's disease have ulcerative colitis have had inflammation of the colon (colitis) or severe diarrhea with past antibiotic use Tell your doctor if you are not sure if you have any of the conditions listed above. What should I tell my doctor before using EVOCLIN Foam? Before you use EVOCLIN Foam, tell your doctor if you: have a history of eczema are planning to have surgery. EVOCLIN Foam may affect how certain medicines work that may be given during surgery. have any other medical conditions are pregnant or planning to become pregnant. It is not known if EVOCLIN Foam may harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if EVOCLIN Foam passes through your breast milk. You and your doctor should decide if you will use EVOCLIN Foam or breastfeed. If you use EVOCLIN Foam while breastfeeding and EVOCLIN Foam is applied on the chest, take care to avoid getting EVOCLIN Foam into your baby's mouth. Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. EVOCLIN Foam may affect the way other medicines work and other medicines may affect how EVOCLIN Foam works. Especially tell your doctor if you take erythromycin or use products on your skin that contain erythromycin. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. How should I use EVOCLIN Foam? EVOCLIN Foam is for use on the skin only. Do not get EVOCLIN Foam in your eyes, mouth or vagina. Use EVOCLIN Foam exactly as your doctor tells you to use it. See the “Instructions for Applying EVOCLIN Foam” below. Apply EVOCLIN Foam 1 time a day. Wash your skin with mild soap and water and dry before applying EVOCLIN Foam. Do not dispense EVOCLIN Foam directly onto your hands or face, because the foam will begin to melt on contact with warm skin. Instructions for Applying EVOCLIN Foam. Remove the clear cap from the EVOCLIN Foam can (See Figure A). Figure A: Remove clear cap Line up the black circle with the nozzle (See Figure B). Figure B: Line up the black circle with the nozzle Hold the can upright and firmly press the nozzle to dispense EVOCLIN Foam (See Figure C). Figure C: Hold can upright and press nozzle firmly to dispense Dispense EVOCLIN Foam into the clear cap or onto a cool surface (see Figure D). Figure D: Dispense EVOCLIN Foam into clear cap Dispense enough EVOCLIN Foam to cover the affected area (see Figure E). Figure E: Dispense enough EVOCLIN Foam to cover affected area If the can seems warm or the foam seems runny, run the can under cold water (See Figure F). Figure F: If the can seems warm or the foam is runny, run the can under cold water Pick up small amounts of EVOCLIN Foam with your fingertips and gently rub the foam into the affected area until the foam disappears (See Figure G). Figure G: Pick up a small amount of EVOCLIN Foam on your fingertips and gently rub into the affected area until the foam disappears Wash your hands after applying EVOCLIN. Throw away any of the unused medicine that you dispensed out of the can. What should I avoid while using EVOCLIN Foam? EVOCLIN Foam is flammable. Avoid fire, flames, or smoking during and right after you apply EVOCLIN Foam to your skin. Avoid getting EVOCLIN Foam in or near your eyes, mouth, lips, or broken skin. If you get EVOCLIN Foam in your eyes, mouth, on lips or broken skin, rinse well with water. What are possible side effects with EVOCLIN Foam? EVOCLIN Foam can cause serious side effects including: Inflammation of the colon (colitis). Clindamycin can cause severe colitis that may lead to death. Stop using EVOCLIN Foam and call your doctor right away if you have severe watery diarrhea, or bloody diarrhea. The most common side effects of EVOCLIN Foam include: Skin irritation. EVOCLIN Foam may cause skin irritation such as burning, itching, or dryness. Stop using EVOCLIN Foam and talk with your doctor if you develop excessive skin irritation. Headache. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the side effects of EVOCLIN Foam. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to Stiefel at 1-888-784-3335 (1-888- STIEFEL). How should I store EVOCLIN Foam? Store EVOCLIN Foam at room temperature between 68°F to 77°F (20°C to 25°C). Keep EVOCLIN Foam away from heat. Never throw the can into a fire, even if the can is empty. Do not store EVOCLIN Foam at temperatures above 120°F (49°C). Do not break through (puncture) the EVOCLIN Foam can. Keep EVOCLIN Foam and all medicines out of the reach of children. General information about the safe and effective use of EVOCLIN Foam: Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use EVOCLIN Foam for a condition for which it was not prescribed. Do not give EVOCLIN Foam to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about EVOCLIN Foam. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about EVOCLIN Foam that is written for health professionals. What are the ingredients in EVOCLIN Foam? Active ingredient: clindamycin phosphate Inactive ingredients: cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol. The can is pressurized with a hydrocarbon (propane/butane) propellant. This Patient Information has been approved by the U.S. Food and Drug Administration.

