DERMA-SMOOTHE/FS

1 INDICATIONS AND USAGE Derma-Smoothe/FS ® Scalp Oil is a corticosteroid indicated for the treatment of psoriasis of the scalp in adults. ( 1 ) DERMA-SMOOTHE/FS ® Scalp Oil is indicated for the treatment of psoriasis of the scalp in adults.

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) ] • Local Adverse Reactions [see Warnings and Precautions (5.2) ] • Ophthalmic Adverse Reactions [see Warnings and Precautions (5.3) ] The most common adverse reactions in pediatric subjects treated for atopic dermatitis (≥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 condition, 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 safety study was conducted in 29 pediatric subjects 3 months to 2 years old to assess the HPA axis by ACTH stimulation testing following use of the formulation of DERMA-SMOOTHE/FS Scalp Oil twice daily for 4 weeks. DERMA-SMOOTHE/FS Scalp Oil is not approved for use in pediatric patients for the treatment of psoriasis of the scalp. The most common adverse reactions were reported in the study: Table 1: Adverse Reactions in ≥2% Pediatric Subjects 3 Months to 2 Years of Age Treated with the Formulation of DERMA-SMOOTHE/FS Scalp 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 Eye Disorders: glaucoma and cataracts Nervous System Disorders: intracranial hypertension including bulging fontanelles, headaches, and bilateral papilledema

4 CONTRAINDICATIONS None. None. ( 4 )

11 DESCRIPTION DERMA-SMOOTHE/FS Scalp Oil (fluocinolone acetonide) topical oil, 0.01% contains fluocinolone acetonide [(6α, 11β, 16α)-6,9-difluoro-11,21-dihydroxy-16,17[(1–methylethylidene) bis(oxy)]-pregna-1,4-diene-3,20-dione, cyclic 16,17 acetal with acetone], a synthetic corticosteroid for topical dermatologic use. Chemically, fluocinolone acetonide is C 24 H 30 F 2 O 6 . It has the following structural formula: Fluocinolone acetonide has a molecular weight of 452.50. It is a white crystalline powder that is odorless, stable in light, and melts at 270°C with decomposition; soluble in alcohol, acetone and methanol; slightly soluble in chloroform; insoluble in water. Each gram of DERMA-SMOOTHE/FS Scalp Oil contains approximately 0.11 mg of fluocinolone acetonide in a blend of oils, which contains isopropyl alcohol, isopropyl myristate, light mineral oil, oleth-2, refined peanut oil and fragrances. Each packaged product contains 2 shower caps. The shower cap is made of low density polyethylene material with rubber elastic. DERMA-SMOOTHE/FS Scalp Oil is formulated with 48% refined peanut oil. The bulk refined peanut oil used in DERMA-SMOOTHE/FS Scalp Oil is heated at 246°C (475°F) for at least 15 minutes. The refined peanut oil used in DERMA-SMOOTHE/FS Scalp Oil is routinely tested for peanut proteins through amino acid analysis; the quantity of amino acids is below 0.5 parts per million (ppm). Chemical Structure

2 DOSAGE AND ADMINISTRATION DERMA-SMOOTHE/FS Scalp Oil is for topical use only. Not for oral, ophthalmic, or intravaginal use. Wet or dampen hair and scalp thoroughly. Apply a thin film of DERMA-SMOOTHE/FS Scalp Oil on the scalp, massage well and cover scalp with the supplied shower cap. Leave on overnight or for a minimum of 4 hours then wash hair with regular shampoo and rinse thoroughly. Use daily as needed. Discontinue DERMA-SMOOTHE/FS Scalp Oil 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 DERMA-SMOOTHE/FS Scalp Oil on the face 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) ] . Do not apply to the diaper area; diapers or plastic pants may constitute occlusive use. [see Warnings and Precautions (5.1) ] DERMA-SMOOTHE/FS Scalp Oil is not for oral, ophthalmic, or intravaginal use. ( 2 ) Do not use on face or intertriginous areas. ( 2 ) Apply a thin film of DERMA-SMOOTHE/FS Scalp Oil on the wet scalp, massage well and cover scalp with the supplied shower cap. Leave on overnight or for a minimum of 4 hours before washing off. ( 2 )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in psoriasis of the scalp is unknown. 12.2 Pharmacodynamics Vasoconstrictor Assay DERMA-SMOOTHE/FS Scalp Oil is in the low to medium range of potency as compared with other topical corticosteroids in vasoconstrictor studies. However, similar blanching scores do not necessarily imply therapeutic equivalence. Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression HPA axis suppression following administration of DERMA-SMOOTHE/FS Scalp Oil was not assessed. 12.3 Pharmacokinetics Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may increase percutaneous absorption. The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids may be necessary due to the fact that circulating levels are often below the level of detection. Once absorbed through the skin, topical corticosteroids are metabolized, primarily in the liver, and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.

