Derma-Smoothe/FS - Royal Pharmaceuticals, LLC | HILL DERMACEUTICALS, INC.

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

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)].

Apply DERMA-SMOOTHE/FS Body Oil as a thin film to the affected areas three times daily.

Moisten skin and apply DERMA-SMOOTHE/FS Body Oil as a thin film to the affected areas twice daily for up to four weeks.

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.

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)] .

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.

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.

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.

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.

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.

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.

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)]

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in atopic dermatitis is unknown.

Vasoconstrictor Assay
DERMA-SMOOTHE/FS Body 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 was evaluated in 29 pediatric subjects 3 months to 2 years old (7 subjects ages 3 to 6 months, 7 subjects ages > 6 to 12 months, and 15 subjects ages > 12 months to 2 years) and 33 pediatric subjects 2 years to 12 years old (20 subjects ages 2 to 6 years, 13 subjects ages 7 to 12 years) with moderate to severe atopic dermatitis. Subjects were treated with DERMA-SMOOTHE/FS Body Oil twice daily for 4 weeks. Morning pre-stimulation and post-ACTH stimulation cortisol levels were obtained in each subject at the beginning of the trial and at the end of 4 weeks of treatment. In subjects 3 months to 2 years old, all subjects had normal responses to 0.125 mg of ACTH stimulation (cortisol > 18 µg/dL). In subjects 2 to 12 years old, 4 out of 18 subjects 2 to 5 years old showed low pre-stimulation cortisol levels (3.2 to 6.6 µg/dL; normal: cortisol > 7µg/dL) but all had normal responses to 0.25 mg of ACTH stimulation (cortisol > 18 µg/dL) at the end of treatment [see Warnings and Precautions (5.1) and  Use in Specific Populations (8.4)] .

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.

No carcinogenicity, genotoxicity, or fertility studies were conducted with DERMA-SMOOTHE/FS Body Oil. However, some corticosteroids are genotoxic in various genotoxicity tests (i.e., the in vitrohuman 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 vitromouse lymphoma gene mutation assay).

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].

Administration Instructions
Advise patients that DERMA-SMOOTHE/FS Body Oil is for topical use only [see Dosage and Administration (2.1)] .

Advise patients to not to apply DERMA-SMOOTHE/FS Body Oil under occlusion unless directed by their healthcare provider. Instruct patients not to apply DERMA-SMOOTHE/FS to the diaper area as diapers or plastic pants may constitute occlusive use [see Dosage and Administration (2.1)] .

Advise patients to avoid use of DERMA-SMOOTHE/FS Body Oil on the face, axillae, or groin unless directed by their healthcare provider [see Dosage and Administration (2.1)] .

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 (2.1)] .

Endocrine System Adverse Reactions
Instruct patients not to use other corticosteroid-containing products while using DERMA-SMOOTHE/FS Body 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 patients to use DERMA-SMOOTHE/FS Body 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 Body Oil directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.1 and 8.2)] .