clobetasol propionate

Warnings and Precautions, Ophthalmic Adverse Reactions ( 5.2 ) 04/2018

1 INDICATIONS AND USAGE Clobetasol Propionate Foam, 0.05% is a corticosteroid indicated for treatment of moderate to severe plaque psoriasis of the scalp and mild to moderate plaque psoriasis of non-scalp regions of the body excluding the face and intertriginous areas in patients 12 years and older. Clobetasol Propionate Foam, 0.05% is a corticosteroid indicated for treatment of moderate to severe plaque psoriasis of the scalp and mild to moderate plaque psoriasis of non-scalp regions of the body excluding the face and intertriginous areas in patients 12 years and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a thin layer of Clobetasol Propionate Foam, 0.05% to the affected skin areas twice daily. Clobetasol Propionate Foam, 0.05% is a super-high-potency topical corticosteroid; therefore, limit treatment to 2 consecutive weeks. Patients should not use greater than 50 grams per week or more than 21 capfuls per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis [see Warnings and Precautions (5.1)]. Therapy should be discontinued when control is achieved. Clobetasol Propionate Foam, 0.05% should not be used with occlusive dressings unless directed by a physician. Clobetasol Propionate Foam, 0.05% is for topical use only. It is not for oral, ophthalmic, or intravaginal use. Avoid contact with eyes. Wash hands after each application. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. • Apply a thin layer to the affected skin areas twice daily. ( 2 ) • Limit treatment to 2 consecutive weeks. ( 2 ) • Do not use more than 50 grams per week or more than 21 capfuls per week. ( 2 ) • Discontinue therapy when control is achieved. ( 2 ) • Do not use with occlusive dressings unless directed by physician. ( 2 ) • Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Clobetasol Propionate Emulsion Foam, 0.05% contains 0.5 mg of clobetasol propionate, USP per gram in a white to off-white emulsion aerosol foam. Foam, 0.05%. ( 3 )

4 CONTRAINDICATIONS None. • None ( 4 )

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 Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 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 emulsion foam and vehicle foam, the pooled incidence of local adverse reactions in trials for atopic dermatitis and psoriasis with clobetasol propionate emulsion foam 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 USE IN SPECIFIC POPULATIONS 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. 8.2 Lactation Risk Summary There is no information regarding the presence of clobetasol propionate in breast milk or its effects on the breastfed infant or on milk production. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of clobetasol propionate could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Clobetasol Propionate Foam, 0.05% (Emulsion) and any potential adverse effects on the breastfed infant from Clobetasol Propionate Foam, 0.05% (Emulsion) or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use Clobetasol Propionate Foam, 0.05% (Emulsion) on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Clobetasol Propionate Foam, 0.05% (Emulsion) directly to the nipple and areola to avoid direct infant exposure. 8.4 Pediatric Use Use in pediatric patients younger than 12 years is not recommended because of the risk of HPA axis suppression. …

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 corticosteroid-responsive dermatoses is unknown.

11 DESCRIPTION Clobetasol Propionate Emulsion Foam, 0.05% is a white to off-white emulsion aerosol foam containing the active ingredient clobetasol propionate, USP, a synthetic corticosteroid for topical dermatologic use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity. Clobetasol propionate, USP is 21-chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate, with the empirical formula C 25 H 32 ClFO 5 , and a molecular weight of 467 g/mol. The following is the chemical structure: Clobetasol Propionate, USP Clobetasol propionate, USP is a white to almost white crystalline powder, practically insoluble in water, slightly soluble in benzene and diethyl ether; sparingly soluble in ethanol; freely soluble in acetone, in dimethylsulfoxide, in chloroform, in methanol and in dioxane. Each gram of Clobetasol Propionate Emulsion Foam, 0.05% contains 0.5 mg clobetasol propionate, USP. The foam also contains anhydrous citric acid, cetyl alcohol, cyclomethicone, isopropyl myristate, light mineral oil, polyoxyl-20 cetostearyl ether, potassium citrate, propylene glycol, purified water, sorbitan monolaurate, white petrolatum, and phenoxyethanol as a preservative. Clobetasol Propionate Emulsion Foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/butane) propellant. structure

10 OVERDOSAGE Topically applied Clobetasol Propionate Foam, 0.05% (Emulsion) can be absorbed in sufficient amounts to produce systemic effects.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clobetasol Propionate Foam, 0.05% contains 0.5 mg of clobetasol propionate, USP per gram. The white thermolabile hydroethanolic aerosol foam is available as follows: • 50-g aluminum can - NDC 68462-608-27 • 100-g aluminum can - NDC 68462-608-94 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. FLAMMABLE. AVOID FIRE, FLAME, OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION . Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C). Keep out of reach of children.