PATIENT INFORMATION Clindesse (clin-DESS) (clindamycin phosphate) Vaginal Cream, 2% For vaginal use only. Do not put Clindesse (clindamycin phosphate) in your eyes, mouth, or on your skin. Read this patient information before you start using Clindesse (clindamycin phosphate) . There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. What is Clindesse (clindamycin phosphate) ? Clindesse (clindamycin phosphate) is a vaginal cream medicine used to treat bacterial vaginal infections in women who are not pregnant. It is not known if Clindesse (clindamycin phosphate) is safe and effective in pregnant women. It is not known if Clindesse (clindamycin phosphate) is safe and effective in females who have not yet reached puberty. Who should not use Clindesse (clindamycin phosphate) ? Do not use Clindesse (clindamycin phosphate) if you: have had an allergic reaction to clindamycin or other lincosamide antibiotic medicines or are allergic to any of the ingredients in Clindesse (clindamycin phosphate) . See the end of this leaflet for a complete list of ingredients in Clindesse (clindamycin phosphate) . have had bowel problems such as: inflammation of your intestines (enteritis) inflammation of your colon (colitis) diarrhea due to a Clostridum difficile infection (CDAD) Talk to your healthcare provider before using this medicine if you have any of these conditions. What should I tell my healthcare provider before using Clindesse (clindamycin phosphate) ? Before you use Clindesse (clindamycin phosphate) , tell your healthcare provider if you: are pregnant or plan to become pregnant. It is not known if Clindesse (clindamycin phosphate) will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Clindesse (clindamycin phosphate) passes into your breast milk. You and your healthcare provider should decide if you will take Clindesse (clindamycin phosphate) or breast feed. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Clindesse (clindamycin phosphate) may affect how other medicines work, and other medicines may affect how Clindesse (clindamycin phosphate) works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use Clindesse (clindamycin phosphate) ? Use Clindesse (clindamycin phosphate) exactly as your healthcare provider tells you. Insert Clindesse (clindamycin phosphate) in the vagina one time. See the “Patient Instructions for Use” at the end of this leaflet. Insert all of the Clindesse (clindamycin phosphate) cream into your vagina. Do not use Clindesse (clindamycin phosphate) after the expiration date on the package. Do not get Clindesse (clindamycin phosphate) in your eyes. If you accidently get Clindesse (clindamycin phosphate) in your eyes rinse your eyes with cool tap water right away and call your healthcare provider. What should I avoid while using Clindesse (clindamycin phosphate) ? After you insert Clindesse (clindamycin phosphate) you should: not have vaginal intercourse or use of other vaginal products (such as tampons or douches) for at least 7 days. not use barrier contraceptive products for 5 days. Barrier contraceptives include condoms or contraceptive diaphragms used for birth control or to protect yourself against HIV or other sexually transmitted diseases. Clindesse (clindamycin phosphate) contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. What are the possible side effects of Clindesse (clindamycin phosphate) ? Clindesse (clindamycin phosphate) may cause serious side effects, including diarrhea. One type of diarrhea is caused by an infection in your intestines called Clostridium difficile-associated diarrhea (CDAD). If you have diarrhea after you use Clindesse (clindamycin phosphate) , call your healthcare provider. The most common side effects of Clindesse (clindamycin phosphate) include: fungal infection in your vagina. You may need to take an anti-fungal medicine if you get a fungal infection. headache back pain constipation urinary tract infection Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of Clindesse (clindamycin phosphate) . For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088. How should I store Clindesse (clindamycin phosphate) ? Store Clindesse (clindamycin phosphate) at 68°F to 77°F (20°C to 25°C). Keep Clindesse (clindamycin phosphate) and all medicines out of the reach of children. General information about the safe and effective use of Clindesse (clindamycin phosphate) . Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use Clindesse (clindamycin phosphate) for a condition for which it was not prescribed. Do not give Clindesse (clindamycin phosphate) to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about Clindesse (clindamycin phosphate) . If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Clindesse (clindamycin phosphate) that is written for health professionals. For more information, go to www.clindesse (clindamycin phosphate) .com or call 1-877-567-7676. What are the ingredients in Clindesse? Active ingredient: clindamycin phosphate Inactive ingredients: edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution Patient Instructions for Use Clindesse (clin-DESS) (clindamycin phosphate) Vaginal Cream, 2% For vaginal use only. Do not put Clindesse (clindamycin phosphate) in your eyes, mouth, or on your skin. It is important that you read and follow these directions on how to use Clindesse (clindamycin phosphate) vaginal cream properly. Clindesse (clindamycin phosphate) comes in a single-dose, pre-filled, disposable applicator that gives you a certain amount of clindamycin cream to be inserted into your vagina. Step 1. Prepare the applicator. Peel back the protective foil and remove the pre-filled applicator. Do not remove the tip. The applicator is made to be used with the tip in place. Do not use the applicator if the tip has been removed (see Figure 1). Activate the plunger before you use it. To activate the plunger, pull the ring back to fully extend the plunger while you firmly hold the applicator (see Figure 2). Step 2. Insert the applicator. Gently insert the applicator into your vagina as far as it will comfortably go (see Figure 3). Figure 3 Step 3. Apply the cream. Push the plunger in until all of the cream goes into your vagina (see Figures 4 and 5). Figure 4 and Figure 5 Step 4. Remove the empty applicator from your vagina and throw it away in the trash.

