DIPROSONE Cream provides in each gram 0.64 mg of betamethasone dipropionate, equivalent to 0.5 mg (0.05%) of betamethasone in a hydrating, hypo-allergenic paraben free cream base containing white petrolatum, mineral oil, cetomacrogol 1000, cetostearyl alcohol, sodium phosphate monobasic dihydrate and phosphoric acid with chlorocresol as a preservative.
Betamethasone dipropionate, a synthetic fluorinated corticosteroid, has the chemical name 9α-fluoro-16 β-methylprednisolone-17, 21-dipropionate.
DIPROSONE Cream is effective because of its anti-inflammatory, antipruritic and vasoconstrictive action. DIPROSONE Cream demonstrates these activities in a sustained manner, thereby permitting twice a day or, in some cases, once-a-day application.
Pharmacology: Pharmacodynamics: 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. While the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in each disease are uncertain. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes, by inhibiting the release of their common precursor, arachadonic acid. Arachadonic acid is released from membrane phospholipids by phospholipase A. 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.
While topical corticosteroids can be absorbed from normal intact skin, dermal inflammation and/or other dermatologic disease processes may increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids.
Pharmacokinetics: After dermal absorption, topical corticosteroids enter pharmacokinetic pathways similar to those of systemically administered corticosteroids. In varying degrees, corticosteroids are bound to plasma proteins. They are metabolized primarily in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites undergo biliary excretion.
Toxicology: Carcinogenesis, Mutagenesis and Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential of betamethasone dipropionate or the effect of fertility of topically applied corticosteroids.
Betamethasone dipropionate was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in vitro human lymphocyte chromosome aberration assay, and equivocal in the in vivo mouse bone marrow micronucleus assay. This pattern of response is similar to that of dexamethasone and hydrocortisone.
Betamethasone dipropionate had been shown to be fetotoxic (increased incidence of resorptions) and teratogenic in rabbits when given by the intramuscular route at doses of 0.015 and 0.05 mg/kg. The abnormalities observed included umbilical hernias (0.015 and 0.05 mg/kg), cephalocele and cleft palate (0.05 mg/kg); an increased incidence of resoprtions also was observed at both levels.
Other corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels, and some corticosteroids have been shown to be teratogenic after dermal application.
DIPROSONE Cream is indicated for the relief of the inflammatory manifestations of corticosteroid-responsive dermatoses such as: psoriasis, contact dermatitis (dermatitis venenata), atopic dermatitis (infantile eczema, allergic dermatitis), neurodermatitis (lichen simplex chronicus), lichen palnus, eczema (including nummular eczema, hand eczema, eczematous dermatitis), intertrigo, dyshidrosis (pompholyx), seborrheic dermatitis, exfoliative dermatitis, solar dermatitis, stasis dermatitis and anogenital and senile pruritus.
A thin film of DIPROSONE Cream should be applied to cover completely the affected area twice daily, in the morning and at night. For some patients adequate maintenance therapy may be achieved with less frequent application. In some cases of moderate to severe psoriasis or atopic dermatitis, once-a-day application may suffice.
Excessive prolonged use of topical steroids can suppress hypothalamic-pituitary adrenal function resulting in adrenal insufficiency. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, reduce the frequency of application, or to substitute with a less potent steroid.
DIPROSONE Cream is contraindicated in those patients with a history of sensitivity to betamethasone dipropionate, other corticosteroids or to any of the components in these preparations.
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 also can be produced in some patients by systemic absorption of topical corticosteroids while on treatment. Patients receiving a large dose of potent topical steroid applied to a large surface area should be evaluated periodically for evidence of HPA axis suppression. 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 corticosteroids.
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.
Any of the side effects that are reported following systemic use of corticosteroids, including adrenal suppression, may also occur with topical corticosteroids, especially infants and children.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios.
If irritation or sensitization develops, treatment 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 corticosteroids should be discontinued until the infection has been controlled adequately.
DIPROSONE Cream is not for ophthalmic use.
Use in children: Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and to exogenous corticosteroid effects than adult patients because of greater absorption due to a larger skin surface area to body weight ratio. HPA axis suppression, Cushing's syndrome and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels and an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include a bulging fontanelle, headaches and bilateral papilledema.
Use in pregnancy: There are no adequate and well controlled studies of the teratogenic potential of topically applied corticosteroids in pregnant women. Therefore topical steroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: It is not known whether topical administration of corticosteroids would result in sufficient systemic absorption to produce detectable quantities in breast milk. Caution should be exercised when this product is administered to nursing mothers.
The following local adverse reactions have been reported with the use of DIPROSONE include: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
Incompatibilities: No known data.
D07AC01 - betamethasone ; Belongs to the class of potent (group III) corticosteroids. Used in the treatment of dermatological diseases.
Cream 0.05% (smooth, uniform white) x 5 g, 15 g.