DESCRIPTION
CLOBEX™ (clobetasol propionate) Lotion, 0.05% contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents.
Clobetasol propionate is 21-chloro-9-fluoro-11(beta),17-dihydroxy-16(beta)-methylpregna-1,4-diene-3, 20-dione17-propionate, with the empirical formula C25H32CIFO5, a molecular weight of 466.98(CAS Registry Number 25122-46-7).
The following is the chemical structure:
Clobetasol propionate is a white to practically-white crystalline powder insoluble in water. Each gram of CLOBEX™ (clobetasol propionate) Lotion, 0.05% contains 0.5 mg of clobetasol propionate, in a vehicle base composed of hypromellose, propylene glycol, mineral oil, polyoxyethylene glycol 300 isostearate, carbomer 1342, sodium hydroxide and purified water.
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CLINICAL PHARMACOLOGY
Like other topical corticosteroids, CLOBEX™ (clobetasol propionate) Lotion, 0.05% 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 induction of phospholipase A2 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 A2.
Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion. For example, 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 other disease processes in the skin may increase percutaneous absorption.
There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systematically administered corticosteroids. Due to the fact that circulating levels are usually below the level of detection, the use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.
CLOBEX™ (clobetasol propionate) Lotion, 0.05% is in the super-high range of potency as compared with other topical corticosteroids in vasoconstrictor studies.
In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, CLOBEX™ Lo-tion, 0.05% demonstrated rates of suppression that were numerically higher than those of a clobetasol propionate 0.05% cream (Temovate E® Emollient, 0.05%), (See PRECAUTIONS).
CLINICAL STUDIES
The efficacy of CLOBEX™ (clobetasol propionate) Lotion, 0.05% in psoriasis and atopic dermatitis has been demonstrated in two adequate and well-controlled clinical trials. The first study was conducted in patients with moderate to severe plaque psoriasis. Patients were treated twice daily for 4 weeks with either CLOBEX™ (clobetasol propionate) Lotion, 0.05% or vehicle lotion. Study results demonstrated that the efficacy of CLOBEX™ Lotion, 0.05% in treating moderate to severe plaque psoriasis was superior to that of vehicle. At the end of treatment (4 weeks), 30 of 82 patients (36.6%) treated with CLOBEX™ Lotion, 0.05% compared with 0 of 29 (0%) treated with vehicle achieved success. Success was defined as a score of none or very mild (no or very slight clinical signs or symptoms of erythema, plaque elevation, or scaling) on the Global Severity scale of psoriasis.
The second study was conducted in patients with moderate to severe atopic dermatitis. Patients were treated twice daily for 2 weeks with either CLOBEX™ (clobetasol propionate) Lotion, 0.05% or vehicle lotion. Study results demonstrated that the efficacy of CLOBEX™ Lotion, 0.05% in treating moderate to severe atopic dermatitis was superior to that of vehicle.
At the end of treatment (2 weeks), 41 of 96 patients (42.7%) treated with CLOBEX™ Lotion, 0.05% compared with 4 of 33 (12.1%) treated with vehicle achieved success. Success was defined as a score of none or very mild (no or very slight clinical signs or symptoms of erythema, induration/papulation, oozing/crusting, or pruritus) on the Global Severity scale of atopic dermatitis.
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