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1 INDICATIONS AND USAGE Clobetasol propionate emulsion foam is indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years and older. Clobetasol propionate emulsion foam is a corticosteroid indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients aged 12 years and older. ( 1 )

2 DOSAGE AND ADMINISTRATION • Apply a thin layer of clobetasol propionate emulsion foam 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 emulsion foam 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 emulsion foam is not for oral, ophthalmic, or intravaginal use. ( 2 ) • Apply clobetasol propionate emulsion foam 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 )

5 WARNINGS AND PRECAUTIONS • Clobetasol propionate emulsion foam has been shown to suppress the HPA axis. Systemic absorption of clobetasol propionate emulsion foam 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 emulsion foam is flammable. Avoid fire, flame, or smoking during and immediately following application. ( 5.5 ) 5.1 Effects on Endocrine System Clobetasol propionate emulsion foam has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Systemic absorption of clobetasol propionate emulsion foam 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 emulsion foam for longer than 2 weeks may suppress the immune system [see Nonclinical Toxicology (13.1) ]. In a trial including 37 subjects ages 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 emulsion foam [see Clinical Pharmacology (12.2 )] . Because of the potential for systemic absorption, use of clobetasol propionate emulsion foam 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) ].

teroids. 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 emulsion foam should be discontinued and appropriate therapy instituted. 5.3 Ophthalmic Adverse Reactions Use of topical corticosteroids, including clobetasol propionate emulsion foam, 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 emulsion foam 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 emulsion foam should be discontinued until the infection has been adequately treated. 5.5 Flammable Contents The propellant in clobetasol propionate emulsion foam 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 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 emulsion foam use in pregnant women to inform of a drug associated risk for adverse developmental outcomes. Published data report a significantly increased risk of low birthweight 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 emulsion foam 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 to 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 to 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 emulsion foam and any potential adverse effects on the breastfed infant from clobetasol propionate emulsion foam or from the underlying maternal condition.

uantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clobetasol propionate emulsion foam and any potential adverse effects on the breastfed infant from clobetasol propionate emulsion foam or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use clobetasol propionate emulsion foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply clobetasol propionate emulsion foam 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. After two weeks of twice-daily treatment with clobetasol propionate emulsion foam, 7 of 15 subjects (47%) aged 6 to 11 years demonstrated HPA axis suppression. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested 4 weeks post-treatment. In 92 subjects aged 12 to 17 years, safety was similar to that observed in the adult population. Based on these data, no adjustment of dosage of clobetasol propionate emulsion foam in adolescent patients aged 12 to 17 years is warranted [see Warnings and Precautions (5.1) ]. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles (in infants), headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children. Adverse effects, including striae, have been reported with inappropriate use of topical corticosteroids in infants and children. 8.5 Geriatric Use A limited number of subjects aged 65 years or older have been treated with clobetasol propionate emulsion foam (n = 58) in U.S. clinical trials. While the number of subjects is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger subjects. Based on available data, no adjustment of dosage of clobetasol propionate emulsion foam in geriatric patients is warranted.

8.1 Pregnancy Risk Summary There are no available data on clobetasol propionate emulsion foam use in pregnant women to inform of a drug associated risk for adverse developmental outcomes. Published data report a significantly increased risk of low birthweight 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 emulsion foam 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 to 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 to 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.

8.4 Pediatric Use Use in pediatric patients younger than 12 years is not recommended because of the risk of HPA axis suppression. After two weeks of twice-daily treatment with clobetasol propionate emulsion foam, 7 of 15 subjects (47%) aged 6 to 11 years demonstrated HPA axis suppression. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested 4 weeks post-treatment. In 92 subjects aged 12 to 17 years, safety was similar to that observed in the adult population. Based on these data, no adjustment of dosage of clobetasol propionate emulsion foam in adolescent patients aged 12 to 17 years is warranted [see Warnings and Precautions (5.1) ]. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles (in infants), headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children. Adverse effects, including striae, have been reported with inappropriate use of topical corticosteroids in infants and children.

8.5 Geriatric Use A limited number of subjects aged 65 years or older have been treated with clobetasol propionate emulsion foam (n = 58) in U.S. clinical trials. While the number of subjects is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger subjects. Based on available data, no adjustment of dosage of clobetasol propionate emulsion foam in geriatric patients is warranted.

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

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 corticosteroid-responsive dermatoses is unknown. 12.2 Pharmacodynamics In a trial evaluating the potential for HPA axis suppression using the cosyntropin stimulation test, clobetasol propionate emulsion foam demonstrated reversible adrenal suppression after two weeks of twice-daily use in subjects with atopic dermatitis of at least 30% body surface area (BSA). The proportion of subjects aged 12 years and older demonstrating HPA axis suppression was 16.2% (6 out of 37). In this trial HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30 minutes post cosyntropin stimulation. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested 4 weeks post treatment [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4)]. 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. Following twice-daily application of clobetasol propionate emulsion foam for one week to 32 adult subjects with mild to moderate plaque-type psoriasis, mean peak plasma concentrations (±SD) of 59 ± 36 pg/mL of clobetasol were observed at around 5 hours post dose on Day 8.

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.

12.2 Pharmacodynamics In a trial evaluating the potential for HPA axis suppression using the cosyntropin stimulation test, clobetasol propionate emulsion foam demonstrated reversible adrenal suppression after two weeks of twice-daily use in subjects with atopic dermatitis of at least 30% body surface area (BSA). The proportion of subjects aged 12 years and older demonstrating HPA axis suppression was 16.2% (6 out of 37). In this trial HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30 minutes post cosyntropin stimulation. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested 4 weeks post treatment [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4)].

