CLINICAL PHARMACOLOGY
Like other topical corticosteroids, mometasone furoate 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 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 and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone for up to 24 hours have not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Studies in humans indicate that approximately 0.4% of the applied dose of Mometasone Furoate Cream USP enters the circulation after 8 hours of contact on normal skin without occlusion. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Studies performed with Mometasone Furoate Cream USP indicate that it is in the medium range of potency as compared with other topical corticosteroids.
In a study evaluating the effects of mometasone furoate cream on the hypothalamic-pituitary-adrenal (HPA) axis, 15 grams were applied twice daily for 7 days to 6 adult patients with psoriasis or atopic dermatitis. The cream was applied without occlusion to at least 30% of the body surface. The results show that the drug caused a slight lowering of adrenal corticosteroid secretion.
In a pediatric trial, 24 atopic dermatitis patients, of which 19 patients were age 2 to 12 years, were treated with Mometasone Furoate Cream USP once daily. The majority of patients cleared within 3 weeks.
Ninety-seven pediatric patients ages 6 to 23 months, with atopic dermatitis, were enrolled in an open-label, HPA axis safety study. Mometasone Furoate Cream USP was applied once daily for approximately 3 weeks over a mean body surface area of 41% (range 15% to 94%). In approximately 16% of patients who showed normal adrenal function by Cortrosyn test before starting treatment, adrenal suppression was observed at the end of treatment with Mometasone Furoate Cream USP. The criteria for suppression were: basal cortisol level of < 5 mcg/dL, 30-minute post-stimulation level of < 18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 5 of the patients, demonstrated suppressed HPA axis function in one patient, using these same criteria.
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