Clindamycin Phosphate and Benzoyl Peroxide

6 ADVERSE REACTIONS The following selected adverse reactions occurred in less than 0.2% of patients: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions observed in the clinical trials of a drug cannot always be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following selected adverse reactions occurred in less than 0.2% of subjects treated with clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5%: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). During clinical trials, subjects were assessed for local cutaneous signs and symptoms of erythema, scaling, itching, burning and stinging. Most local skin reactions increased and peaked around Week 4 and continually decreased over time reaching near baseline levels by Week 12. The percentage of subjects that had symptoms present before treatment, the maximum value recorded during treatment, and the percent with symptoms present at Week 12 are shown in Table 1. Table 1: Percent of Subjects with Local Skin Reactions. Combined Results from the Two Phase 3 Trials (N = 773) Combined Results from the Two Phase 3 Trials (N=773) Before Treatment (Baseline) Maximum During Treatment End of Treatment (Week 12) Mild Mod.* Severe Mild Mod.* Severe Mild Mod.* Severe Erythema 22 4 0 25 5 <1 15 2 0 Scaling 8 <1 0 18 3 0 8 1 0 Itching 10 2 0 15 2 0 6 <1 0 Burning 3 <1 0 8 2 0 2 <1 0 Stinging 2 <1 0 6 1 0 1 <1 0 *Mod. = Moderate 6.2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Anaphylaxis, as well as allergic reactions leading to hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide.

4 CONTRAINDICATIONS Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is contraindicated in: • Patients who have demonstrated hypersensitivity (e.g., anaphylaxis) to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. (4.1) • Patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. (4.2) 4.1 Hypersensitivity Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is contraindicated in those individuals who have shown hypersensitivity to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. Anaphylaxis, as well as allergic reactions leading to hospitalization, has been reported in postmarketing use with clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5%. [ See Postmarketing Experience (6.2) . ] 4.2 Colitis/Enteritis Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. [ See Warnings and Precautions (5.1) . ]

11 DESCRIPTION Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is a combination product with two active ingredients in a white to off-white, opaque, smooth, aqueous gel formulation intended for topical use. Clindamycin phosphate is a water-soluble ester of the semisynthetic 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 - Dgalacto-octopyranoside 2 -(dihydrogen phosphate). The structural formula or clindamycin phosphate is represented below: Clindamycin phosphate: Molecular Formula: C 18 H 34 ClN 2 O 8 PS Molecular Weight: 504.97 Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula for benzoyl peroxide is represented below: Benzoyl peroxide: Molecular Formula: C 14 H 10 O 4 Molecular Weight: 242.23 Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% contains the following inactive ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide. Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% contains 1.2% of clindamycin phosphate which is equivalent to 1% clindamycin.

2 DOSAGE AND ADMINISTRATION Before applying Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%, wash your face gently with a mild soap, rinse with warm water, and pat your skin dry. Apply a pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% to the face once daily. Avoid the eyes, mouth, mucous membranes, or areas of broken skin. Use of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% beyond 12 weeks has not been evaluated. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is not for oral, ophthalmic, or intravaginal use. • Apply a pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% to the face once daily. (2) • Not for oral, ophthalmic, or intravaginal use. (2)

1 INDICATIONS AND USAGE Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is indicated for the topical treatment of acne vulgaris in patients 12 years or older. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is a combination of clindamycin phosphate (a lincosamide antibacterial) and benzoyl peroxide indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