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. Following twice-daily application of clobetasol propionate emulsion foam for one week to 32 adult subjects with mild to moderate plaque-type psoriasis, mean peak plasma concentrations (±SD) of 59 ± 36 pg/mL of clobetasol were observed at around 5 hours post dose on Day 8.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate emulsion foam or clobetasol propionate. In a 90-day repeat-dose toxicity study in rats, topical administration of clobetasol propionate emulsion foam at dose concentrations from 0.001% to 0.1% or from 0.03 to 0.3 mg/kg/day of clobetasol propionate resulted in a toxicity profile consistent with long term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression and opportunistic fungal and bacterial infections. A no observable adverse effect level could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk for carcinogenesis. Clobetasol propionate was non-mutagenic in the Ames test, the mouse lymphoma test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test. In the in vivo mouse micronucleus test, a positive finding was observed at 24 hours, but not at 48 hours, following oral administration at a dose of 2,000 mg/kg. Studies in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate emulsion foam or clobetasol propionate. In a 90-day repeat-dose toxicity study in rats, topical administration of clobetasol propionate emulsion foam at dose concentrations from 0.001% to 0.1% or from 0.03 to 0.3 mg/kg/day of clobetasol propionate resulted in a toxicity profile consistent with long term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression and opportunistic fungal and bacterial infections. A no observable adverse effect level could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk for carcinogenesis. Clobetasol propionate was non-mutagenic in the Ames test, the mouse lymphoma test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test. In the in vivo mouse micronucleus test, a positive finding was observed at 24 hours, but not at 48 hours, following oral administration at a dose of 2,000 mg/kg. Studies in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

14 CLINICAL STUDIES In a randomized trial of subjects 12 years and older with moderate to severe atopic dermatitis, 251 subjects were treated with clobetasol propionate emulsion foam and 126 subjects were treated with vehicle foam. Subjects were treated twice daily for 2 weeks. At the end of treatment, 131 of 251 subjects (52%) treated with clobetasol propionate emulsion foam compared with 18 of 126 subjects (14%) treated with vehicle foam achieved treatment success. Treatment success was defined by an Investigator’s Static Global Assessment (ISGA) score of clear (0) or almost clear (1) with at least 2 grades improvement from baseline, and scores of absent or minimal (0 or 1) for erythema and induration/papulation. In an additional randomized trial of subjects 12 years and older with mild to moderate plaque-type psoriasis, 253 subjects were treated with clobetasol propionate emulsion foam and 123 subjects were treated with vehicle foam. Subjects were treated twice daily for 2 weeks. At the end of treatment, 41 of 253 subjects (16%) treated with clobetasol propionate emulsion foam compared with 5 of 123 subjects (4%) treated with vehicle foam achieved treatment success. Treatment success was defined by an ISGA score of clear (0) or almost clear (1) with at least 2 grades improvement from baseline, scores of none or faint/minimal (0 or 1) for erythema and scaling, and a score of none (0) for plaque thickness.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clobetasol Propionate Emulsion Foam, 0.05% contains 0.5 mg of clobetasol propionate, USP per gram. The white to off-white emulsion aerosol foam is available as follows • 50 g aluminum can NDC 68462-625-27 • 100 g aluminum can NDC 68462-625-94 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.

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information) Effects on Endocrine System Clobetasol propionate emulsion foam may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including clobetasol propionate emulsion foam, may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. Concomitant use of multiple corticosteroid-containing products may increase the total systemic exposure to topical corticosteroids. Patients should inform their physician(s) that they are using clobetasol propionate emulsion foam if surgery is contemplated [see Warnings and Precautions (5.1) ]. Ophthalmic Adverse Reactions Advise patients to report any visual symptoms to their healthcare providers [see Warnings and Precautions (5.3) ] . Local Adverse Reactions Report any signs of local adverse reactions to the physician. Advise patients that local reactions and skin atrophy are more likely to occur with occlusive use or prolonged use [see Warnings and Precautions (5.2) ] . Pregnancy Advise a pregnant woman that use of clobetasol propionate emulsion foam may cause fetal harm and to use clobetasol propionate emulsion foam on the smallest area of skin and for the shortest duration possible [see Use in Specific Populations (8.1) ]. Lactation Advise a woman to use clobetasol propionate emulsion foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply clobetasol propionate emulsion foam directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.2) ]. Important Administration Instructions Patients using topical corticosteroids should receive the following information and instructions: • This medication is to be used as directed by the physician. It is for external use only. Unless directed by the prescriber, it should not be used on the face or in skin-fold areas, such as the underarms or groin. Avoid contact with the eyes or other mucous membranes. Wash hands after use. • As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician. • Do not use for more than 50 grams per week of clobetasol propionate emulsion foam, or an amount greater than 21 capfuls per week [see Dosage and Administration ( 2 )] . • This medication is flammable; avoid heat, flame, or smoking when applying this product. For additional information, call Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com August 2025 logo

PATIENT INFORMATION Clobetasol Propionate (kloe bay’ ta sol proe’ pee oh nate) Foam Important: For skin use only. Do not get clobetasol propionate emulsion foam in your eyes, mouth, or vagina. What is clobetasol propionate emulsion foam? Clobetasol propionate emulsion foam is a prescription corticosteroid medicine used on the skin (topical) to treat people 12 years of age and older with certain skin conditions that cause red, flaky, and itchy skin. Clobetasol propionate emulsion foam is not recommended for use in children under 12 years of age. Clobetasol propionate emulsion foam should not be used: • on your face, underarms, or groin area • if you have skin thinning (atrophy) at the treatment area You should not use clobetasol propionate emulsion foam for longer than 2 weeks in a row. You should not use more than 50 grams or 21 capfuls of clobetasol propionate emulsion foam in 1 week. Before using clobetasol propionate emulsion foam, tell your healthcare provider about all of your medical conditions, including if you: • have had irritation or other skin reaction to a steroid medicine in the past. • have a skin infection. You may need medicine to treat the skin infection before using clobetasol propionate emulsion foam. • have diabetes. • have adrenal gland problems. • have liver problems. • plan to have surgery. • are pregnant or plan to become pregnant. It is not known if clobetasol propionate emulsion foam will harm your unborn baby. If you use clobetasol propionate emulsion foam during pregnancy, use clobetasol propionate emulsion foam on the smallest area of skin and for the shortest time needed. • are breastfeeding or plan to breastfeed. It is not known if clobetasol propionate passes into your breast milk. If you use clobetasol propionate emulsion foam while breastfeeding, use clobetasol propionate emulsion foam on the smallest area of skin and for the shortest time needed. Do not apply clobetasol propionate emulsion foam directly to the nipple and areola to avoid getting clobetasol propionate emulsion foam into your baby’s mouth. Tell your healthcare provider about all the medicine you take including prescription and over-the‑counter medicines, vitamins, and herbal supplements. Do not use other products containing a corticosteroid medicine during treatment with clobetasol propionate emulsion foam without talking to your healthcare provider first. How should I use clobetasol propionate emulsion foam? See the“Instructions for Use” for detailed information about the right way to apply clobetasol propionate emulsion foam . • Use clobetasol propionate emulsion foam exactly as your healthcare provider tells you to use it. • Apply a thin layer of clobetasol propionate emulsion foam to the affected area 2 times each day, 1 time in the morning and 1 time at night, or as directed by your healthcare provider. • Do not bandage, wrap or cover your treated area unless your healthcare provider tells you to. • Talk to your healthcare provider if your skin does not improve after 2 weeks of treatment with clobetasol propionate emulsion foam. • Wash your hands after using clobetasol propionate emulsion foam. What should I avoid while using clobetasol propionate emulsion foam? Clobetasol propionate emulsion foam is flammable . Avoid heat, flame, or smoking during and right after you apply clobetasol propionate emulsion foam to your skin. What are the possible side effects of clobetasol propionate emulsion foam?