PATIENT INFORMATION The patient should be instructed not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with this product. The patient should also be advised that this cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, use of such products within 72 hours following treatment with ClindaMax® Vaginal Cream (clindamycin phosphate vaginal cream 2%), is not recommended. Directions For Use 7 Disposable plastic applicators are provided with this package. They are designed to allow proper vaginal administration of the cream. Remove cap from cream tube. Screw a plastic applicator on the threaded end of the tube. Rolling tube from the bottom, squeeze gently and force the medication into the applicator. The applicator is filled when the plunger reaches its predetermined stopping point. Unscrew the applicator from the tube and replace the cap. While lying on your back, firmly grasp the applicator barrel and insert into vagina as far as possible without causing discomfort. Slowly push the plunger until it stops. Carefully withdraw applicator from vagina, and discard applicator. REMEMBER TO APPLY ONE APPLICATORFUL EACH NIGHT BEFORE BEDTIME, OR AS PRESCRIBED BY YOUR DOCTOR.

PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

OVERDOSE No information provided. CONTRAINDICATIONS EVOCLIN Foam is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis (including pseudomembranous colitis).

OVERDOSE Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. CONTRAINDICATIONS Hypersensitivity Do not administer Clindesse (clindamycin phosphate) to individuals with a history of hypersensitivity to clindamycin or other lincosamides. Reported reactions to other formulations of clindamycin include rashes, urticaria, erythema multiforme, and anaphylactoid reactions [see ADVERSE REACTIONS]. History of Bowel Disease Do not administer Clindesse (clindamycin phosphate) to patients with regional enteritis, ulcerative colitis, or a history of Clostridium difficile-associated diarrhea.

OVERDOSE Vaginally applied ClindaMax® Vaginal Cream could be absorbed in sufficient amounts to produce systemic effects. (See WARNINGS.) CONTRAINDICATIONS ClindaMax® Vaginal Cream, is contraindicated in individuals with a history of hypersensitivity to clindamycin, lincomycin, or any of the components of this vaginal cream. ClindaMax® Vaginal Cream, is also contraindicated in individuals with a history of regional enteritis, ulcerative colitis, or a history of "antibiotic-associated" colitis.

OVERDOSE Topically applied Clindagel® may be absorbed in sufficient amounts to produce systemic effects (see WARNINGS). CONTRAINDICATIONS Clindagel® is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcerative colitis, or a history of antibioticassociated colitis.

