clobetasol propionate emollient formulation

1 INDICATIONS AND USAGE Clobetasol Propionate Foam, 0.05% (Emulsion) is indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years and older. • Clobetasol Propionate Foam, 0.05% (Emulsion) is a corticosteroid indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years and older. ( 1 )

2 DOSAGE AND ADMINISTRATION • Apply a thin layer of Clobetasol Propionate Foam, 0.05% (Emulsion) to the affected area(s) twice daily, morning and evening, for up to 2 consecutive weeks; therapy should be discontinued when control has been achieved. • The maximum weekly dose should not exceed 50 g or an amount greater than 21 capfuls per week. • For proper dispensing of foam, shake the can, hold it upside down, and depress the actuator. • Dispense a small amount of foam (about a capful) and gently massage the medication into the affected areas (excluding the face, groin, and axillae) until the foam is absorbed. • Clobetasol Propionate Foam, 0.05% (Emulsion) is not for oral, ophthalmic, or intravaginal use. • Avoid contact with the eyes. • Avoid use on face, axillae, and groin, or if skin atrophy is present at the treatment site. • Wash hands after each application. Clobetasol Propionate Foam, 0.05% (Emulsion) is not for oral, ophthalmic, or intravaginal use ( 2 ). • Apply Clobetasol Propionate Foam, 0.05% (Emulsion) to the affected area(s) twice daily, morning and evening, for up to 2 consecutive weeks. The maximum weekly dose should not exceed 50 g. ( 2 ) • Avoid use on face, axilla, and groin, or if skin atrophy is present at the treatment site. ( 2 )

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS • Clobetasol Propionate Foam, 0.05% (Emulsion) has been shown to suppress the HPA axis. Systemic absorption of Clobetasol Propionate Foam, 0.05% (Emulsion) may produce reversible HPA axis suppression, Cushing’s syndrome, hyperglycemia, and unmask latent diabetes. ( 5.1 ) • Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. ( 5.1 ) • Modify use should HPA axis suppression develop. ( 5.1 ) • High potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, and liver failure may predispose patients to HPA axis suppression. ( 5.1 ) • May increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist for evaluation. ( 5.3 ) • Pediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. ( 5.1 , 8.4 ) • The propellant in Clobetasol Propionate Foam, 0.05% (Emulsion) is flammable. Avoid fire, flame, or smoking during and immediately following application. ( 5.5 ) 5.1 Effects on Endocrine System Clobetasol propionate foam, 0.05% (emulsion) has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Systemic absorption of clobetasol propionate foam, 0.05% (emulsion) has caused reversible HPA axis suppression with the potential for clinical glucocorticoid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. Use of clobetasol propionate foam, 0.05% (emulsion) for longer than 2 weeks may suppress the immune system [see Nonclinical Toxicology (13.1)] . In a trial including 37 subjects 12 years and older with atopic dermatitis of at least 30% body surface area (BSA), adrenal suppression was identified in 6 out of 37 subjects (16.2%) after 2 weeks of treatment with clobetasol propionate foam, 0.05% (emulsion) [see Clinical Pharmacology (12.2)] . Because of the potential for systemic absorption, use of clobetasol propionate foam, 0.05% (emulsion) may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure. An adrenocorticotrophic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than 1 corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses because of their larger skin surface-to-body mass ratios [see Use in Specific Populations (8.4)] . 5.2 Local Adverse Reactions with Topical Corticosteroids Local adverse reactions may be more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. 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. If irritation develops, treatment with Clobetasol Propionate Foam, 0.05% (Emulsion) should be discontinued and appropriate therapy instituted. 5.3 Ophthalmic Adverse Reactions Use of topical corticosteroids, including Clobetasol Propionate Foam, 0.05% (Emulsion), may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing with the use of topical corticosteroids, including topical clobetasol products [see Adverse Reactions (6.2)] . Avoid contact of Clobetasol Propionate Foam, 0.05% (Emulsion) with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.4 Concomitant Skin Infections Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, Clobetasol Propionate Foam, 0.05% (Emulsion) should be discontinued until the infection has been adequately treated. 5.5 Flammable Contents The propellant in Clobetasol Propionate Foam, 0.05% (Emulsion) is flammable. Avoid fire, flame, or smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Effects on Endocrine System [see Warnings and Precautions (5.1)] • Ophthalmic Adverse Reactions [see Warnings and Precautions (5.3)] • The most common adverse reactions (incidence ≥ 1%) are application site atrophy and application site reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis at 1-866-634-9120 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 controlled clinical trials involving 821 subjects exposed to clobetasol propionate foam, 0.05% (emulsion) and vehicle foam, the pooled incidence of local adverse reactions in trials for atopic dermatitis and psoriasis with clobetasol propionate foam, 0.05% (emulsion) was 1.9% for application site atrophy and 1.6% for application site reaction. Most local adverse events were rated as mild to moderate and they were not affected by age, race, or gender. 6.2 Postmarketing Experience Because these 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. The following adverse reactions have been identified during post-approval use of clobetasol formulations: erythema, pruritus, burning, alopecia, and dryness. The following additional local adverse reactions have been reported with topical corticosteroids: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, irritation, striae, and miliaria. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, such as clobetasol propionate. Cushing’s syndrome has been reported in infants and adults as a result of prolonged use of topical clobetasol propionate formulations. Ophthalmic adverse reactions may include cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy.

8.1 Pregnancy Risk Summary There are no available data on Clobetasol Propionate Foam, 0.05% (Emulsion) use in pregnant women to inform of a drug associated risk for adverse developmental outcomes. Published data report a significantly increased risk of low birth weight with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. Advise pregnant women of the potential risk to a fetus and to use Clobetasol Propionate Foam, 0.05% (Emulsion) on the smallest area of skin and for the shortest duration possible ( see Data ). In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits. No comparison of animal exposure with human exposure was computed. 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. Data Human Data Multiple observational studies found no significant associations between maternal use of topical corticosteroids of any potency and congenital malformations, preterm delivery, or fetal mortality. However, when the dispensed amount of potent or very potent topical corticosteroid exceeded 300 g during the entire pregnancy, use was associated with an increase in low birth weight infants (adjusted RR, 7.74 [95% CI, 1.49–40.11]). In addition, a small cohort study, in which 28 sub-Saharan women using potent topical corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during pregnancy, noted a higher incidence of low birth weight infants in the exposed group. The majority of exposed subjects treated large areas of the body (a mean quantity of 60 g/month [range, 12–170 g]) over long periods of time. Animal Data Embryofetal development studies conducted with clobetasol propionate in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and malformations at all dose levels tested down to 0.03 mg/kg. Malformations seen included cleft palate and skeletal abnormalities. In an embryofetal development study in rabbits, subcutaneous administration of clobetasol propionate resulted in malformations at doses of 0.003 and 0.01 mg/kg. Malformations seen included cleft palate, cranioschisis, and other skeletal abnormalities.