ulsion foam. What should I avoid while using clobetasol propionate emulsion foam? Clobetasol propionate emulsion foam is flammable . Avoid heat, flame, or smoking during and right after you apply clobetasol propionate emulsion foam to your skin. What are the possible side effects of clobetasol propionate emulsion foam? Clobetasol propionate emulsion foam may cause serious side effects, including: • Clobetasol propionate emulsion foam can pass through your skin. Too much clobetasol propionate emulsion foam passing through your skin can cause adrenal glands to stop working. • Cushing’s syndrome, a condition that happens when the body is exposed to too much of the hormone cortisol. • High blood sugar (hyperglycemia) • Vision problems. Clobetasol propionate emulsion foam may increase your chance of developing vision problems such as cataract(s) and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during your treatment with clobetasol propionate emulsion foam. • Skin reactions at the treated site. Tell your healthcare provider if you get any skin reactions or skin infections. • Effects on growth and weight in children. Your healthcare provider may do certain blood tests to check for side effects. The most common side effects of clobetasol propionate emulsion foam include: • thinning of skin • itching • burning • dryness • redness These are not all the side effects of clobetasol propionate emulsion foam. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store clobetasol propionate emulsion foam? • Store clobetasol propionate emulsion foam at room temperature between 68°F to 77°F (20°C to 25°C). • Do not break through (puncture) clobetasol propionate emulsion foam can. • Never throw the can into a fire, even if the can is empty. • Do not store clobetasol propionate emulsion foam near heat or at temperatures above 120°F (49°C). Keep clobetasol propionate emulsion foam and all medicines out of the reach of children . General information about the safe and effective use of clobetasol propionate emulsion foam Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use clobetasol propionate emulsion foam for a condition for which it was not prescribed. Do not give clobetasol propionate emulsion foam to other people, even if they have the same condition that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about clobetasol propionate emulsion foam that is written for health professionals. What are the ingredients in clobetasol propionate emulsion foam? Active ingredient : clobetasol propionate Inactive ingredients : 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; pressurized with a hydrocarbon (propane/butane) propellant. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com August 2025 This Patient Information has been approved by the U.S. Food and Drug Administration. logo1

INSTRUCTIONS FOR USE Clobetasol Propionate (kloe bay’ ta sol proe’ pee oh nate) Foam Important information: Clobetasol propionate emulsion foam is for use on the skin only. Do not get clobetasol propionate emulsion foam in your eyes, mouth, or vagina; if contact happens, rinse well with water. How to apply clobetasol propionate emulsion foam Figure A Step 1 : Before applying clobetasol propionate emulsion foam for the first time, break the tiny plastic piece at the base of the can's rim by gently pushing back (away from the piece) on the nozzle. (See Figure A). Figure B Step 2 : Shake the can of clobetasol propionate emulsion foam before use. (See Figure B). Figure C Step 3 : Turn the can of clobetasol propionate emulsion foam upside down and press the nozzle. See Figure C. Figure D Step 4 : Press down on the actuator to dispense a small amount of clobetasol propionate emulsion foam into the palm of your hand. (See Figure D). Figure E Step 5 : Apply a thin layer of clobetasol propionate emulsion foam to cover the affected area. Gently rub the foam into the affected area until the foam disappears. (See Figure E). Step 6 : Wash your hands after applying clobetasol propionate emulsion foam. • Throw away any of the unused medicine that you dispensed out of the can. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com August 2025 figure1 figure2 figure3 figure4 figure5 logo2

