FDA Label for Clobetasol Propionate

View Indications, Usage & Precautions

Clobetasol Propionate Product Label

The following document was submitted to the FDA by the labeler of this product Glenmark Pharmaceuticals Inc., Usa. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.

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.

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.

3 Dosage Forms And Strengths

Clobetasol Propionate Emulsion Foam, 0.05% contains 0.5 mg of clobetasol propionate, USP per gram in a white to off-white emulsion aerosol foam.

4 Contraindications

None.

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)].

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)]

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.

8.1 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.

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.

10 Overdosage

Topically applied clobetasol propionate emulsion foam can be absorbed in sufficient amounts to produce systemic effects.

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 C₂₅H₃₂ClFO₅, and a molecular weight of 467 g/mol.

The following is the chemical structure:

structure - 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.

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.

13.1 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.

16.1 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.

Manufactured by:

Glenmark Pharmaceuticals Limited

Plot No. B-25, MIDC, Shendra

Aurangabad, Maharashtra - 431210, India

Manufactured for:

logo - Logo

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888) 721-7115

www.glenmarkpharma.com/usa

June 2019

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.

Instructions For Use