Acanya

1 INDICATIONS AND USAGE ACANYA ® Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older. ACANYA Gel is a combination of clindamycin phosphate (a lincosamide antibacterial) and benzoyl peroxide indicated for the topical treatment of acne vulgaris in patients 12 years or older. ( 1 )

2 DOSAGE AND ADMINISTRATION Before applying ACANYA Gel, wash your face gently with a mild soap, rinse with warm water, and pat your skin dry. Apply a pea-sized amount of ACANYA Gel to the face once daily. Avoid the eyes, mouth, mucous membranes, or areas of broken skin. Use of ACANYA Gel 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. ACANYA Gel is not for oral, ophthalmic, or intravaginal use. • Apply a pea-sized amount of ACANYA Gel to the face once daily. ( 2 ) • Not for oral, ophthalmic, or intravaginal use. ( 2 )

4 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. ( 4.1 ) • Patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. ( 4.2 ) 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 Postmarketing Experience (6.2) ] . 4.2 Colitis/Enteritis ACANYA Gel is contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [see Warnings and Precautions (5.1) ] .

5 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. ( 5.1 ) • Ultraviolet Light and Environmental Exposure: Minimize sun exposure following drug application. ( 5.2 ) 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. 5.3 Concomitant Topical Medications Concomitant topical acne therapy 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 DRUG INTERACTIONS • Avoid using ACANYA Gel in combination with topical or oral erythromycin-containing products because of its clindamycin component. ( 7.1 ) 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.

6 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%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 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 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 subjects 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 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: Percent of Subjects with Local Skin Reactions. Combined Results from the Two Phase 3 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 4 0 25 5 < 1 15 2 0 Scaling 8 < 1 0 18 3 0 8 1 0 Itching 10 2 0 15 2 0 6 < 1 0 Burning 3 < 1 0 8 2 0 2 < 1 0 Stinging 2 < 1 0 6 1 0 1 < 1 0 6.2 Postmarketing Experience 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 hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide.

8.1 Pregnancy Risk Summary There are no available data on ACANYA Gel use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The limited published data on use of clindamycin in pregnant women with exposure during the first trimester are insufficient to inform a drug-associated risk of pregnancy-related adverse outcomes (see Data) .In limited published clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of major birth defects. In animal reproduction studies, clindamycin did not cause malformations or embryo-fetal development toxicity in pregnant rats and mice when administered during the period of organogenesis at systemic doses up to 240 times the maximum recommended human dose (MRHD) of 2.5 g ACANYA Gel, based on body surface area (BSA) comparisons (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy. Animal Data Animal reproductive/developmental toxicity studies have not been conducted with ACANYA Gel or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for, respectively, based on BSA comparisons) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the MRHD for clindamycin, respectively, based on BSA comparisons) revealed no malformations or embryo-fetal development toxicity.