<table width="100%"><col width="63%"/><col width="37%"/><tbody><tr><td align="center" valign="top" styleCode="Toprule "><renderMultiMedia referencedObject="ID_0c44b8e3-3096-49bd-b6cc-1bd9ec5a9e35" ID="id40950351"/><paragraph><content styleCode="bold">Figure A</content></paragraph></td><td valign="top" styleCode="Toprule "><paragraph><content styleCode="bold">Step 1</content>: Before applying clobetasol propionate emulsion foam for the first time, break the tiny plastic piece at the base of the can&apos;s rim by gently pushing back (away from the piece) on the nozzle. (See Figure A).</paragraph></td></tr><tr><td align="center" valign="top"><renderMultiMedia referencedObject="ID_14f62e8f-02de-40b9-8d85-3af3e6ae279a" ID="id1923839236"/><paragraph><content styleCode="bold">Figure B</content></paragraph></td><td valign="top"><paragraph><content styleCode="bold">Step 2</content>: Shake the can of clobetasol propionate emulsion foam before use. (See Figure B).</paragraph></td></tr><tr><td align="center" valign="top"><renderMultiMedia referencedObject="E1A120D5-2363-4DA4-A4CC-2756BCC10A07" ID="id1786156615"/><paragraph><content styleCode="bold">Figure C</content></paragraph></td><td valign="top"><paragraph><content styleCode="bold">Step 3</content>: Turn the can of clobetasol propionate emulsion foam upside down and press the nozzle. See Figure C.</paragraph></td></tr><tr><td align="center" valign="top"><renderMultiMedia referencedObject="ID_6e4d7967-e44e-4fb7-a44d-c0c95316396d" ID="id-1825267046"/><paragraph><content styleCode="bold">Figure D</content></paragraph></td><td valign="top"><paragraph><content styleCode="bold">Step 4</content>: Press down on the actuator to dispense a small amount of clobetasol propionate emulsion foam into the palm of your hand. (See Figure D).</paragraph></td></tr><tr><td align="center" valign="top" styleCode="Botrule "><renderMultiMedia referencedObject="ID_851dd8a1-d714-4bcd-a3ae-c93b00b23980" ID="id1603525601"/><paragraph><content styleCode="bold">Figure E</content></paragraph></td><td valign="top" styleCode="Botrule "><paragraph><content styleCode="bold">Step 5</content>: Apply a thin layer of clobetasol propionate emulsion foam to cover the affected area. Gently rub the foam into the affected area until the foam disappears. (See Figure E).</paragraph></td></tr></tbody></table>

1 INDICATIONS AND USAGE Clobetasol propionate cream USP, 0.05% (emollient) is a corticosteroid indicated for: The relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years of age or older. (1.1) The treatment of moderate to severe plaque-type psoriasis in patients 16 years of age and older. (1.2) Limitations of Use Clobetasol propionate cream USP, 0.05% (emollient) should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae. (1.3) The total dosage should not exceed 50 grams per week. (1.3) Avoid use if skin atrophy is present at the treatment site. (1.3) Clobetasol propionate cream USP, 0.05% (emollient) is a super-high potency corticosteroid indicated for: 1.1 Corticosteroid-Responsive Dermatoses Clobetasol propionate cream USP, 0.05% (emollient) is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years of age and older. Treatment should be limited to 2 consecutive weeks, and the total dosage should not exceed 50 grams per week. 1.2 Moderate to Severe Plaque-Type Psoriasis Clobetasol propionate cream USP, 0.05% (emollient) is indicated for the topical treatment of moderate to severe plaque-type psoriasis. Treatment beyond 4 consecutive weeks is not recommended. Use in pediatric patients under 16 years of age is not recommended. 1.3 Limitations of Use Clobetasol propionate cream USP, 0.05% (emollient) should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae. The total dosage should not exceed 50 grams per week. Avoid use if skin atrophy is present at the treatment site.

2 DOSAGE AND ADMINISTRATION Apply a thin layer of Clobetasol propionate cream USP, 0.05% (emollient) to the affected skin areas twice daily and rub in gently and completely. Wash hands after each application. Clobetasol propionate cream USP, 0.05% (emollient) is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks, and amounts greater than 50 grams per week should not be used. In moderate to severe plaque-type psoriasis, Clobetasol propionate cream USP, 0.05% (emollient) applied to 5% to 10% of body surface area can be used for up to 4 weeks. The total dosage should not exceed 50 grams per week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. Therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Treatment beyond 4 consecutive weeks is not recommended. Clobetasol propionate cream USP, 0.05% (emollient) should not be used with occlusive dressings. Apply a thin layer of Clobetasol propionate cream USP, 0.05% (emollient) to the affected skin areas twice daily and rub in gently and completely. (2) Treatment should be limited to 2 consecutive weeks, and amounts greater than 50 grams per week should not be used. (2) In moderate to severe plaque-type psoriasis, Clobetasol propionate cream USP, 0.05% (emollient) applied to 5% to 10% of body surface area can be used for up to 4 weeks. The total dosage should not exceed 50 grams per week. When dosing for more than 2 weeks, any additional benefit of extending treatment should be weighed against the risk of HPA suppression. (2)

3 DOSAGE FORMS AND STRENGTHS Cream, 0.05%. Each gram of Clobetasol propionate cream USP, 0.05% (emollient) contains 0.5 mg of clobetasol propionate in a white to off-white cream base. Cream: 0.05% (3)

5 WARNINGS AND PRECAUTIONS Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis doses as low as 2 grams per day. (5.1) Cushing's syndrome, hyperglycemia, and glucosuria can also result from systemic absorption of topical corticosteroids. (5.1) Systemic absorption may require periodic evaluation for HPA axis suppression. Modify use if HPA axis suppression develops. (5.1) Children may be more susceptible to systemic toxicity from use of topical corticosteroids. (5.1 , 8.4) Local adverse reactions with topical corticosteroids may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions include: folliculitis, acneiform eruptions, hypertrichosis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria. (5.2) 5.1 Effects on the Endocrine System Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 grams per day. Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. In a study including 12 subjects ages 18 years and older with psoriasis or atopic dermatitis involving at least 30% body surface area (BSA), adrenal suppression was identified in 3 out of 12 subjects (25%) following 1 week of treatment. 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 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 supplemental 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 one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure. Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. [ 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, hypertrichosis, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis.

n, dryness, folliculitis, acneiform eruptions, hypopigmentation, hypertrichosis, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis. 5.3 Allergic Contact Dermatitis Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed with patch testing. If irritation develops, Clobetasol propionate cream, 0.05% (emollient) should be discontinued and appropriate therapy instituted. 5.4 Concomitant Skin Infections If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of Clobetasol propionate cream, 0.05% (emollient) should be discontinued until the infection has been adequately controlled.

