Browse the corpus

1 INDICATIONS AND USAGE Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is a combination of clindamycin phosphate (a lincosamide antibacterial) and benzoyl peroxide indicated for the topical treatment of inflammatory acne vulgaris. ( 1.1 ) Limitation of Use: Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% has not been demonstrated to have any additional benefit when compared with benzoyl peroxide alone in the same vehicle when used for the treatment of non-inflammatory acne. ( 1.2 ) 1.1 Indication Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is indicated for the topical treatment of inflammatory acne vulgaris in patients 12 years and older. 1.2 Limitations of Use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% has not been demonstrated to have any additional benefit when compared with benzoyl peroxide alone in the same vehicle when used for the treatment of non-inflammatory acne.

2 DOSAGE AND ADMINISTRATION Apply a thin layer of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% to the face once daily, in the evening or as directed by the physician. The skin should be gently washed, rinsed with warm water, and patted dry before applying Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Avoid the eyes, mouth, lips, mucous membranes, or areas of broken skin. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is not for oral, ophthalmic, or intravaginal use. Apply a thin layer of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% to the face once daily, in the evening. ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Gel, 1.2%/5% Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is a white to slightly yellow, opaque gel. Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% contains 12 mg clindamycin phosphate (equivalent to 10 mg of clindamycin) and 50 mg benzoyl peroxide. Gel, 1.2%/5%: Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% contains 12 mg clindamycin phosphate (equivalent to 10 mg of clindamycin) and 50 mg benzoyl peroxide. ( 3 )

4 CONTRAINDICATIONS Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is contraindicated in: Patients who have demonstrated hypersensitivity (e.g., anaphylaxis) to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. (4) Patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis (including pseudomembranous colitis). (4) 4.1 Hypersensitivity Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/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%/5%. [See Adverse Reactions ( 6.2 ).] 4.2 Colitis/Enteritis Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is contraindicated in those individuals with a history of regional enteritis, ulcerative colitis, pseudomembranous colitis, or antibiotic-associated colitis [see Warnings and Precautions ( 5.1 )].

5 WARNINGS AND PRECAUTIONS Colitis: Clindamycin can cause severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of clindamycin. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should be discontinued if significant diarrhea occurs. ( 5.1 ) Ultraviolet light and environmental exposure (including use of tanning beds or sun lamps): Minimize sun exposure following drug application. ( 5.2 ) 5.1 Colitis Systemic absorption of clindamycin has been demonstrated following topical use of clindamycin. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. If significant diarrhea occurs, Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should be discontinued. Severe colitis has occurred following oral and 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. 5.2 Ultraviolet Light and Environmental Exposure Benzoyl peroxide, a component of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, may cause increased sensitivity to sunlight. Minimize sun exposure (including use of tanning beds or sun lamps) following drug application. [See Nonclinical Toxicology ( 13.1 .)] Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution.

6 ADVERSE REACTIONS The following adverse reaction is described in more detail in the Warnings and Precautions section of the label: Colitis [see Warnings and Precautions ( 5.1 )]. The most common local adverse reactions (≥5%) are erythema, peeling, dryness and burning. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 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 reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical trials, 397 subjects used Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% once daily for 11 weeks for the treatment of moderate to moderately severe facial acne vulgaris. All subjects were graded for facial local skin reactions (erythema, peeling, burning, and dryness) on the following scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. The percentage of subjects that had symptoms present before treatment (at baseline) and during treatment is presented in Table 1. Table 1. Local Skin Reactions with Use of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% Combined Results from Five Trials (n = 397) % of Subjects Using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% with Symptom Present Before Treatment (Baseline) During Treatment Symptom Mild Moderate Severe Mild Moderate Severe Erythema 28% 3% 0 26% 5% 0 Peeling 6% <1% 0 17% 2% 0 Burning 3% <1% 0 5% <1% 0 Dryness 6% <1% 0 15% 1% 0 (Percentages derived by number of subjects receiving Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% with symptom score/number of enrolled subjects receiving Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%). 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. 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 hospitalization, has been reported in postmarketing use with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Urticaria, application site reactions, including discoloration have been reported.

<table cellspacing="0" cellpadding="0" border="0" width="621.775"><colgroup><col width="14.2887700534759%"/><col width="14.2780748663102%"/><col width="14.2887700534759%"/><col width="14.2887700534759%"/><col width="14.2887700534759%"/><col width="14.2780748663102%"/><col width="14.2887700534759%"/></colgroup><tbody><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" rowspan="2" align="center"/><td valign="top" styleCode="Rrule" colspan="6" align="center"><content styleCode="bold">% of Subjects Using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% with Symptom Present</content> </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" colspan="3" align="center"><content styleCode="bold">Before Treatment (Baseline)</content> </td><td valign="top" styleCode="Rrule" colspan="3" align="center"><content styleCode="bold">During Treatment</content> </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center"><content styleCode="bold">Symptom</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Mild</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Moderate</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Severe</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Mild</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Moderate</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Severe</content> </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center">Erythema </td><td valign="top" styleCode="Rrule" align="center">28% </td><td valign="top" styleCode="Rrule" align="center">3% </td><td valign="top" styleCode="Rrule" align="center">0 </td><td valign="top" styleCode="Rrule" align="center">26% </td><td valign="top" styleCode="Rrule" align="center">5% </td><td valign="top" styleCode="Rrule" align="center">0 </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center">Peeling </td><td valign="top" styleCode="Rrule" align="center">6% </td><td valign="top" styleCode="Rrule" align="center">&lt;1% </td><td valign="top" styleCode="Rrule" align="center">0 </td><td valign="top" styleCode="Rrule" align="center">17% </td><td valign="top" styleCode="Rrule" align="center">2% </td><td valign="top" styleCode="Rrule" align="center">0 </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center">Burning </td><td valign="top" styleCode="Rrule" align="center">3% </td><td valign="top" styleCode="Rrule" align="center">&lt;1% </td><td valign="top" styleCode="Rrule" align="center">0 </td><td valign="top" styleCode="Rrule" align="center">5% </td><td valign="top" styleCode="Rrule" align="center">&lt;1% </td><td valign="top" styleCode="Rrule" align="center">0 </td></tr><tr><td valign="top" styleCode="Lrule Rrule" align="center">Dryness </td><td valign="top" styleCode="Rrule" align="center">6% </td><td valign="top" styleCode="Rrule" align="center">&lt;1% </td><td valign="top" styleCode="Rrule" align="center">0 </td><td valign="top" styleCode="Rrule" align="center">15% </td><td valign="top" styleCode="Rrule" align="center">1% </td><td valign="top" styleCode="Rrule" align="center">0 </td></tr></tbody></table>

