betamethasone 0.05 % / clotrimazole 1 % Topical Cream
OVERDOSAGE
Amounts greater than 45 g/week of Clotrimazole and Betamethasone Dipropionate Cream, USP or 45 mL /week of Clotrimazole and Betamethasone Dipropionate Lotion should not be used.
Acute overdosage with topical application of Clotrimazole and Betamethasone Dipropionate Cream or Lotion is unlikely and would not be expected to lead to a life-threatening situation.
Clotrimazole and Betamethasone Dipropionate Cream or Lotion should not be used for longer than the prescribed time period.
Topically applied corticosteroids, such as the one contained in Clotrimazole and Betamethasone Dipropionate Cream or Lotion, can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS section).
DESCRIPTION
Clotrimazole and Betamethasone Dipropionate Cream and Lotion contain combinations of clotrimazole, a synthetic antifungal agent, and betamethasone dipropionate, a synthetic corticosteroid, for dermatologic use.
Chemically, clotrimazole is 1-( o -chloro-α,α-diphenylbenzyl)imidazole, with the empirical formula C 22 H 17 ClN 2 , a molecular weight of 344.84, and the following structural formula: Clotrimazole is an odorless, white crystalline powder, insoluble in water and soluble in ethanol.
Betamethasone dipropionate has the chemical name 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate, with the empirical formula C 28 H 37 FO 7 , a molecular weight of 504.59, and the following structural formula: Betamethasone dipropionate is a white to creamy white, odorless crystalline powder, insoluble in water.
Each gram of Clotrimazole and Betamethasone Dipropionate Cream, USP contains 10.0 mg clotrimazole, USP and 0.64 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone), in a hydrophilic cream consisting of ceteareth-30, cetostearyl alcohol, mineral oil, phosphoric acid, propylene glycol, purified water, sodium phosphate monobasic, white petrolatum; benzyl alcohol as preservative.
Clotrimazole and betamethasone dipropionate cream is smooth, uniform and white to off-white in color.
Each gram of Clotrimazole and Betamethasone Dipropionate Lotion contains 10.0 mg clotrimazole, USP and 0.64 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone), in a hydrophilic base of ceteareth-30, cetyl alcohol, mineral oil, phosphoric acid, propylene glycol, purified water, sodium phosphate monobasic, stearyl alcohol, white petrolatum; benzyl alcohol as preservative.
Clotrimazole and Betamethasone Dipropionate Lotion is opaque and white in color.
Chemical Structure Chemical Structure
CLINICAL STUDIES
(Clotrimazole and Betamethasone Dipropionate Cream, USP) In clinical studies of tinea corporis, tinea cruris, and tinea pedis, patients treated with Clotrimazole and Betamethasone Dipropionate Cream, USP showed a better clinical response at the first return visit than patients treated with clotrimazole cream.
In tinea corporis and tinea cruris, the patient returned 3 to 5 days after starting treatment, and in tinea pedis, after 1 week.
Mycological cure rates observed in patients treated with Clotrimazole and Betamethasone Dipropionate Cream, USP were as good as or better than in those patients treated with clotrimazole cream.
In these same clinical studies, patients treated with Clotrimazole and Betamethasone Dipropionate Cream, USP showed better clinical responses and mycological cure rates when compared with patients treated with betamethasone dipropionate cream.
HOW SUPPLIED
Clotrimazole and Betamethasone Dipropionate Cream, USP is supplied in 15-gram (NDC 54868-4546-1) and 45-gram (NDC 54868-4546-0) tubes; boxes of one.
Clotrimazole and Betamethasone Dipropionate Lotion is supplied in 30-mL bottles (NDC 54868-5232-0); box of one.
Store at 20° – 25°C (68° – 77°F) [see USP Controlled Room Temperature].
GERIATRIC USE
Geriatric Use Clinical studies of Clotrimazole and Betamethasone Dipropionate Cream or Lotion did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Postmarket adverse event reporting for Clotrimazole and Betamethasone Dipropionate Cream in patients aged 65 and above includes reports of skin atrophy and rare reports of skin ulceration.
Caution should be exercised with the use of these corticosteroid-containing topical products on thinning skin.
THE USE OF CLOTRIMAZOLE AND BETAMETHASONE DIPROPIONATE CREAM OR LOTION UNDER OCCLUSION, SUCH AS IN DIAPER DERMATITIS, IS NOT RECOMMENDED.
MECHANISM OF ACTION
Mechanism of Action Clotrimazole is an imidazole antifungal agent.
Imidazoles inhibit 14-α-demethylation of lanosterol in fungi by binding to one of the cytochrome P-450 enzymes.
This leads to the accumulation of 14-α-methylsterols and reduced concentrations of ergosterol, a sterol essential for a normal fungal cytoplasmic membrane.
The methylsterols may affect the electron transport system, thereby inhibiting growth of fungi.
