Clindamycin Phosphate

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 Perrigo at 1-866-634-9120 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, 1%. The incidence of adverse reactions occurring in > 1% of the subjects in clinical trials comparing clindamycin phosphate foam, 1% 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, 1% N = 439 Vehicle Foam 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, 1%. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of clindamycin phosphate foam, 1%: 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.

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 )

11 DESCRIPTION Clindamycin Phosphate Foam, 1% 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: Clindamycin Phosphate Foam, 1% contains clindamycin (1%) as clindamycin phosphate, 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. Image 2

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 )

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 )

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.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mechanism of action in acne vulgaris is unknown. [ See Microbiology (12.4) ] 12.2 Pharmacodynamics Pharmacodynamics of Clindamycin Phosphate Foam, 1% is unknown. 12.3 Pharmacokinetics In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of clindamycin phosphate foam, 1% once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean C max and AUC (0-12) were 23% and 9% lower, respectively, for clindamycin phosphate foam, 1% than for the clindamycin gel, 1%. Following multiple applications of clindamycin phosphate foam, 1%, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5. 12.4 Microbiology No microbiology studies were conducted in the clinical trials with this product. Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes ( P. acnes ), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with Clindamycin Phosphate Foam, 1%. P. acnes resistance to clindamycin has been documented. Inducible Clindamycin Resistance The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes ). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing. Cross Resistance Resistance to clindamycin is often associated with resistance to erythromycin.

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

12.2 Pharmacodynamics Pharmacodynamics of Clindamycin Phosphate Foam, 1% is unknown.

12.3 Pharmacokinetics In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of clindamycin phosphate foam, 1% once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean C max and AUC (0-12) were 23% and 9% lower, respectively, for clindamycin phosphate foam, 1% than for the clindamycin gel, 1%. Following multiple applications of clindamycin phosphate foam, 1%, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.

20230717

103

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

Clindamycin Phosphate clindamycin phosphate ALCOHOL POLYSORBATE 60 PROPYLENE GLYCOL WATER STEARYL ALCOHOL CETYL ALCOHOL CLINDAMYCIN PHOSPHATE CLINDAMYCIN

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenicity of a 1.2% clindamycin phosphate gel similar to Clindamycin Phosphate Foam, 1% was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of Clindamycin Phosphate Foam, 1%, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. A 1.2% clindamycin phosphate gel similar to Clindamycin Phosphate Foam, 1% caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenicity of a 1.2% clindamycin phosphate gel similar to Clindamycin Phosphate Foam, 1% was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of Clindamycin Phosphate Foam, 1%, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. A 1.2% clindamycin phosphate gel similar to Clindamycin Phosphate Foam, 1% caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.

ANDA090785

Clindamycin Phosphate

clindamycin phosphate

63629-8629

HUMAN PRESCRIPTION DRUG

TOPICAL

12.4 Microbiology No microbiology studies were conducted in the clinical trials with this product. Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes ( P. acnes ), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with Clindamycin Phosphate Foam, 1%. P. acnes resistance to clindamycin has been documented. Inducible Clindamycin Resistance The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes ). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing. Cross Resistance Resistance to clindamycin is often associated with resistance to erythromycin.

Clindamycin Phosphate 1% Foam, #100 Label

Made in Israel Manufactured by Perrigo Yeruham, Israel Distributed by Perrigo Allegan, MI 49010 www.perrigo.com Rev 08-19 4T500 RC J4

17 PATIENT COUNSELING INFORMATION See FDA-Approved patient labeling (Patient Information) . 17.1 Instructions for Use Patients should be advised to wash their skin with mild soap and allow it to dry before applying Clindamycin Phosphate Foam, 1%. Patients should use enough Clindamycin Phosphate Foam, 1% to cover the face and to apply once daily. Patients should dispense Clindamycin Phosphate Foam, 1% directly into the cap or onto a cool surface. Patients should wash their hands after applying Clindamycin Phosphate Foam, 1%. 17.2 Skin Irritation Clindamycin Phosphate Foam, 1% may cause irritation such as erythema, scaling, itching, burning, or stinging. Patients should be advised to discontinue use if excessive irritancy or dermatitis occur. 17.3 Colitis In the event a patient treated with Clindamycin Phosphate Foam, 1% experiences severe diarrhea or gastrointestinal discomfort, Clindamycin Phosphate Foam, 1% should be discontinued and a physician should be contacted. Made in Israel Manufactured by Perrigo Yeruham, Israel Distributed by Perrigo Allegan, MI 49010 www.perrigo.com Rev 08-19 4T500 RC J4 Pharmacist-Detach here and Give Instructions to Patient

14 CLINICAL STUDIES In one multicenter, randomized, double-blind, vehicle-controlled clinical trial, subjects with mild to moderate acne vulgaris used clindamycin phosphate foam, 1% or the vehicle Foam once daily for twelve weeks. Treatment response, defined as the proportion of subjects clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in Table 2. Table 2: Efficacy Results at Week 12 Efficacy Parameters Clindamycin Phosphate Foam, 1% N = 386 Vehicle Foam N = 127 Treatment response (ISGA) 31% 18%* Percent reduction in lesion counts Inflammatory Lesions 49% 35%* Noninflammatory Lesions 38% 27%* Total Lesions 43% 31%* *P<0.05

8.5 Geriatric Use The clinical study with clindamycin phosphate foam, 1% did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.

8.3 Nursing Mothers It is not known whether clindamycin is excreted in human milk following use of Clindamycin Phosphate Foam, 1%. 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 discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If used during lactation and Clindamycin Phosphate Foam, 1% 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, 1% in children under the age of 12 have not been studied.

8.1 Pregnancy Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with clindamycin phosphate foam, 1%. Clindamycin Phosphate Foam, 1% should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus. Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from clindamycin phosphate foam, 1% based on a mg/m 2 comparison.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with clindamycin phosphate foam, 1%. Clindamycin Phosphate Foam, 1% should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus. Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from clindamycin phosphate foam, 1% based on a mg/m 2 comparison. 8.3 Nursing Mothers It is not known whether clindamycin is excreted in human milk following use of Clindamycin Phosphate Foam, 1%. 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 discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If used during lactation and Clindamycin Phosphate Foam, 1% 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, 1% in children under the age of 12 have not been studied. 8.5 Geriatric Use The clinical study with clindamycin phosphate foam, 1% did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clindamycin Phosphate Foam, 1% containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is white to off-white in color and thermolabile. It is available in the following sizes: 100 gram aerosol can - NDC 63629-8629-1 16.2 Storage and Handling Store at 20-25°C (68-77°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.