7 DRUG INTERACTIONS Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should not be used in combination with erythromycin-containing products because of its clindamycin component. ( 7.1 ) 7.1 Erythromycin Avoid using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% in combination with 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 Concomitant Topical Medications Concomitant topical acne therapies should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. If irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. Treatment should be discontinued if the irritation persists. 7.3 Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should be used with caution in patients receiving such agents. 7.4 Topical Sulfone Products Use of topical benzoyl-peroxide-containing preparations with topical sulfone products may cause skin and facial hair to temporarily change color (yellow/orange).

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women treated with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg per kg per day (240 and 120 times the amount of clindamycin in the highest recommended adult human dose based on mg per m 2 , respectively) or subcutaneous doses of clindamycin up to 250 mg per kg per day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg per m 2 , respectively) revealed no evidence of teratogenicity. 8.3 Nursing Mothers It is not known whether Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is excreted into human milk after topical application. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Because many drugs are excreted in human milk, caution should be exercised when Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% in pediatric patients below the age of 12 have not been established. 8.5 Geriatric Use Clinical studies of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% did not include sufficient numbers of subjects ages 65 and over to determine whether they respond differently from younger subjects.

8.1 Pregnancy Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women treated with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg per kg per day (240 and 120 times the amount of clindamycin in the highest recommended adult human dose based on mg per m 2 , respectively) or subcutaneous doses of clindamycin up to 250 mg per kg per day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg per m 2 , respectively) revealed no evidence of teratogenicity.

8.3 Nursing Mothers It is not known whether Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is excreted into human milk after topical application. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Because many drugs are excreted in human milk, caution should be exercised when Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is administered to a nursing woman.

8.5 Geriatric Use Clinical studies of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% did not include sufficient numbers of subjects ages 65 and over to determine whether they respond differently from younger subjects.

11 DESCRIPTION Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is a fixed combination product with two active ingredients in a white to slightly yellow, opaque, aqueous gel formulation. 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. Clindamycin phosphate is C 18 H 34 ClN 2 O 8 PS. The structural formula for clindamycin phosphate is represented below: Clindamycin phosphate has a molecular weight of 504.97 and its chemical name 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). Benzoyl peroxide is C 14 H 14 O 4 . It has the following structural formula: Benzoyl Peroxide has a molecular weight of 242.23. Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% contains 10 mg (1%) clindamycin, as clindamycin phosphate, and 50 mg (5%) benzoyl peroxide in a base consisting of carbomer homopolymer (type C), dimethicone, edetate disodium, glycerin, poloxamer 182, purified water, silicon dioxide, and sodium hydroxide. clinda-structure.jpg BPO.jpg

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Clindamycin Clindamycin is a lincosamide antibacterial [see Clinical Pharmacology ( 12.4 )]. Benzoyl Peroxide Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects, but the precise mechanism of action is unknown. 12.3 Pharmacokinetics A comparative trial of the pharmacokinetics of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and 1% clindamycin solution alone in 78 subjects indicated that mean plasma clindamycin levels during the 4-week dosing period were less than 0.5 ng per mL for both treatment groups. Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. Less than 2% of the dose enters systemic circulation as 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 protein synthesis. In Vivo Activity No microbiology studies were conducted in the clinical trials with this product. In Vitro Activity The clindamycin and benzoyl peroxide components 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 in vitro activity is not known. Drug Resistance There are reports of an increase of P. acnes resistance to clindamycin in the treatment of acne. In patients with P. acnes resistant to clindamycin, the clindamycin component may provide no additional benefit beyond benzoyl peroxide alone .

12.1 Mechanism of Action Clindamycin Clindamycin is a lincosamide antibacterial [see Clinical Pharmacology ( 12.4 )]. Benzoyl Peroxide Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects, but the precise mechanism of action is unknown.

12.3 Pharmacokinetics A comparative trial of the pharmacokinetics of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and 1% clindamycin solution alone in 78 subjects indicated that mean plasma clindamycin levels during the 4-week dosing period were less than 0.5 ng per mL for both treatment groups. Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. Less than 2% of the dose enters systemic circulation as benzoic acid.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered twice per week induced squamous cell skin tumors in transgenic TgAC mice in a study using 20 weeks of topical treatment. The clinical significance of this is unknown. In a 2-year dermal carcinogenicity study in mice, treatment with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% at doses up to 8,000 mg per kg per day (16 times the highest recommended adult human dose of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, based on mg per m 2 ) did not cause an increase in skin tumors. However, topical treatment with another formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, or 2,000 mg per kg per day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In a 52-week photocarcinogenicity study in hairless mice (40 weeks of treatment followed by 12 weeks of observation), the median time to onset of skin tumor formation decreased and the number of tumors per mouse increased relative to controls following chronic concurrent topical treatment with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and exposure to ultraviolet radiation. Genotoxicity studies were not conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Clindamycin phosphate was not genotoxic in Salmonella typhimurium or in a rat micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in Salmonella typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% or benzoyl peroxide to evaluate the effect on fertility. Fertility studies in rats treated orally with up to 300 mg per kg per day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, based on mg per m 2 ) revealed no effects on fertility or mating ability.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered twice per week induced squamous cell skin tumors in transgenic TgAC mice in a study using 20 weeks of topical treatment. The clinical significance of this is unknown. In a 2-year dermal carcinogenicity study in mice, treatment with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% at doses up to 8,000 mg per kg per day (16 times the highest recommended adult human dose of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, based on mg per m 2 ) did not cause an increase in skin tumors. However, topical treatment with another formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, or 2,000 mg per kg per day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In a 52-week photocarcinogenicity study in hairless mice (40 weeks of treatment followed by 12 weeks of observation), the median time to onset of skin tumor formation decreased and the number of tumors per mouse increased relative to controls following chronic concurrent topical treatment with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and exposure to ultraviolet radiation. Genotoxicity studies were not conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Clindamycin phosphate was not genotoxic in Salmonella typhimurium or in a rat micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in Salmonella typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% or benzoyl peroxide to evaluate the effect on fertility. Fertility studies in rats treated orally with up to 300 mg per kg per day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, based on mg per m 2 ) revealed no effects on fertility or mating ability.

