Lotrisone Information
Lotrisone (Clotrimazole)
Lotrisone (Clotrimazole) Description
Lotrisone (Clotrimazole) Cream and Lotion contain combinations of clotrimazole, a synthetic antifungal agent, and betamethasone dipropionate, a synthetic corticosteroid, for dermatologic use.
Chemically, clotrimazole is 1–(-chloro-α,α-diphenylbenzyl) imidazole, with the empirical formula CHClN, 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 CHFO, 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 contains 10 mg clotrimazole and 0.643 mg betamethasone dipropionate (equivalent to 0.5 mg betamethasone), in a hydrophilic cream consisting of purified water, mineral oil, white petrolatum, cetyl alcohol plus stearyl alcohol, ceteareth-30, propylene glycol, sodium phosphate monobasic monohydrate, and phosphoric acid; benzyl alcohol as preservative.
Lotrisone (Clotrimazole) Cream may contain sodium hydroxide. Lotrisone (Clotrimazole) Cream is smooth, uniform, and white to off-white in color.
Each gram of contains 10 mg clotrimazole and 0.643 mg betamethasone dipropionate (equivalent to 0.5 mg betamethasone), in a hydrophilic base of purified water, mineral oil, white petrolatum, cetyl alcohol plus stearyl alcohol, ceteareth-30, propylene glycol, sodium phosphate monobasic monohydrate, and phosphoric acid; benzyl alcohol as a preservative.
Lotrisone (Clotrimazole) Lotion may contain sodium hydroxide. Lotrisone (Clotrimazole) Lotion is opaque and white in color.
Lotrisone (Clotrimazole) Clinical Studies (lotrisone Cream)
In clinical studies of tinea corporis, tinea cruris, and tinea pedis, patients treated with Lotrisone (Clotrimazole) Cream 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 Lotrisone (Clotrimazole) Cream were as good as or better than in those patients treated with clotrimazole cream. In these same clinical studies, patients treated with Lotrisone (Clotrimazole) Cream showed better clinical responses and mycological cure rates when compared with patients treated with betamethasone dipropionate cream.
Lotrisone (Clotrimazole) Clinical Studies (lotrisone Lotion)
In the treatment of tinea pedis twice daily for 4 weeks, Lotrisone (Clotrimazole) Lotion was shown to be superior to vehicle in relieving symptoms of erythema, scaling, pruritus, and maceration at Week 2. Lotrisone (Clotrimazole) Lotion was also shown to have a superior mycological cure rate compared to vehicle 2 weeks after discontinuation of treatment. It is unclear if the relief of symptoms at 2 weeks in this clinical study with Lotrisone (Clotrimazole) Lotion was due to the contribution of betamethasone dipropionate, clotrimazole, or both.
In the treatment of tinea cruris twice daily for 2 weeks, Lotrisone (Clotrimazole) Lotion was shown to be superior to vehicle in the relief of symptoms of erythema, scaling, and pruritus after 3 days. It is unclear if the relief of symptoms after 3 days in this clinical study with Lotrisone (Clotrimazole) Lotion was due to the contribution of betamethasone dipropionate, clotrimazole, or both.
The comparative efficacy and safety of Lotrisone (Clotrimazole) Lotion versus clotrimazole alone in a lotion vehicle have not been studied in the treatment of tinea pedis or tinea cruris or tinea corporis. The comparative efficacy and safety of Lotrisone (Clotrimazole) Lotion and Lotrisone (Clotrimazole) Cream have also not been studied.
Lotrisone (Clotrimazole) Indications And Usage
Lotrisone (Clotrimazole) 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 and 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 Lotrisone (Clotrimazole) Cream or Lotion for the treatment of infections caused by zoophilic dermatophytes (eg, ) has not been established. Several cases of treatment failure of Lotrisone (Clotrimazole) Cream in the treatment of infections caused by have been reported.
Lotrisone (Clotrimazole) Contraindications
Lotrisone (Clotrimazole) Cream or Lotion is contraindicated in patients who are sensitive to clotrimazole, betamethasone dipropionate, other corticosteroids or imidazoles, or to any ingredient in these preparations.
Lotrisone (Clotrimazole) Precautions
Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.
Conditions which augment systemic absorption include use over large surface areas, prolonged use, and use under occlusive dressings. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure. Patients applying Lotrisone (Clotrimazole) Cream or Lotion to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, morning plasma cortisol, and urinary-free cortisol tests.
If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids.
