FOR TOPICAL DERMATOLOGIC
USE ONLY--NOT FOR OPHTHALMIC,
ORAL, OR INTRAVAGINAL USE
Embeline E (Clobetasol Propionate Cream--Emollient) Emollient contains the active compound clobetasol propionate, 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.
Chemically, clobetasol propionate is 21-chloro-9-fluoro-11(beta), 17-dihydroxy-16(beta)-methylpregna-1,4 diene-3,20-dione 17-propionate, and it has the following structural formula:
Clobetasol propionate has the molecular formula C 25 H 32 CIFO 5 and a molecular weight of 466.96. It is a white to cream-colored crystalline powder insoluble in water.
Each gram of Embeline E Emollient contains 0.5 mg clobetasol propionate in an emollient base of cetostearyl alcohol, isopropyl myristate, propylene glycol, cetomacrogol 1000, dimethicone 360, citric acid, sodium citrate, purified water, and imidurea as a preservative.
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 .
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and integrity of the epidermal barrier. Occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Studies performed with Clobetasol Propionate Cream--Emollient indicate that it is in the super-high range of potency as compared with other topical corticosteroids.
Embeline E (Clobetasol Propionate Cream--Emollient) Emollient is a super-high potency corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond 2 consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use in children under 12 years of age is not recommended.
In the treatment of moderate to severe plaque-type psoriasis, Embeline E Emollient applied to 5% to 10% of body surface area can be used up to 4 consecutive weeks. The total dosage should not exceed 50 g/week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. Treatment beyond 4 consecutive weeks is not recommended. Patients should be instructed to use Embeline E Emollient for the minimum amount of time necessary to achieve the desired results (see PRECAUTIONS and ). Use in pediatric patients under 16 years of age has not been studied.
Embeline E (Clobetasol Propionate Cream--Emollient) Emollient is contraindicated in those patients with a history of hypersensitivity to any of the components of this preparation.
General: Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g/day.
Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing' syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy.
Patients applying a dose to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time, and only small areas should be treated at any one time due to the increased risk of HPA suppression.
If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur that require supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see PRECAUTIONS: Pediatric Use ).
If irritation develops, Embeline E (Clobetasol Propionate Cream--Emollient) Emollient should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.
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 Embeline E Emollient should be discontinued until the infection has been adequately controlled.
Embeline E Emollient should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.
Information for Patients: Patients using topical corticosteroids should receive the following information and instructions:
Laboratory Tests: The following tests may be helpful in evaluating patients for HPA axis suppression:
ACTH stimulation test
A.M. plasma cortisol test
Urinary free cortisol test
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.
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.
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.
Pregnancy: Teratogenic Effects: Pregnancy Category C: 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 (1mg/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 Embeline E 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 Embeline E Emollient. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.
There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Embeline E Emollient should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: 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 Embeline E Emollient is administered to a nursing woman.
Pediatric Use: Safety and effectiveness of Embeline E Emollient in pediatric patients have not been established, and its use in pediatric patients under 12 years of age 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 HPA axis suppression and Cushing' 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 pediatric patients.
HPA axis suppression, Cushing' syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients 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.
In controlled trials with all clobetasol propionate formulations, the following adverse reactions have been reported: burning/stinging, pruritus, 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--Emollient was less than 2% of patients treated with the exception of burning/stinging, which occurred in 5% of treated patients.
Cushing' syndrome has been reported in infants and adults as a result of prolonged use of topical clobetasol propionate formulations.
The following additional local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with super-high potency corticosteroids such as Embeline E (Clobetasol Propionate Cream--Emollient) Emollient. These reactions are listed in an approximately decreasing order of occurrence: dryness, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria.
Topically applied Embeline E (Clobetasol Propionate Cream--Emollient) Emollient can be absorbed in sufficient amounts to produce systemic effects.
Apply a thin layer of Embeline E (Clobetasol Propionate Cream--Emollient) Emollient to the affected skin areas twice daily and rub in gently and completely (see ).
Embeline E Emollient is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks, and amounts greater than 50 g/week should not be used. Use in children under 12 years of age is not recommended.
In moderate to severe plaque-type psoriasis, Embeline E Emollient applied to 5% to 10% of body surface area can be used up to 4 weeks. The total dosage should not exceed 50 g/week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. They 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. Use in pediatric patients under 16 years of age has not been studied.
Embeline E Emollient should not be used with occlusive dressings.
Embeline E (Clobetasol Propionate Cream--Emollient) Emollient, 0.05% is supplied in 15 g (NDC 0064-0440-15), 30 g (NDC 0064-0440-30), and 60 g (NDC 0064-0440-60) tubes.
Store between 15° and 30°C (59°-86°F). Embeline E Emollient should not be refrigerated.
San Antonio, Texas 78215
DPT Laboratories, Ltd.
San Antonio, Texas 78215