14 CLINICAL STUDIES In five randomized, double-blind clinical trials of 1,319 subjects, 397 used Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, 396 used benzoyl peroxide, 349 used clindamycin, and 177 used vehicle. Subjects were instructed to wash the face, wait 10 to 20 minutes, and then apply medication to the entire face, once daily in the evening before retiring. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% applied once daily for 11 weeks was significantly more effective than vehicle, benzoyl peroxide, and clindamycin in the treatment of inflammatory lesions of moderate to moderately severe facial acne vulgaris in three of the five trials (Trials 1, 2, and 5). Subjects were evaluated and acne lesions counted at each clinical visit at Weeks 2, 5, 8, 11. The primary efficacy measures were the lesion counts and the investigator's global assessment evaluated at Week 11. Percent reductions in inflammatory lesion counts after treatment for 11 weeks in these 5 trials are shown in Table 2. Table 2. Mean Percent Reduction in Inflammatory Lesion Counts Treatment Trial 1 (n = 120) Trial 2 (n = 273) Trial 3 (n = 280) Trial 4 (n = 288) Trial 5 (n = 358) Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% 65% 56% 42% 57% 52% Benzoyl Peroxide 36% 37% 32% 57% 41% Clindamycin 34% 30% 38% 49% 33% Vehicle 19% -0.4% 29% 29% The group treated with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% showed greater overall improvement in the investigator's global assessment than the benzoyl peroxide, clindamycin, and vehicle groups in three of the five trials (Trials 1, 2, and 5). Clinical trials have not adequately demonstrated the effectiveness of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% versus benzoyl peroxide alone in the treatment of non-inflammatory lesions of acne.

<table cellspacing="0" cellpadding="0" border="0" width="624"><colgroup><col width="27.2435897435897%"/><col width="19.7115384615385%"/><col width="15.0641025641026%"/><col width="13.6217948717949%"/><col width="12.1794871794872%"/><col width="12.1794871794872%"/></colgroup><tbody><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center"><content styleCode="bold">Treatment</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Trial 1</content> <content styleCode="bold">(n = 120)</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Trial 2</content> <content styleCode="bold">(n = 273)</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Trial 3</content> <content styleCode="bold">(n = 280)</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Trial 4</content> <content styleCode="bold">(n = 288)</content> </td><td valign="top" styleCode="Rrule" align="center"><content styleCode="bold">Trial 5</content> <content styleCode="bold">(n = 358)</content> </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center">Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% </td><td valign="top" styleCode="Rrule" align="center">65% </td><td valign="top" styleCode="Rrule" align="center">56% </td><td valign="top" styleCode="Rrule" align="center">42% </td><td valign="top" styleCode="Rrule" align="center">57% </td><td valign="top" styleCode="Rrule" align="center">52% </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center">Benzoyl Peroxide </td><td valign="top" styleCode="Rrule" align="center">36% </td><td valign="top" styleCode="Rrule" align="center">37% </td><td valign="top" styleCode="Rrule" align="center">32% </td><td valign="top" styleCode="Rrule" align="center">57% </td><td valign="top" styleCode="Rrule" align="center">41% </td></tr><tr styleCode="Botrule"><td valign="top" styleCode="Lrule Rrule" align="center">Clindamycin </td><td valign="top" styleCode="Rrule" align="center">34% </td><td valign="top" styleCode="Rrule" align="center">30% </td><td valign="top" styleCode="Rrule" align="center">38% </td><td valign="top" styleCode="Rrule" align="center">49% </td><td valign="top" styleCode="Rrule" align="center">33% </td></tr><tr><td valign="top" styleCode="Lrule Rrule" align="center">Vehicle </td><td valign="top" styleCode="Rrule" align="center">19% </td><td valign="top" styleCode="Rrule" align="center">-0.4% </td><td valign="top" styleCode="Rrule" align="center">29% </td><td valign="top" styleCode="Rrule" align="center"> </td><td valign="top" styleCode="Rrule" align="center">29% </td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is a white to slightly yellow, opaque gel. It is supplied as follows: 45 gram tube NDC 21922-022-06 16.2 Storage and Handling Pharmacist: Prior to Dispensing: Store in a cold place, preferably in a refrigerator, between 2°C and 8°C (36°F and 46°F). Do not freeze. 16.3 Dispensing Instructions for the Pharmacist Dispense Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% with a 60 day expiration date. Specify “Store at room temperature up to 25°C (77°F). Do not freeze.” Keep tube tightly closed. Keep out of the reach of small children.

