CLINDAMYCIN PHOSPHATE AND BENZOYL PEROXIDE

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

2 DOSAGE AND ADMINISTRATION Apply a pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% to the face once daily. Use of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% beyond 12 weeks has not been evaluated. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% is not for oral, ophthalmic, or intravaginal use. • Apply a pea-sized amount of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% to the face once daily. (2) • Not for oral, ophthalmic, or intravaginal use. (2)

5 WARNINGS AND PRECAUTIONS • Colitis: Orally and parenterally administered clindamycin has been associated with severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% 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. When significant diarrhea occurs, Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 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 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 [ See Nonclinical Toxicology ( 13.1 ) ].

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

7 DRUG INTERACTIONS • Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% should not be used in combination with erythromycin containing products because of its clindamycin component. (7.1) 7.1 Erythromycin Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% should not be used in combination with topical or oral erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between erythromycin and clindamycin. The clinical significance of this in vitro antagonism is not known. 7.2 Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% should be used with caution in patients receiving such agents.

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% / 2.5%. Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproductive/developmental toxicity studies have not been conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in rats and mice using oral doses of up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m 2 , respectively) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the amount of clindamycin in the highest recommended adult human dose based on mg/m 2 , respectively) revealed no evidence of teratogenicity.

8.3 Nursing Mothers It is not known whether clindamycin is excreted in human milk after topical application of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5%. 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 use Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% while nursing, taking into account the importance of the drug to the mother.

6 ADVERSE REACTIONS The following selected adverse reactions occurred in less than 0.2% of patients: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact 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 prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. Because clinical trials are also conducted under widely varying conditions, adverse reactions observed in the clinical trials of a drug cannot always be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following selected adverse reactions occurred in less than 0.2% of patients treated with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5%: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). During clinical trials, subjects were assessed for local cutaneous signs and symptoms of erythema, scaling, itching, burning and stinging. Most local skin reactions increased and peaked around week 4 and continually decreased over time reaching near baseline levels by week 12. The percentage of subjects that had symptoms present before treatment, the maximum value recorded during treatment, and the percent with symptoms present at week 12 are shown in Table 1. Table 1: Local Skin Reactions - Percent of Subjects with Symptoms Present. Combined Results from the Two Phase 3 Trials (N = 773) Before Treatment (Baseline) Maximum During Treatment End of Treatment (Week 12) Mild Mod.* Severe Mild Mod.* Severe Mild Mod.* Severe Erythema 22 4 0 25 5 <1 15 2 0 Scaling 8 <1 0 18 3 0 8 1 0 Itching 10 2 0 15 2 0 6 <1 0 Burning 3 <1 0 8 2 0 2 <1 0 Stinging 2 <1 0 6 1 0 1 <1 0 *Mod. = Moderate 6.2 Postmarketing Experience Anaphylaxis, as well as allergic reactions leading to hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide. 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.