6 ADVERSE REACTIONS The most common adverse reaction is burning/stinging (incidence 5%); common adverse reactions (incidence < 2%) are pruritis, irritation, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, tenderness in the elbow, skin atrophy, and telangiectasia. (6.1) . To report SUSPECTED ADVERSE REACTIONS, contact The J. Molner Company LLC at 1-800-552-8750 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 trials with clobetasol propionate formulations, the following adverse reactions have been reported: burning/stinging, pruritis, irritation, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, tenderness in the elbow, skin atrophy, and telangiectasia. The incidence of local adverse reactions reported in the trials with Clobetasol propionate cream, 0.05% (emollient) was less than 2% of patients treated with the exception of burning/stinging which occurred in 5% of treated patients.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy There are no adequate and well-controlled studies in pregnant women. Therefore, Clobetasol propionate cream, 0.05% (emollient) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals. Clobetasol propionate has not been tested for teratogenicity by this route; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent. Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 0.33 and 0.01 times, respectively, the human topical dose of Clobetasol propionate cream, 0.05% (emollient). Abnormalities seen included cleft palate and skeletal abnormalities. In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.001 and 0.003 times, respectively, the human topical dose of Clobetasol propionate cream, 0.05% (emollient). Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities. 8.2 Lactation 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 corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clobetasol propionate cream, 0.05% (emollient) is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness of Clobetasol propionate cream, 0.05% (emollient) in pediatric patients have not been established and its use in pediatric patients under 12 years of age is not recommended. In a study including 12 subjects ages 18 years and older with psoriasis or atopic dermatitis involving at least 30% body surface area (BSA), adrenal suppression was identified in 3 out of 12 subjects (25%) following 1 week of treatment. Four-week HPA axis suppression studies with Clobetasol propionate cream, 0.05% (emollient) in pediatric subjects have not been conducted. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation.

ren. HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. The use of Clobetasol propionate cream, 0.05% (emollient) for 4 consecutive weeks has not been studied in pediatric patients under 16 years of age. 8.5 Geriatric Use Clinical studies of Clobetasol propionate cream, 0.05% (emollient) did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious.

8.1 Pregnancy There are no adequate and well-controlled studies in pregnant women. Therefore, Clobetasol propionate cream, 0.05% (emollient) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals. Clobetasol propionate has not been tested for teratogenicity by this route; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent. Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 0.33 and 0.01 times, respectively, the human topical dose of Clobetasol propionate cream, 0.05% (emollient). Abnormalities seen included cleft palate and skeletal abnormalities. In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.001 and 0.003 times, respectively, the human topical dose of Clobetasol propionate cream, 0.05% (emollient). Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.

8.4 Pediatric Use Safety and effectiveness of Clobetasol propionate cream, 0.05% (emollient) in pediatric patients have not been established and its use in pediatric patients under 12 years of age is not recommended. In a study including 12 subjects ages 18 years and older with psoriasis or atopic dermatitis involving at least 30% body surface area (BSA), adrenal suppression was identified in 3 out of 12 subjects (25%) following 1 week of treatment. Four-week HPA axis suppression studies with Clobetasol propionate cream, 0.05% (emollient) in pediatric subjects have not been conducted. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. The use of Clobetasol propionate cream, 0.05% (emollient) for 4 consecutive weeks has not been studied in pediatric patients under 16 years of age.

8.5 Geriatric Use Clinical studies of Clobetasol propionate cream, 0.05% (emollient) did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious.

11 DESCRIPTION Clobetasol propionate cream USP, 0.05% (emollient) contains the active compound clobetasol propionate, a synthetic corticosteroid, for topical use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity. Chemically, clobetasol propionate is (11β,16β)-21-chloro-9-fluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)-pregna-1,4-diene-3,20-dione, and it has the following structural formula: Clobetasol propionate has the molecular formula C 25 H 32 ClFO 5 and a molecular weight of 467. It is a white to cream-colored crystalline powder insoluble in water. Each gram of Clobetasol propionate cream USP, 0.05% (emollient) contains 0.5 mg of clobetasol propionate in a white to off-white cream base consisting of cetostearyl alcohol, isopropyl myristate, propylene glycol, polyoxyl 20 cetostearyl ether, dimethicone 350, citric acid, sodium citrate, purified water, and imidurea as a preservative. structural formula

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2 . 12.2 Pharmacodynamics Clobetasol propionate cream, 0.05% (emollient) is in the super-high range of potency as demonstrated in a vasoconstrictor study in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence. 12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

12.1 Mechanism of Action Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2 .

12.2 Pharmacodynamics Clobetasol propionate cream, 0.05% (emollient) is in the super-high range of potency as demonstrated in a vasoconstrictor study in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate. Mutagenesis Clobetasol propionate was nonmutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. Coli B WP2 fluctuation test. Impairment of Fertility Studies in the rat following oral administration at dosage levels up to 50 mg/kg per day revealed no significant effect on the males. The females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate. Mutagenesis Clobetasol propionate was nonmutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. Coli B WP2 fluctuation test. Impairment of Fertility Studies in the rat following oral administration at dosage levels up to 50 mg/kg per day revealed no significant effect on the males. The females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

14 CLINICAL STUDIES In a controlled clinical trial involving patients with moderate to severe plaque-type psoriasis, Clobetasol propionate cream, 0.05% (emollient) was applied to 5% to 10% of body surface area. In this trial, there were no clobetasol-treated patients with clinically significant decreases in morning cortisol levels after 4 weeks of treatment; however, morning cortisol levels may not identify patients with adrenal dysfunction.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Clobetasol Propionate Cream USP, 0.05% (emollient), is a white to off-white cream, supplied as follows: NDC 83148-064-15 15 g tube NDC 83148-064-30 30 g tube NDC 83148-064-60 60 g tube Storage and Handling Store at 25°C (77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Clobetasol Propionate Cream USP, 0.05% (emollient) should not be refrigerated.

Storage and Handling Store at 25°C (77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Clobetasol Propionate Cream USP, 0.05% (emollient) should not be refrigerated.

