Derma-Smoothe/FS

1 INDICATIONS AND USAGE DERMA-SMOOTHE/FS Body Oil is a corticosteroid indicated for the topical treatment of: • atopic dermatitis in adults (1) • moderate to severe atopic dermatitis in pediatric patients 3 months of age and older (1) Derma-Smoothe/FS ® Body Oil is indicated for the topical treatment of: • atopic dermatitis in adults • moderate to severe atopic dermatitis in pediatric patients 3 months of age and older

2 DOSAGE AND ADMINISTRATION • DERMA-SMOOTHE/FS Body Oil is not for oral, ophthalmic, or intravaginal use. ( 2.1 ) • Do not use on face or intertriginous areas. ( 2.1 ) • Adult patients: Apply to affected areas 3 times daily. ( 2.2 ) • Pediatric patients: Moisten skin and apply to affected areas twice daily for up to 4 weeks. ( 2.3 ) 2.1 Important Administration Instructions DERMA-SMOOTHE/FS Body Oil is for topical use only. Not for oral, ophthalmic, or intravaginal use. Apply the least amount of DERMA-SMOOTHE/FS Body Oil needed to cover the affected areas. Discontinue use when control of disease is achieved within 2 weeks or contact the healthcare provider if no improvement is seen within 2 weeks. Do not use on the face, axillae, or groin unless directed by the healthcare provider. Do not apply to intertriginous areas due to the increased risk of local adverse reactions [see Adverse Reactions (6) and Use in Specific Populations (8.4) ] . Do not apply to the diaper area; diapers or plastic pants may constitute occlusive use [see Warnings and Precautions (5.1)] . 2.2 Recommended Dosage in Adults Apply DERMA-SMOOTHE/FS Body Oil as a thin film to the affected areas three times daily. 2.3 Recommended Dosage in Pediatric Patients Moisten skin and apply DERMA-SMOOTHE/FS Body Oil as a thin film to the affected areas twice daily for up to four weeks.

