Dosage Forms And Strengths

Gel, 1.2%/2.5%

Each gram of %medicine_name% contains 10 mg (1%) clindamycin as phosphate, and 25 mg (2.5%) benzoyl peroxide in a white to off-white, opaque, smooth gel.

%medicine_name% is supplied as a 50 g pump (NDC 13548-132-50).

Dispensing Instructions For The Pharmacist

• Dispense %medicine_name% with a 10 week expiration date.
• Specify “Store at room temperature up to 25°C (77°F). Do not freeze.”

Storage And Handling

• PHARMACIST: Prior to Dispensing: Store in a refrigerator, 2°C to 8°C (36°F to 46°F).
• PATIENT: Store at room temperature at or below 25°C (77°F).
• Protect from freezing.
• Keep out of the reach of children.
• Keep container tightly closed.

Distributed by: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807. Manufactured by: Contract Pharmaceuticals Limited Mississauga, Ontario, Canada L5N 6L6. Revised 02/2014

ACANYA® Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older.

Apply a pea-sized amount of %medicine_name% to the face once daily.

Use of %medicine_name% 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. %medicine_name% is not for oral, ophthalmic, or intravaginal use.

Hypersensitivity

%medicine_name% 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 ACANYA Gel.

Colitis/Enteritis

%medicine_name% is contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis..

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Colitis

Systemic absorption of clindamycin has been demonstrated following topical use of clindamycin. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. When significant diarrhea occurs, %medicine_name% should be discontinued.

Severe colitis has occurred following oral and parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.

Studies indicate toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

Ultraviolet Light And Environmental Exposure

Minimize sun exposure including use of tanning beds or sun lamps following drug application.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION).

• Patients who develop allergic reactions such as severe swelling or shortness of breath should discontinue use and contact their physician immediately.
• %medicine_name% may cause irritation such as erythema, scaling, itching, or burning, especially when used in combination with other topical acne therapies.
• Excessive or prolonged exposure to sunlight should be limited. To minimize exposure to sunlight, a hat or other clothing should be worn. Sunscreen may also be used.
• %medicine_name% may bleach hair or colored fabric.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity, mutagenicity and impairment of fertility testing of %medicine_name% have not been performed.

Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered topically twice per week for 20 weeks induced skin tumors in transgenic Tg.AC mice. The clinical significance of this is unknown.

Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses of 900, 2700, and 15000 mg/kg/day (1.8, 5.4, and 30 times amount of clindamycin and 3.6, 10.8, and 60 times amount of benzoyl peroxide in the highest recommended adult human dose of 2.5 g %medicine_name% based on mg/m², respectively) did not cause any increase in tumors. However, topical treatment with a different gel formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900 and 3000 mg/kg/day (1.2, 3.6, and 12 times amount of clindamycin and 2.4, 7.2, and 24 times amount of benzoyl peroxide in the highest recommended adult human dose of 2.5 g %medicine_name% based on mg/m², respectively) for up to 97 weeks did not cause any increase in tumors. In a 52-week dermal photocarcinogenicity study in hairless mice, (40 weeks of treatment followed by 12 weeks of observation), the median time to onset of skin tumor formation decreased and the number of tumors per mouse increased relative to controls following chronic concurrent topical administration of the higher concentration benzoyl peroxide formulation (5000 and 10000 mg/kg/day, 5 days/week) and exposure to ultraviolet radiation.

Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells.

Fertility studies have not been performed with %medicine_name% or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g %medicine_name%, based on mg/m²) revealed no effects on fertility or mating ability.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled trials studies in pregnant women treated with %medicine_name%. %medicine_name% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal reproductive/developmental toxicity studies have not been conducted with %medicine_name% or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in rats and mice using oral doses of up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) revealed no evidence of teratogenicity.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk after topical application of %medicine_name%. 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 use %medicine_name% while nursing, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of %medicine_name% in pediatric patients under the age of 12 have not been evaluated.

Geriatric Use

Clinical trials of %medicine_name% did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

SIDE EFFECTS

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 %medicine_name%: 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)

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.

DRUG INTERACTIONS

Erythromycin

%medicine_name% 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.

Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, %medicine_name% should be used with caution in patients receiving such agents.

Pregnancy Category C

There are no adequate and well-controlled trials studies in pregnant women treated with %medicine_name%. %medicine_name% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal reproductive/developmental toxicity studies have not been conducted with %medicine_name% or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in rats and mice using oral doses of up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) revealed no evidence of teratogenicity.

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 %medicine_name%: 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)

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.

No information provided.

The systemic absorption of clindamycin was investigated in an open-label, multiple-dose trial in 16 adult subjects with moderate to severe acne vulgaris treated with 1 gram of ACANYA Gel applied to the face once daily for 30 days. Twelve subjects (75%) had at least one quantifiable clindamycin plasma concentration above the lower limit of quantification (LOQ = 0.5 ng/mL) on Day 1 or Day 30. On Day 1, the mean (± standard deviation) peak plasma concentration (Cmax) was 0.78 ± 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC0-t was 5.29 ± 0.81 h.ng/mL (n=4). On Day 30, the mean Cmax was 1.22 ± 0.88 ng/mL (n=10), and the mean AUC0-t was 8.42 ± 6.01 h.ng/mL (n=6). Clindamycin plasma concentrations were below LOQ in all subjects at 24 hours post-dose on the three tested days (Day 1, 15, and 30).

Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.