12.1 Mechanism of Action Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in psoriasis of the scalp is unknown.

12.2 Pharmacodynamics Vasoconstrictor Assay DERMA-SMOOTHE/FS Scalp Oil is in the low to medium range of potency as compared with other topical corticosteroids in vasoconstrictor studies. However, similar blanching scores do not necessarily imply therapeutic equivalence. Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression HPA axis suppression following administration of DERMA-SMOOTHE/FS Scalp Oil was not assessed.

12.3 Pharmacokinetics Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may increase percutaneous absorption. The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids may be necessary due to the fact that circulating levels are often below the level of detection. Once absorbed through the skin, topical corticosteroids are metabolized, primarily in the liver, and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.

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3 DOSAGE FORMS AND STRENGTHS DERMA-SMOOTHE/FS Scalp Oil is a topical oil containing 0.01% fluocinolone acetonide, supplied in bottles containing 4 fluid ounces and with 2 shower caps. DERMA-SMOOTHE/FS Scalp Oil is a topical oil containing 0.01% fluocinolone acetonide, supplied in bottles containing 4 fluid ounces and with 2 shower caps. ( 3 )

DERMA-SMOOTHE/FS fluocinolone acetonide fluocinolone acetonide fluocinolone acetonide ISOPROPYL ALCOHOL ISOPROPYL MYRISTATE LIGHT MINERAL OIL OLETH-2 PEANUT OIL

13.1 Carcinogenesis, mutagenesis, impairment of fertility No carcinogenicity, genotoxicity, or fertility studies were conducted with DERMA-SMOOTHE/FS Scalp Oil. However, some corticosteroids are genotoxic in various genotoxicity tests (i.e., the in vitro human peripheral blood lymphocyte chromosome aberration assay with metabolic activation, the in vivo mouse bone marrow micronucleus assay, the Chinese hamster micronucleus test, and the in vitro mouse lymphoma gene mutation assay).

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, mutagenesis, impairment of fertility No carcinogenicity, genotoxicity, or fertility studies were conducted with DERMA-SMOOTHE/FS Scalp Oil. However, some corticosteroids are genotoxic in various genotoxicity tests (i.e., the in vitro human peripheral blood lymphocyte chromosome aberration assay with metabolic activation, the in vivo mouse bone marrow micronucleus assay, the Chinese hamster micronucleus test, and the in vitro mouse lymphoma gene mutation assay).

NDA019452

DERMA-SMOOTHE/FS

fluocinolone acetonide

68791-102

HUMAN PRESCRIPTION DRUG

TOPICAL

Principal Display Panel PRINCIPAL DISPLAY PANEL - 118.28 mL Carton Label NDC 68791-102-04 Rx only Derma-Smoothe/FS® Fluocinolone Acetonide 0.01% Topical Oil (SCALP OIL) FOR TOPICAL USE ONLY NOT FOR ORAL, OPHTHALMIC, OR INTRAVAGINAL USE SHAKE WELL BEFORE USE Net Contents 118.28 mL (4 Fl. oz.) ROYAL PHARMACEUTICALS® PRINCIPAL DISPLAY PANEL - 20 mL Carton Physcian Sample Label NOT FOR SALE PHYSICIAN SAMPLE NDC 68791-102-01 Rx only Derma-Smoothe/FS® Fluocinolone Acetonide 0.01% Topical Oil (SCALP OIL) FOR TOPICAL USE ONLY NOT FOR ORAL OPHTHALMIC, OR INTRAVAGINAL USE SHAKE WELL BEFORE USE NET Contents: 20 mL Royal Pharmaceuticals® PRINCIPAL DISPLAY PANEL - 118.28 mL Carton Label

