DIPROLENE® AF Cream contains betamethasone dipropionate, USP, a synthetic adrenocorticosteroid, for dermatologic use in an emollient base. 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:

Betamethasone dipropionate is a white to creamy white, odorless crystalline powder, insoluble in water.

Each gram of DIPROLENE AF Cream 0.05% contains: 0.643 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone) in an emollient cream base of purified water, USP; chlorocresol NF; propylene glycol, USP; white petrolatum, USP; white wax NF; cyclomethicone; sorbitol solution, USP; glyceryl oleate/propylene glycol; ceteareth-30; carbomer 940 NF; and sodium hydroxide R.

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, 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 dipropionate, a corticosteroid, has been shown to have topical (dermatologic) and systemic pharmacologic and metabolic effects characteristic of this class of drugs.

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 AF Cream was applied once daily at 7 grams per day for one week to diseased skin, in patients with psoriasis or atopic dermatitis, to study its effects on the hypothalamic-pituitary-adrenal (HPA) axis. The results suggested that the drug caused a slight lowering of adrenal corticosteroid secretion, although in no case did plasma cortisol levels go below the lower limit of the normal range.

DIPROLENE AF Cream is indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

CONTRAINDICATIONS

DIPROLENE AF Cream is contraindicated in patients who are hypersensitive to betamethasone dipropionate, to other corticosteroids, or to any ingredient in this preparation.

PRECAUTIONS

General: Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing' syndrome, hyperglycemia, and glucosuria in some patients.

Conditions which augment systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. (See DOSAGE AND ADMINISTRATION section.)

Therefore, patients receiving a large dose 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.

This medication is to be used as directed by the physician and should not be used longer than the prescribed time period. It is for external use only. Avoid contact with the eyes.
Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.
The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive. (See DOSAGE AND ADMINISTRATION section.)
Patients should report any signs of local adverse reactions.

Laboratory Tests: The following tests may be helpful in evaluating 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 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. 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: Use of DIPROLENE AF Cream in children under 12 years is not recommended.

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing' syndrome than mature patients because of a larger skin surface area to body weight ratio.

Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing' 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.

ADVERSE REACTIONS

The only local adverse reaction reported to be possibly or probably related to treatment with DIPROLENE AF Cream during controlled clinical studies was stinging. It occurred in 0.4% of the 242 patients or subjects involved in the studies.

The following local adverse reactions are reported infrequently when topical corticosteroids are used as recommended. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.

OVERDOSAGE

Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS .)

DOSAGE AND ADMINISTRATION

Apply a thin film of DIPROLENE AF Cream to the affected skin areas once or twice daily. Treatment with DIPROLENE AF Cream should be limited to 45 g per week.

DIPROLENE AF Cream is not to be used with occlusive dressings.

HOW SUPPLIED

DIPROLENE AF Cream 0.05% is supplied in 15 g (NDC 0085-0517-01), and 50 g (NDC 0085-0517-04) tubes; boxes of one.

Store between 2° and 30°C (36° and 86°F).

DIPROLENE® AF

brand of augmented
betamethasone dipropionate*

Cream, 0.05*
(potency expressed as betamethasone)

*Vehicle augments the penetration of the steroid.

For Dermatologic Use Only--
Not for Ophthalmic Use

Schering Corporation

Kenilworth, NJ 07033 USA

Rev. 1/99 17968629

18670313T

PRODUCT PHOTO(S):

NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.