Clotrimazole and Betamethasone Dipropionate
(betamethasone / clotrimazole)Clotrimazole and Betamethasone Dipropionate Prescribing Information
Clotrimazole and betamethasone dipropionate lotion is indicated in patients 17 years and older for the topical treatment of symptomatic inflammatory tinea pedis, tinea cruris, and tinea corporis due to Epidermophyton floccosum, Trichophyton mentagrophytes and Trichophyton rubrum. Effective treatment without the risks associated with topical corticosteroid use may be obtained using a topical antifungal agent that does not contain a corticosteroid, especially for noninflammatory tinea infections. The efficacy of clotrimazole and betamethasone dipropionate lotion for the treatment of infections caused by zoophilic dermatophytes (e.g., Microsporum canis) has not been established.
Gently massage sufficient clotrimazole and betamethasone dipropionate lotion into the affected skin areas twice a day, in the morning and evening.
Clotrimazole and betamethasone dipropionate lotion should not be used longer than 2 weeks in the treatment of tinea corporis or tinea cruris, and amounts greater than 45 mL per week of clotrimazole and betamethasone dipropionate lotion should not be used. If a patient with tinea corporis or tinea cruris shows no clinical improvement after one week of treatment with clotrimazole and betamethasone dipropionate lotion, the diagnosis should be reviewed.
Clotrimazole and betamethasone dipropionate lotion should not be used longer than 4 weeks in the treatment of tinea pedis and amounts greater than 45 mL per week of clotrimazole and betamethasone dipropionate lotion should not be used. If a patient with tinea pedis shows no clinical improvement after 2 weeks of treatment with clotrimazole and betamethasone dipropionate lotion, the diagnosis should be reviewed.
Clotrimazole and betamethasone dipropionate lotion should not be used with occlusive dressings.
Clotrimazole and betamethasone dipropionate lotion is contraindicated in patients who are sensitive to clotrimazole, betamethasone dipropionate, other corticosteroids or imidazoles, or to any ingredient in this preparation.
Adverse reactions reported for clotrimazole and betamethasone dipropionate lotion in clinical trials were burning and dry skin in 1.6% of patients and stinging in less than 1% of patients.
The following local adverse reactions have been reported with topical corticosteroids and may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria, capillary fragility (ecchymoses), telangiectasia, and sensitization (local reactions upon repeated application of product).
Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.
Adverse reactions reported with the use of clotrimazole are as follows: erythema, stinging, blistering, peeling, edema, pruritus, urticaria, and general irritation of the skin.
Clotrimazole and Betamethasone Dipropionate Lotion contains combinations of clotrimazole, a synthetic antifungal agent, and betamethasone dipropionate, a synthetic corticosteroid, for dermatologic use.
Chemically, clotrimazole is 1-(o-chloro-α,α-diphenylbenzyl) imidazole, with the empirical formula C22H17CIN2, a molecular weight of 344.84, and the following structural formula:
Clotrimazole is an odorless, white crystalline powder, insoluble in water and soluble in ethanol.
Betamethasone dipropionate has the chemical name 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate, with the empirical formula C28H37FO7, a molecular weight of 504.59, and the following structural formula:
Betamethasone dipropionate is a white to creamy white, odorless crystalline powder, insoluble in water.
Each gram of clotrimazole and betamethasone dipropionate lotion contains 10 mg clotrimazole, USP and 0.64 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone), in a hydrophilic base of ceteareth-30, cetyl alcohol, mineral oil, phosphoric acid, propylene glycol, purified water, sodium phosphate monobasic, stearyl alcohol, white petrolatum; benzyl alcohol as preservative.
Clotrimazole and betamethasone dipropionate lotion is opaque and white in color.
Clotrimazole and Betamethasone Dipropionate
No comparative studies have been conducted with clotrimazole and betamethasone dipropionate lotion and clotrimazole alone. Use of corticosteroids in the treatment of a fungal infection may lead to suppression of host inflammation leading to worsening or decreased cure rate.
Clotrimazole
Skin penetration and systemic absorption of clotrimazole following topical application of clotrimazole and betamethasone dipropionate lotion have not been studied. The following information was obtained using 1% clotrimazole solution formulations. Six hours after the application of radioactive clotrimazole 1% solution onto intact and acutely inflamed skin, the concentration of clotrimazole varied from 100 mcg/cm3 in the stratum corneum, to 0.5 to 1 mcg/cm3 in the reticular dermis, and 0.1 mcg/cm3 in the subcutis. No measurable amount of radioactivity (<0.001 mcg/mL) was found in the serum within 48 hours after application under occlusive dressing of 0.5 mL of the solution. Only 0.5% or less of the applied radioactivity was excreted in the urine.
Microbiology
Mechanism of Action
Clotrimazole is an imidazole antifungal agent. Imidazoles inhibit 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 Vivo
Clotrimazole has been shown to be active against most strains of the following dermatophytes, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum.
Activity In Vitro
In vitro, clotrimazole has been shown to have activity against many dermatophytes, but the clinical significance of this information is unknown.
Drug Resistance
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.
Betamethasone Dipropionate
Betamethasone dipropionate, a corticosteroid, has been shown to have topical (dermatologic) and systemic pharmacologic and metabolic effects characteristic of this class of drugs.
Pharmacokinetics
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 (see DOSAGE AND ADMINISTRATION). 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. Studies performed with clotrimazole and betamethasone dipropionate lotion indicate that this topical combination antifungal/corticosteroid may have vasoconstrictor potencies in a range that is comparable to high-potency topical corticosteroids. Therefore, use is not recommended in patients less than 17 years of age, in diaper dermatitis, and under occlusion.
In the treatment of tinea pedis twice daily for 4 weeks, clotrimazole and betamethasone dipropionate lotion was shown to be superior to vehicle in relieving symptoms of erythema, scaling, pruritus, and maceration at Week 2. Clotrimazole and betamethasone dipropionate lotion was also shown to have a superior mycological cure rate compared to vehicle 2 weeks after discontinuation of treatment. It is unclear if the relief of symptoms at 2 weeks in this clinical study with clotrimazole and betamethasone dipropionate lotion was due to the contribution of betamethasone dipropionate, clotrimazole, or both.
In the treatment of tinea cruris twice daily for 2 weeks, clotrimazole and betamethasone dipropionate lotion was shown to be superior to vehicle in the relief of symptoms of erythema, scaling, and pruritus after 3 days. It is unclear if the relief of symptoms after 3 days in this clinical study with clotrimazole and betamethasone dipropionate lotion was due to the contribution of betamethasone dipropionate, clotrimazole, or both.
The comparative efficacy and safety of clotrimazole and betamethasone dipropionate lotion versus clotrimazole alone in a lotion vehicle have not been studied in the treatment of tinea pedis or tinea cruris or tinea corporis. The comparative efficacy and safety of clotrimazole and betamethasone dipropionate lotion and clotrimazole and betamethasone dipropionate cream have also not been studied.
Clotrimazole and Betamethasone Dipropionate Lotion is supplied in 30-mL bottles (NDC 51672-1308-3); box of one.
Store at 20° to 25°C (68° to 77°F) in the upright position only; [see USP Controlled Room Temperature].
SHAKE WELL BEFORE EACH USE.
Mechanism of Action
Clotrimazole is an imidazole antifungal agent. Imidazoles inhibit 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.