CLOBETASOL PROPIONATE (Page 2 of 4)

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 can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of clobetasol propionate could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clobetasol propionate foam and any potential adverse effects on the breastfed infant from clobetasol propionate foam or from the underlying maternal condition.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breast milk, use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply clobetasol propionate foam directly to the nipple and areola to avoid direct infant exposure.

8.4 Pediatric Use

Safety and effectiveness of clobetasol propionate foam in patients younger than 12 years of age have not been established; therefore, use in children younger than 12 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 when they are treated with topical drugs. They are, therefore, also at greater risk of adrenal insufficiency upon the use of topical corticosteroids.

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 have also been reported with use of topical corticosteroids in pediatric patients.

Avoid use of clobetasol propionate foam in the treatment of diaper dermatitis.

8.5 Geriatric Use

Clinical studies of clobetasol propionate foam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.

11 DESCRIPTION

Clobetasol propionate foam, 0.05%, is a white to off white thermolabile hydroethanolic aerosol foam containing the active ingredient, clobetasol propionate, USP, 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.

Clobetasol propionate is 21-chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate, with the empirical formula C25 H32 ClFO5 , a molecular weight of 466.97.

The following is the chemical structure:

Image

Clobetasol propionate is a white or almost white crystalline powder, practically insoluble in water.

Each gram of clobetasol propionate foam contains 0.5 mg clobetasol propionate, USP. The foam also contains cetyl alcohol, citric acid, ethanol (60%), polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.

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 controlled pharmacokinetic trial, 5 of 13 subjects experienced reversible suppression of the adrenals at any time during the 14 days of therapy with clobetasol propionate foam applied to at least 20% of involved body surface area. Of the 13 subjects studied, 1 of 9 with psoriasis was suppressed after 14 days and all 4 of the subjects with atopic dermatitis had abnormal cortisol levels indicative of adrenal suppression at some time after starting therapy with clobetasol propionate foam (See Table 1 below).

Table 1: Subjects With Reversible HPA Axis Suppression at Any Time During Treatment

a Clobetasol propionate foam is not indicated for non-scalp atopic dermatitis, as the safety and efficacy of clobetasol propionate foam in non-scalp atopic dermatitis has not been established. Use in children under 12 years of age is not recommended.

Dermatosis Clobetasol Propionate Foam
Psoriasis 1 of 9
Atopic Dermatitisa 4 of 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 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.

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 foam or clobetasol propionate.

In a 90-day repeat-dose toxicity study in rats, topical administration of clobetasol propionate 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 nonmutagenic 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

14.1 Scalp Psoriasis

A well-controlled clinical trial evaluated 188 subjects with moderate to severe scalp psoriasis. Subjects were treated twice daily for 2 weeks with one of 4 treatments: clobetasol propionate foam, vehicle foam, a commercially available clobetasol propionate solution (TEMOVATE® Scalp Application), or vehicle solution. The efficacy of clobetasol propionate foam in treating scalp psoriasis at the end of the 2 weeks’ treatment was superior to that of vehicle (foam and solution), and was comparable to that of TEMOVATE Scalp Application (Table 2).

Table 2. Efficacy Results From a Controlled Clinical Trial in Scalp Psoriasis

a Defined as a composite of an Investigator’s Global Assessment of “completely clear ” or “almost clear,” a plaque thickness score of 0, an erythema score of 0 or 1, and a scaling score of 0 or 1 at endpoint, scored on a severity scale of 0 to 4.

Clobetasol Propionate Foam n (%) Vehicle Foam n (%)
Total number of subjects 62 31
Subjects with treatment successa 39 (63) 1 (3)
Subjects with parameter Clear at endpoint (scalp psoriasis) Scaling — Clear at endpoint 42 (68) 3 (10)
Erythema — Clear at endpoint 27 (44) 2 (6)
Plaque Thickness — Clear at endpoint 41 (66) 3 (10)

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