17 PATIENT COUNSELING INFORMATION Inform patients using topical corticosteroids of the following information and instructions: Clobetasol propionate cream USP, 0.05% (emollient) is for external use only. Avoid contact with the eyes. Use as directed. Do not use Clobetasol propionate cream USP, 0.05% (emollient) for any disorder other than that for which it was prescribed. Do not use longer than the prescribed time period. Do not use other corticosteroid-containing products while using Clobetasol propionate cream USP, 0.05% (emollient) unless directed by the physician. The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician. Wash hands after applying the medication. Report any signs of local or systemic adverse reactions to the physician. Inform their physicians that they are using Clobetasol propionate cream USP, 0.05% (emollient) if surgery is contemplated. If you go to another doctor for illness, injury or surgery, tell the doctor you are using Clobetasol propionate cream USP, 0.05% (emollient). Do not use Clobetasol propionate cream USP, 0.05% (emollient) on the face, underarms or groin areas. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician. Use no more than 50 grams per week of Clobetasol propionate cream USP, 0.05% (emollient). Store between 59°F and 86°F (15°C and 30°C). Do not refrigerate.

2 DOSAGE AND ADMINISTRATION Apply a thin layer of Clobetasol Propionate Cream to the affected skin areas twice daily and rub in gently and completely. Wash hands after each application. Use Clobetasol Propionate Cream for up to 2 consecutive weeks of treatment. (2) • Discontinue Clobetasol Propionate Cream when control is achieved. (2) • The total dosage should not exceed 50 g per week. (2) • Do not use if atrophy is present at the treatment site. (2) • Do not bandage, cover, or wrap the treated skin area unless directed by a physician. (2) • Avoid use on the face, scalp, axilla, groin, or other intertriginous areas. (2) • Clobetasol Propionate Cream is for topical use only. It is not for oral, ophthalmic, or intravaginal use. (2)

5 WARNINGS AND PRECAUTIONS • Clobetasol propionate has been shown to suppress the HPA axis at the dose tested. (5.1) • Cushing’s syndrome, hyperglycemia, and glucosuria can also result from systemic absorption of topical corticosteroids. (5.1) • Systemic absorption may require periodic evaluation for HPA axis suppression. Modify use if HPA axis suppression develops. (5.1) • Children may be more susceptible to systemic toxicity from use of topical corticosteroids. (5.1, 8.4) • Local adverse reactions with topical corticosteroids may occur more frequently with the use of occlusive dressings, prolonged use, or use of higher potency corticosteroids, including clobetasol propionate. These reactions include: irritation, dryness, acneiform eruptions, hypertrichosis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria. (5.1, 6.2) 5.1 Effects on the Endocrine System Clobetasol Propionate Cream can cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or after withdrawal of treatment. Because of the potential for systemic absorption, use of topical corticosteroids, including Clobetasol Propionate Cream, may require that patients be evaluated periodically for evidence of HPA axis suppression. Factors that predispose a patient to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test. In a trial evaluating the effects of Clobetasol Propionate Cream on the HPA axis, subjects with plaque psoriasis applied Clobetasol Propionate Cream twice daily to at least 20% of involved Body Surface Area (BSA) for 15 days. Abnormal ACTH stimulation tests suggestive of HPA axis suppression were seen in 3 of 24 (12.5%) subjects on Clobetasol Propionate Cream [see Clinical Pharmacology (12.2)]. In another trial to evaluate the effects of Clobetasol Propionate Cream on the HPA axis, subjects with moderate to severe plaque psoriasis applied Clobetasol Propionate Cream twice daily to at least 25% of involved BSA for 28 consecutive days. Abnormal ACTH stimulation test suggestive of HPA axis suppression was seen in 8 of 26 (30.8%) of subjects on Clobetasol Propionate Cream. If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental systemic corticosteroids may be required. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Systemic effects of topical corticosteroids may also manifest as Cushing’s syndrome, hyperglycemia, and glucosuria. These complications are rare and generally occur after prolonged exposure to larger than recommended doses, particularly with high-potency topical corticosteroids. Use of more than one corticosteroid-containing product at the same time may increase the total systemic exposure to topical corticosteroids. Minimize the unwanted risks from endocrine effects by mitigating risk factors favoring increased systemic bioavailability and by using the product as recommended [see Dosage and Administration (2)].

e corticosteroid-containing product at the same time may increase the total systemic exposure to topical corticosteroids. Minimize the unwanted risks from endocrine effects by mitigating risk factors favoring increased systemic bioavailability and by using the product as recommended [see Dosage and Administration (2)]. Pediatric patients may be more susceptible to systemic toxicity 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 from topical corticosteroids may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. These may be more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids, including Clobetasol Propionate Cream. Some local adverse reactions may be irreversible. 5.3 Concomitant Skin Infections Use an appropriate antimicrobial agent if a skin infection is present or develops. If a favorable response does not occur promptly, discontinue use of Clobetasol Propionate Cream until the infection has been adequately treated. 5.4 Allergic Contact Dermatitis Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing. If irritation develops, discontinue the topical corticosteroid and institute appropriate therapy.

6 ADVERSE REACTIONS The most common adverse reaction (incidence ≥ 1%) is application site discoloration. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact INA Pharmaceutics, Inc. at 1-866-835-0469 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 practice. Clobetasol Propionate Cream was evaluated in two randomized, multicenter, prospective, vehicle-controlled clinical trials in subjects with moderate to severe plaque psoriasis. Subjects applied Clobetasol Propionate Cream or vehicle cream twice daily for 14 days. A total of 354 subjects applied Clobetasol Propionate Cream and 178 subjects applied vehicle. The adverse reaction that occurred in at least 1% of subjects treated with Clobetasol Propionate Cream and at a higher incidence than in subjects treated with vehicle cream was application site discoloration (2% versus 1%). Less common local adverse events occurring in < 1% of subjects treated with Clobetasol Propionate Cream were application site atrophy, telangiectasia and rash. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of clobetasol propionate: striae, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis and miliaria. 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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on Clobetasol Propionate Cream in pregnant women to inform a drug-associated risk for adverse development outcomes. Published data report a significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroids during a pregnancy. Advise pregnant women of the potential risk to a fetus and to use Clobetasol Propionate Cream 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 comparisons of animal exposure with human exposure are provided due to minimal systemic exposure noted after topical administration of Clobetasol Propionate Cream [see Clinical Pharmacology (12.3) ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk or 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, 12-170g)] over long periods of time. Animal Data In an embryofetal development study in mice, subcutaneous administration of clobetasol propionate resulted in fetotoxicity at the highest dose tested ( 1mg/kg) and malformations at the lowest dose tested (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.

