Each gram of Betamethasone (DIPROLENE) Ointment 640 mcg betamethasone dipropionate (equivalent to 500 mcg betamethasone).
Betamethasone (DIPROLENE) Ointment contain betamethasone dipropionate, a synthetic corticosteroid with anti-inflammatory activity to be administered topically.
Betamethasone dipropionate is a white to creamy white odorless crystalline powder insoluble in water; freely soluble in acetone and in chloroform; sparingly soluble in alcohol.
It has a molecular weight of 504.16 and the empirical formula C28H37FO7; a chemical name of 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione,17,21-dipropionate.
Pharmacology: 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, arachidonic acid. Arachidonic 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.
In patients with psoriasis, application of 14 grams per day (7 grams twice daily) of Betamethasone (DIPROLENE) Cream for eight days produced depressed adrenocortical hormonal levels in plasma. Shortly after treatment cessation, adrenal output returned to normal. Application of 7 grams per day (once daily or 3.5 grams twice daily) of Betamethasone (DIPROLENE) Cream for one, two or three weeks produced hypothalamic-pituitary-adrenal (HPA) axis suppression in patients with psoriasis or atopic dermatitis. Suppression of HPA axis in these patients was usually mild to moderate, transient, and returned to normal during treatment or shortly after treatment cessation.
At 14 grams per day for nine days, Betamethasone (DIPROLENE) Ointment was shown to depress plasma cortisol levels following repeated applications to diseased skin in patients with psoriasis. These effects were reversible upon discontinuation of treatment. At 7 grams per day (applied as 3.5 grams twice daily), Betamethasone (DIPROLENE) Ointment was shown to cause minimal inhibition of the HPA axis when applied for two to three weeks in normal patients and in patients with psoriasis and eczematous disorders. With 6 to 7 grams of Betamethasone (DIPROLENE) Ointment applied once daily for three weeks, no significant inhibition of the HPA axis was observed in patients with psoriasis and atopic dermatitis, as measured by plasma cortisol and 24-hour urinary 17-hydroxy-corticosteroid levels.
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: Preclinical information: 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 on 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.
Studies in rabbits, mice, and rats using intramuscular doses up to 1, 33, and 2 mg/kg respectively, resulted in dose related increases in fetal resorptions in the rabbits and mice.
Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. Betamethasone dipropionate has 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. This dose is approximately 26 times the human topical dose of Betamethasone (DIPROLENE) assuming human percutaneous absorption of approximately 3% and the use in a 70 kg person of 7 g per day. 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 resorptions also was observed at both dose 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 teratogenic after dermal application.
Betamethasone (DIPROLENE) Ointment are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses.
For Dermatologic Use Only.
Apply a thin film of Betamethasone (DIPROLENE) Ointment to the affected areas once or twice daily. Treatment with Betamethasone (DIPROLENE) Ointment should be limited to 50 grams per week.
Extensive, 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 a less potent steroid.
Betamethasone (DIPROLENE) Ointment are contraindicated in those patients with a history of sensitivity to betamethasone dipropionate, other corticosteroids or to any of the components in these preparations.
General: Systemic absorption of topical corticosteroids can produce reversible 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.
Therefore, patients who apply a large dose of a potent topical steroid 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 corticosteroid. 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 in 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 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 corticosteroid should be discontinued until the infection has been controlled adequately.
Betamethasone (DIPROLENE) is not for ophthalmic use.
Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes of visual disturbances which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Drug Abuse and Dependence: There is no information to indicate that abuse or dependency occurs with betamethasone dipropionate.
Other Relevant and Safety Information: None.
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. 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 the drug, taking into account the importance of the drug to the mother.
Use in Children: Safety and effectiveness of Betamethasone (DIPROLENE) products in pediatric patients have not been established. Therefore, use of Betamethasone (DIPROLENE) products in pediatric patients under 12 years of age is not recommended. Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and to exogenous corticosteroid effects than adult mature 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 children 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.
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.
Nursing Mothers: It is not known whether topical administration of corticosteroids would 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 the drug, taking into account the importance of the drug to the mother.
The following local adverse reactions have been reported with Betamethasone (DIPROLENE):
Burning/stinging, dry skin, pruritis and irritation, tingling, prickly skin, tightening or cracking of skin, warm feeling, laminar and perilesional scaling, follicular rash, skin atrophy, erythema and telangiectasia.
Erythema, folliculitis, pruritis/itching, and vesiculation.
Other local adverse reactions that have been reported with the use of topical corticosteroids include: hypertrichosis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin disorders (examples of which include skin atrophy and dryness), striae and miliaria.
Systemic adverse reactions, such as vision blurred, have also been reported with the use of topical corticosteroids.
Drug Interactions: No data available.
Interference with Laboratory Tests: None identified.
D07AC01 - betamethasone ; Belongs to the class of potent (group III) corticosteroids. Used in the treatment of dermatological diseases.