ZORYVE

ZORYVE (roflumilast) topical foam, 0.3%, is a white to off-white foam for topical use. The active ingredient, roflumilast, is a phosphodiesterase 4 (PDE4) inhibitor. The chemical name of roflumilast is 3-cyclopropylmethoxy- N -(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide with a molecular formula of C 17 H 14 Cl 2 F 2 N 2 O 3 and the molecular weight of 403.21. The structural formula of roflumilast is: Roflumilast is practically insoluble in water and hexane, sparingly soluble in ethanol, and freely soluble in acetone. Each gram of ZORYVE topical foam, 0.3%, contains 3 mg of roflumilast in a foam base containing ceteareth-10 phosphate, cetearyl phosphate, cetostearyl alcohol, diethylene glycol monoethyl ether, hexylene glycol, isopropyl palmitate, methylparaben, propylparaben, purified water, sodium hydroxide, and white petrolatum. Hydrochloric acid may have been added to adjust pH. ZORYVE topical foam, 0.3%, is dispensed from an aluminum can pressurized with propellant (butane, isobutane, and propane). Chemical Structure

ZORYVE topical foam, 0.3%, is a phosphodiesterase 4 inhibitor indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. ( 1.1 ) plaque psoriasis of the scalp and body in adult and pediatric patients 12 years of age and older. ( 1.2 ) 1.1 Seborrheic Dermatitis ZORYVE ® topical foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. 1.2 Plaque Psoriasis ZORYVE topical foam, 0.3%, is indicated for the treatment of plaque psoriasis of the scalp and body in adult and pediatric patients 12 years of age and older.

Shake can prior to each use. Apply a thin layer of ZORYVE foam, 0.3%, once daily to affected areas of body and/or scalp when they are not wet. Rub in completely. Wash hands after application. Avoid fire, flame, and smoking during and immediately following application [see Warnings and Precautions (5.1) ] . ZORYVE foam, 0.3%, is for topical use only and not for ophthalmic, oral, or intravaginal use. Apply once daily to affected areas. ( 2 ) For topical use only. Not for ophthalmic, oral, or intravaginal use. ( 2 )

ZORYVE foam, 0.3%, is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C) [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ] . Moderate to severe liver impairment (Child-Pugh B or C). ( 4 )

The most common adverse reactions (reported in ≥ 1% of patients) are: Seborrheic dermatitis : nasopharyngitis, nausea, and headache. ( 6.1 ) Plaque psoriasis of the scalp and body : headache, diarrhea, nausea, and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Arcutis Biotherapeutics, Inc. at 1-844-692-6729 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. Seborrheic Dermatitis In two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 203 and STRATUM), 683 adult and pediatric subjects 9 years of age or older with seborrheic dermatitis were treated with ZORYVE foam, 0.3%, or vehicle foam once daily for 8 weeks [see Clinical Studies (14.1) ]. Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE foam, 0.3%. Table 1: Adverse Reactions Reported in ≥1% of Adult and Pediatric Subjects 9 Years of Age and Older with Seborrheic Dermatitis Treated with ZORYVE Foam, 0.3%, for 8 Weeks in Trial 203 and Trial STRATUM Adverse Reaction ZORYVE foam, 0.3% (N=458) n (%) Vehicle foam (N=225) n (%) Nasopharyngitis 7 (1.5) 1 (0.4) Nausea 6 (1.3) 0 (0) Headache 5 (1.1) 0 (0) The following additional adverse reactions were reported in fewer than 1% of subjects treated with ZORYVE foam, 0.3%: diarrhea and insomnia. The adverse reaction profile in pediatric subjects was consistent with that observed in adults [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) ] . In 408 subjects who continued treatment with ZORYVE foam, 0.3%, for up to 24 to 52 weeks in an open-label, long-term trial, the adverse reaction profile was consistent with that observed in vehicle-controlled trials. Plaque Psoriasis In two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 204 and ARRECTOR), 734 adult and pediatric subjects 12 years of age and older with plaque psoriasis of the scalp and body were treated with ZORYVE foam, 0.3%, or vehicle foam once daily for 8 weeks [see Clinical Studies (14.2) ]. Table 2 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE foam, 0.3%. Table 2: Adverse Reactions Reported in ≥1% of Adult and Pediatric Subjects 12 Years of Age and Older with Plaque Psoriasis of the Scalp and Body Treated with ZORYVE Foam, 0.3%, for 8 Weeks in Trial 204 and Trial ARRECTOR Adverse Reaction ZORYVE foam, 0.3% (N=479) n (%) Vehicle foam (N=255) n (%) Headache 15 (3.1) 3 (1.2) Diarrhea 12 (2.5) 4 (1.6) Nausea 8 (1.7) 0 (0) Nasopharyngitis 6 (1.3) 2 (0.8) The following additional adverse reaction was reported in fewer than 1% of subjects treated with ZORYVE foam, 0.3%: insomnia. The adverse reaction profile in pediatric subjects was consistent with that observed in adults [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) ] .

Co-administration of roflumilast with systemic CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously may increase roflumilast systemic exposure and may result in increased adverse reactions. If these products are co-administered with ZORYVE foam, 0.3%, weigh the potential for increased adverse reactions against benefit. ( 7.1 ) Co-administration of roflumilast with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased adverse reactions. If these products are co-administered with ZORYVE foam, 0.3%, weigh the potential for increased adverse reactions against benefit. ( 7.1 ) 7.1 Effects of Other Drugs on ZORYVE Foam, 0.3% Drugs that Inhibit Cytochrome P450 (CYP) Enzymes No formal drug-drug interaction studies were conducted with ZORYVE foam, 0.3%; however, the co-administration of oral roflumilast with systemic CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously may increase roflumilast systemic exposure and may result in increased adverse reactions. If these products are co-administered with ZORYVE foam, 0.3%, weigh the potential for increased adverse reactions against benefit [see Clinical Pharmacology (12.3) ] . Oral Contraceptives Containing Gestodene and Ethinyl Estradiol The co-administration of roflumilast with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased adverse reactions. If these products are co-administered with ZORYVE foam, 0.3%, weigh the potential for increased adverse reactions against benefit [see Clinical Pharmacology (12.3) ] .

Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Do not freeze. Store upright. Flammable. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 49°C (120°F) [see Warnings and Precautions (5.1) ] .