Lotrimin topical solution 1%

Description

LOTRIMIN products contain clotrimazole, USP, a synthetic antifungal agent having the chemical name 1-( o -Chloro-(alpha),(alpha)-diphenylbenzyl)imidazole; the empirical formula, C 22 H 17 CIN 2 ; a molecular weight of 344.84; and the chemical structure:

images/17/40039501.jpg

Clotrimazole is an odorless, white crystalline substance. It is practically insoluble in water, sparingly soluble in ether, and very soluble in polyethylene glycol 400, ethanol, and chloroform.

Each gram of LOTRIMIN Cream contains 10 mg clotrimazole, USP in a vanishing cream base of benzyl alcohol NF (1%), cetearyl alcohol 70/30 (10%), cetyl esters wax NF, octyldodecanol NF, polysorbate 60 NF, sorbitan monostearate NF, and purified water USP.

Each gram of LOTRIMIN Lotion contains 10 mg clotrimazole, USP dispersed in an emulsion vehicle composed of benzyl alcohol NF (1%), cetearyl alcohol 70/30 (3.7%), cetyl esters wax NF, octyldodecanol NF, polysorbate 60 NF, sodium phosphate dibasic anhydrous R, sodium phosphate monobasic monohydrate USP, sorbitan monostearate NF, and purified water USP.

Each mL of LOTRIMIN Topical Solution contains 10 mg clotrimazole, USP in a nonaqueous vehicle of PEG 400 NF.

Clinical Pharmacology

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 miconazole 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 guilliermondii 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 passages 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 a C. albicans strain with considerable resistance to flucytosine and miconazole, and with cross-resistance to clotrimazole; the strain remained sensitive to nystatin and amphotericin B.

In studies of the mechanism of action, the minimum fungicidal 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/cm 3 in the stratum corneum to 0.5 to 1 mcg/cm 3 in the stratum reticulare and 0.1 mcg/cm 3 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 14 C-clotrimazole vaginal tablets to nine adult females, an average peak serum level, corresponding to only 0.03 µg equivalents/mL of clotrimazole, was reached 1 to 2 days after application. After intravaginal administration of 5 g of 1% 14 C-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.

Indications and Usage

Prescription LOTRIMIN (clotrimazole cream, lotion, and solution 1%) products are indicated for the topical treatment of candidiasis due to Candida albicans and tinea versicolor due to Malassezia furfur .

These formulations are also available as the LOTRIMIN AF (clotrimazole cream, lotion, and solution 1%) line of nonprescription products which are indicated for the topical treatment of the following dermal infections: tinea pedis, tinea cruris, and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum , and Microsporum canis .

Contraindications

LOTRIMIN products are contraindicated in individuals who have shown hypersensitivity to any of their components.

Warnings

LOTRIMIN products are not for ophthalmic use.

Precautions

General:   If irritation or sensitivity develops with the use of clotrimazole, treatment should be discontinued and appropriate therapy instituted.

Information For Patients:   This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

The patient should be advised to:

  1. Use the medication for the full treatment time even though the symptoms may have improved. Notify the physician if there is no improvement after 4 weeks of treatment.
  2. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burn-ing, blistering, swelling, oozing) indicative of possible sensitization.
  3. Avoid sources of infection or reinfection.

Laboratory Tests:    If there is lack of response to clotrimazole, appropriate microbiological studies should be repeated to confirm the diagnosis and rule out other pathogens before instituting another course of antimycotic therapy.

Drug Interactions

Synergism or antagonism between clotrimazole and nystatin, or amphotericin B, or flucytosine against strains of C. albicans has not been reported.

Carcinogenesis, Mutagenesis, Impairment of Fertility:   An 18-month oral dosing study with clotrimazole in rats has not revealed any carcinogenic effect.

In tests for mutagenesis, chromosomes of the spermatophores of Chinese hamsters which had been exposed to clotrimazole were examined for structural changes during the metaphase. Prior to testing, the hamsters had received five oral clotrimazole doses of 100 mg/kg body weight. The results of this study showed that clotrimazole had no mutagenic effect.

Usage in Pregnancy: Pregnancy Category B:   The disposition of 14 C-clotrimazole has been studied in humans and animals. Clotrimazole is very poorly absorbed following dermal application or intravaginal administration to humans. (See CLINICAL PHARMACOLOGY .)

In clinical trials, use of vaginally applied clotrimazole in pregnant women in their second and third trimesters has not been associated with ill effects. There are, however, no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy.

Studies in pregnant rats with intravaginal doses up to 100 mg/kg have revealed no evidence of harm to the fetus due to clotrimazole.

High oral doses of clotrimazole in rats and mice ranging from 50 to 120 mg/kg resulted in embryotoxicity (possibly secondary to maternal toxicity), impairment of mating, decreased litter size and number of viable young and decreased pup survival to weaning. However, clotrimazole was not teratogenic in mice, rabbits, and rats at oral doses up to 200, 180, and 100 mg/kg, respectively. Oral absorption in the rat amounts to approximately 90% of the administered dose.

Because animal reproduction studies are not always predictive of human response, this drug should be used only if clearly indicated during the first trimester of pregnancy.

Nursing Mothers:   It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when clotrimazole is used by a nursing woman.

Pediatric Use:   Safety and effectiveness in children have been established for clotrimazole when used as indicated and in the recommended dosage.

Adverse Reactions

The following adverse reactions have been reported in connection with the use of clotrimazole: erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin.

Overdosage

Acute overdosage with topical application of clotrimazole is unlikely and would not be expected to lead to a life-threatening situation.

Dosage and Administration

Gently massage sufficient LOTRIMIN into the affected and surrounding skin areas twice a day, in the morning and evening.

Clinical improvement, with relief of pruritus, usually occurs within the first week of treatment with LOTRIMIN. If the patient shows no clinical improvement after 4 weeks of treatment with LOTRIMIN, the diagnosis should be reviewed.

How Supplied

LOTRIMIN Cream 1% is supplied in 15, 30, and 45-g tubes (NDC 0085-0613-02, 05, 04, respectively); boxes of one.

Store between 2° and 30°C (36° and 86°F).

LOTRIMIN Lotion 1% is supplied in 30-mL bottles (NDC 0085-0707-02); boxes of one.

Store between 2° and 25°C (36° and 77°F).

Shake well before using.

LOTRIMIN Topical Solution 1% is supplied in 10-mL and 30-mL plastic bottles (NDC 0085-0182-02, 04, respectively); boxes of one.

Store between 2°and 30°C (36° and 86°F).

Schering Corporation

Kenilworth, NJ 07033 USA

Rev. 1/99 B-17981013

                 22592203T

Copyright © 1984, 1991, 1993, 1994, 1999, Schering Corporation. All rights reserved.

LOTRIMIN

brand of clotrimazole

   Cream, USP 1% *

   Lotion, USP 1% *

   Topical Solution, USP 1% *

For Dermatologic Use Only -- Not For Ophthalmic Use

*These preparations are also available without a prescription as LOTRIMIN AF.






















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