SIDE EFFECTS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with EVOCLIN Foam. The incidence of adverse reactions occurring in ≥1% of the subjects in clinical trials comparing EVOCLIN Foam and its vehicle is presented in Table 1. Table 1: Adverse Reactions Occurring in ≥1% of Subjects Adverse Reactions Number (%) of Subjects EVOCLIN Foam N = 439 Vehicle Foam N = 154 Headache 12 (3%) 1 (1%) Application site burning 27 (6%) 14 (9%) Application site pruritus 5 (1%) 5 (3%) Application site dryness 4 (1%) 5 (3%) Application site reaction, not otherwise specified 3 (1%) 4 (3%) In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to EVOCLIN Foam. Postmarketing Experience The following adverse reactions have been identified during post approval use of EVOCLIN Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorrhagic diarrhea. 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. Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally. DRUG INTERACTIONS Erythromycin EVOCLIN Foam should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known. Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, EVOCLIN Foam should be used with caution in patients receiving such agents.

SIDE EFFECTS Clinical Study Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Clindesse (clindamycin phosphate) in 368 patients. Clindesse (clindamycin phosphate) was studied in three clinical studies: placebo-controlled (n=85), active-controlled (n=263), and single-arm (n=20). The population was female, aged 18 to 78, who were diagnosed with bacterial vaginosis. Patient demographics in the trials were 51% Caucasian, 36% Black, 10% Hispanic, and 3% Asian, other or unknown. All patients received 100 mg clindamycin phosphate cream intravaginally in a single dose. Of the 368 women treated with a single dose of Clindesse (clindamycin phosphate) , 1.6% of the patients discontinued therapy due to adverse reactions. Adverse reactions occurred in 126 of 368 patients (34%) treated with Clindesse (clindamycin phosphate) and in 32 of 85 patients (38%) treated with placebo. Adverse reactions occurring in ≥ 1% of patients receiving Clindesse (clindamycin phosphate) in the three clinical studies are shown in Table 1. Table 1: Adverse Reactions Occurring in ≥ 1% of Clindesse (clindamycin phosphate) -Treated Patients and at a Higher Rate than Placebo-Treated Patients Adverse Event Clindesse (clindamycin phosphate) N=368 n (%) Placebo N=85 n (%) Vaginosis fungal NOS* 52 (14) 7 (8) Headache NOS 10 (3) 2 (2) Back pain 6 (2) 1 (1) Constipation 4 (1) 0 (0) Urinary tract infection NOS 4 (1) 0 (0) N = number of patients in intent-to-treat population n (%) = number and percentage of patients with reported adverse reaction NOS = not otherwise specified * The use of clindamycin may result in the overgrowth of non-susceptible fungal organisms in the vagina and may require antifungal treatment Other reactions reported by < 1% of those women treated with Clindesse (clindamycin phosphate) include: Dermatologic: Pruritic rash Gastrointestinal: Diarrhea, vomiting General: Fatigue Immune System: Hypersensitivity Nervous System: Dizziness Reproductive System: Dysfunctional uterine bleeding, dysmennorrhea, intermenstrual bleeding, pelvic pain, vaginal burning, vaginal irritation, vulvar erythema