INDICATIONS AND USAGE
Clotrimazole and Betamethasone Dipropionate Cream and Lotion are 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 Cream or Lotion for the treatment of infections caused by zoophilic dermatophytes (e.g.
Microsporum canis ) has not been established.
Several cases of treatment failure of Clotrimazole and Betamethasone Dipropionate Cream, USP in the treatment of infections caused by Microsporum canis have been reported.
PEDIATRIC USE
Pediatric Use Adverse events consistent with corticosteroid use have been observed in patients under 12 years of age treated with Clotrimazole and Betamethasone Dipropionate Cream, USP.
In openlabel studies, 17 of 43 (39.5%) evaluable pediatric patients (aged 12 to 16 years old) using Clotrimazole and Betamethasone Dipropionate Cream for treatment of tinea pedis demonstrated adrenal suppression as determined by cosyntropin testing.
In another open-label study, 8 of 17 (47.1%) evaluable pediatric patients (aged 12 to 16 years old) using Clotrimazole and Betamethasone Dipropionate Cream for treatment of tinea cruris demonstrated adrenal suppression as determined by cosyntropin testing.
THE USE OF CLOTRIMAZOLE AND BETAMETHASONE DIPROPIONATE CREAM OR LOTION IN THE TREATMENT OF PATIENTS UNDER 17 YEARS OF AGE OR PATIENTS WITH DIAPER DERMATITIS IS NOT RECOMMENDED.
Because of higher ratio of skin surface area to body mass, pediatric patients under the age of 12 years are at a higher risk with Clotrimazole and Betamethasone Dipropionate Cream or Lotion.
The studies described above suggest that pediatric patients under the age of 17 years may also have this risk.
They are at increased risk of developing Cushing’s syndrome while on treatment and adrenal insufficiency after withdrawal of treatment.
Adverse effects, including striae and growth retardation, have been reported with inappropriate use of Clotrimazole and Betamethasone Dipropionate Cream, USP in infants and children (see PRECAUTIONS and ADVERSE REACTIONS sections).
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids.
Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation.
Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
PREGNANCY
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 6-15.
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 (2-15 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 (18-55 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 Cream or Lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
NUSRING MOTHERS
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 Cream or Lotion is administered to a nursing woman.
INFORMATION FOR PATIENTS
Information for Patients Patients using Clotrimazole and Betamethasone Dipropionate Cream or Lotion should receive the following information and instructions: The medication is to be used as directed by the physician and is not recommended for use longer than the prescribed time period.
It is for external use only.
Avoid contact with the eyes, the mouth, or intravaginally.
This medication is to be used for the full prescribed treatment time, even though the symptoms may have improved.
Notify the physician if there is no improvement after 1 week of treatment for tinea cruris or tinea corporis, or after 2 weeks for tinea pedis.
This medication should only be used for the disorder for which it was prescribed.
Other corticosteroid-containing products should not be used with Clotrimazole and Betamethasone Dipropionate Cream or Lotion without first talking with your physician.
The treated skin area should not be bandaged, covered, or wrapped so as to be occluded (See DOSAGE AND ADMINISTRATION section).
Any signs of local adverse reactions should be reported to your physician.
Patients should avoid sources of infection or reinfection.
When using Clotrimazole and Betamethasone Dipropionate Cream or Lotion in the groin area, patients should use the medication for 2 weeks only, and apply the cream or lotion sparingly.
Patients should wear loose-fitting clothing.
Notify the physician if the condition persists after 2 weeks.
The safety of Clotrimazole and Betamethasone Dipropionate Cream or Lotion has not been demonstrated in the treatment of diaper dermatitis.
Adverse events consistent with corticosteroid use have been observed in patients treated with Clotrimazole and Betamethasone Dipropionate Cream, USP for diaper dermatitis.
The use of Clotrimazole and Betamethasone Dipropionate Cream or Lotion in the treatment of diaper dermatitis is not recommended.
DOSAGE AND ADMINISTRATION
Gently massage sufficient Clotrimazole and Betamethasone Dipropionate Cream or Lotion into the affected skin areas twice a day, in the morning and evening.
Clotrimazole and Betamethasone Dipropionate Cream or Lotion should not be used longer than 2 weeks in the treatment of tinea corporis or tinea cruris, and amounts greater than 45 g per week of Clotrimazole and Betamethasone Dipropionate Cream, USP or 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 Cream or Lotion, the diagnosis should be reviewed.
Clotrimazole and Betamethasone Dipropionate Cream or Lotion should not be used longer than 4 weeks in the treatment of tinea pedis, and amounts greater than 45 g per week of Clotrimazole and Betamethasone Dipropionate Cream, USP or 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 Cream or Lotion, the diagnosis should be reviewed.
Clotrimazole and Betamethasone Dipropionate Cream or Lotion should not be used with occlusive dressings.