Betamethasone Valerate
Indications: Dermatosis, corticosteroid-responsive
DESCRIPTION:
For Dermatologic Use Only--Not for Ophthalmic Use.
Betamethasone valerate cream, reduced strength cream, ointment and lotion contains betamethasone valerate, USP, a synthetic adrenocorticoid, for dermatologic use. Betamethasone, an analog of prednisolone, has a slight degree of mineralocorticosteroid activity. Betamethasone valerate is the 17-valerate ester of betamethasone.
Chemically, betamethasone valerate is 9-fluoro-11beta,17,21-trihydroxy-16beta,methylpregna-1, 4-diene-3,20-dione 17-valerate, with the empirical formula C27H37FO6, and a molecular weight of 476.58. Betamethasone valerate is a white to practically white, odorless crystalline powder, and is practically insoluble in water, freely soluble in acetone and in chloroform, soluble in alcohol and slightly soluble in benzene and either.
CLINICAL PHARMACOLOGY:
The corticosteroids are a class of compounds comprising steroid hormones secreted by the adrenal cortex and their synthetic analogs. In pharmacologic doses corticosteroids are used primarily for their anti-inflammatory and/or immunosuppressive effects.
Topical corticosteroids, such as betamethasone valerate, are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, anti-pruritic, and vasoconstrictive actions. However, while the physiologic, pharmacologic, and clinical effects of the corticosteroids are well-known, the exact mechanisms of their actions in each disease are uncertain. Betamethasone valerate, a corticosteroid, has been shown to have topical (dermatologic) and systemic pharmacologic and metabolic effects characteristic of this class of drugs.
Pharmacokinetics
The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses.
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
INDICATIONS AND USAGE:
Betamethasone valerate cream, reduced strength cream, ointment and lotion indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
CONTRAINDICATIONS:
Betamethasone valerate cream, reduced strength cream, ointment and lotion contraindicated in those patients who are hypersensitive to betamethasone valerate, to other corticosteroids, or to any ingredient in this preparation.
PRECAUTIONS:
General
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.
Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation 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 steroid.
Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity.
If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.
In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be discontinued until the infection has been adequately controlled.
Information for the Patient
Patients using topical corticosteroids should receive the following information and instructions:
1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.
2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.
4. Patients should report any signs of local adverse reactions especially under occlusive dressing.
5. Parents of pediatric patient should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings.
Laboratory Tests
The Following Tests May Be Helpful in Evaluating the Hpa Axis Suppression:
Urinary free cortisol test.
ACTH stimulation test.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids.
Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results.
Pregnancy Category C
Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.
Nursing Mothers
It is not know whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are prescribed to a nursing woman.
Pediatric Use
Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio .
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.
ADVERSE REACTIONS:
The following local adverse reactions are reported infrequently with topical dermatologic corticosteroids, especially under occlusive dressings: burning; itching; irritation; dryness; folliculitis; hypertrichosis; aceneform eruptions; hypopigmentation; periol dermatitis; allergic contact dermatitis; maceration of the skin; secondary infection; skin atrophy; striae; miliaria.
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.
OVERDOSAGE:
Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)
DOSAGE AND ADMINISTRATION:
Betamethasone Valerate Cream and Bethamethasone Valerate Ointment: Apply a thin film to the affected skin areas one to three times a day. Dosage once or twice daily is often effective.
Betamethasone Valerate Lotion: Apply a few drops of betamethasone valerate 0.1% to the affected area and massage lightly until it disappears. Apply twice daily, in the morning and at night. Dosage may be increased in stubborn cases. Following improvement, apply once daily. For the most effective and economical use, apply nozzle very close to affected area and gently squeeze bottle. Protect from light. Store in carton until contents are used.
Betamethasone Valerate Reduced Strength Cream: Apply a thin film of betamethasone valerate reduced strength cream to the affected skin areas one to three times daily. Commonly, treatment twice a day is adequate. In some cases, treatment three times a day is necessary; in others, once a day suffices.