SIDE EFFECTS Clinical Trials Non-Pregnant Women In clinical trials involving non-pregnant women, 1.8% of 600 patients who received treatment with clindamycin phosphate vaginal cream 2% for 3 days and 2.7% of 1325 patients who received treatment for 7 days discontinued therapy due to drug-related adverse events. Medical events judged to be related, probably related, possibly related, or of unknown relationship to vaginally administered clindamycin phosphate vaginal cream 2%, were reported for 20.7% of the patients receiving treatment for 3 days and 21.3% of the patients receiving treatment for 7 days. Events occurring in ≥1% of patients receiving clindamycin phosphate vaginal cream 2% are shown in Table 1. Table 1- Events Occurring in ≥1% of Non-pregnant Patients Receiving Clindamycin Phosphate Vaginal Cream 2% Event Clindamycin Phosphate Vaginal Cream 3 Day n=600 7 Day n=1325 Urogenital Vaginal moniliasis 7.7 10.4 Vulvovaginitis 6.0 4.4 Vulvovaginal disorder 3.2 5.3 Trichomonal vaginitis 0 1.3 Body as a Whole Moniliasis (body) 1.3 0.2 Other events occurring in <1% of the clindamycin vaginal cream 2% groups include: Urogenital system: vaginal discharge, metrorrhagia, urinary tract infection, endometriosis, menstrual disorder, vaginitis/vaginal infection, and vaginal pain. Body as a whole: localized abdominal pain, generalized abdominal pain, abdominal cramps, halitosis, headache, bacterial infection, inflammatory swelling, allergic reaction, and fungal infection. Digestive system: nausea, vomiting, constipation, dyspepsia, flatulence, diarrhea, and gastrointestinal disorder. Endocrine system: hyperthyroidism. Central nervous system: dizziness and vertigo. Respiratory system: epistaxis. Skin: pruritus (non-application site), moniliasis, rash, maculopapular rash, erythema, and urticaria. Special senses: taste perversion. Pregnant Women In a clinical trial involving pregnant women during the second trimester, 1.7% of 180 patients who received treatment for 7 days discontinued therapy due to drug-related adverse events. Medical events judged to be related, probably related, possibly related, or of unknown relationship to vaginally administered clindamycin phosphate vaginal cream 2%, were reported for 22.8% of pregnant patients. Events occurring in ≥1% of patients receiving either clindamycin phosphate vaginal cream 2% or placebo are shown in Table 2. Table 2- Events Occurring in ≥1% of Preg nant Patients Receiving Clindamycin Phosphate Vaginal Cream 2% or Placebo Event Clindamycin Placebo 7 Day n=180 7 Day n=184 Urogenital Vaginal moniliasis 13.3 7.1 Vulvovaginal disorder 6.7 7.1 Abnormal labor 1.1 0.5 Body as a Whole Fungal infection 1.7 0 Skin Pruritus, non-application site 0 Other events occurring in <1% of the clindamycin vaginal cream 2% group include: Urogenital system: dysuria, metrorrhagia, vaginal pain, and trichomonal vaginitis. Body as a whole: upper respiratory infection. Skin: pruritus (topical application site) and erythema. Other clindamycin formulations: Clindamycin vaginal cream affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to 100 mg oral clindamycin dosing. Although these lower levels of exposure are less likely to produce the common reactions seen with oral clindamycin, the possibility of these and other reactions cannot be excluded presently. Data from well-controlled trials directly comparing clindamycin administered orally to clindamycin administered vaginally are not available. The following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of clindamycin: Gastrointestinal: Abdominal pain, esophagitis, nausea, vomiting, and diarrhea. (See WARNINGS.) Hematopoietic: Transient neutropenia (leukopenia), eosinophilia, agranulocytosis, and thrombocytopenia have been reported. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of these reports. Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. A few cases of anaphylactoid reactions have been reported. If a hypersensitivity reaction occurs, the drug should be discontinued. Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy. Musculoskeletal: Rare instances of polyarthritis have been reported. Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances. DRUG INTERACTIONS Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