Manufactured by: Hill Dermaceuticals, Inc. Sanford, Florida 32773 For: Royal Pharmaceutical, Inc. Wall, NJ 07719 DERMA-SMOOTHE/FS is a registered trademark of Hill Dermaceuticals, Inc. © 2024 Hill Dermaceuticals, Inc. All rights reserved.

17 PATIENT COUNSELING INFORMATION Administration Instructions Advise patients that DERMA-SMOOTHE/FS Scalp Oil is for topical use only [see Dosage and Administration (2) ] . Instruct patients not to apply DERMA-SMOOTHE/FS Scalp Oil to the diaper area as diapers or plastic pants may constitute occlusive use [see Dosage and Administration (2) ] . Advise patients to avoid use of DERMA-SMOOTHE/FS Scalp Oil on the face, axillae, or groin unless directed by their healthcare provider [see Dosage and Administration (2) ] . Advise patients to discontinue therapy when control of disease is achieved. Instruct patients to contact their healthcare provider if no improvement is seen within 2 weeks [see Dosage and Administration (2) ] . Endocrine System Adverse Reactions Instruct patients not to use other corticosteroid-containing products while using DERMA-SMOOTHE/FS Scalp Oil without first consulting their healthcare provider [see Warnings and Precautions (5.1) ] . Ophthalmic Adverse Reactions Advise patients to avoid contact with the eyes and in case of contact, wash eyes liberally with water. Instruct patients to tell their healthcare provider if they develop any visual symptoms [see Warnings and Precautions (5.3) ] . Pregnancy and Lactation Advise women to use DERMA-SMOOTHE/FS Scalp Oil on the smallest area of skin and for the shortest duration possible while pregnant or breastfeeding. Advise patients that are breastfeeding not to apply DERMA-SMOOTHE/FS Scalp Oil directly to the nipple and areola to avoid direct infant exposure [See Use in Specific Populations (8.1 and 8.2) ] .

Administration Instructions Advise patients that DERMA-SMOOTHE/FS Scalp Oil is for topical use only [see Dosage and Administration (2) ] . Instruct patients not to apply DERMA-SMOOTHE/FS Scalp Oil to the diaper area as diapers or plastic pants may constitute occlusive use [see Dosage and Administration (2) ] . Advise patients to avoid use of DERMA-SMOOTHE/FS Scalp Oil on the face, axillae, or groin unless directed by their healthcare provider [see Dosage and Administration (2) ] . Advise patients to discontinue therapy when control of disease is achieved. Instruct patients to contact their healthcare provider if no improvement is seen within 2 weeks [see Dosage and Administration (2) ] . Endocrine System Adverse Reactions Instruct patients not to use other corticosteroid-containing products while using DERMA-SMOOTHE/FS Scalp Oil without first consulting their healthcare provider [see Warnings and Precautions (5.1) ] . Ophthalmic Adverse Reactions Advise patients to avoid contact with the eyes and in case of contact, wash eyes liberally with water. Instruct patients to tell their healthcare provider if they develop any visual symptoms [see Warnings and Precautions (5.3) ] . Pregnancy and Lactation Advise women to use DERMA-SMOOTHE/FS Scalp Oil on the smallest area of skin and for the shortest duration possible while pregnant or breastfeeding. Advise patients that are breastfeeding not to apply DERMA-SMOOTHE/FS Scalp Oil directly to the nipple and areola to avoid direct infant exposure [See Use in Specific Populations (8.1 and 8.2) ] .

