Clotrimazole and Betamethasone Dipropionate

INDICATIONS AND USAGE 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.

DOSAGE AND ADMINISTRATION 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.

CONTRAINDICATIONS 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.

Pregnancy Teratogenic Effects Pregnancy Category C There have been no teratogenic studies performed in animals or humans with the combination of clotrimazole and betamethasone dipropionate. Corticosteroids are generally teratogenic in laboratory animals when administered at relatively low dosage levels. Studies in pregnant rats with intravaginal doses up to 100 mg/kg (15 times the maximum human dose) revealed no evidence of fetotoxicity due to clotrimazole exposure. No increase in fetal malformations was noted in pregnant rats receiving oral (gastric tube) clotrimazole doses up to 100 mg/kg/day during gestation Days 6 to 15. However, clotrimazole dosed at 100 mg/kg/day was embryotoxic (increased resorptions), fetotoxic (reduced fetal weights), and maternally toxic (reduced body weight gain) to rats. Clotrimazole dosed at 200 mg/kg/day (30 times the maximum human dose) was maternally lethal, and therefore fetuses were not evaluated in this group. Also in this study, doses up to 50 mg/kg/day (8 times the maximum human dose) had no adverse effects on dams or fetuses. However, in the combined fertility, teratogenicity, and postnatal development study described above, 50 mg/kg clotrimazole, was associated with reduced maternal weight gain and reduced numbers of offspring reared to 4 weeks. Oral clotrimazole doses of 25, 50, 100, and 200 mg/kg/day (2 to 15 times the maximum human dose) were not teratogenic in mice. No evidence of maternal toxicity or embryotoxicity was seen in pregnant rabbits dosed orally with 60, 120, or 180 mg/kg/day (18 to 55 times the maximum human dose). Betamethasone dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. This dose is approximately one-fifth the maximum human dose. The abnormalities observed included umbilical hernias, cephalocele and cleft palates. Betamethasone dipropionate has not been tested for teratogenic potential by the dermal route of administration. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals. There are no adequate and well-controlled studies in pregnant women of the teratogenic effects of topically applied corticosteroids. Therefore, clotrimazole and betamethasone dipropionate lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when clotrimazole and betamethasone dipropionate lotion is administered to a nursing woman.

ADVERSE REACTIONS 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.