SIDE EFFECTS In the one well-controlled clinical study comparing Clindagel® and its vehicle, the incidence of skin and appendages adverse events occurring in ≥ 1% of the patients in either group is presented below: Body System/Adverse Event Number (%) of Patients Clindagel® QD N=168 Vehicle Gel QD N=84 Skin and appendages disorders Dermatitis 0 (0.0) 1 (1.2) Dermatitis contact 0 (0.0) 1 (1.2) Dermatitis fungal 0 (0.0) 1 (1.2) Folliculitis 0 (0.0) 1 (1.2) Photosensitivity reaction 0 (0.0) 1 (1.2) Pruritus 1 (0.6) 1 (1.2) Rash erythematous 0 (0.0) 0 (0.0) Skin dry 0 (0.0) 0 (0.0) Peeling 1 (0.6) 0 (0.0) Orally and parenterally administered clindamycin has been associated with severe colitis, which may end fatally. Cases of diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported as adverse reactions in patients treated with oral and parenteral formulations of clindamycin and rarely with topical clindamycin (see WARNINGS). Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Colitis Systemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. If significant diarrhea occurs, EVOCLIN Foam should be discontinued. [See ADVERSE REACTIONS.] Severe colitis has occurred following oral or parenteral administration of clindamycin with an onset of up to several 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 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. Irritation EVOCLIN Foam can cause irritation. 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 irritation or dermatitis occurs, clindamycin should be discontinued. Avoid contact of EVOCLIN Foam with eyes, mouth, lips, other mucous membranes or areas of broken skin. If contact occurs, rinse thoroughly with water. EVOCLIN Foam should be prescribed with caution in atopic individuals. Patient Counseling Information See FDA-Approved patient labeling (PATIENT INFORMATION). Instructions for Use Patients should be advised to wash their skin with mild soap and allow it to dry before applying EVOCLIN Foam. Patients should use enough EVOCLIN Foam to cover the face and to apply once daily. Patients should dispense EVOCLIN Foam directly into the cap or onto a cool surface. Patients should wash their hands after applying EVOCLIN Foam. Skin Irritation EVOCLIN Foam may cause irritation such as erythema, scaling, itching, burning, or stinging. Patients should be advised to discontinue use if excessive irritancy or dermatitis occur. Colitis In the event a patient treated with EVOCLIN Foam experiences severe diarrhea or gastrointestinal discomfort, EVOCLIN Foam should be discontinued and a physician should be contacted. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenicity of a 1.2% clindamycin phosphate gel similar to EVOCLIN Foam was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of EVOCLIN Foam, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. A 1.2% clindamycin phosphate gel similar to EVOCLIN Foam caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility. Use In Specific Populations Pregnancy Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with EVOCLIN Foam. EVOCLIN Foam should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus. Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from EVOCLIN Foam based on a mg/m² comparison. Nursing Mothers It is not known whether clindamycin is excreted in human milk following use of EVOCLIN Foam. 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. If used during lactation and EVOCLIN Foam is applied to the chest, care should be taken to avoid accidental ingestion by the infant. Pediatric Use Safety and effectiveness of EVOCLIN Foam in children under the age of 12 have not been studied. Geriatric Use The clinical study with EVOCLIN Foam did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Clostridium difficile-Associated Diarrhea (CDAD) Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see ADVERSE REACTIONS]. Use with Condoms and Vaginal Contraceptive Diaphragms This cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, the use of such barrier contraceptives is not recommended concurrently or for 5 days following treatment with Clindesse (clindamycin phosphate) . During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases. Patient Counseling Information Vaginal Intercourse and Use with Vaginal Products Instruct the patient not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with this product. Use with Condoms and Vaginal Contraceptive Diaphragms Advise the patient that this cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, do not use barrier contraceptives concurrently or for 5 days following treatment with Clindesse (clindamycin phosphate) . During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases [see WARNINGS AND PRECAUTIONS]. Fungal Vaginal Infections Inform the patient that vaginal fungal infections can occur following use of Clindesse (clindamycin phosphate) and may require treatment with an antifungal drug [see ADVERSE REACTIONS]. Accidental Exposure to the Eye Inform the patient that Clindesse (clindamycin phosphate) contains ingredients which cause burning and irritation of the eye. In the event of accidental contact with the eye, rinse the eye with copious amounts of cool tap water and consult a physician. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames test. Both tests were negative. Fertility studies in rats treated orally with up to 300 mg/kg/day (29 times the recommended human dose based on body surface area comparisons) revealed no effects on fertility or mating ability. Use In Specific Populations Pregnancy Pregnancy Category B Clindesse (clindamycin phosphate) should be used during pregnancy only if clearly needed. There are no adequate and well-controlled studies of Clindesse (clindamycin phosphate) in pregnant women. Another intravaginal formulation containing 2% clindamycin phosphate has been studied in pregnant women during the second trimester. In women treated for seven days, abnormal labor was reported in 1.1% of patients who received that clindamycin vaginal cream formulation compared with 0.5% of patients who received placebo. Reproduction studies have been performed in rats and mice using oral and parenteral doses of clindamycin up to 600 mg/kg/day (58 and 29 times, respectively, the recommended human dose based on body surface area comparisons) and have revealed no evidence of harm to the fetus due to clindamycin. Because animal reproduction studies are not always predictive of human response, Clindesse (clindamycin phosphate) should be used during pregnancy only if clearly needed. Nursing Mothers Caution should be exercised when Clindesse (clindamycin phosphate) is administered to a nursing woman. It is not known if clindamycin is excreted in human milk following the use of vaginally administered clindamycin. Clindamycin has been detected in human milk after oral or parenteral administration. Because of the potential for serious adverse reactions in nursing infants, a decision to continue or discontinue nursing should take into account the importance of the drug to the mother. Pediatric Use The safety and efficacy of Clindesse (clindamycin phosphate) in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. The safety and efficacy of Clindesse (clindamycin phosphate) in pre-menarchal females have not been established. Geriatric Use Clinical studies with Clindesse (clindamycin phosphate) did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