14 CLINICAL STUDIES In a vehicle-controlled study for the treatment of psoriasis of the scalp in adults, after 21 days of treatment, 60% of patients on active treatment and 21% of patients on the drug vehicle had excellent to cleared clinical response.

8.4 Pediatric Use The safety and effectiveness of DERMA-SMOOTHE/FS Scalp Oil have not been established in pediatric patients with psoriasis of the scalp. Evaluation in Peanut-Sensitive Pediatric Patients A clinical trial was conducted to assess the safety of the formulation of DERMA-SMOOTHE/FS Scalp Oil, which contains refined peanut oil, in patients with known peanut allergies. The trial enrolled 13 pediatric subjects with atopic dermatitis, 6 to 17 years of age. DERMA-SMOOTHE/FS Scalp Oil is not approved for the treatment of atopic dermatitis. Of the 13 subjects, 9 were Radioallergosorbent Test (RAST) positive to peanuts and 4 had no peanut sensitivity (controls). The trial evaluated the subjects’ responses to both prick test and patch test utilizing refined peanut oil, the formulation of DERMA-SMOOTHE/FS Scalp Oil and histamine/saline controls. Subjects were also treated with the formulation of DERMA-SMOOTHE/FS Scalp Oil twice daily for 7 days. Prick test and patch test results for all 13 subjects were negative to the formulation of DERMA-SMOOTHE/FS Scalp Oil and the refined peanut oil. One of the 9 peanut-sensitive subjects experienced an exacerbation of atopic dermatitis after 5 days of use on the formulation of DERMA-SMOOTHE/FS Scalp Oil.

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 Scalp 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.

8 USE IN SPECIFIC POPULATIONS 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 Scalp 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. 8.2 Lactation Risk Summary There is no information regarding the presence of fluocinolone acetonide in breast milk or its effects on the breastfed infant or on milk production. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. To minimize potential exposure to the breastfed infant via breast milk, use DERMA-SMOOTHE/FS Scalp Oil on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply DERMA-SMOOTHE/FS Scalp Oil directly to the nipple and areola to avoid direct infant exposure [see Warnings and Precautions (5.1) ] . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DERMA-SMOOTHE/FS Scalp Oil and any potential adverse effects on the breastfed infant from DERMA-SMOOTHE/FS Scalp Oil or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of DERMA-SMOOTHE/FS Scalp Oil have not been established in pediatric patients with psoriasis of the scalp. Evaluation in Peanut-Sensitive Pediatric Patients A clinical trial was conducted to assess the safety of the formulation of DERMA-SMOOTHE/FS Scalp Oil, which contains refined peanut oil, in patients with known peanut allergies. The trial enrolled 13 pediatric subjects with atopic dermatitis, 6 to 17 years of age. DERMA-SMOOTHE/FS Scalp Oil is not approved for the treatment of atopic dermatitis. Of the 13 subjects, 9 were Radioallergosorbent Test (RAST) positive to peanuts and 4 had no peanut sensitivity (controls). The trial evaluated the subjects’ responses to both prick test and patch test utilizing refined peanut oil, the formulation of DERMA-SMOOTHE/FS Scalp Oil and histamine/saline controls. Subjects were also treated with the formulation of DERMA-SMOOTHE/FS Scalp Oil twice daily for 7 days. Prick test and patch test results for all 13 subjects were negative to the formulation of DERMA-SMOOTHE/FS Scalp Oil and the refined peanut oil. One of the 9 peanut-sensitive subjects experienced an exacerbation of atopic dermatitis after 5 days of use on the formulation of DERMA-SMOOTHE/FS Scalp Oil.

16 HOW SUPPLIED / STORAGE AND HANDLING DERMA-SMOOTHE/FS Scalp Oil (fluocinolone acetonide) topical oil, 0.01% (NDC # 68791-102-04) is supplied in bottles containing 4 fluid ounces and with 2 shower caps. Storage: Keep tightly closed. Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature] .

Storage: Keep tightly closed. Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature] .