Roflumilastside effects

The most common adverse reactions (reported in ≥1% of subjects) are: Plaque Psoriasis: diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection.

Atopic Dermatitis: headache, nausea, application site pain, diarrhea, vomiting, upper respiratory tract infection, rhinitis, and conjunctivitis. 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. Plaque Psoriasis Adult and Pediatric Subjects 6 Years of Age and Older In two multicenter, randomized, double-blind, vehicle-controlled trials (DERMIS-1 and DERMIS-2), 881 adult and pediatric subjects 6 years of age or older with plaque psoriasis were treated with ZORYVE cream, 0.3%, or vehicle cream once daily for 8 weeks. The proportion of subjects who discontinued treatment due to an adverse reaction was 1.0% for subjects treated with ZORYVE cream, 0.3%, and 1.3% for subjects treated with vehicle cream. The most common adverse reaction that led to discontinuation of ZORYVE cream, 0.3%, was application site urticaria (0.3%). Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE cream, 0.3%, and for which the rate exceeded the rate for vehicle cream.

Table 1: Adverse Reactions Reported in ≥1% of Adult and Pediatric Subjects 6 Years of Age and Older with Plaque Psoriasis Treated with ZORYVE Cream, 0.3%, (and More Frequently than Vehicle Cream) for 8 Weeks in Trials DERMIS-1 and DERMIS-2 Adverse Reaction ZORYVE Cream, 0.3% (N=576) n (%) Vehicle Cream (N=305) n (%) Diarrhea 18 0 Headache 14 3 Insomnia 8 2 Nausea 7 1 Application site pain 6 1 Upper respiratory tract infection 6 1 Urinary tract infection 6 2 In 644 subjects 6 years of age and older with plaque psoriasis who continued treatment with ZORYVE cream, 0.3%, for up to 64 weeks in open-label extension trials, the adverse reaction profile was consistent with that observed in vehicle-controlled trials. Pediatric Subjects 2 to 5 Years of Age The safety of ZORYVE cream, 0.3%, once daily was assessed in an open-label trial for up to 24 weeks. The adverse reaction profile in pediatric subjects 2 years to 5 years of age with plaque psoriasis was consistent with that observed in adult and pediatric subjects 6 years of age and older. Atopic Dermatitis Adult and Pediatric Subjects 6 Years of Age and Older In two multicenter, randomized, double-blind, vehicle-controlled trials (INTEGUMENT-1 and INTEGUMENT-2), 1336 adult and pediatric subjects 6 years of age or older with mild to moderate atopic dermatitis were treated with ZORYVE cream, 0.15%, or vehicle cream once daily for 4 weeks. The proportion of subjects who discontinued treatment due to an adverse reaction was 1.6% for subjects treated with ZORYVE cream, 0.15%, and 1.1% for subjects treated with vehicle cream. Table 2 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE cream, 0.15%, and for which the rate exceeded the rate for vehicle cream.

Table 2: Adverse Reactions Reported in ≥1% of Adult and Pediatric Subjects 6 Years of Age and Older with Atopic Dermatitis Treated with ZORYVE Cream, 0.15%, (and More Frequently than Vehicle Cream) for 4 Weeks in Trials INTEGUMENT-1 and INTEGUMENT-2 Adverse Reaction ZORYVE Cream, 0.15% (N=885) n (%) Vehicle Cream (N=451) n (%) Headache 26 4 Nausea 17 2 Application site pain 13 3 Diarrhea 13 2 Vomiting 13 2 The adverse reaction of insomnia was reported in fewer than 1% of subjects treated with ZORYVE cream, 0.15%. Pediatric Subjects 2 to 5 Years of Age In a multicenter, randomized, double-blind, vehicle-controlled trial (INTEGUMENT-PED), 652 pediatric subjects 2 to 5 years of age with mild to moderate atopic dermatitis were treated with ZORYVE cream, 0.05%, or vehicle cream once daily for 4 weeks. Table 3 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE cream, 0.05%, and for which the rate exceeded the rate for vehicle cream.

Table 3: Adverse Reactions Reported in ≥1% of Pediatric Subjects 2 to 5 Years of Age with Atopic Dermatitis Treated with ZORYVE Cream, 0.05%, (and More Frequently than Vehicle) for 4 Weeks in Trial INTEGUMENT-PED Adverse Reaction ZORYVE Cream, 0.05% (N=437) n (%) Vehicle Cream (N=215) n (%) Upper respiratory tract infection 18 3 Diarrhea 11 1 Vomiting 9 0 Rhinitis 7 0 Conjunctivitis 6 0 Headache 5 0 Adult and Pediatric Subjects 2 Years of Age and Older The long-term safety of ZORYVE cream, 0.15%, and ZORYVE cream, 0.05%, was assessed in an open-label extension trial of 1219 subjects 2 years of age and older with mild to moderate atopic dermatitis who had completed one of the 4-week, vehicle-controlled trials. The safety profile observed in the open-label extension trial was generally consistent with the safety profile observed at Week 4.