WARNINGS Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild to life-threatening. Orally and parenterally administered clindamycin has been associated with severe colitis which may end fatally. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of orally and parenterally administered clindamycin, as well as with topical (dermal) formulations of clindamycin. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of clindamycin, even when administered by the vaginal route, because approximately 5% of the clindamycin dose is systemically absorbed from the vagina. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibioticassociated" colitis. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug 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 difficile colitis. Onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment. PRECAUTIONS General ClindaMax® Vaginal Cream, contains ingredients that will cause burning and irritation of the eye. In the event of accidental contact with the eye, rinse the eye with copious amounts of cool tap water. The use of ClindaMax® Vaginal Cream may result in the overgrowth of nonsusceptible organisms in the vagina. In clinical studies involving 600 non-pregnant women who received treatment for 3 days, Candida albicans was detected, either symptomatically or by culture, in 8.8% of patients. In 9% of the patients, vaginitis was recorded. In clinical studies involving 1325 non-pregnant women who received treatment for 7 days, Candida albicans was detected, either symptomatically or by culture, in 10.5% of patients. Vaginitis was recorded in 10.7% of the patients. In 180 pregnant women who received treatment for 7 days, Candida albicans was detected, either symptomatically or by culture, in 13.3% of patients. In 7.2% of the patients, vaginitis was recorded. Candida albicans, as reported here, includes the terms: vaginal moniliasis and moniliasis (body as a whole). Vaginitis includes the terms: vulvo-vaginal disorder, vulvovaginitis, vaginal discharge, trichomonal vaginitis, and vaginitis. Carcinogenesis, Mutagenesis, Impairment Of Fertility Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames test. Both tests were negative. Fertility studies in rats treated orally with up to 300 mg/kg/day (31 times the human exposure based on mg/m2 ) revealed no effects on fertility or mating ability. Pregnancy Teratogenic Effects Pregnancy Category B There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. This drug should be used during the first trimester of pregnancy only if clearly needed. Clindamycin phosphate vaginal cream 2% has been studied in pregnant women during the second trimester. In women treated for seven days, abnormal labor was reported in 1.1% of patients who received clindamycin phosphate vaginal cream 2% compared with 0.5% of patients who received placebo. Reproduction studies have been performed in rats and mice using oral and parenteral doses of clindamycin up to 600 mg/kg/day (62 and 25 times, respectively, the maximum human exposure based on mg/m2 ) and have revealed no evidence of harm to the fetus due to clindamycin. In one mouse strain, cleft palates were observed in treated fetuses; this outcome was not produced in other mouse strains or in other species and is, therefore, considered to be a strain specific effect. See INDICATIONS AND USAGE; PRECAUTIONS, General; and ADVERSE REACTIONS. Nursing Mothers Clindamycin has been detected in human milk after oral or parenteral administration. It is not known if clindamycin is excreted in human milk following the use of vaginally administered clindamycin phosphate. Because of the potential for serious adverse reactions in nursing infants from clindamycin phosphate, 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 in pediatric patients have not been established. Geriatric Use Clinical studies for clindamycin vaginal cream 2% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

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 stoolassay 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. PRECAUTIONS General Clindagel® should be prescribed with caution in atopic individuals. Carcinogenesis, Mutagenesis, Impairment Of Fertility The carcinogenicity of a 1% clindamycin phosphate gel similar to Clindagel® was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of Clindagel® , assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. A 1% clindamycin phosphate gel similar to Clindagel® caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility. Pregnancy Teratogenic Effects Pregnancy Category B Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from Clindagel® based on a mg/m comparison. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether clindamycin is excreted in human milk following use of Clindagel®. 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 in children under the age of 12 have not been established. Geriatric Use The clinical study with Clindagel® did not include sufficient numbers of patients aged 65 and over to determine if they respond differently than younger patients.