CLINDAMYCIN PHOSPHATE AND BENZOYL PEROXIDE

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 10 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, disodium lauryl sulfosuccinate, edetate disodium, glycerin, methylparaben, poloxamer 182, purified water, silicon dioxide, and sodium hydroxide. Chemical Structure Chemical Structure

Clindamycin phosphate and benzoyl peroxide gel 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 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 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.

Apply a thin layer of clindamycin phosphate and benzoyl peroxide gel 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. Avoid the eyes, mouth, lips, mucous membranes, or areas of broken skin. Clindamycin phosphate and benzoyl peroxide gel is not for oral, ophthalmic, or intravaginal use. Apply a thin layer of clindamycin phosphate and benzoyl peroxide gel to the face once daily, in the evening. ( 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 ) 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 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 Adverse Reactions (6.2) ]. 4.2 Colitis/Enteritis Clindamycin phosphate and benzoyl peroxide gel 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) ].

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 Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 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 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 are presented in Table 1. Table 1: Local Skin Reactions with Use of Clindamycin Phosphate and Benzoyl Peroxide Gel Combined Results from Five Trials (n = 397) Symptoms % of Subjects Using Clindamycin Phosphate and Benzoyl Peroxide Gel with Symptom Present Before Treatment (Baseline) During Treatment Mild Moderate Severe Mild Moderate Severe (Percentages derived by number of subjects receiving clindamycin phosphate and benzoyl peroxide with symptom score/number of enrolled subjects receiving clindamycin phosphate and benzoyl peroxide gel). 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 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of clindamycin phosphate and benzoyl peroxide gel. 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. Urticaria, application site reactions, including discoloration have been reported.

Clindamycin phosphate and benzoyl peroxide gel 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 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 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).

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.