Action And Clinical Pharmacology: Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole brings about inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is completely or partially inhibited, the cell is no longer able to construct an intact cell membrane. This leads to death of the fungus.
Exposure of C. albicans to clotrimazole causes leakage of intracellular phosphorus compounds into the ambient medium with a concomitant breakdown of cellular nucleic acids and potassium efflux. The onset of these events is rapid and extensive after exposure of the organism to the drug, and causes a time-dependent and concentration-dependent inhibition of fungal growth.
Pharmacokinetics: Metabolism studies performed after oral or i.v. administration have shown that in most species studied, levels of clotrimazole in tissue and serum are low. The majority of the drug is excreted as metabolites in the feces, with small amounts excreted in the urine. Human studies indicate slow excretion following oral administration of 4-labeled clotrimazole (greater than 6 days). After intraperitoneal and s.c. administration, very low levels have been observed in the urine. The absorption and organ distribution of the drug is very poor when administered parenterally.
The pharmacokinetics of topically applied clotrimazole in human subjects have been evaluated by Duhm et al. who reported on the penetration of radioactive clotrimazole 1% cream and 1% solution into intact and acutely inflamed skin. Six hours after application of the drug, the concentration of clotrimazole found in skin layers varied from 100 Âµg/cmin the stratum corneum to 0.5 to 1 Âµg/cmin the stratum reticulare and
In animal experiments, clotrimazole exerts an in vitro and in vivo, dose-dependent stimulating effect on certain microsomal enzyme systems which is approximately equal to that of phenobarbital in its inductive potential. However, this stimulating effect subsides rapidly when treatment is discontinued. The enzyme-inductive effect of clotrimazole has been found to be intact in adrenalectomized animals.
Results of 22 mycologically controlled double-blind, 1 mycologically controlled single blind, and 4 mycologically controlled open studies show that 1% solution and cream are effective in the treatment of tinea cruris, tinea corporis, tinea pedis, tinea versicolor and cutaneous candidiasis. For the cream, mycological cure rates were 80% for tinea cruris/tinea corporis, 67% for tinea pedis, 88% for tinea versicolor and 92% for cutaneous candidiasis as compared to 4.7%, 0%, 37.5% and 0%, respectively, for the vehicle control (total of 238 patients). The corresponding values for the solution are 92% for tinea cruris/tinea corporis, 64% for tinea pedis, 83% for tinea versicolor, 83% for cutaneous candidiasis, 100% for C. paronychia and 93% for mixed dermatophytoses as compared to 30%, 31%, 64%, 28% and 0%, respectively, (there is no corresponding value for mixed dermatophytoses) for the vehicle control (total of 874 patients).
Indications And Clinical Uses: For the topical treatment of the following dermal infections: tinea pedis, tinea cruris and tinea corporis due to T. rubrum, T. mentagrophytes and E. floccosum; candidiasis due to C. albicans; tinea versicolor due to M. furfur.
Contra-Indications: Hypersensitivity to clotrimazole.
Precautions: As with all topical agents, skin sensitization may result. Use of clotrimazole topical preparations should be discontinued should such reactions occur, and appropriate therapy instituted.
Pregnancy and Lactation: Although the topical application of clotrimazole has resulted in very low serum and tissue levels, the use of clotrimazole topical preparations by pregnant or lactating women is not recommended unless it is on the advice of a physician.
Clotrimazole topical preparations are not suitable for treating fungal infections of the nail or scalp.
Occlusive dressings should not be applied over clotrimazole topical preparations unless directed by a physician.
The topical preparations are not for ophthalmic use.
Adverse Reactions: Experimental, therapeutic, and large scale clinical studies have shown clotrimazole to be well tolerated after topical application.
Erythema, stinging, blistering, peeling, edema, pruritus, urticaria and general irritation of the skin have been reported infrequently.
Out of a total of 184 patients treated with the 1% cream, irritation was reported in 12 and soreness in 1 patient; therapy was discontinued in 3 patients. In comparison, 1 case of increased inflammation and pruritus and 1 case of folliculitis was reported in the 54 patients treated with the vehicle control.
Out of 518 patients treated with the 1% solution, burning, itching or drying effect was reported in 2, burning and erythema in 1, irritation in 4, warm sensation or burning in 14, erythema in 1, itching in 5, stinging in 1, blisters in 1 and increased scaling and peeling in 2; therapy was discontinued in 4 patients. Of the 356 patients treated with the vehicle control, burning, itching or drying effect was reported in 3, irritation in 5, warm sensation or burning in 12, odor in 1, erythema in 1, itching in 4, stinging in 2, urticaria in 2, maculopapular rash in 1, and increased sweating in 1; therapy was discontinued in 4 patients.
Dosage And Administration: Thinly apply and gently massage sufficient solution or cream into the affected and surrounding skin areas twice daily, in the morning and evening. For the treatment to be completely successful, the solution or cream should be applied regularly and in sufficient quantities.
Clinical improvement with relief of pruritus, usually occurs within the first week of treatment. The symptoms of jock itch and ringworm usually resolve within 2 to 4 weeks. Athlete’s foot may require at least 4 weeks. In mycoses of the foot, treatment should be continued – even when it has led to rapid subjective improvement – for about 2 weeks after all symptoms have disappeared so that relapses may be prevented. If the signs and symptoms of the infection have not been resolved after 4 weeks of treatment with clotrimazole, a physician should be consulted.
If a cure is not mycologically confirmed, treatment should, as a rule, be continued for 2 weeks after all clinical symptoms have disappeared. Candida infections are generally treated for only 2 weeks.
Added hygienic measures are of special importance in the management of the often refractory fungal diseases of the foot. After washing, the feet – particularly between the toes – should be dried thoroughly to avoid trapped moisture. Well-fitting, ventilated shoes and cotton or wool socks are recommended to ensure a successful treatment outcome and to help prevent a recurrence.
Availability And Storage: Cream: Each g of topical cream contains: clotrimazole 10 mg in a vanishing cream base. Nonmedicinal ingredients: benzyl alcohol, cetostearyl alcohol, cetyl esters wax, 2-octyl dodecanol, polysorbate 60, purified water and sorbitan monostearate. Tubes of 15 and 30 g. Plastic tubs of 500 g.
Solution: Each mL of topical solution contains: clotrimazole 10 mg. Nonmedicinal ingredients: isopropanol, polyethylene glycol and propylene glycol. Plastic pump spray bottles of 40 mL.
Store below 30°C. Avoid freezing.
CANESTEN® Topical Bayer Consumer Clotrimazole Antifungal
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