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%/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%/5% may bleach hair or colored fabric. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% may cause skin and facial hair to temporarily change color (yellow/orange) when used with topical sulfone products. Manufactured by: Encube Ethicals Pvt. Ltd. Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post Mardol, Ponda, Goa-403 404, India. Distributed by: Encube Ethicals , Inc. 200 Meredith Avenue, Suite 101A Durham, NC 27713 USA lg

PATIENT INFORMATION PHARMACIST – DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT PATIENT INFORMATION Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% Important: For use on the skin only (topical use). Do not get Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% in your mouth, eyes, vagina or on your lips. Read this Patient Information before you start using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is a prescription medicine used on the skin (topical) to treat inflamed acne in people 12 years and older. Who should not use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Do not use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% if you have: had an allergic reaction to clindamycin, lincomycin, benzoyl peroxide, or any of the ingredients in Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. See the end of this leaflet for a complete list of ingredients in Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Crohn's disease or ulcerative colitis. had inflammation of the colon (colitis) with past antibiotic use. What should I tell my healthcare provider before using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Before using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, tell your healthcare provider about all of your medical conditions, including if you: plan to have surgery with general anesthesia. are sensitive to sunlight. are pregnant or plan to become pregnant.It is not known if Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% passes into your breast milk. One of the medicines in Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is clindamycin. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. You and your healthcare provider should decide if you will use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% while breastfeeding. Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, herbal supplements, and skin products you use. Using other topical acne products may increase the irritation of your skin when used with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Especially tell your healthcare provider if you take a medicine that contains erythromycin. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% should not be used with products that contain erythromycin. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% may cause skin and facial hair to temporarily change color (yellow or orange) when used with topical products that contain sulfones. How should I use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% exactly as your healthcare provider tells you to use it. Before you apply Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, wash your face gently with a mild soap, rinse with warm water, and pat the skin dry.

Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% exactly as your healthcare provider tells you to use it. Before you apply Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%, wash your face gently with a mild soap, rinse with warm water, and pat the skin dry. Apply a thin layer of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% to your face 1 time a day, in the evening or as directed by your healthcare provider. Wash your hands with soap and water after applying Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Do not get Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% in your mouth, eyes, nose, vagina, or on your lips. Do not get Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% on cuts or open wounds. What should I avoid while using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Limit your time in sunlight. Avoid using tanning beds or sun lamps. If you have to be in sunlight, wear a wide-brimmed hat or other protective clothing. Sunscreen may also be used. Talk to your healthcare provider if you spend a lot of time in the sun. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% may bleach hair or colored fabric. What are the possible side effects with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% may cause serious side effects, including: Inflammation of the colon (colitis). Stop using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and call your healthcare provider right away if you have severe watery diarrhea, or bloody diarrhea. Allergic reactions. Stop using Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and call your healthcare provider or get help right away if you have any of the following symptoms: o severe itching o swelling of your face, eyes, lips, tongue, or throat o trouble breathing The most common side effects with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% are skin reactions and may include redness, peeling, dryness, and burning. These are not all the possible side effects with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088. How should I store Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Store Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% at room temperature up to 25°C (77°F). Do not freeze Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. The expiration date of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% is 60 days from the date when you fill your prescription. Safely throw away expired Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%. Keep the tube tightly closed. Keep Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% and all medicines out of the reach of children. General information about Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% for a condition for which it was not prescribed. Do not give Clindamycin Phosphate and Benzoyl PeroxideGel, 1.2%/5% to other people, even if they have the same symptoms you have. It may harm them. If you would like more information, talk with your healthcare provider. You can also ask your pharmacist or healthcare provider for information about Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% that is written for health professionals. For more information, call 1-833-285-4151. What are the ingredients in Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%?

thcare provider. You can also ask your pharmacist or healthcare provider for information about Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% that is written for health professionals. For more information, call 1-833-285-4151. What are the ingredients in Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5%? Active ingredients: clindamycin phosphate 1.2% and benzoyl peroxide 5% Inactive ingredients: carbomer homopolymer (type C), dimethicone, edetate disodium, glycerin, poloxamer 182, purified water, silicon dioxide, and sodium hydroxide. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured by: Encube Ethicals Pvt. Ltd. Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post Mardol, Ponda, Goa-403 404, India. Distributed by: Encube Ethicals , Inc. 200 Meredith Avenue, Suite 101A Durham, NC 27713 USA Rev: 01 July 2020 lg

<table styleCode="Noautorules" width="100%"><col width="100%" align="left" valign="middle"/><tbody><tr><td styleCode="Rrule Lrule"><paragraph>Important: For use on the skin only (topical use). Do not get Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/5% in your mouth, eyes, vagina or on your lips.</paragraph></td></tr></tbody></table>

1 INDICATIONS AND USAGE Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/3.75% is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. Clindamycin Phosphate and Benzoyl Peroxide Gel 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. ( 1 )

2 DOSAGE AND ADMINISTRATION Before applying clindamycin phosphate and benzoyl peroxide gel, wash the face gently with a mild soap, rinse with warm water, and pat the skin dry. Apply a pea-sized amount of clindamycin phosphate and benzoyl peroxide gel to the face once daily. Avoid the eyes, mouth, mucous membranes, or areas of broken skin. Use of clindamycin phosphate and benzoyl peroxide gel beyond 12 weeks has not been evaluated. Clindamycin Phosphate and Benzoyl Peroxide Gel is not for oral, ophthalmic, or intravaginal use. • Apply a pea-sized amount of clindamycin phosphate and benzoyl peroxide gel to the face once daily. ( 2 ) • Not for oral, ophthalmic, or intravaginal use. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Gel, 1.2%/3.75% Each gram of clindamycin phosphate and benzoyl peroxide gel contains 12 mg (1.2%) clindamycin phosphate, equivalent to 10 mg (1%) clindamycin, and 37.5 mg (3.75%) benzoyl peroxide in a white to off-white, opaque, smooth gel. Gel, 1.2% clindamycin phosphate/3.75% benzoyl peroxide

4 CONTRAINDICATIONS Clindamycin Phosphate and Benzoyl Peroxide Gel 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 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 [see Postmarketing Experience (6.2) ] . 4.2 Colitis/Enteritis Clindamycin Phosphate and Benzoyl Peroxide Gel is contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [see Warnings and Precautions (5.1) ] .

5 WARNINGS AND PRECAUTIONS • Colitis: Clindamycin can cause severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of clindamycin. Clindamycin Phosphate and Benzoyl Peroxide Gel should be discontinued if significant diarrhea occurs. ( 5.1 ) • Ultraviolet Light and Environmental Exposure: Minimize sun exposure following drug application. ( 5.2 ) 5.1 Colitis Systemic absorption of clindamycin has been demonstrated following topical use of clindamycin. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. If significant diarrhea occurs, clindamycin phosphate and benzoyl peroxide gel should be discontinued. Severe colitis has occurred following oral and 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 toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically. 5.2 Ultraviolet Light and Environmental Exposure Minimize sun exposure (including use of tanning beds or sun lamps) following drug application. 5.3 Concomitant Topical Medications Concomitant topical acne therapy should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. If irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. Treatment should be discontinued if the irritation persists.