red 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 other’s clinical need for Clobetasol Propionate Cream and any potential adverse effects on the breastfed infant from Clobetasol Propionate Cream or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use Clobetasol Propionate Cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to applyClobetasol Propionate Cream directly to the nipple and areola to avoid direct infant exposure. 8.4 Pediatric Use The safety and effectiveness of Clobetasol Propionate Cream in patients younger than 18 years of age have not been established; therefore, use in children younger than 18 years is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity, including HPA axis suppression when treated with topical drugs [see Warnings and Precautions (5.1) ]. Rare systemic toxicities such as Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids. Local adverse reactions including striae and skin atrophy have also been reported with use of topical corticosteroids in pediatric patients. Avoid use of Clobetasol Propionate Cream in the treatment of diaper dermatitis. 8.5 Geriatric Use Clinical studies of Clobetasol Propionate Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with topical corticosteroids has not identified differences in responses between the elderly and younger patients.

8.1 Pregnancy Risk Summary There are no available data on Clobetasol Propionate Cream in pregnant women to inform a drug-associated risk for adverse development outcomes. Published data report a significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroids during a pregnancy. Advise pregnant women of the potential risk to a fetus and to use Clobetasol Propionate Cream 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 comparisons of animal exposure with human exposure are provided due to minimal systemic exposure noted after topical administration of Clobetasol Propionate Cream [see Clinical Pharmacology (12.3) ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk or 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, 12-170g)] over long periods of time. Animal Data In an embryofetal development study in mice, subcutaneous administration of clobetasol propionate resulted in fetotoxicity at the highest dose tested ( 1mg/kg) and malformations at the lowest dose tested (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.

8.4 Pediatric Use The safety and effectiveness of Clobetasol Propionate Cream in patients younger than 18 years of age have not been established; therefore, use in children younger than 18 years is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity, including HPA axis suppression when treated with topical drugs [see Warnings and Precautions (5.1) ]. Rare systemic toxicities such as Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids. Local adverse reactions including striae and skin atrophy have also been reported with use of topical corticosteroids in pediatric patients. Avoid use of Clobetasol Propionate Cream in the treatment of diaper dermatitis.

8.5 Geriatric Use Clinical studies of Clobetasol Propionate Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with topical corticosteroids has not identified differences in responses between the elderly and younger patients.

11 DESCRIPTION Clobetasol propionate Cream, 0.025% for topical use contains clobetasol propionate, a synthetic and fluorinated corticosteroid. Chemically, clobetasol propionate is 21-chloro-9-fluoro-11β-hydroxy-16 β-methyl-3,20-dioxopregna-1,4-dien-17-yl propanoate, and it has the following structural formula. Clobetasol propionate has a molecular formula of C 25 H 32 CIFO 5 and a molecular weight of 467. It is a white to cream-colored crystalline powder practically insoluble in water. Each gram of Clobetasol propionate Cream contains 0.25 mg clobetasol propionate. It is an oil-in-water emulsion intended for topical application and contains the following inactive ingredients: butylated hydroxytoluene, cetostearyl alcohol, cyclomethicone, diethylene glycol monoethyl ether, glyceryl stearate and PEG 100 stearate, isopropyl myristate, methyl paraben, propyl paraben. purified water and white wax. Chemical Structure

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 corticosteroid responsive dermatoses is unknown. The contribution to efficacy by individual components of the vehicle has not been established. 12.2 Pharmacodynamics Vasoconstrictor Assay Clobetasol Propionate Cream, 0.025% is in the high range of potency as demonstrated in vasoconstrictor studies in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence. Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression: HPA axis suppression was evaluated in a clinical trial in adult subjects (N=24) with moderate to severe plaque psoriasis involving a mean BSA of 26.5 +8.6%. Treatment consisted of twice daily application of Clobetasol Propionate Cream, 0.025% for 15 days. Adrenal suppression, as indicated by a 30-minute post-stimulation cortisol level ≤18 mcg/dL, was observed in 3 out of 24 subjects (12.5%) after 15 days. 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 also increase percutaneous absorption. 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. In a pharmacokinetic study in 24 adult male and female subjects with moderate to severe psoriasis were treated twice daily for 15 days with a mean dose of approximately 3.7 g of Clobetasol Propionate Cream, 0.025% per application to a mean BSA of 26.5 ± 8.6%. On day 15, the mean + SD pre-treatment and post-treatment systemic concentrations of clobetasol propionate were 50.7 ± 96.0 pg/mL and 56.3 ± 104.7 pg/mL, respectively.

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. The contribution to efficacy by individual components of the vehicle has not been established. 16.1 How Supplied Clobetasol Propionate Cream, 0.025% is a white to off-white cream, supplied as follows: 100g aluminum tube NDC 74157-710-10

12.2 Pharmacodynamics Vasoconstrictor Assay Clobetasol Propionate Cream, 0.025% is in the high range of potency as demonstrated in vasoconstrictor studies in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence. Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression: HPA axis suppression was evaluated in a clinical trial in adult subjects (N=24) with moderate to severe plaque psoriasis involving a mean BSA of 26.5 +8.6%. Treatment consisted of twice daily application of Clobetasol Propionate Cream, 0.025% for 15 days. Adrenal suppression, as indicated by a 30-minute post-stimulation cortisol level ≤18 mcg/dL, was observed in 3 out of 24 subjects (12.5%) after 15 days.

