clindamycin phosphate

1 INDICATIONS AND USAGE Clindamycin Phosphate Foam, 1% is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older. Clindamycin Phosphate Foam, 1% is a lincosamide product indicated for acne vulgaris in patients 12 years and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Clindamycin Phosphate Foam, 1% is for topical use only, and not for oral, ophthalmic or intravaginal use. Apply Clindamycin Phosphate Foam, 1% once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area. If there has been no improvement after 6 to 8 weeks or if the condition becomes worse, treatment should be discontinued. The contents of Clindamycin Phosphate Foam, 1% are flammable; avoid fire, flame and/or smoking during and immediately following application. For topical use only; not for oral, ophthalmic, or intravaginal use. ( 2 ) Apply Clindamycin Phosphate Foam, 1% once daily to affected areas. ( 2 ) Flammable; avoid fire, flame and/or smoking during and immediately following application. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Clindamycin Phosphate Foam is a white thermolabile hydroethanolic aerosol foam. Each gram of clindamycin phosphate foam contains, as dispensed, 12 mg (1.2%) of clindamycin phosphate, USP equivalent to 10 mg (1%) of clindamycin. Foam containing 1% clindamycin as clindamycin phosphate, USP. ( 3 )

4 CONTRAINDICATIONS Clindamycin Phosphate Foam, 1% is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis (including pseudomembranous colitis). Clindamycin Phosphate Foam, 1% is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis, (including pseudomembranous colitis). ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions (>1%) are headache and application site reactions including burning, pruritus, and dryness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with clindamycin phosphate foam. The incidence of adverse reactions occurring in ≥ 1% of the subjects in clinical trials comparing clindamycin phosphate foam and its vehicle is presented in Table 1. Table 1: Adverse Reactions Occurring in ≥ 1% of Subjects Adverse Reactions Number (%) of Subjects Clindamycin Phosphate Foam Vehicle Foam N = 439 N = 154 Headache 12 (3%) 1 (1%) Application site burning 27 (6%) 14 (9%) Application site pruritus 5 (1%) 5 (3%) Application site dryness 4 (1%) 5 (3%) Application site reaction, not otherwise specified 3 (1%) 4 (3%) In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to clindamycin phosphate foam. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of clindamycin phosphate foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorrhagic diarrhea. 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. Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally.

7 DRUG INTERACTIONS 7.1 Erythromycin Clindamycin Phosphate Foam, 1% should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. 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 Foam, 1% 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 foam use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Animal reproduction studies have not been conducted with clindamycin phosphate foam. No evidence of fetal harm or malformations was observed in pregnant rats and mice administered daily subcutaneous or oral doses of clindamycin salts during organogenesis at doses that produced exposures up to 84 and 42 times, respectively, the maximum recommended human dose (MRHD) of clindamycin phosphate foam based on body surface area (BSA) comparisons and assuming 100% absorption [see Data] . 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 Animal Data Reproduction studies have been conducted in rats and mice using subcutaneous or oral doses of clindamycin phosphate, clindamycin hydrochloride or clindamycin palmitate hydrochloride administered daily during organogenesis at doses up to the equivalent of 432 mg/kg/day clindamycin phosphate. These studies produced no evidence of fetal harm or malformations in rats or mice at exposures 84 or 42 times, respectively, the MRHD of clindamycin phosphate (i.e., 5 milliliters of clindamycin phosphate foam) based on BSA comparison and assuming 100% absorption. 8.2 Lactation Risk Summary There is no information on the presence of clindamycin in human milk, or the effects on the breast-fed child, or the effects on milk production following use of clindamycin phosphate foam. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin phosphate foam and any potential adverse effects on the breast-fed child from clindamycin phosphate foam or from the underlying maternal condition. Clinical Considerations If used during lactation and clindamycin phosphate foam 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 foam in children under the age of 12 have not been studied. 8.5 Geriatric Use The clinical study with clindamycin phosphate foam did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.

12.1 Mechanism of Action Mechanism of action of clindamycin in acne vulgaris is unknown [see Microbiology (12.4) ] .

11 DESCRIPTION Clindamycin phosphate foam contains clindamycin (1%) as clindamycin phosphate. 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 -α-D- galacto - octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below: Molecular Formula: C 18 H 34 CIN 2 O 8 PS Molecular Weight: 504.97 g/mol Clindamycin phosphate foam contains clindamycin (1%) as clindamycin phosphate, USP at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant. clindamycin phosphate structural formula

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clindamycin Phosphate Foam, 1% contains 10 mg of clindamycin as clindamycin phosphate, USP per gram. The white to off-white thermolabile foam is available as follows: • 50 gram aerosol can - NDC 45802- 660 -32 • 100 gram aerosol can - NDC 45802- 660 -33 16.2 Storage and Handling Store at 20o to 25°C (68o to 77°F) [See USP Controlled Room Temperature]. Flammable. Avoid fire, flame or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C). Keep out of reach of children.

16.1 How Supplied Clindamycin Phosphate Foam, 1% contains 10 mg of clindamycin as clindamycin phosphate, USP per gram. The white to off-white thermolabile foam is available as follows: • 50 gram aerosol can - NDC 45802- 660 -32 • 100 gram aerosol can - NDC 45802- 660 -33