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS Endocrine System Adverse Reactions: o Topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome, hyperglycemia, and glucosuria. ( 5.1 ) o Pediatric patients may be more susceptible to systemic toxicity from equivalent doses. ( 5.1 , 8.4 ) o Systemic absorption may require evaluation for HPA axis suppression. Potent corticosteroids use on large areas, prolonged use, occlusive use, altered skin barrier, liver failure, and young age may increase systemic absorption. Modify use should HPA axis suppression develop. ( 5.1 ) Local Adverse Reactions: Local adverse reactions may include atrophy, striae, irritation, acneiform eruptions, hypopigmentation, and allergic contact dermatitis and may be more likely with occlusive use or more potent corticosteroids ( 5.2 , 6.1 ) Ophthalmic Adverse Reactions: May increase the risks of glaucoma and posterior subcapsular cataract. Avoid contact of DERMA-SMOOTHE/FS Body Oil with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. ( 5.3 ) 5.1 Endocrine System Adverse Reactions Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. Cushing’s syndrome, hyperglycemia, and glucosuria can result from systemic absorption of topical corticosteroids. HPA axis suppression and Cushing’s syndrome have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and subnormal response to ACTH stimulation. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios [see Use in Specific Populations (8.4) ] . Conditions which increase systemic absorption include the use of more potent corticosteroids, use over large surface areas, use over prolonged periods, use of occlusive dressings, altered skin barrier, liver failure, and young age. Use of more than one corticosteroid-containing product at the same time may increase total systemic corticosteroid exposure. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. The ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, reduce the frequency of application or discontinue DERMA-SMOOTHE/FS Body Oil, or substitute with a less potent corticosteroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. 5.2 Local Adverse Reactions Local adverse reactions may occur with use of topical corticosteroids, including DERMA-SMOOTHE/FS Body Oil, and may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Some local adverse reactions may be irreversible. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria [see Adverse Reactions (6.1) ] . 5.3 Ophthalmic Adverse Reactions Use of topical corticosteroids may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products. Avoid contact of DERMA-SMOOTHE/FS Body Oil with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.4 Allergic Contact Dermatitis Use of topical corticosteroids can cause allergic contact dermatitis. Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing. 5.5 Concomitant Skin Infections Use of topical corticosteroids may delay healing or worsen concomitant skin infections. Treat concomitant skin infections with an appropriate antimicrobial agent. If the infection persists unchanged, discontinue DERMA-SMOOTHE/FS Body Oil until the infection has been adequately treated. 5.6 Use in Peanut-Sensitive Individuals Use caution in prescribing DERMA-SMOOTHE/FS Body Oil for peanut-sensitive individuals [see Description (11) ] . Should signs of hypersensitivity present (wheal and flare reactions, pruritus, or other manifestations), or should disease exacerbations occur, discontinue DERMA-SMOOTHE/FS Body Oil immediately and institute appropriate therapy.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in more detail in other sections of the labeling: • Endocrine System Adverse Reactions [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 )] • Local Adverse Reactions [see Warnings and Precautions ( 5.2 )] • Ophthalmic Adverse Reactions [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (≥ 5%) were cough (20%), rhinorrhea (13%), pyrexia (10%), telangiectasia (7%), nasopharyngitis (7%), and hypopigmentation (7%). ( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Hill Dermaceuticals, Inc. at 1-800-344-5707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies 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. An open-label trial was conducted in 58 pediatric subjects 2 years to 12 years of age with moderate to severe atopic dermatitis to evaluate the safety of DERMA-SMOOTHE/FS Body Oil when applied to the face twice daily for 4 weeks. Adverse reactions reported by ≥2% of pediatric subjects treated with DERMA-SMOOTHE/FS Body Oil are shown in Table 1. Table 1: Adverse Reactions in ≥ 2% of Pediatric Subjects 2 Years to 12 Years of Age with Moderate to Severe Atopic Dermatitis, Treated with DERMA-SMOOTHE/FS Body Oil, N=58 Adverse Reaction (AR) The number of individual adverse reactions reported does not necessarily reflect the number of individual subjects, since one subject could have multiple reports of an adverse reaction. n (%) Day 14 Day 28 End of Treatment Day 56 Four Weeks Post Treatment Any AE 15 (26) 6 (10) 7 (12) 7 (12) Telangiectasia 5 (9) 3 (5) 4 (7) 2 (4) Erythema 3 (5) 3 (5) Itching 3 (5) 3 (5) Irritation 3 (5) 3 (5) Burning 3 (5) 3 (5) Hypopigmentation 2 (4) 2 (4) Shiny skin 1 (2) 1 (2) Secondary atopic dermatitis 1 (2) 1 (2) Papules and pustules 1 (2) 1 (2) Keratosis pilaris 1 (2) 1 (2) Folliculitis 1 (2) 1 (2) Facial herpes simplex 1 (2) 1 (2) Acneiform eruption 1 (2) 1 (2) Ear infection 1 (2) 1 (2) An open-label safety trial was conducted in 29 pediatric subjects 3 months to 2 years of age to assess the HPA axis by ACTH stimulation testing following use of DERMA-SMOOTHE/FS Body Oil twice daily for 4 weeks. The trial included 7 subjects ages 3 to 6 months, 7 subjects ages > 6 to 12 months, and 15 subjects ages > 12 months to 2 years. All subjects had moderate to severe atopic dermatitis with disease involvement on at least 20% body surface area (BSA). Eleven (11) subjects had baseline BSA involvement of 50% to 75% and 7 subjects had BSA involvement of greater than 75% [see Use in Specific Populations (8.4) ] . The most common adverse reactions reported in the study (≥2%) are shown in Table 2. Table 2: Adverse Reactions in ≥2% of Pediatric Subjects 3 Months to 2 Years of Age with Moderate to Severe Atopic Dermatitis, Treated with DERMA-SMOOTHE/FS Body Oil, N=30 Includes one subject who withdrew at Week 2 Adverse Reaction n (%) Cough 6 (20) Rhinorrhea 4 (13) Pyrexia 3 (10) Nasopharyngitis 2 (7) Hypopigmentation 2 (7) Abscess 1 (3) Atopic Dermatitis 1 (3) Eczema 1 (3) Hyperpigmentation 1 (3) Molluscum 1 (3) Rash 1 (3) Diarrhea 1 (3) Otitis Media 1 (3) URI 1 (3) Vomiting 1 (3) 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of products containing topical corticosteroids. Because postmarketing 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. • Endocrine Disorders: HPA axis suppression and Cushing’s syndrome [see Use in Specific Populations (8.4) ] • Eye Disorders: glaucoma and cataracts [see Warnings and Precautions (5.3) ] • Nervous System Disorders: intracranial hypertension including bulging fontanelles, headaches, and bilateral papilledema [see Use in Specific Populations (8.4) ]

8.1 Pregnancy Risk Summary Available data from case reports, case series, and observational studies on fluocinolone acetonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Observational studies suggest maternal use of high to super-high potency topical steroids may be associated with an increased risk of low birthweight infants. Advise pregnant women to use DERMA-SMOOTHE/FS Body Oil on the smallest area of skin and for the shortest duration possible. Corticosteroids can cause fetal malformations in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids cause fetal malformations after dermal application in laboratory animals. 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.