Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Glaxo Wellcome UK Ltd trading as Glaxo Laboratories and/or GlaxoSmithKline UK, 980 Great West Road, Brentford, Middlesex, TW8 9GS
Pharmacotherapeutic group: Corticosteroids, very potent (group IV)
ATC code: D07AD
Topical corticosteroids act as anti-inflammatory agents via multiple mechanisms to inhibit late phase allergic reactions including decreasing the density of mast cells, decreasing chemotaxis and activation of eosinophils, decreasing cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibiting the metabolism of arachidonic acid.
Topical corticosteroids have anti-inflammatory, antipruritic, and vasoconstrictive properties.
Topical corticosteroids can be systemically absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.
The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection.
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver.
Topical corticosteroids are excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.
Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.
Clobetasol propionate was not mutagenic in a range of in vitro bacterial cell assays.
In fertility studies, subcutaneous administration of clobetasol propionate to rats at doses of 6.25 to 50 micrograms/kg/day produced no effects on mating, and fertility was only decreased at 50 micrograms/kg/day.
Subcutaneous administration of clobetasol propionate to mice (≥100 micrograms/kg/day), rats (400 micrograms/kg/day) or rabbits (1 to 10 micrograms/kg/day) during pregnancy produced foetal abnormalities including cleft palate and intrauterine growth retardation.
In the rat study, where some animals were allowed to litter, developmental delay was observed in the F1 generation at ≥100 micrograms/kg/day and survival was reduced at 400 micrograms/kg/day. No treatment-related effects were observed in F1 reproductive performance or in the F2 generation.
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