Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Pierre Fabre Dermatologie, 45 Place Abel-Gance, 92100 Boulogne Cedex, France
Pharmacotherapeutic group: Corticosteroids, very potent (group IV)
ATC code: D07AD01
Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The precise mechanism of the anti-inflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the 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.
A vasoconstrictor study has shown that CLARELUX has a comparable potency, based upon skin blanching response, as other clobetasol propionate formulations.
The efficacy and safety of clobetasol propionate (CP) foam 0.05% has been demonstrated in a double-blind placebo and active comparator (CP solution) controlled study: 188 adult participants were treated for moderate to severe psoriasis of the scalp during 2 weeks. Products were applied twice a day over the entire scalp area. Pruritus, scaling, erythema and plaque thickness were evaluated after 2 weeks of treatment. 74% of participants using CP foam were rated completely clear or almost clear compared 6-10% of the placebo group and 61% of the CP solution group. All disease signs and symptoms were significantly improved after 2 weeks and also following 2 weeks off treatment.
Clinical data in children and adolescents established that Clobetasol foam is safe and effective for treatment of mild-to-moderate plaque-type psoriasis in patients aged 12 years or older. A double-blind randomised placebo vehicle-controlled trial was performed in 497 patients aged 12 years or older. (253 were given clobetasol EF foam, 123 received vehicle foam, and 121 received clobetasol ointment, each for two weeks). About 27% of the participants were adolescents. Compared with the vehicle foam, clobetasol foam was almost 4 times more effective in treating mild-to-moderate plaque-type psoriasis in the total population (47% vs 12%). Efficacy was similar between adolescents and adults and the incidence of AEs was comparable between clobetasol foam and vehicle foam for adults and paediatric participants as young as 12 years.
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the carrier, the integrity of the epidermal barrier, the severity of the disease and the area treated. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.
Topical corticosteroids can be absorbed from intact healthy skin.
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.
In a controlled pharmacokinetic study, 3 of 13 subjects experienced reversible suppression of the adrenals at any time during the 14 days of CLARELUX therapy to at least 20% of the body surface area.
Non-clinical data reveal no special hazard for humans based on studies of repeated dose toxicity and genotoxicity. No topical studies were performed to assess the safety, pharmacology and the carcinogenic potential of clobetasol.
Parenteral administration of corticosteroids, including clobetasol propionate, to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation. Animal studies have indicated that intrauterine exposure to corticosteroids may contribute to the development of cardiovascular and metabolic diseases in adult life, but there is a lack of evidence for the occurrence of such effects in humans (see section 4.6).
In fertility studies, subcutaneous administration of clobetasol propionate to rats at doses of 6.25 to 50 micrograms/kg/day produced no effects on male fertility. In females, increased embryofetal loss and growth suppression and thymic atrophy in the litters were observed at the highest dose.
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