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DIPROLENE® Lotion contains betamethasone dipropionate, USP, a synthetic adrenocorticosteroid, for dermatologic use. Betamethasone, an analog of prednisolone, has a high degree of corticosteroid activity and a slight degree of mineralocorticoid activity. Betamethasone dipropionate is the 17, 21-dipropionate ester of betamethasone.
Chemically, betamethasone dipropionate is 9-fluoro-11(beta),17,21-trihydroxy-16(beta)-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate, with the empirical formula C 28 H 37 FO 7 , a molecular weight of 504.6, and the following structural formula:
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Betamethasone dipropionate is a white to creamy white, odorless crystalline powder, insoluble in water.
Each gram of DIPROLENE Lotion 0.05% contains: 0.643 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone), in a lotion base of purified water; isopropyl alcohol (30%); hydroxypropyl cellulose; propylene glycol; sodium phosphate monobasic monohydrate R; phosphoric acid used to adjust the pH to 4.5.
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 dipropionate, are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, antipruritic, 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 dipropionate, 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. (See DOSAGE AND ADMINISTRATION section.)
Topical corticosteroids can be absorbed through normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. (See DOSAGE AND ADMINISTRATION section.)
Once absorbed through the skin, topical corticosteroids enter pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees, are metabolized primarily in the liver and excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
DIPROLENE Lotion was applied once daily at 7 mL per day for 21 days to diseased skin (in patients with scalp psoriasis) to study its effects on the hypothalamic-pituitary-adrenal (HPA) axis. In 2 out of 11 patients, the drug lowered plasma cortisol levels below normal limits. Adrenal depression in these patients was transient and returned to normal within a week. In one of these patients, plasma cortisol levels returned to normal while treatment continued.
DIPROLENE Lotion is indicated for treatment of the inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses.
Treatment beyond 2 weeks is not recommended, and the total dosage should not exceed 50 mL per week because of potential for the drug to suppress the hypothalamic-pituitary-adrenal axis.
DIPROLENE Lotion is contraindicated in patients who are hypersensitive to betamethasone dipropionate, to other corticosteroids, or to any ingredient in this preparation.
General: DIPROLENE Lotion is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at 7 mL per day.
Systemic absorption of topical corticosteroids has produced reversible 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 corticosteroids such as DIPROLENE, use over large surface areas, prolonged use, and the addition of occlusive dressings. (See DOSAGE AND ADMINISTRATION section.)
Therefore, patients receiving large doses of a potent topical steroid applied to a large surface area 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. (See PRECAUTIONS - Pediatric Use .)
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 instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.
Information for Patients: Patients using topical corticosteroids should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
Laboratory Tests: The following tests may be helpful in evaluating HPA axis suppression:
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 topically applied 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. Betamethasone dipropionate has not been tested for teratogenicity by this route; however, it appears to be fairly well absorbed percutaneously. There are no adequate and well-controlled studies of the teratogenic effects of topically applied corticosteroids in pregnant women. 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 known whether topical administration of corticosteroids can 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, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Data regarding use of DIPROLENE Lotion in pediatric patients are not available, so use of this product in patients under the age of 12 is not recommended.
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. Chronic corticosteroid therapy may interfere with the growth and development of children.
The overall incidence of drug-related adverse reactions in the DIPROLENE Lotion clinical studies was 5%. The adverse reactions that were reported to be possibly or probably related to treatment with DIPROLENE Lotion during controlled clinical studies involving 327 patients or normal volunteers were as follows: folliculitis occurred in 2%, burning and acneiform papules each occurred in 1%, and hyperesthesia and irritation each occurred in less than 1% of patients.
The following adverse reactions are also reported infrequently when topical corticosteroids are used as recommended. These reactions are listed in approximate decreasing order of occurrence: itching, dryness, hypertrichosis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.
Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS .)
Apply a few drops of DIPROLENE Lotion to the affected area once or twice daily and massage lightly until the lotion disappears. Treatment must be limited to 14 days, and amounts greater than 50 mL per week should not be used.
DIPROLENE Lotion is not to be used with occlusive dressings.
DIPROLENE Lotion 0.05% is supplied in 30-mL (29 g) (NDC 0085-0962-01) and 60-mL (58 g) (NDC 0085-0962-02) plastic squeeze bottles; boxes of one.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]
Schering Corporation
Kenilworth, NJ 07033 USA
Rev. 9/03
B-23409828
23816415T
Copyright © 1988, 1992, 1994, 1999, Schering Corporation.
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