"The US Food and Drug Administration (FDA) has approved the tumor necrosis factor inhibitor adalimumab (Humira, AbbVie) for the treatment of moderate to severe hidradenitis suppurativa (HS), making it the first and only FDA-approved therapy"...
Mechanism Of Action
Clotrimazole is an azole antifungal [see Microbiology].
Betamethasone dipropionate is a corticosteroid. Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action for the treatment of tinea pedis, tinea cruris and tinea corporis is unknown.
Studies performed with LOTRISONE cream indicate that these topical combination antifungal/corticosteroids may have vasoconstrictor potencies in a range that is comparable to high-potency topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.
Skin penetration and systemic absorption of clotrimazole and betamethasone dipropionate following topical application of LOTRISONE cream has not been studied.
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption of topical corticosteroids. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids [see DOSAGE AND ADMINISTRATION].
Once absorbed through the skin, the pharmacokinetics of topical corticosteroids are similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
Mechanism of Action
Clotrimazole, an azole antifungal agent, inhibits 14-α-demethylation of lanosterol in fungi by binding to one of the cytochrome P-450 enzymes. This leads to the accumulation of 14-α-methylsterols and reduced concentrations of ergosterol, a sterol essential for a normal fungal cytoplasmic membrane. The methylsterols may affect the electron transport system, thereby inhibiting growth of fungi.
Activity In Vitro and In Vivo
Clotrimazole has been shown to be active against most strains of the following dermatophytes, both in vitro and in clinical infections, Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum [see INDICATIONS AND USAGE].
Strains of dermatophytes having a natural resistance to clotrimazole have not been reported. Resistance to azoles, including clotrimazole, has been reported in some Candida species.
No single-step or multiple-step resistance to clotrimazole has developed during successive passages of Trichophyton mentagrophytes.
In clinical trials of tinea corporis, tinea cruris, and tinea pedis, subjects treated with LOTRISONE cream showed a better clinical response at the first return visit than subjects treated with clotrimazole cream. In tinea corporis and tinea cruris, the subject returned 3 to 5 days after starting treatment, and in tinea pedis, after 1 week. Mycological cure rates observed in subjects treated with LOTRISONE cream were as good as, or better than, in those subjects treated with clotrimazole cream. In these same clinical studies, patients treated with LOTRISONE cream showed better clinical responses and mycological cure rates when compared with subjects treated with betamethasone dipropionate cream.
Last reviewed on RxList: 2/23/2016
This monograph has been modified to include the generic and brand name in many instances.
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