CLINDAMYCIN PHOSPHATE AND BENZOYL PEROXIDE

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

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 )

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 )

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) ] .

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.

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.