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Betsolan Actions |
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Pharmacology:
Topical corticosteroids, such as Betsolan dipropionate, are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, antipruritic 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 Betsolan 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 Betsolan 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, Betsolan 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), Betsolan 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 Betsolan 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 Betsolan dipropionate or the effect on fertility of topically applied corticosteroids.
Betsolan 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. Betsolan 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 Betsolan 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.
A nurse or other trained health professional will give you Betsolan sodium phosphate and Betsolan acetate. It may be given as a shot into a muscle, joint, or skin, or as a shot into a lesion on your skin.
You may need to be on a salt-restricted diet or take potassium supplements when you receive Betsolan sodium phosphate and Betsolan acetate. Talk to your doctor if you have concerns.
Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.
Your doctor may occasionally change your dose to make sure you get the best results from this medication.
Your steroid medication needs may change if you have unusual stress such as a serious illness, fever or infection, or if you have surgery or a medical emergency. Tell your doctor about any such situation that affects you.
Measure the liquid form of Betsolan with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using Betsolan.
Do not stop using Betsolan suddenly, or you could have unpleasant withdrawal symptoms. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication.
Carry an ID card or wear a medical alert bracelet stating that you are taking a steroid, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are taking steroid medication.
Store Betsolan at room temperature away from moisture and heat.
Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Betsolan dipropionate lotion (augmented), 0.05% in corticosteroid responsive dermatoses is unknown.
Vasoconstrictor Assay
Trials performed with Betsolan dipropionate lotion (augmented), 0.05% indicate that it is in the super-high range of potency as demonstrated in vasoconstrictor trials in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.
No pharmacokinetic trials have been conducted with Betsolan dipropionate lotion (augmented), 0.05%.
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 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.
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.
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Information checked by Dr. Sachin Kumar, MD Pharmacology
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