7 DRUG INTERACTIONS • Avoid using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% in combination with topical or oral erythromycin-containing products because of its clindamycin component. (7.1) 7.1 Erythromycin Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% should not be used in combination with topical or oral erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between erythromycin and clindamycin. The clinical significance of this in vitro antagonism is not known. 7.2 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 and Benzoyl Peroxide Gel, 1.2%/2.5% should be used with caution in patients receiving such agents.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Clindamycin: Clindamycin is a lincosamide antibacterial [ See Microbiology (12.4) ]. Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action is unknown. 12.3 Pharmacokinetics The systemic absorption of clindamycin was investigated in an open-label, multiple-dose trial in 16 adult subjects with moderate to severe acne vulgaris treated with 1 gram of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% applied to the face once daily for 30 days. Twelve subjects (75%) had at least one quantifiable clindamycin plasma concentration above the lower limit of quantification (LOQ = 0.5 ng/mL) on Day 1 or Day 30. On Day 1, the mean (± standard deviation) peak plasma concentration (C max ) was 0.78 ± 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC 0-t was 5.29 ± 0.81 h.ng/mL (n=4). On Day 30, the mean C max was 1.22 ± 0.88 ng/mL (n=10), and the mean AUC 0-t was 8.42 ± 6.01 h.ng/mL (n=6). Clindamycin plasma concentrations were below LOQ in all subjects at 24 hours post-dose on the three tested days (Day 1, 15, and 30). Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. 12.4 Microbiology Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin and benzoyl peroxide individually have been shown to 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 is not known. P. acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.

12.1 Mechanism of Action Clindamycin: Clindamycin is a lincosamide antibacterial [ See Microbiology (12.4) ]. Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action is unknown.

12.3 Pharmacokinetics The systemic absorption of clindamycin was investigated in an open-label, multiple-dose trial in 16 adult subjects with moderate to severe acne vulgaris treated with 1 gram of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% applied to the face once daily for 30 days. Twelve subjects (75%) had at least one quantifiable clindamycin plasma concentration above the lower limit of quantification (LOQ = 0.5 ng/mL) on Day 1 or Day 30. On Day 1, the mean (± standard deviation) peak plasma concentration (C max ) was 0.78 ± 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC 0-t was 5.29 ± 0.81 h.ng/mL (n=4). On Day 30, the mean C max was 1.22 ± 0.88 ng/mL (n=10), and the mean AUC 0-t was 8.42 ± 6.01 h.ng/mL (n=6). Clindamycin plasma concentrations were below LOQ in all subjects at 24 hours post-dose on the three tested days (Day 1, 15, and 30). Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.

20230816

100

3 DOSAGE FORMS AND STRENGTHS Gel, 1.2%/2.5% Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% contains 10 mg (1%) clindamycin as phosphate, and 25 mg (2.5%) benzoyl peroxide in a white to off-white, opaque, smooth gel. Gel, 1.2% clindamycin phosphate/2.5% benzoyl peroxide

Clindamycin Phosphate and Benzoyl Peroxide Clindamycin Phosphate, Benzoyl Peroxide BENZOYL PEROXIDE BENZOYL PEROXIDE CLINDAMYCIN PHOSPHATE CLINDAMYCIN WATER CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) PROPYLENE GLYCOL POTASSIUM HYDROXIDE White-to-off-white structure1 structure2 figure-1 figure-2

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility testing of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% have not been performed. Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered topically twice per week for 20 weeks induced skin tumors in transgenic Tg.AC mice. The clinical significance of this is unknown. Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses of 900, 2700, and 15000 mg/kg/day (1.8, 5.4, and 30 times the MRHD for clindamycin and 3.6, 10.8, and 60 times the MRHD for benzoyl peroxide, respectively, based on BSA comparisons) did not cause any increase in tumors. However, topical treatment with a different gel formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900, and 3000 mg/kg/day (1.2, 3.6, and 12 times the MRHD for clindamycin and 2.4, 7.2, and 24 times the MRHD for benzoyl peroxide, respectively, based on BSA comparisons) for up to 97 weeks did not cause any increase in tumors. Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Fertility studies have not been performed with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the MRHD for clindamycin, based on BSA comparisons) revealed no effects on fertility or mating ability.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility testing of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% have not been performed. Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered topically twice per week for 20 weeks induced skin tumors in transgenic Tg.AC mice. The clinical significance of this is unknown. Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses of 900, 2700, and 15000 mg/kg/day (1.8, 5.4, and 30 times the MRHD for clindamycin and 3.6, 10.8, and 60 times the MRHD for benzoyl peroxide, respectively, based on BSA comparisons) did not cause any increase in tumors. However, topical treatment with a different gel formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900, and 3000 mg/kg/day (1.2, 3.6, and 12 times the MRHD for clindamycin and 2.4, 7.2, and 24 times the MRHD for benzoyl peroxide, respectively, based on BSA comparisons) for up to 97 weeks did not cause any increase in tumors. Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Fertility studies have not been performed with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the MRHD for clindamycin, based on BSA comparisons) revealed no effects on fertility or mating ability.

