Epsolay

Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with the use of benzoyl peroxide products. (5.1) Skin irritation/contact dermatitis: Erythema, scaling, dryness, stinging/burning, irritation and allergic contact dermatitis may occur with use of EPSOLAY and may necessitate discontinuation. (5.2) Photosensitivity: Avoid or minimize exposure to natural or artificial sunlight and use sun protection measures. (5.3)

5.1Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with the use of benzoyl peroxide products. If a serious hypersensitivity reaction occurs, discontinue EPSOLAY immediately and initiate appropriate therapy. 5.2 Skin Irritation/Contact Dermatitis Erythema, scaling, dryness and stinging/burning may be experienced with use of EPSOLAY. Irritation and contact dermatitis may occur. Apply a moisturizer and discontinue EPSOLAY if symptoms do not improve. Avoid application of EPSOLAY to cuts, abrasions, eczematous or sunburned skin. 5.3 Photosensitivity Benzoyl peroxide may increase sensitivity to sunlight. Minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using EPSOLAY. Instruct the patient to implement sun protection measures (e.g., sunscreen and loose- fitting clothes) when sun exposure cannot be avoided. Discontinue EPSOLAY at the first evidence of sunburn.

Most common adverse reactions (incidence ≥ 1%) are application site reactions: pain, erythema, pruritis and edema. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 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. In two randomized, double-blind, vehicle-controlled trials, adult subjects with rosacea applied EPSOLAY (N = 488) or vehicle (N = 234) once daily for 12 weeks. The majority of subjects were Caucasian (93%) and female (73%) with a mean age of 51 years. Table 1 presents the most common adverse reactions occurring in ≥ 1% of subjects treated with EPSOLAY and more frequently than in subjects treated with vehicle. Table 1: Adverse Reactions Occurring in ≥ 1% of Subjects Treated with EPSOLAY and with Greater Frequency than Subjects Treated with Vehicle EPSOLAY N=488 Vehicle N=234 Application site pain 11 (2%) 2 (1%) Application site erythema 11 (2%) 2 (1%) Application site pruritus 6 (1%) 1 (<1%) Application site edema Application site edema includes: application site swelling and application site edema 4 (1%) 0 (0%) During the clinical trials, local tolerability evaluations were conducted at baseline and at each study visit by assessment of dryness, itching, scaling and stinging/burning. Table 2 presents the local tolerability assessments by severity grade at Week 12. Table 2: Facial Cutaneous Tolerability Assessment Sign/Symptom EPSOLAY N=455 Of the 488 subjects treated with EPSOLAY, 455 subjects had local tolerability assessments at Week 12. Severity at Week 12 Mild Moderate Severe Dryness 25% 7% 0% Itching 24% 6% 0% Scaling 13% 4% 0% Stinging/Burning 20% 3% 1% In a 40-week open-label extension safety study (for a total of up to 52 weeks of treatment) the frequency and severity of local tolerability signs and symptoms at Week 52 were comparable to those reported at Week 12.

8.1Pregnancy Risk Summary

The systemic exposure of benzoyl peroxide is unknown. Based on the published literature, benzoyl peroxide is metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Hence, maternal use is not expected to result in fetal exposure to the drug. Animal reproductive studies have not been conducted with EPSOLAY or benzoyl peroxide. 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. 8.2 Lactation Risk Summary There are no data on the presence of benzoyl peroxide in human milk, its effects on the breastfed infant or its effects on milk production. The systemic exposure of benzoyl peroxide is unknown. Based on the published literature, benzoyl peroxide is metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Any amount of benzoyl peroxide excreted into human milk by a nursing mother would be expected to be metabolized by tissue and stomach esterases. Therefore, breastfeeding is not expected to result in exposure of the infant to EPSOLAY. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for EPSOLAY and any potential adverse effects on the breastfed child from EPSOLAY or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of EPSOLAY for the treatment of inflammatory lesions of rosacea have not been established in pediatric patients. 8.5 Geriatric Use Of the 733 subjects in the clinical trials of EPSOLAY, 127 (17%) subjects were 65 and over, while 37 (3%) subjects were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.