Bryhali

1 INDICATIONS AND USAGE BRYHALI ® (halobetasol propionate) lotion, 0.01% is indicated for the topical treatment of plaque psoriasis in adults. BRYHALI lotion is a corticosteroid indicated for the topical treatment of plaque psoriasis in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a thin layer of BRYHALI Lotion to affected areas once daily. Rub in gently. Wash hands after each application, unless BRYHALI Lotion is for treatment of the hands. BRYHALI Lotion treatment beyond 8 weeks is not recommended, and the total dosage should not exceed approximately 50 g per week. Discontinue treatment if control is achieved before 8 weeks. Do not use with occlusive dressings unless directed by a physician. BRYHALI Lotion should not be used on the face, groin, or in the axillae. BRYHALI Lotion is not for oral, ophthalmic, or intravaginal use. • Apply a thin layer of BRYHALI Lotion to the affected areas once daily. ( 2 ) • Treatment beyond 8 weeks is not recommended. Discontinue treatment if control is achieved before 8 weeks. ( 2 ) • Do not use with occlusive dressings unless directed by a physician. ( 2 ) • Avoid use on the face, groin, or axillae. ( 2 ) • Not for oral, ophthalmic, or intravaginal use. ( 2 )

5 WARNINGS AND PRECAUTIONS • Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression was observed and may occur with the potential for glucocorticosteroid insufficiency during or after treatment. ( 5.1 ) • Systemic effects of topical corticosteroids may also include Cushing’s syndrome, hyperglycemia, and glucosuria. ( 5.1 ) • Systemic absorption may require evaluation for HPA axis suppression. ( 5.1 ) • Use of potent corticosteroids on large areas, for prolonged durations, under occlusive dressings, or on an altered skin barrier may increase systemic exposure. ( 5.1 ) • Children may be more susceptible to systemic toxicity when treated with topical corticosteroids. ( 5.1 , 8.4 ) • Local adverse reactions may include atrophy, striae, telangiectasias, hypopigmentation, and allergic contact dermatitis. Some local adverse reactions may be irreversible. ( 5.2 ) • Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist for evaluation. ( 5.3 ) 5.1 Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression BRYHALI Lotion has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Systemic effects of topical corticosteroids may include reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of treatment with the topical corticosteroid. The potential for hypothalamic-pituitary-adrenal (HPA) axis suppression with BRYHALI Lotion was evaluated in a study of 19 adult subjects with moderate to severe plaque psoriasis involving ≥20% of their body surface area (BSA). HPA axis suppression was reported for 1 (5.6%) subject at Week 4 and for 3 (15.8%) subjects at Week 8. All 3 subjects had normal HPA axis suppression test with discontinuation of treatment [see Clinical Pharmacology (12.2) ] . Because of the potential for systemic absorption, use of topical corticosteroids, including BRYHALI Lotion, may require that patients be evaluated periodically for evidence of HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent corticosteroids, use over large surface areas, occlusive use, use on an altered skin barrier, concomitant use of multiple corticosteroid-containing products, liver failure, and young age. An adrenocorticotropic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, attempt to gradually withdraw the drug, reduce the frequency of application, or substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Systemic effects of topical corticosteroids may also include Cushing’s syndrome, hyperglycemia, and glucosuria. Use of more than one corticosteroid-containing product at the same time may increase the total systemic exposure to corticosteroids. Pediatric patients may be more susceptible than adults to systemic toxicity from the use of topical corticosteroids due to their larger surface-to-body-mass ratios [see Use in Specific Populations (8.4) ] . 5.2 Local Adverse Reactions Local adverse reactions from topical corticosteroids may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. These may be more likely with occlusive use, prolonged use, or use of higher potency corticosteroids, including BRYHALI Lotion. Some local adverse reactions may be irreversible. 5.3 Ophthalmic Adverse Reactions Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been …

4 CONTRAINDICATIONS None. None ( 4 ).

8.1 Pregnancy Risk Summary There are no available data on BRYHALI Lotion use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, increased malformations, including cleft palate and omphalocele, were observed after oral administration of halobetasol propionate during organogenesis to pregnant rats and rabbits. The available data do not support relevant comparisons of systemic halobetasol propionate exposures achieved in the animal studies to exposures observed in humans after topical use of BRYHALI Lotion. The background risk of major birth defects and miscarriage for the indicated population is unknown. 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 Halobetasol propionate has been shown to cause malformations in rats and rabbits when given orally during organogenesis at doses of 0.04 to 0.1 mg/kg/day in rats and 0.01 mg/kg/day in rabbits. Halobetasol propionate was embryotoxic in rabbits but not in rats. Cleft palate was observed in both rats and rabbits. Omphalocele was seen in rats but not in rabbits.

6 ADVERSE REACTIONS • The most common adverse reactions (≥1%) were upper respiratory tract infection, application site dermatitis and hyperglycemia. ( 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 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 clinical practice. In randomized, double-blind, multicenter, vehicle-controlled clinical trials, 426 adults with plaque psoriasis were treated with BRYHALI Lotion and had post-baseline safety data. Subjects applied BRYHALI Lotion once daily for up to 8 weeks. Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with BRYHALI Lotion and more frequently than in vehicle-treated subjects. Table 1: Adverse Reactions Occurring in ≥1% of the Subjects Treated with BRYHALI Lotion through Week 8 BRYHALI Lotion (N=284) Vehicle Lotion (N=142) Adverse Reaction % % Upper Respiratory Tract Infection 2% 1% Application Site Dermatitis 1% 0 Hyperglycemia 1% 0