ANDA205397

Clindamycin Phosphate and Benzoyl Peroxide

Clindamycin Phosphate, Benzoyl Peroxide

72162-2077

HUMAN PRESCRIPTION DRUG

TOPICAL

12.4 Microbiology Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin and benzoyl peroxide individually have been shown to 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 is not known. P. acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.

Clindamycin-Benzoyl 1.2%/2.5% Gel Label

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). • Patients who develop allergic reactions such as severe swelling or shortness of breath should discontinue use and contact their physician immediately. • Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% may cause irritation such as erythema, scaling, itching, or burning, especially when used in combination with other topical acne therapies. • Excessive or prolonged exposure to sunlight should be limited. To minimize exposure to sunlight, a hat or other clothing should be worn. Sunscreen may also be used. • Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% may bleach hair or colored fabric.

INSTRUCTIONS FOR USE Clindamycin Phosphate (klin-da-MYE-sin fos-fate) and Benzoyl Peroxide (BEN-zoe-il peer-OKS-ide) Gel, 1.2%/2.5% Important Information: Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is for use on skin only (topical use). Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is not for use in your mouth, eyes or vagina Read this Instructions for Use before you start using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment. • Apply Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% to your face 1 time each day as prescribed. • Before you apply Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%, wash your face gently with a mild soap, rinse with warm water, and pat your skin dry. • To apply Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% to your face, use the pump to dispense one pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% onto your fingertip. See Figure 1. • One pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% should be enough to cover your entire face. Figure 1 • Dot the one pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% onto six areas of your face (chin, left cheek, right cheek, nose, left forehead, right forehead). See Figure 2. Figure 2 • Spread the gel over your face and gently rub it in. It is important to spread the gel over your entire face. If your doctor tells you to put Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% on other areas of your skin with acne, be sure to ask how much you should use. • Wash your hands with soap and water after applying Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%. How should I store Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%? • Store Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% at room temperature at or below 77°F (25°C). • Do not freeze Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%. • Throw away (discard) Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% that has passed the expiration date. • Store pump upright. • Keep the container tightly closed. Keep Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% and all medicines out of the reach of children. The Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. Made in Israel Manufactured By Perrigo Yeruham, Israel Distributed By Perrigo Allegan, MI 49010 www.perrigorx.com Rev 07-20

14 CLINICAL STUDIES The safety and efficacy of once daily use of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% were assessed in two 12-week multi-center, randomized, blinded trials in subjects 12 years and older with moderate to severe acne vulgaris. The two trials were identical in design and compared clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% to clindamycin in the vehicle gel, benzoyl peroxide in the vehicle gel, and the vehicle gel alone. The co-primary efficacy variables were: (1) Mean absolute change from baseline at Week 12 in: • Inflammatory lesion counts • Non-inflammatory lesion counts (2) Percent of subjects who had a 2-grade improvement from baseline on an Evaluator’s Global Severity (EGS) score. The EGS scoring scale used in all of the clinical trials for clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% is as follows: Grade Description 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 nodulocystic lesion Severe Inflammatory lesions are more apparent, many comedones and papules/pustules, there may or may not be a few nodulocystic lesions Very Severe Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions The results of Trial 1 at Week 12 are presented in Table 2: Table 2: Trial 1 Results Trial 1 Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% N=399 Clindamycin Gel N=408 Benzoyl Peroxide Gel N=408 Vehicle Gel N=201 EGSS Clear or Almost Clear 115 (29%) 84 (21%) 76 (19%) 29 (14%) 2-grade reduction from baseline 131 (33%) 100 (25%) 96 (24%) 38 (19%) Inflammatory Lesions: Mean absolute change 14.8 12.2 13.0 9.0 Mean percent (%) reduction 55.0% 47.1% 49.3% 34.5% Non-Inflammatory Lesions: Mean absolute change 22.1 17.9 20.6 13.2 Mean percent (%) reduction 45.3% 38.0% 40.2% 28.6% The results of Trial 2 at Week 12 are presented in Table 3: Table 3: Trial 2 Results Trial 2 Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% N=398 Clindamycin Gel N=404 Benzoyl Peroxide Gel N=403 Vehicle Gel N=194 EGSS Clear or Almost Clear 113 (28%) 94 (23%) 94 (23%) 21 (11%) 2-grade reduction from baseline 147 (37%) 114 (28%) 114 (28%) 27 (14%) Inflammatory Lesions: Mean absolute change 13.7 11.3 11.2 5.7 Mean percent (%) reduction 54.2% 45.3% 45.7% 23.3% Non-Inflammatory Lesions: Mean absolute change 19.0 14.9 15.2 8.3 Mean percent (%) reduction 41.2% 34.3% 34.5% 19.2%

