CLINDAMYCIN PHOSPHATE AND BENZOYL PEROXIDE

Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% is a combination product with two active ingredients in a white to off-white, opaque, smooth, aqueous gel formulation intended for topical use. Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. The chemical name for clindamycin phosphate is Methyl 7 chloro-6,7,8-trideoxy- 6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo a-D-galacto octopyranoside 2- (dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below: Clindamycin phosphate: Molecular Formula: C 18 H 34 CIN 2 O 8 PS Molecular Weight: 504.97 Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula for benzoyl peroxide is represented below: Benzoyl peroxide: Molecular Formula: C 14 H 10 O 4 Molecular Weight: 242.23 Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% contains the following inactive ingredients: carbopol 980, poloxamer 182, polysorbate 80, propylene glycol, purified water and sodium hydroxide. Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 2.5% contains 1.2% of clindamycin phosphate which is equivalent to 1% clindamycin. clinda-str benzoyl-str

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)

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)

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 ) ].

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.

• 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.