6 ADVERSE REACTIONS The following adverse reaction is described in more detail in the Warnings and Precautions section of the label: • Colitis [see Warnings and Precautions (5.1) ] . The most common adverse reactions are: burning sensation (0.4%); contact dermatitis (0.4%); pruritus (0.4%); and rash (0.4%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 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 reaction rates observed in clinical trials of a drug cannot be directly compared to rates observed in clinical trials of another drug and may not reflect the rates observed in clinical practice. These adverse reactions occurred in less than 0.5% of subjects treated with clindamycin phosphate and benzoyl peroxide gel: burning sensation (0.4%); contact dermatitis (0.4%); pruritus (0.4%); and rash (0.4%). During the clinical trial, subjects were assessed for local cutaneous signs and symptoms of erythema, scaling, itching, burning and stinging. Most local skin reactions either were the same as baseline or increased and peaked around Week 4 and were near or improved from baseline levels by Week 12. The percentage of subjects that had symptoms present before treatment (at baseline), 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. Results from the Phase 3 Trial (N = 243) Before Treatment (Baseline) During Treatment End of Treatment (Week 12) Mild Mod. * Severe Mild Mod. * Severe Mild Mod. * Severe Erythema 20 6 0 28 5 <1 15 2 0 Scaling 10 1 0 19 3 0 10 <1 0 Itching 14 3 <1 15 3 0 7 2 0 Burning 5 <1 <1 7 1 <1 3 <1 0 Stinging 5 <1 0 7 0 <1 3 0 <1 *Mod. = Moderate 6.2 Postmarketing Experience Because postmarketing adverse 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 phosphate/benzoyl peroxide.

<table ID="_RefID0EMJAC" width="98.04%"><caption>Table 1: Percent of Subjects with Local Skin Reactions. Results from the Phase 3 Trial (N = 243)</caption><col width="11%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="12%"/><thead><tr><th align="left" styleCode="Lrule Toprule " valign="top"/><th align="center" colspan="3" styleCode="Botrule Lrule Toprule " valign="top"><content styleCode="bold">Before Treatment </content> <content styleCode="bold">(Baseline)</content></th><th align="center" colspan="3" styleCode="Botrule Lrule Toprule " valign="top"><content styleCode="bold">During</content> <content styleCode="bold">Treatment</content></th><th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">End of Treatment </content> <content styleCode="bold">(Week 12)</content></th></tr><tr><th align="left" styleCode="Lrule Botrule " valign="top"/><th align="center" styleCode="Lrule Botrule " valign="top"><content styleCode="bold">Mild</content></th><th align="center" styleCode="Botrule " valign="top"><content styleCode="bold">Mod.^*</content></th><th align="center" styleCode="Botrule " valign="top"><content styleCode="bold">Severe</content></th><th align="center" styleCode="Lrule Botrule " valign="top"><content styleCode="bold">Mild</content></th><th align="center" styleCode="Botrule " valign="top"><content styleCode="bold">Mod.^*</content></th><th align="center" styleCode="Botrule " valign="top"><content styleCode="bold">Severe</content></th><th align="center" styleCode="Lrule Botrule " valign="top"><content styleCode="bold">Mild</content></th><th align="center" styleCode="Botrule " valign="top"><content styleCode="bold">Mod.^*</content></th><th align="center" styleCode="Rrule Botrule " valign="top"><content styleCode="bold">Severe</content></th></tr></thead><tbody><tr><td styleCode="Lrule Toprule " valign="top"><paragraph> Erythema</paragraph></td><td align="center" styleCode="Lrule Toprule " valign="top"><paragraph>20</paragraph></td><td align="center" styleCode="Toprule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Toprule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Lrule Toprule " valign="top"><paragraph>28</paragraph></td><td align="center" styleCode="Toprule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Toprule " valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Lrule Toprule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Toprule " valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Toprule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule " valign="top"><paragraph> Scaling</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>10</paragraph></td><td align="center" valign="top"><paragraph>1</paragraph></td><td align="center" valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>19</paragraph></td><td align="center" valign="top"><paragraph>3</paragraph></td><td align="center" valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>10</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Rrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule " valign="top"><paragrap

lign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>10</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Rrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule " valign="top"><paragrap h> Itching</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>14</paragraph></td><td align="center" valign="top"><paragraph>3</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>15</paragraph></td><td align="center" valign="top"><paragraph>3</paragraph></td><td align="center" valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>7</paragraph></td><td align="center" valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule " valign="top"><paragraph> Burning</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>5</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>7</paragraph></td><td align="center" valign="top"><paragraph>1</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Lrule " valign="top"><paragraph>3</paragraph></td><td align="center" valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Rrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Botrule Lrule " valign="top"><paragraph> Stinging</paragraph></td><td align="center" styleCode="Botrule Lrule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Botrule Lrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>&lt;1</paragraph></td><td align="center" styleCode="Botrule Lrule " valign="top"><paragraph>3</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;1</paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS Avoid using clindamycin phosphate and benzoyl peroxide gel in combination with topical or oral erythromycin-containing products because of its clindamycin component. ( 7.1 ) 7.1 Erythromycin Avoid using clindamycin phosphate and benzoyl peroxide gel 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. Clindamycin Phosphate and Benzoyl Peroxide Gel should be used with caution in patients receiving such agents.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on clindamycin phosphate and benzoyl peroxide gel 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, 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 to 4% and 15 to 20%, respectively. Data Human Data In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. Animal Data Animal reproductive/developmental toxicity studies have not been conducted with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for 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 and any potential adverse effects on the breastfed child from clindamycin phosphate and benzoyl peroxide gel or from the underlying maternal condition. Clinical Considerations If used during lactation and clindamycin phosphate and benzoyl peroxide gel is applied to the chest, care should be taken to avoid accidental ingestion by the infant. 8.4 Pediatric Use Safety and effectiveness of clindamycin phosphate and benzoyl peroxide gel in pediatric patients under the age of 12 years have not been evaluated.

ng lactation and clindamycin phosphate and benzoyl peroxide gel is applied to the chest, care should be taken to avoid accidental ingestion by the infant. 8.4 Pediatric Use Safety and effectiveness of clindamycin phosphate and benzoyl peroxide gel in pediatric patients under the age of 12 years have not been evaluated. 8.5 Geriatric Use Clinical trials of clindamycin phosphate and benzoyl peroxide gel did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.