8.5 Geriatric Use Clinical trials of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

8.4 Pediatric Use Safety and effectiveness of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% in pediatric patients under the age of 12 have not been evaluated.

8.1 Pregnancy Risk Summary There are no available data on Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The limited published data on use of clindamycin in pregnant women with exposure during the first trimester are insufficient to inform a drug-associated risk of pregnancy-related adverse outcomes (see Data) . In limited published clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of major birth defects. In animal reproduction studies, clindamycin did not cause malformations or embryo-fetal development toxicity in pregnant rats and mice when administered during the period of organogenesis at systemic doses up to 240 times the maximum recommended human dose (MRHD) of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%, based on body surface area (BSA) comparisons (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. Animal Data Animal reproductive/developmental toxicity studies have not been conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for clindamycin, respectively, based on BSA comparisons) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the MRHD for clindamycin, respectively, based on BSA comparisons) revealed no malformations or embryo-fetal development toxicity.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The limited published data on use of clindamycin in pregnant women with exposure during the first trimester are insufficient to inform a drug-associated risk of pregnancy-related adverse outcomes (see Data) . In limited published clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of major birth defects. In animal reproduction studies, clindamycin did not cause malformations or embryo-fetal development toxicity in pregnant rats and mice when administered during the period of organogenesis at systemic doses up to 240 times the maximum recommended human dose (MRHD) of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%, based on body surface area (BSA) comparisons (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. Animal Data Animal reproductive/developmental toxicity studies have not been conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for clindamycin, respectively, based on BSA comparisons) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the MRHD for clindamycin, respectively, based on BSA comparisons) revealed no malformations or embryo-fetal development toxicity. 8.2 Lactation Risk Summary There are no data on the presence of clindamycin or benzoyl peroxide in human milk, the effects on the breastfed child, or the effects on milk production following topical administration. However, clindamycin has been reported to be present in breast milk in small amounts following oral and parenteral administration. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% and any potential adverse effects on the breastfed child from Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or from the underlying maternal condition. Clinical Considerations If used during lactation and Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is applied to the chest, care should be taken to avoid accidental ingestion by the infant. 8.4 Pediatric Use Safety and effectiveness of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% in pediatric patients under the age of 12 have not been evaluated. 8.5 Geriatric Use Clinical trials of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is a white to off-white smooth gel supplied as: NDC 72162-2077-1 50 g pump 16.2 Dispensing Instructions for the Pharmacist •Dispense Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% with a 10-week expiration date. •Specify “Store at room temperature up to 25°C (77°F). Do not freeze.” 16.3 Storage and Handling • PHARMACIST: Prior to Dispensing: Store in a refrigerator, 2°C to 8°C (36°F to 46°F). • PATIENT: Store at room temperature at or below 25°C (77°F). • Protect from freezing. • Store pump upright. • Keep out of the reach of children. • Keep container tightly closed.