Clobetasol (Temovate)
Clobevate™ , Cormax®, Embeline™ E, Olux®, Temovate®, Clobex® | Embeline™ Scalp Application | Temovate E®
Classification:
Dermatological Agents
- Topical Antiinflammatory Agents
Hormones and Hormone Modifiers
Description: Clobetasol is a topical, synthetic fluorinated corticosteroid. Clobetasol is used to relieve the inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses and psoriasis. Clobetasol is the most potent topical corticosteroid, and is for short-term therapy only. Very high potency topical corticosteroids are used as an alternative to systemic therapy for localized conditions. Long-term use can lead to systemic side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression. Clobetasol was approved by the FDA in 1985. Temovate E® emollient cream was approved in 1997. A foam formulation (Olux®), for the treatment of scalp psoriasis was approved in May 2000, followed by approval for the short-term topical treatment of non-scalp regions affected by plaque-type psoriasis in December 2002. A spray formulation (Clobex®) for the treatment of moderate to severe plaque psoriasis was approved in October 2005. Clinical trials are assessing the efficacy of topical clobetasol treatments followed by topical calcipotriene regimens for the treatment of chronic plaque-type psoriasis.
Mechanism of Action: Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2 , an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.
Pharmacokinetics: Clobetasol is administered topically to the skin as a cream, gel, ointment, or topical solution. The extent of percutaneous absorption of the topical corticosteroids is dependent on many factors, including the pharmaceutical vehicle and the integrity of the epidermis. Absorption after topical application of clobetasol is increased in areas that have skin damage, inflammation, or occlusion, or in areas where the stratum corneum is thin such as the eyelids, genitalia, axillae, and face. The use of occlusive dressings with the application of clobetasol enhances penetration into the skin, and may increase the chance of systemic absorption. Ointments have a hydrating effect, are lipophilic, and enhance the penetration of clobetasol into the skin. Clobetasol gels, foams, and solutions also have enhanced topical penetration versus cream preparations. Once absorbed, maximal vasoconstrictive effects of clobetasol occur within 1.5 hours of application. Anti-inflammatory effects are usually not seen for hours after clobetasol application, since the mechanism of action requires alterations in synthesis of proteins. Because clobetasol is fluorinated and also contains a substituted 17-hydroxyl group, it is not metabolized in the skin. Repeated application results in a cumulative depot effect in the skin, which may lead to a prolonged duration of action and increased systemic absorption. Due to the fact that circulating levels are below the level of detection, the use of pharmacodynamic endpoints for assessing the systemic exposure of topical clobetasol is necessary. Once in the systemic circulation, clobetasol is metabolized in the liver, but systemic metabolism has not been fully quantified. Excretion of clobetasol propionate and its metabolites occurs via the urine and bile.
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[ Revised 7/19/2004 1:30:00 PM ]
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