8.1 Pregnancy Risk Summary There are no available data on clindamycin phosphate and benzoyl peroxide gel 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, 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 to 4% and 15 to 20%, respectively. Data Human Data In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. Animal Data Animal reproductive/developmental toxicity studies have not been conducted with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for 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.

Risk Summary There are no available data on clindamycin phosphate and benzoyl peroxide gel 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, 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 to 4% and 15 to 20%, respectively. Data Human Data In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. Animal Data Animal reproductive/developmental toxicity studies have not been conducted with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for 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.

8.5 Geriatric Use Clinical trials of clindamycin phosphate and benzoyl peroxide gel did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.

11 DESCRIPTION Clindamycin Phosphate and Benzoyl Peroxide Gel 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-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for 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 contains the following inactive ingredients: carbomer 980, potassium hydroxide, propylene glycol, and purified water. Each gram of clindamycin phosphate and benzoyl peroxide gel contains 12 mg (1.2%) clindamycin phosphate, equivalent to 10 mg (1%) clindamycin, and 37.5 mg (3.75%) benzoyl peroxide. chemstructure chemstructure2

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 phosphate and benzoyl peroxide gel has not been evaluated. 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 a marketed gel containing clindamycin 1%/benzoyl peroxide 2.5% applied to the face once daily for 30 days. This product has the same formulation as clindamycin phosphate and benzoyl peroxide gel but with a lower concentration of benzoyl peroxide. 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 concentrations (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. In an in vitro study, the minimum inhibitory concentration (MIC) for benzoyl peroxide against Propionibacterium acnes is 128 mg/L. 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 phosphate and benzoyl peroxide gel has not been evaluated. 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 a marketed gel containing clindamycin 1%/benzoyl peroxide 2.5% applied to the face once daily for 30 days. This product has the same formulation as clindamycin phosphate and benzoyl peroxide gel but with a lower concentration of benzoyl peroxide. 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 concentrations (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. In an in vitro study, the minimum inhibitory concentration (MIC) for benzoyl peroxide against Propionibacterium acnes is 128 mg/L. 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.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility testing of clindamycin phosphate and benzoyl peroxide gel 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 2.4, 7.2, and 40 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 1.6, 4.8, and 16 times the MRHD for benzoyl peroxide, respectively, based on BSA comparisons) for up to 97 weeks did not cause any increase in tumors. Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Fertility studies have not been performed with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the MRHD for clindamycin based on BSA comparisons) revealed no effects on fertility or mating ability.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility testing of clindamycin phosphate and benzoyl peroxide gel 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 2.4, 7.2, and 40 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 1.6, 4.8, and 16 times the MRHD for benzoyl peroxide, respectively, based on BSA comparisons) for up to 97 weeks did not cause any increase in tumors. Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Fertility studies have not been performed with clindamycin phosphate and benzoyl peroxide gel or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the MRHD for clindamycin based on BSA comparisons) revealed no effects on fertility or mating ability.

14 CLINICAL STUDIES The safety and efficacy of once-daily use of clindamycin phosphate and benzoyl peroxide gel was assessed in a 12-week multi-center, randomized, blinded trial in subjects 12 years and older with moderate to severe acne vulgaris. This trial evaluated clindamycin phosphate and benzoyl peroxide gel compared to vehicle gel. The co-primary efficacy variables for this trial 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 reduction from baseline on an Evaluator’s Global Severity (EGS) score. The EGS scoring scale used in the clinical trial for clindamycin phosphate and benzoyl peroxide gel is as follows: Table 2: EGS Scoring Scale Grade Description Clear Normal, clear skin with no evidence of acne 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 up to 2 nodulocystic lesions Very Severe Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and more than 2 nodulocystic lesions The results of the trial at Week 12 are presented in Table 3: Table 3: Results of Phase 3 Trial at Week 12 Clindamycin Phosphate and Benzoyl Peroxide Gel N = 253 Vehicle Gel N = 245 EGSS: Clear or Almost Clear 29% 15% 2-grade reduction from baseline 35% 17% Inflammatory Lesions: Mean absolute reduction 16.3 8.2 Mean percent (%) reduction 60.4% 31.3% Non-Inflammatory Lesions: Mean absolute reduction 19.2 9.6 Mean percent (%) reduction 51.8% 27.6%

<table width="98.04%"><col width="22%"/><col width="78%"/><thead><tr><th align="center" styleCode="Botrule Lrule Toprule " valign="top"><content styleCode="bold">Grade</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">Description</content></th></tr></thead><tbody><tr><td styleCode="Lrule Toprule Botrule " valign="top"><paragraph>Clear</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Normal, clear skin with no evidence of acne</paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Almost Clear</paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red)</paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Mild</paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions)</paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Moderate</paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>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</paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Severe</paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Inflammatory lesions are more apparent, many comedones and papules/pustules, there may or may not be up to 2 nodulocystic lesions</paragraph></td></tr><tr><td styleCode="Botrule Lrule " valign="top"><paragraph>Very Severe</paragraph></td><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and more than 2 nodulocystic lesions</paragraph></td></tr></tbody></table>

