Item info. These highlights do not include all the info. needed to use ACANYA Gel safely and effectively. See full prescribing info. for ACANYA Gel. ACANYA (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5%, for topical use Initial U.S. Approval: 2000 INDICATIONS AND USAGE ACANYA Gel is lincosamide antibiotic and benzoyl peroxide indicated for the topical treatment of acne vulgaris. -- DOSAGE AND ADMINISTRATION -- Apply pea-sized amount of ACANYA Gel to the face once daily. Not for oral, ophthalmic, or intravaginal use. - DOSAGE FORMS AND STRENGTHS - ACANYA Gel contains clindamycin phosphate 1.2% and benzoyl peroxide 2.5% in topical gel in 50 gram pumps. CONTRAINDICATIONS ACANYA Gel is contraindicated in: Patients who have demonstrated hypersensitivity (e.g., anaphylaxis) to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. Patients with history of regional enteritis, ulcerative colitis, or antibiotic?associated colitis. - WARNINGS AND PRECAUTIONS - Colitis: Orally and parenterally administered clindamycin has been associated with severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. ACANYA Gel should be discontinued if significant diarrhea occurs. Ultraviolet Light and Environmental Exposure: Minimize sun exposure following drug application. ADVERSE REACTIONS The following selected adverse reactions occurred in less than 0.2% of patients: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS ? ACANYA Gel should not be used in combination with erythromycin-containing products because of its clindamycin component. See 17 for PATIENT COUNSELING info. and FDA-approved patient labeling. Revised: 02/2014 FULL Item info.: CONTENTS* INDICATIONS AND USAGE DOSAGE AND ADMINISTRATION DOSAGE FORMS AND STRENGTHS CONTRAINDICATIONS 4.1 Hypersensitivity 4.2 Colitis/Enteritis WARNINGS AND PRECAUTIONS 5.1 Colitis 5.2 Ultraviolet Light and Environmental Exposure ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Postmarketing Experience DRUG INTERACTIONS 7.1 ERythromycin 7.2 Neuromuscular Blocking Agents USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanisms of Action 12.3 Pharmacokinetics 12.4 Microbiology 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied 16.2 Dispensing Instructions for the Pharmacist 16.3 Storage and Handling 17 PATIENT COUNSELING info. *Sections or subsections omitted from the full prescribing info. are not listed. FULL Item info. INDICATIONS AND USAGE ACANYA Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older. DOSAGE AND ADMINISTRATION Apply pea-sized amount of ACANYA Gel to the face once daily. Use of ACANYA Gel beyond 12 weeks has not been evaluated. Concomitant topical acne therapy should be used with caution because possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. ACANYA Gel is not for oral, ophthalmic, or intravaginal use. DOSAGE FORMS AND STRENGTHS Gel, 1.2%/2.5% Each gram of ACANYA Gel contains 10 mg (1%) clindamycin as phosphate, and 25 mg (2.5%) benzoyl peroxide in white to off-white, opaque, smooth gel. CONTRAINDICATIONS 4.1 Hypersensitivity ACANYA 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 ACANYA Gel [see Adverse Reactions ]. 4.2 Colitis/Enteritis ACANYA Gel is contraindicated in patients with history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [see Warnings and Precautions ]. WARNINGS AND PRECAUTIONS 5.1 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, ACANYA Gel 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. 5.2 Ultraviolet Light and Environmental Exposure Minimize sun exposure including use of tanning beds or sun lamps following drug application [see Nonclinical Toxicology (13.1) ]. ADVERSE REACTIONS 6.1 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 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 ACANYA Gel: 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 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 Trials (N 773) Before Treatment (Baseline) Maximum During Treatment End of Treatment (Week 12) Mild Mod.* Severe Mild Mod.* Severe Mild Mod.* Severe ERythema 22 0 25 < 15 0 Scaling < 0 18 0 1 Itching 10 0 15 0 < 0 Burning < 0 2 2 1 Stinging < 0 1 1 1 *Mod. Moderate 6.2 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 population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. DRUG INTERACTIONS 7.1 ERythromycin ACANYA Gel 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. 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, ACANYA Gel should be used with caution in patients receiving such agents. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women treated with ACANYA Gel. ACANYA Gel 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 ACANYA Gel 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/m , 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/m , respectively) revealed no evidence of teratogenicity. 8.3 Nursing Mothers It is not known whether clindamycin is excreted in human milk after topical application of ACANYA Gel. 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, decision should be made whether to use ACANYA Gel while nursing, taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness of ACANYA Gel in pediatric patients under the age of 12 have not been evaluated. 8.5 Geriatric Use Clinical trials of ACANYA Gel did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. 11 DESCRIPTION ACANYA (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5% is combination product with two active ingredients in white to off-white, opaque, smooth, aqueous gel formulation intended for topical use. Clindamycin phosphate is water-soluble ester of the semi-synthetic antibiotic produced by 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- -D-galacto- octopyranoside -(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below: Clindamycin phosphate: Molecular Formula: 18 34 ClN O PS Molecular Weight: 504.97 Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula for benzoyl peroxide is represented below: Benzoyl peroxide: benzoyl_peroxide_v1.ai Molecular Formula: 14 10 4 Molecular Weight: 242.23 ACANYA Gel contains the following inactive ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide. Each gram of ACANYA Gel contains 1.2% of clindamycin phosphate which is equivalent to 1% clindamycin. 12 CLINICAL PHARMACOLOGY 12.1 Mechanisms of Action Clindamycin: Clindamycin is lincosamide antibacterial [see Clinical Pharmacology (12.4)]. Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects but the precise mechanism of action is unknown. 12.3 Pharmacokinetics 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 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 or Day 30. On Day 1, the mean (? standard deviation) peak plasma concentrations (C max was 0.78 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC 0-t was 5.29 0.81 h.ng/mL (n=4). On Day 30, the mean max was 1.22 0.88 ng/mL (n=10), and the mean AUC 0-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. 12.4 Microbiology Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin and benzoyl peroxide individually have been shown to have in vitro activity against Propionibacterium acnes an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes is not known. P. acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity and impairment of fertility testing of ACANYA Gel have not been performed. Benzoyl peroxide has been shown to be tumor promoter and progression agent in number of animal studies. Benzoyl peroxide in acetone at doses of 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 gel formulation containing 1% clindamycin and 5% benzoyl peroxide. In 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 ACANYA Gel based on mg/m , respectively) did not cause any increase in tumors. However, topical treatment with different gel formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, and 2000 mg/kg/day caused dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in 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 ACANYA Gel based on mg/m , respectively) for up