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 also increase percutaneous absorption. 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. In a pharmacokinetic study in 24 adult male and female subjects with moderate to severe psoriasis were treated twice daily for 15 days with a mean dose of approximately 3.7 g of Clobetasol Propionate Cream, 0.025% per application to a mean BSA of 26.5 ± 8.6%. On day 15, the mean + SD pre-treatment and post-treatment systemic concentrations of clobetasol propionate were 50.7 ± 96.0 pg/mL and 56.3 ± 104.7 pg/mL, respectively.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate cream. In a 13-week repeat dose toxicity study in rats, topical administration of clobetasol propionate cream, 0.001, 0.005 and 0.025% at corresponding doses of 0.004, 0.02 and 0.1 mg/kg/day resulted in corticosteroid class-related systemic effects such as reductions in body weight gain, reductions in total leukocytes and individual white cells, decrease in weight of adrenals, thymus, spleen, liver and lung. Histologically, there were decreased hematopoiesis in the bone marrow, thymic atrophy and mast cell infiltration of the mesenteric lymph nodes. All these effects were indicative of severe immune suppression consistent with long-term exposure to corticosteroids. A no observable adverse effect level (NOAEL) was determined to be clobetasol propionate cream, 0.001% (0.004 mg/kg/day) in male rats while a NOAEL could not be determined in females. The clinical relevance of the findings in animals to humans is not clear, but sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk of carcinogenesis. Clobetasol propionate was not mutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay , and the E. coli B WP2 fluctuation test. Fertility studies conducted in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg/day revealed that females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate cream. In a 13-week repeat dose toxicity study in rats, topical administration of clobetasol propionate cream, 0.001, 0.005 and 0.025% at corresponding doses of 0.004, 0.02 and 0.1 mg/kg/day resulted in corticosteroid class-related systemic effects such as reductions in body weight gain, reductions in total leukocytes and individual white cells, decrease in weight of adrenals, thymus, spleen, liver and lung. Histologically, there were decreased hematopoiesis in the bone marrow, thymic atrophy and mast cell infiltration of the mesenteric lymph nodes. All these effects were indicative of severe immune suppression consistent with long-term exposure to corticosteroids. A no observable adverse effect level (NOAEL) was determined to be clobetasol propionate cream, 0.001% (0.004 mg/kg/day) in male rats while a NOAEL could not be determined in females. The clinical relevance of the findings in animals to humans is not clear, but sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk of carcinogenesis. Clobetasol propionate was not mutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay , and the E. coli B WP2 fluctuation test. Fertility studies conducted in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg/day revealed that females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

14 CLINICAL STUDIES Clobetasol PropionateTwo double-blind, randomized, vehicle-controlled trials evaluated 532 subjects aged 18 years and older with moderate to severe plaque psoriasis (IGA 3 or 4 and BSA > 3%). Subjects were treated twice daily with Clobetasol Propionate Cream or vehicle cream for 14 days. The primary endpoint was the proportion of subjects who achieved treatment success at Day 15, where treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a 2-grade reduction from baseline. The proportion of subjects who achieved treatment success was also assessed at Day 8 Table 1 presents the efficacy results at Day 8 and Day 15 Table 1. Treatment Success * Results * Treatment success is defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a 2-grade reduction from baseline. Trial 1 Trial 2 Clobetasol Propionate (N=178) Vehicle (N=89) Clobetasol Propionate (N=176) Vehicle (N=89) Day 15 (primary endpoint) 30.2% 9.0% 30.1% 9.7% Day 8 (secondary endpoint) 15.7% 5.6% 14.2% 1.6%

<table ID="table3" width="700"><col width="28%" align="left"/><col width="18%" align="center"/><col width="18%" align="center"/><col width="18%" align="center"/><col width="18%" align="center"/><tfoot><tr styleCode="First Last"><td colspan="5" align="left">^*Treatment success is defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a 2-grade reduction from baseline. </td></tr></tfoot><tbody><tr valign="top"><td align="left" styleCode="Botrule Lrule Rrule Toprule"/><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Trial 1</content></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Trial 2</content></td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule Toprule"/><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Clobetasol Propionate (N=178) </content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Vehicle (N=89) </content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Clobetasol Propionate (N=176) </content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Vehicle (N=89) </content></td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule Toprule">Day 15 (primary endpoint)</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">30.2%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">9.0%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">30.1%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">9.7%</td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule Toprule">Day 8 (secondary endpoint)</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">15.7%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">5.6%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">14.2%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">1.6%</td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Clobetasol Propionate Cream, 0.025% is a white to off-white cream, supplied as follows: 100g aluminum tube NDC 74157-710-10 16.2 Storage Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature] Do not freeze.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ) Pregnancy Advise pregnant women of the potential risk to a fetus and to use Clobetasol Propionate Cream on the smallest area of skin and for the shortest duration possible [see Use in Specific Populations (8.1) ] . Lactation Advise a woman to use Clobetasol Propionate cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Clobetasol Propionate Cream directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.2) ] . Important Administration Instructions Instruct patients to discontinue Clobetasol Propionate Cream when psoriasis is controlled. Clobetasol Propionate Cream should not be used for longer than 2 weeks. Advise patients to contact the physician if no improvement is seen within 2 weeks. Inform patients that total dosage should not exceed 50 grams per week [see Dosage and Administration (2) ]. Instruct patients to avoid bandaging, wrapping or otherwise occluding the treatment area(s) unless directed by physician. Advise patients to avoid use on the face, scalp, groin, or axillae [see Dosage and Administration (2) ]. Inform patients that Clobetasol Propionate Cream is for external use only. Advise patients that Clobetasol Propionate Cream is not for ophthalmic, oral or intravaginal use. Patients should wash their hands after applying the medication [see Dosage and Administration (2) ] . Do not use other corticosteroid-containing products while using Clobetasol Propionate Cream. Effects on Endocrine System Clobetasol Propionate Cream may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including Clobetasol Propionate Cream, may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. Concomitant use of multiple corticosteroid-containing products may increase the total systemic exposure to topical corticosteroids. Patients should inform their physician(s) that they are using Clobetasol Propionate Cream if surgery is contemplated [see Warnings and Precautions (5.1) ] . Local Adverse Reactions Informed patients that topical corticosteroids may cause local adverse reactions, some of which may be irreversible. These reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids, including Clobetasol Propionate Cream [see Warnings and Precautions (5.2) ] . Patients should report any sign of local or systemic adverse reactions to their physician. Manufactured for: INA Pharmaceutics, Inc., Fairmont, WV 26554 Revised: 01/2025 22542-01