FINACEA FOAM

1 INDICATIONS AND USAGE FINACEA Foam, 15% is indicated for topical treatment of the inflammatory papules and pustules of mild to moderate rosacea. FINACEA Foam is indicated for the topical treatment of inflammatory papules and pustules of mild to moderate rosacea. ( 1 )

2 DOSAGE AND ADMINISTRATION Shake well before use. Cleanse affected area(s) using only very mild soaps or soapless cleansing lotion and pat dry with a soft towel before application of FINACEA Foam. Apply FINACEA Foam twice daily (morning and evening) to the entire facial area (cheeks, chin, forehead, and nose). For a single application, dispense the smallest amount of foam necessary to adequately cover the affected area(s) with a thin layer. Use FINACEA Foam continuously over 12 weeks. Wash hands immediately following application of FINACEA Foam. Cosmetics may be applied after the application of FINACEA Foam has dried. Reassess the diagnosis if no improvement is observed upon completing 12 weeks of therapy. Avoid the use of occlusive dressings or wrappings. Instruct patients to avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents. For topical use. Not for oral, ophthalmic or intravaginal use. Apply a thin layer twice daily (morning and evening) to the entire facial area (cheeks, chin, forehead, and nose). ( 2 ) Use only very mild soaps or soapless cleansing lotion and pat dry with a soft towel before applying FINACEA Foam. ( 2 ) Wash hands immediately following application. ( 2 ) Cosmetics may be applied after the application of FINACEA Foam has dried. ( 2 ) Avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents. ( 2 ) For topical use. ( 2 ) Not for oral, ophthalmic or intravaginal use. ( 2 )

5 WARNINGS AND PRECAUTIONS Hypopigmentation: Isolated cases of hypopigmentation occurred after azelaic acid use. Monitor patients with dark complexion for early signs of hypopigmentation ( 5.1 ) Eye and Mucous Membrane Irritation: Azelaic acid has been reported to cause irritation of the eyes. Avoid contact with the eyes and mucous membranes. ( 5.2 ) Flammability: Contents are flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. ( 5.3 ) 5.1 Hypopigmentation There have been reports of hypopigmentation after use of azelaic acid. Because azelaic acid has not been well studied in patients with dark complexion, monitor these patients for early signs of hypopigmentation. 5.2 Eye and Mucous Membranes Irritation Azelaic acid has been reported to cause irritation of the eyes. Avoid contact with the eyes, mouth and other mucous membranes. If FINACEA Foam does come in contact with the eyes, wash the eyes with large amounts of water and consult a physician if eye irritation persists. 5.3 Flammability The propellant in FINACEA Foam is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

4 CONTRAINDICATIONS None. None. ( 4 )

8.1 Pregnancy Risk Summary Azelaic acid is minimally absorbed systemically following topical route of administration, and maternal use is not expected to result in fetal exposure to the drug [see Clinical Pharmacology (12.3) ]. In animal reproduction studies, embryofetal toxicity was noted when azelaic acid was administered orally during the period of organogenesis at doses 162, 19, and 65 times the maximum recommended human dose (MRHD) in rats, rabbits, and monkeys, respectively. Maternal toxicity was noted at these doses but no malformations were observed in these embryofetal developmental studies ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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 to 4% and 15 to 20%, respectively. Data Animal Data Dermal embryofetal developmental toxicology studies have not been performed with azelaic acid, 15% foam. Oral embryofetal developmental studies were conducted with azelaic acid in rats, rabbits, and cynomolgus monkeys. Azelaic acid was administered during the period of organogenesis in all three animal species. Embryotoxicity was observed in rats, rabbits, and monkeys at oral doses of azelaic acid that generated some maternal toxicity. Embryotoxicity was observed in rats given 2500 mg/kg/day [162 times the MRHD based on body surface area (BSA) comparison], rabbits given 150 or 500 mg/kg/day (19 or 65 times the MRHD based on BSA comparison) and cynomolgus monkeys given 500 mg/kg/day (65 times the MRHD based on BSA comparison) azelaic acid. No malformations were observed in the oral embryofetal developmental studies conducted in rats, rabbits and cynomolgus monkeys. An oral peri- and post-natal developmental study was conducted in rats. Azelaic acid was administered from gestational day 15 through day 21 postpartum up to a dose level of 2500 mg/kg/day. Embryotoxicity was observed in rats at an oral dose of 2500 mg/kg/day (162 times the MRHD based on BSA comparison) that generated some maternal toxicity. In addition, slight disturbances in the post-natal development of fetuses was noted in rats at oral doses that generated some maternal toxicity (500 and 2500 mg/kg/day; 32 and 162 times the MRHD based on BSA comparison). No effects on sexual maturation of the fetuses were noted in this study.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the prescribing information: Hypopigmentation [see Warnings and Precautions (5.1) ]. Eye and Mucous Membranes Irritation [see Warnings and Precautions (5.2) ]. The most common adverse reactions (incidence ≥ 0.5% of subjects treated with FINACEA Foam) are local site pain (6.2%), pruritus (2.5%), dryness (0.7%), and erythema (0.7%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LEO Pharma Inc. at 1-877-494-4536 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 practice. FINACEA Foam was evaluated for the treatment of papulopustular rosacea in two multicenter, randomized, double-blind, vehicle-controlled, 12-week clinical trials involving a total of 1362 (FINACEA Foam, 15%: 681; vehicle: 681) subjects. Overall, 95.7% of subjects were White, 73.4% were female, and the mean age was 50.6 years. Table 1: Adverse Reactions Occurring in ≥ 0.5% of Subjects Treated with FINACEA Foam Compared with Subjects Treated with Vehicle System/Organ Class Preferred FINACEA Foam, 15% (N=681) n (%) Vehicle (N=681) n (%) General disorders and application site conditions Application site pain "Application site pain" is a term used to describe disagreeable skin sensations, including burning, stinging, paraesthesia and tenderness. 42 (6.2%) 10 (1.5%) Application site pruritus 17 (2.5%) 2 (0.3%) Application site dryness 5 (0.7%) 5 (0.7%) Application site erythema 5 (0.7%) 6 (0.9%) Local Tolerability Studies In a 21-day cumulative irritation study under occlusive conditions, mild-to-moderate irritation was observed for azelaic acid pre-foam emulsion. In a human repeat insult patch test (HRIPT) study, no sensitization potential was observed for azelaic acid pre-foam emulsion. 6.2 Postmarketing Experience Hypersensitivity, rash and worsening of asthma have been reported from the postmarketing experience of azelaic acid-containing formulations. 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.