</tr><tr><td styleCode="Botrule Lrule " valign="top"><paragraph>Very Severe</paragraph></td><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and more than 2 nodulocystic lesions</paragraph></td></tr></tbody></table> <table ID="_RefID0EXMAE" width="98.04%"><caption>Table 3: Results of Phase 3 Trial at Week 12</caption><col width="34%"/><col width="33%"/><col width="34%"/><thead><tr><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"/><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><content styleCode="bold">Clindamycin Phosphate and Benzoyl Peroxide Gel</content> <content styleCode="bold">N = 253</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><content styleCode="bold">Vehicle Gel</content> <content styleCode="bold">N = 245</content></th></tr></thead><tbody><tr><td styleCode="Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">EGSS:</content></paragraph></td><td styleCode="Lrule Toprule " valign="bottom"/><td styleCode="Rrule Lrule Toprule " valign="bottom"/></tr><tr><td styleCode="Lrule " valign="middle"><list listType="unordered"><item><caption> </caption>Clear or Almost Clear</item></list></td><td align="center" styleCode="Lrule " valign="bottom"><paragraph>29%</paragraph></td><td align="center" styleCode="Rrule Lrule " valign="bottom"><paragraph>15%</paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="middle"><list listType="unordered"><item><caption> </caption>2-grade reduction from baseline</item></list></td><td align="center" styleCode="Lrule Botrule " valign="bottom"><paragraph>35%</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="bottom"><paragraph>17%</paragraph></td></tr><tr><td styleCode="Lrule " valign="middle"><paragraph><content styleCode="bold">Inflammatory Lesions:</content></paragraph></td><td styleCode="Lrule " valign="bottom"/><td styleCode="Rrule Lrule " valign="bottom"/></tr><tr><td styleCode="Lrule " valign="middle"><list listType="unordered"><item><caption> </caption>Mean absolute reduction</item></list></td><td align="center" styleCode="Lrule " valign="bottom"><paragraph>16.3</paragraph></td><td align="center" styleCode="Rrule Lrule " valign="bottom"><paragraph>8.2</paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="middle"><list listType="unordered"><item><caption> </caption>Mean percent (%) reduction</item></list></td><td align="center" styleCode="Lrule Botrule " valign="bottom"><paragraph>60.4%</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="bottom"><paragraph>31.3%</paragraph></td></tr><tr><td styleCode="Lrule " valign="middle"><paragraph><content styleCode="bold">Non-Inflammatory Lesions:</content></paragraph></td><td styleCode="Lrule " valign="bottom"/><td styleCode="Rrule Lrule " valign="bottom"/></tr><tr><td styleCode="Lrule " valign="middle"><list listType="unordered"><item><caption> </caption>Mean absolute reduction</item></list></td><td align="center" styleCode="Lrule " valign="bottom"><paragraph>19.2</paragraph></td><td align="center" styleCode="Rrule Lrule " valign="bottom"><paragraph>9.6</paragraph></td></tr><tr><td styleCode="Botrule Lrule " valign="middle"><list listType="unordered"><item><caption> </caption>Mean percent (%) reduction</item></list></td><td align="center" styleCode="Botrule Lrule " valign="bottom"><paragraph>51.8%</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="bottom"><paragraph>27.6%</paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/3.75% is a white to off-white smooth gel supplied as: NDC 68682-133-50 50 g pump Dispensing Instructions for the Pharmacist • Dispense clindamycin phosphate and benzoyl peroxide gel with a 8-week expiration date. • Specify “Store at room temperature up to 25°C (77°F). Do not freeze.” Storage and Handling • PHARMACIST: Prior to Dispensing: Store in a refrigerator, 2° to 8°C (36° to 46°F). • PATIENT: After Dispensing: Discard unused portion 8 weeks after date of dispensing. 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.

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 may cause irritation, such as erythema, scaling, itching, or burning, especially when used in combination with other topical acne therapies. • Patients should limit excessive or prolonged exposure to sunlight. To minimize exposure to sunlight, a hat or other clothing should be worn. Sunscreen may also be used. • Clindamycin Phosphate and Benzoyl Peroxide Gel may bleach hair or colored fabric. Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Companies Inc. Laval, Quebec H7L 4A8, Canada Patented. See https://patents.ortho-dermatologics.com for US patent information. © 2025 Bausch Health Companies Inc. or its affiliates 90000202

PATIENT INFORMATION Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/3.75% Important information: Clindamycin Phosphate and Benzoyl Peroxide Gel is for use on skin only (topical use). Do not use clindamycin phosphate and benzoyl peroxide gel in your mouth, eyes, or vagina. What is clindamycin phosphate and benzoyl peroxide gel? Clindamycin Phosphate and Benzoyl Peroxide Gel is a prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years of age and older. It is not known if clindamycin phosphate and benzoyl peroxide gel is safe and effective for use longer than 12 weeks. It is not known if clindamycin phosphate and benzoyl peroxide gel is safe and effective in children under 12 years of age. Do not use clindamycin phosphate and benzoyl peroxide gel if you have: • had an allergic reaction to clindamycin, benzoyl peroxide, lincomycin, or any of the ingredients in clindamycin phosphate and benzoyl peroxide gel. See the end of this leaflet for a complete list of ingredients in clindamycin phosphate and benzoyl peroxide gel. • Crohn’s disease or ulcerative colitis. • had inflammation of the colon (colitis) or severe diarrhea with past antibiotic use. Talk with your doctor if you are not sure if you have any of the conditions listed above. Before using clindamycin phosphate and benzoyl peroxide gel, tell your doctor about all of your medical conditions, including if you: • plan to have surgery. Clindamycin Phosphate and Benzoyl Peroxide Gel may affect how certain medicines work that may be given during surgery. • are pregnant or plan to become pregnant. It is not known if clindamycin phosphate and benzoyl peroxide gel will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if clindamycin phosphate and benzoyl peroxide gel passes into your breast milk. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. Talk to your doctor about the best way to feed your baby during treatment with clindamycin phosphate and benzoyl peroxide gel. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Clindamycin Phosphate and Benzoyl Peroxide Gel may affect the way other medicines work and other medicines may affect how clindamycin phosphate and benzoyl peroxide gel works. • Especially tell your doctor if you take medicine by mouth that contains erythromycin or use products on your skin that contain erythromycin. Clindamycin Phosphate and Benzoyl Peroxide Gel should not be used with products that contain erythromycin. • Tell your doctor about any skin products you use. Other skin and topical acne products may increase the irritation of your skin when used with clindamycin phosphate and benzoyl peroxide gel. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I use clindamycin phosphate and benzoyl peroxide gel? • Use clindamycin phosphate and benzoyl peroxide gel exactly as your doctor tells you to use it. See the detailed “Instructions for Use” for directions about how to apply clindamycin phosphate and benzoyl peroxide gel. • Your doctor will tell you how long to use clindamycin phosphate and benzoyl peroxide gel. • Apply clindamycin phosphate and benzoyl peroxide gel to your face 1 time each day.