In a small study, Lotrisone (Clotrimazole) Cream was applied using large dosages, 7 g daily for 14 days (BID) to the crural area of normal adult subjects. Three of the eight normal subjects on whom Lotrisone (Clotrimazole) Cream was applied exhibited low morning plasma cortisol levels during treatment. One of these subjects had an abnormal Cortrosyn test. The effect on morning plasma cortisol was transient and subjects recovered 1 week after discontinuing dosing. In addition, two separate studies in pediatric patients demonstrated adrenal suppression as determined by cosyntropin testing (see section).
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see section).
If irritation develops, Lotrisone (Clotrimazole) Cream or Lotion should be discontinued and appropriate therapy instituted.
THE SAFETY OF Lotrisone (Clotrimazole) 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 Lotrisone (Clotrimazole) CREAM FOR DIAPER DERMATITIS. THE USE OF Lotrisone (Clotrimazole) CREAM OR LOTION IN THE TREATMENT OF DIAPER DERMATITIS IS NOT RECOMMENDED.
If there is a lack of response to Lotrisone (Clotrimazole) Cream or Lotion, appropriate confirmation of the diagnosis, including possible mycological studies, is indicated before instituting another course of therapy.
The following tests may be helpful in evaluating HPA axis suppression due to the corticosteroid components:
There are no adequate laboratory animal studies with either the combination of clotrimazole and betamethasone dipropionate or with either component individually to evaluate carcinogenesis.
Betamethasone was negative in the bacterial mutagenicity assay ( and ) and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the human lymphocyte chromosome aberration assay, and equivocal in the mouse bone marrow micronucleus assay. This pattern of response is similar to that of dexamethasone and hydrocortisone.
Reproductive studies with betamethasone dipropionate carried out in rabbits at doses of 1.0 mg/kg by the intramuscular route and in mice up to 33 mg/kg by the intramuscular route indicated no impairment of fertility except for dose-related increases in fetal resorption rates in both species. These doses are approximately 5- and 38-fold the maximum human dose based on body surface areas, respectively.
In a combined study of the effects of clotrimazole on fertility, teratogenicity, and postnatal development, male and female rats were dosed orally (diet admixture) with levels of 5, 10, 25, or 50 mg/kg/day (approximately 1–8 times the maximum dose in a 60-kg adult based on body surface area) from 10 weeks prior to mating until 4 weeks postpartum. No adverse effects on the duration of estrous cycle, fertility, or duration of pregnancy were noted.
Adverse events consistent with corticosteroid use have been observed in patients under 12 years of age treated with Lotrisone (Clotrimazole) Cream. In open-label studies, 17 of 43 (39.5%) evaluable pediatric patients (aged 12 – 16 years old) using Lotrisone (Clotrimazole) 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 – 16 years old) using Lotrisone (Clotrimazole) Cream for treatment of tinea cruris demonstrated adrenal suppression as determined by cosyntropin testing.
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 Lotrisone (Clotrimazole) 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 Lotrisone (Clotrimazole) Cream in infants and children (see and ).
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.
Lotrisone (Clotrimazole) Adverse Reactions
Adverse reactions reported for Lotrisone (Clotrimazole) Cream in clinical trials were paresthesia in 1.9% of patients, and rash, edema, and secondary infection, each in less than 1% of patients.
Adverse reactions reported for Lotrisone (Clotrimazole) 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). In the pediatric population, reported adverse events for Lotrisone (Clotrimazole) Cream include growth retardation, benign intracranial hypertension, Cushing's syndrome (HPA axis suppression), and local cutaneous reactions, including skin atrophy.
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.
Lotrisone (Clotrimazole) Overdosage
Amounts greater than 45 g/week of Lotrisone (Clotrimazole) Cream or 45 mL/week of Lotrisone (Clotrimazole) Lotion should not be used. Acute overdosage with topical application of Lotrisone (Clotrimazole) Cream or Lotion is unlikely and would not be expected to lead to a life-threatening situation. Lotrisone (Clotrimazole) Cream or Lotion should not be used for longer than the prescribed time period.
Topically applied corticosteroids, such as the one contained in Lotrisone (Clotrimazole) Cream or Lotion can be absorbed in sufficient amounts to produce systemic effects (see ).
Lotrisone (Clotrimazole) Dosage And Administration
Gently massage sufficient Lotrisone (Clotrimazole) Cream or Lotion into the affected skin areas twice a day, in the morning and evening.
Lotrisone (Clotrimazole) Cream or Lotion should not be used with occlusive dressings.
Lotrisone (Clotrimazole) How Supplied
Lotrisone (Clotrimazole) Cream is supplied in 15-g (NDC 0085-0924-01) and 45-g tubes (NDC 0085-0924-02); boxes of one.
Lotrisone (Clotrimazole) Lotion is supplied in 30-mL bottles (NDC 0085-0809-01), box of one.
Lotrisone (Clotrimazole)
Lotrisone (Clotrimazole)
