FDA label 6aee426d-f03e-480d-9ef6-040df5f5575b

5 WARNINGS AND PRECAUTIONS SERNIVO Spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. High potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure and use in pediatric patients may predispose to HPA axis suppression. Use of topical corticosteroids may require periodic evaluation for HPA axis suppression. Modify use if HPA axis suppression develops. ( 5.1 ) Topical corticosteroids may increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. ( 5.2 ) 5.1 Effects on Endocrine System SERNIVO Spray can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test. In a study including 48 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, abnormal ACTH stimulation test results suggestive of adrenal suppression were identified in 5 out of 24 (20.8%) subjects after treatment with SERNIVO Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with SERNIVO Spray twice daily for 29 days [ see Clinical Pharmacology ( 12.2 ) ]. If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental systemic corticosteroids may be required. Systemic effects of topical corticosteroids may also manifest as Cushing’s syndrome, hyperglycemia, and glucosuria. These events are rare and generally occur after prolonged exposure to larger than recommended doses, particularly with high-potency topical corticosteroids. Minimize the unwanted risks from endocrine effects by mitigating the risk factors favoring increased systemic bioavailability and by using the product as recommended [ see Dosage and Administration ( 2 ) ]. Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios. Use of SERNIVO Spray is not recommended in pediatric patients [ see Use in Specific Populations ( 8.4 ) ]. 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids, including SERNIVO Spray, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing with the use of topical corticosteroid products, including betamethasone dipropionate [ see Adverse Reactions ( 6.2 ) ]. Avoid contact of SERNIVO Spray with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Allergic Contact Dermatitis Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Corroborate such an observation with appropriate diagnostic patch testing. If irritation develops, discontinue the topical corticosteroid and institute appropriate therapy.

6 ADVERSE REACTIONS The most common adverse reactions (≥1%) are application site reactions, including pruritus, burning and/or stinging, pain, and atrophy. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Promius Pharma, LLC. at 1-888-966-8766 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 two randomized, multicenter, prospective vehicle-controlled clinical trials, subjects with moderate plaque psoriasis of the body applied SERNIVO Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied SERNIVO Spray and 180 subjects applied vehicle spray. Adverse reactions that occurred in at least 1% of subjects treated with SERNIVO Spray for up to 28 days are presented in Table 1 . Table 1: Adverse Reactions Occurring in ≥1% of Subjects Treated with SERNIVO Spray for up to Four Weeks SERNIVO Spray b.i.d. (N=352) Vehicle Spray b.i.d. (N=180) Application site pruritus 6.0% 9.4% Application site burning and/or stinging 4.5% 10.0% Application site pain 2.3% 3.9% Application site atrophy 1.1% 1.7% Less common adverse reactions (with occurrence lower than 1% but higher than 0.1%) in subjects treated with SERNIVO Spray were application site reactions including telangiectasia, dermatitis, discoloration, folliculitis and skin rash, in addition to dysgeusia and hyperglycemia. These adverse reactions were not observed in subjects treated with vehicle. 6.2 Postmarketing Experience Because adverse 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. Postmarketing reports for local adverse reactions to topical corticosteroids have also included striae, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria. Hypersensitivity reactions, consisting of predominantly skin signs and symptoms, e.g., contact dermatitis, pruritus, bullous dermatitis, and erythematous rash have been reported. Ophthalmic adverse reactions of cataracts, glaucoma, and increased intraocular pressure have been reported with the use of topical corticosteroids, including topical betamethasone products.

<table ID="table1" width="550" styleCode="Noautorules"><caption>Table 1: Adverse Reactions Occurring in &#x2265;1% of Subjects Treated with SERNIVO Spray for up to Four Weeks</caption><col width="40%" align="left"/><col width="30%" align="center"/><col width="30%" align="center"/><tbody><tr valign="top"><td styleCode="Toprule Botrule Lrule Rrule"/><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">SERNIVO Spray <content styleCode="italics">b.i.d.</content> (N=352)</content></td><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Vehicle Spray <content styleCode="italics">b.i.d.</content> (N=180)</content></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">Application site pruritus</td><td styleCode="Toprule Botrule Lrule Rrule">6.0%</td><td styleCode="Toprule Botrule Lrule Rrule">9.4%</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">Application site burning and/or stinging </td><td styleCode="Toprule Botrule Lrule Rrule">4.5%</td><td styleCode="Toprule Botrule Lrule Rrule">10.0%</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">Application site pain </td><td styleCode="Toprule Botrule Lrule Rrule">2.3%</td><td styleCode="Toprule Botrule Lrule Rrule">3.9%</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">Application site atrophy</td><td styleCode="Toprule Botrule Lrule Rrule">1.1%</td><td styleCode="Toprule Botrule Lrule Rrule">1.7%</td></tr></tbody></table>