Pharmacology: Clotrimazole contains Clotrimazole, a new generation imidazole derivative possessing a potent and broad-spectrum antifungal, anticandidal and antitrichomonal activity. In vitro, depending on the concentration, Clotrimazole exhibits fungistatic or fungicidal activity against a wide range of isolates of deratophytes eg, Trichophyton rubrum, Trichophyton mentagrophyte, Epidermatophyton floccosum. Clotrimazole exhibits a high degree of anti-candidal action on pathogenic strains of Candida eg, Candida albicans; it also shows a good antimicrobial action on Malassezia furfur. Strains of fungi having a natural resistance to Clotrimazole are rare. No single step or multiple step resistance to Clotrimazole has developed during successive passages of Candida albicans.
Clotrimazole is known to possess anti-trichomonal and antibacterial activity particularly against some of the gram-positive organisms. Clotrimazole causes alteration in the cell wall permeability and leads to leakage of intracellular phosphorus compounds with concomitant breakdown of cellular nucleic acid and accelerated potassium influx. These rapidly and extensively developing changes contribute to fungicidal activity of Clotrimazole. Following the vaginal administration, Clotrimazole appears to be minimally absorbed.
Pharmacokinetics: Pharmacokinetic investigations after vaginal application have shown that only a small amount of Clotrimazole is absorbed. Due to rapid hepatic metabolism of absorbed Clotrimazole into pharmacologically inactive metabolites, the resulting peak plasma concentrations of Clotrimazole after vaginal application of a 500-mg dose were <10 ng/mL, reflecting that Clotrimazole applied intravaginally does not lead to measurable systemic effects or side effects.
Clotrimazole lozenges should be held in the mouth and allowed to dissolve slowly and completely. This may take 15 to 30 minutes. Swallow saliva during this time. Do not chew the lozenges or swallow them whole.
Do not give Clotrimazole lozenges to infants or children under 3 years of age. They may be too young to use the lozenges safely.
To help clear up your infection completely, it is very important that you keep using Clotrimazole for the full time of treatment, even if your symptoms begin to clear up after a few days. Since fungus infections may be very slow to clear up, you may have to continue using Clotrimazole every day for two weeks or more. If you stop using Clotrimazole too soon, your symptoms may return. Do not miss any doses.
The dose of Clotrimazole will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Clotrimazole. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of Clotrimazole, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Oral: Allow troche to dissolve slowly in the mouth. Dissolution is complete in approximately 30 minutes.
Clotrimazole is a broad-spectrum antifungal agent that is used for the treatment of dermal infections caused by various species of pathogenic dermatophytes, yeasts, and Malassezia furfur. The primary action of Clotrimazole is against dividing and growing organisms.
In vitro,Clotrimazole exhibits fungistatic and fungicidal activity against isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum,Microsporum canis and Candida species including Candida albicans. In general, the in vitro activity of Clotrimazole corresponds to that of tolnaftate and griseofulvin against the mycelia of dermatophytes (Trichophyton, Microsporum, and Epidermophyton), and to that of the polyenes (amphotericin B and nystatin) against budding fungi (Candida). Using an in vivo (mouse) and an in vitro (mouse kidney homogenate) testing system, Clotrimazole and micronazole were equally effective in preventing the growth of the pseudomycelia and mycelia of Candida albicans.
Strains of fungi having a natural resistance to Clotrimazole are rare. Only a single isolate of Candida guilliermondi has been reported to have primary resistance to Clotrimazole.
No single-step or multiple-step resistance to Clotrimazole has developed during successive passages of Candida albicans and Trichophyton mentagrophytes. No appreciable change in sensitivity was detected after successive passage of isolates of C. albicans, C krusei, or C. pseudotropicalis in liquid or solid media containing Clotrimazole. Also, resistance could not be developed in chemically induced mutant strains of polyene-resistant isolates of C. albicans. Slight, reversible resistance was noted in three isolates of C. albicans tested by one investigator. There is a single report that records the clinical emergence of C. albicans strain with considerable resistance to flucytosine and micronazole, and with cross-resistance to Clotrimazole, the strain remained sensitive to nystatin and amphotericin B.
In studies of the mechanism of action, the minimum fungicide concentration of Clotrimazole caused leakage of intracellular phosphorus compounds into the ambient medium with concomitant breakdown of cellular nucleic acids and accelerated potassium efflux. Both these events began rapidly and extensively after addition of the drug.
Clotrimazole appears to be well absorbed in humans following oral administration and is eliminated mainly as inactive metabolites. Following topical and vaginal administration, however, Clotrimazole appears to be minimally absorbed.
Six hours after the application of radioactive Clotrimazole 1% cream and 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 stratum reticulare, 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 or 0.8 g of the cream. Only 0.5% or less of the applied radioactivity was excreted in the urine.
Following intravaginal administration of 100 mg 14C-Clotrimazole vaginal tablets to nine adult females, an average peak serum level, corresponding to only 0.03 μg equivalent/mL of Clotrimazole, was reached one to two days after application. After intravaginal administration of 5 g of 1% 14C-Clotrimazole vaginal cream containing 50 mg active drug, to five subjects (one with candidal colpitis), serum levels corresponding to approximately 0.01 μg equivalents/mL were reached between 8 and 24 hours after application.
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Information checked by Dr. Sachin Kumar, MD Pharmacology