PRINCIPAL DISPLAY PANEL - 2 x 45 g Tube Carton

NDC 51672-1275-7

2 x 45 g

Clotrimazole
** Cream USP, 1%**

FOR EXTERNAL USE ONLY.
NOT FOR OPHTHALMIC USE.

Rx only

Keep this and all medications out of the reach of children.

TARO

INDICATIONS AND USAGE

Clotrimazole cream USP is indicated for the topical treatment of candidiasis due to Candida albicansand tinea versicolor due to Malassezia furfur.

Clotrimazole is also available as a nonprescription item which is 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.

ADVERSE REACTIONS

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

To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 canisand Candidaspecies including Candida albicans. In general, the in vitroactivity 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 guilliermondihas been reported to have primary resistance to clotrimazole.

No single-step or multiple-step resistance to clotrimazole has developed during successive passages of Candida albicansand Trichophyton mentagrophytes. No appreciable change in sensitivity was detected after successive passage of isolates of C. albicans, C. krusei,or C. pseudotropicalisin liquid or solid media containing clotrimazole. Also, resistance could not be developed in chemically induced mutant strains of polyene-resistant strains of polyene- resistant isolates of C. albicans. Slight, reversible resistance was noted in three isolates of C. albicanstested by one investigator. There is a single report that records the clinical emergence of C. albicansstrain 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 3in the stratum corneum to 0.5 to 1 mcg/cm 3in the stratum reticulare, and 0.1 mcg/cm 3in 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 equivalents/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.

HOW SUPPLIED

Clotrimazole Cream USP, 1% is supplied in 15 g (NDC 51672-1275-1), 30 g (NDC 51672-1275-2), 45 g (NDC 51672-1275-6) and (2 × 45) g (NDC 51672-1275-7) tubes.

Store at 20˚-25˚C (68˚-77˚F)[see USP Controlled Room Temperature].

Mfd. by: Sun Pharma Canada Inc., Brampton, Ontario, Canada L6T 1C1
Dist. by:**Sun Pharmaceutical Industries Inc.,**Cranbury, NJ 08512

Revised: August 2025

5264349-0825-01 359

PRECAUTIONS

General

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

Information for Patients

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 four weeks of treatment.

2. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, oozing) indicative of possible sensitization.

3. Avoid the use of occlusive wrappings or dressings.

4. Avoid sources of infection or reinfection.

Laboratory Tests

If there is a lack of response to clotrimazole cream, 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. albicanshas 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 not mutagenic effect.

Usage in Pregnancy

Pregnancy Category B

The disposition of 14C-clotrimazole has been studied in humans and animals. Clotrimazole is very poorly absorbed following dermal application or intravaginal administration to humans. (SeeCLINICAL 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 their first trimester of pregnancy.

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

High oraldoses 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 notteratogenic in mice, rabbits and rats at oral doses up to 200, 180 and 100 mg/kg respectively. Oral absorption in the rats amounts to approximately 90% of the administered dose.

Because animal reproductive 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, 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.

DESCRIPTION

Clotrimazole Cream USP, 1% contains clotrimazole, a synthetic antifungal agent having the chemical name {1-(o-Chloro-α, α-diphenylbenzyl)imidazole}; the molecular formula C 22H 17ClN 2; a molecular weight of 344.84; and the structural formula:

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 clotrimazole cream USP contains 10 mg clotrimazole, dispersed in a vanishing cream base of cetostearyl alcohol, cetyl esters wax, 2-octyldodecanol, polysorbate 60, purified water, sorbitan monostearate, and benzyl alcohol (1%) as preservative.