tells you to use it. See the detailed “Instructions for Use” for directions about how to apply clindamycin phosphate and benzoyl peroxide gel. • Your doctor will tell you how long to use clindamycin phosphate and benzoyl peroxide gel. • Apply clindamycin phosphate and benzoyl peroxide gel to your face 1 time each day. Before you apply clindamycin phosphate and benzoyl peroxide gel, wash your face gently with a mild soap, rinse with warm water, and pat your skin dry. What should I avoid while using clindamycin phosphate and benzoyl peroxide gel? • Limit your time in sunlight. You should avoid using tanning beds or sun lamps during treatment with clindamycin phosphate and benzoyl peroxide gel. If you have to be in sunlight, wear a wide-brimmed hat or other protective clothing, and use sunscreen to cover the treated areas. • Avoid getting clindamycin phosphate and benzoyl peroxide gel in your hair or on colored fabric. Clindamycin Phosphate And Benzoyl Peroxide Gel may bleach hair or colored fabric. What are possible side effects of clindamycin phosphate and benzoyl peroxide gel? Clindamycin Phosphate and Benzoyl Peroxide Gel can cause serious side effects including: • Inflammation of the colon (colitis). Stop using clindamycin phosphate and benzoyl peroxide gel and call your doctor right away if you have severe stomach (abdominal) cramps watery diarrhea, or bloody diarrhea during treatment, and within several weeks after treatment with clindamycin phosphate and benzoyl peroxide gel. • Allergic reactions. Stop using clindamycin phosphate and benzoyl peroxide gel, call your doctor and get help right away if you have any of the following symptoms during treatment with clindamycin phosphate and benzoyl peroxide gel: o severe itching o swelling of your face, eyes, lips, tongue or throat o trouble breathing The most common side effects of clindamycin phosphate and benzoyl peroxide gel include burning sensation, skin redness or swelling, itching and rash. Stop using clindamycin phosphate and benzoyl peroxide gel and call your doctor if you have a skin rash or your skin becomes very red, itchy or swollen. Talk to your doctor about any side effect that bothers you or that does not go away. These are not all of the possible side effects with clindamycin phosphate and benzoyl peroxide gel. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store clindamycin phosphate and benzoyl peroxide gel? • Store clindamycin phosphate and benzoyl peroxide gel at room temperature at or below 77°F (25°C). • Do not freeze clindamycin phosphate and benzoyl peroxide gel. • Throw away (discard) clindamycin phosphate and benzoyl peroxide gel 8 weeks after date of dispensing. • Store pump upright. • Keep the container tightly closed. Keep clindamycin phosphate and benzoyl peroxide gel and all medicines out of the reach of children. General information about the safe and effective use of clindamycin phosphate and benzoyl peroxide gel. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use clindamycin phosphate and benzoyl peroxide gel for a condition for which it was not prescribed. Do not give clindamycin phosphate and benzoyl peroxide gel to other people, even if they have the same condition you have. It may harm them. You can also ask your doctor or pharmacist for information about clindamycin phosphate and benzoyl peroxide gel that is written for healthcare professionals. What are the ingredients in clindamycin phosphate and benzoyl peroxide gel? Active Ingredients: clindamycin phosphate and benzoyl peroxide Inactive Ingredients: carbomer 980, potassium hydroxide, propylene glycol, and purified water.

mycin phosphate and benzoyl peroxide gel that is written for healthcare professionals. What are the ingredients in clindamycin phosphate and benzoyl peroxide gel? Active Ingredients: clindamycin phosphate and benzoyl peroxide Inactive Ingredients: carbomer 980, potassium hydroxide, propylene glycol, and purified water. Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC, Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada Patented. See https://patents.ortho-dermatologics.com for US patent information. © 2025 Bausch Health Companies Inc. or its affiliates This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 07/2025 90000202

INSTRUCTIONS FOR USE Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/3.75% Important Information: Clindamycin Phosphate and Benzoyl Peroxide Gel is for use on skin only (topical use). Clindamycin Phosphate and Benzoyl Peroxide Gel 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 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 to your face 1 time each day as prescribed. • Before you apply clindamycin phosphate and benzoyl peroxide gel, 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 to your face, use the pump to dispense one pea-sized amount of clindamycin phosphate and benzoyl peroxide gel onto your fingertip. See Figure 1. • One pea-sized amount of clindamycin phosphate and benzoyl peroxide gel should be enough to cover your entire face. Figure 1 • Dot the one pea-sized amount of clindamycin phosphate and benzoyl peroxide gel 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 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. How should I store clindamycin phosphate and benzoyl peroxide gel? • Store clindamycin phosphate and benzoyl peroxide gel at room temperature at or below 77°F (25°C). • Do not freeze clindamycin phosphate and benzoyl peroxide gel. • Throw away (discard) clindamycin phosphate and benzoyl peroxide 8 weeks after date of dispensing. • Store pump upright. • Keep the container tightly closed Keep clindamycin phosphate and benzoyl peroxide gel and all medicines out of the reach of children. Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada Patented. See https://patents.ortho-dermatologics.com for US patent information. © 2025 Bausch Health Companies Inc. or its affiliates This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: July 2025 90000202 figure-1 figure-2

<table width="98.04%"><col width="49%"/><col width="51%"/><tbody><tr><td colspan="2" styleCode="Toprule " valign="top"><paragraph>This Instructions for Use has been approved by the U.S. Food and Drug Administration.</paragraph></td></tr><tr><td styleCode="Botrule " valign="top"><paragraph>Revised: July 2025</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph> 90000202</paragraph></td></tr></tbody></table>