Clobetasol propionate emulsion

Overdose

Topically applied Clobetasol Propionate Emulsion (clobetasol propionate) Foam can be absorbed in sufficient amounts to produce systemic effects. See PRECAUTIONS.

Contraindications

Clobetasol Propionate Emulsion (clobetasol propionate) Foam is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

Pharmaceutical form

Undesirable effects

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Effects on Endocrine System
• Ophthalmic Adverse Reactions

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 a controlled clinical trial involving 188 subjects with psoriasis of the scalp, there were no localized scalp adverse reactions reported in the subjects treated with Clobetasol Propionate Emulsion Foam. In 2 controlled clinical trials with Clobetasol Propionate Emulsion Foam in 360 subjects with psoriasis of non-scalp regions, localized adverse events that occurred in the subjects treated with Clobetasol Propionate Emulsion Foam included application site burning (10%), application site dryness (<1%), and other application site reactions (4%).

In larger controlled trials with other clobetasol propionate formulations, the most frequently reported local adverse reactions have included burning, stinging, irritation, pruritus, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, skin atrophy, and telangiectasia (all less than 2%).

Because adverse 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.

Local adverse reactions to topical corticosteroids may include: striae, itching, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria.

Ophthalmic adverse reactions may include: cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy.

Therapeutic indications

Clobetasol Propionate Emulsion Foam is a corticosteroid indicated for treatment of moderate to severe plaque psoriasis of the scalp and mild to moderate plaque psoriasis of non-scalp regions of the body excluding the face and intertriginous areas in patients 12 years and older.

Pharmacodynamic properties

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 Emulsion 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 Emulsion Foam (See Table 1 below).

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

Pharmacokinetic properties

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.

Name of the medicinal product

Clobetasol Propionate Emulsion price

Qualitative and quantitative composition

Special warnings and precautions for use

Included as part of the "PRECAUTIONS" Section

Clobetasol Propionate Emulsion Foam 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. 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 Emulsion Foam on the HPA axis, 13 subjects applied Clobetasol Propionate Emulsion Foam to at least 20% of involved body surface area for 14 days. HPA axis suppression was identified in 5 out of 13 subjects (38%).

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid.

Cushing’s syndrome and hyperglycemia may also occur due to the systemic effects of the topical corticosteroid. These complications are rare and generally occur after prolonged exposure to excessively large doses, especially of high-potency topical corticosteroids.

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios.

Use of topical corticosteroids, including Clobetasol Propionate Emulsion Foam, may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including topical clobetasol products.

Avoid contact of Clobetasol Propionate Emulsion Foam with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

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.

Clobetasol Propionate Emulsion Foam is flammable. Avoid fire, flame, or smoking during and immediately following application.

See FDA-approved patient labeling (PATIENT INFORMATION and Instructions For Use)

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.

Advise patients to report any visual symptoms to their healthcare providers.

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.

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.

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.

Inform patients of the following:

• Avoid use of Clobetasol Propionate Emulsion Foam on the face, underarms, or groin areas unless directed by the physician.
• Do not occlude the treatment area with bandage or other covering, unless directed by the physician.
• Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, contact the physician.
• For proper dispensing of foam, hold the can upside down and depress the actuator. Dispensing directly onto hands is not recommended (unless the hands are the affected area), as the foam will begin to melt immediately upon contact with warm skin.
• Limit treatment to 2 consecutive weeks. Use no more than 50 grams of Clobetasol Propionate Emulsion Foam per week, or more than 21 capfuls per week.
• Avoid use of Clobetasol Propionate Emulsion Foam in the diaper area, as diapers or plastic pants may constitute occlusive dressing.
• The product is flammable; avoid heat, flame, and smoking when applying this product.
• Do not use other corticosteroid-containing products without first consulting with the physician.

Clobetasol Propionate Emulsion is a registered trademark of Stiefel Laboratories, Inc., a GSK Company, exclusively licensed to the Mylan Companies.

For additional information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or visit www.Clobetasol Propionate Emulsion.com.

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 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.

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 estimated 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.

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

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.

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 Emulsion Foam and any potential adverse effects on the breastfed infant from Clobetasol Propionate Emulsion Foam or from the underlying maternal condition.

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.

Safety and effectiveness of Clobetasol Propionate Emulsion 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 Emulsion Foam in the treatment of diaper dermatitis.

Clinical studies of Clobetasol Propionate Emulsion 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.

Dosage (Posology) and method of administration

Apply a thin layer of Clobetasol Propionate Emulsion Foam to the affected skin areas twice daily.

Clobetasol Propionate Emulsion Foam is a super-high-potency topical corticosteroid; therefore, limit treatment to 2 consecutive weeks. Patients should not use greater than 50 grams per week or more than 21 capfuls per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis.

Therapy should be discontinued when control is achieved.

Clobetasol Propionate Emulsion Foam should not be used with occlusive dressings unless directed by a physician.

Clobetasol Propionate Emulsion Foam is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

Avoid contact with eyes. Wash hands after each application.

Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site.