Taro-Desoximetasone

TARO-DESOXIMETASONE

Taro Desoximetasone

Topical Corticosteroid

Action and Clinical Pharmacology:

Desoximetasone cream is a potent fluorinated corticosteroid. Topical corticosteroids are synthetic derivatives of cortisone which are effective when applied locally to control many types of inflammatory, allergic and pruritic dermatoses. Modifications to the chemical structure, such as fluorination, generally enhance both anti-inflammatory activity and increase the likelihood of adverse effects. The mechanism of anti-inflammatory activity of topical corticosteroids is generally unclear. However, corticosteroids are thought to induce phospholipase A2 inhibitor proteins, preventing arachidonic acid release and the biosynthesis of potent mediators of inflammation.:

Topical corticosteroids are primarily effective because of their anti-inflammatory, antipruritic and vasoconstrictive actions.

Topical absorption of corticosteroids follow the same pharmacologic fate as systemically administered doses: Corticosteroids in the circulation are bound to plasma proteins, although the fluorinated compounds are bound to a lesser degree, accounting for their increased potency compared to natural corticosteroids.

It is generally known that steroid hormones are metabolized predominantly in the liver and to a lesser extent in the kidney, intestines, spleen, muscles and other tissues and then excreted in the urine as conjugates.

Indications And Clinical Uses :

For the relief of acute or chronic corticosteroid-responsive dermatoses.

Contra-Indications:

In bacterial/fungal skin infections, tuberculosis of the skin, syphilitic skin infections, chicken pox, eruptions following vaccinations and viral diseases of the skin in general. Corticosteroids should not be used in those patients with a history of hypersensitivity to any of the components of the preparation. This formulation contains lanolin and should not be used by patients who may be allergic to wool or wool products.:

Desoximetasone cream is not recommended for ophthalmic use.

Warnings in Clinical States:

Systemic side effects may occur with topical corticosteroid preparations, particularly when these preparations are used over large areas or for an extended period of time or with occlusive dressings, or when used on the face, scalp, axillae and scrotum. A patient who has been on prolonged therapy, especially occlusive therapy, may develop adrenal suppression due to sufficient absorption of the steroid.

Pregnancy and Lactation: The safety of topical corticosteroid preparations during pregnancy and lactation has not been established. The potential benefit should be weighed in these conditions against possible hazard to the fetus or the nursing infant. When indicated, they should not be used extensively, in large amounts or for prolonged periods of time in pregnant patients or nursing mothers.

Precautions:

General: 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, hyperglycemia and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids.

Conditions which augment systemic absorption include application of the more potent steroids, use over a large surface area, prolonged use, occlusive dressings. Patients receiving a large dose of potent topical steroids to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACT stimulation test or other recognized/validated test. 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 topical corticosteroids. Infrequently, signs and symptoms of glucocorticoid insufficiency may occur requiring supplemental systemic corticosteroids. Occlusive dressings should not be applied if body temperature is elevated. To minimize systemic absorption when long-term therapy or large surface area for treatment is likely, periodic interruption of treatment or treatment of one area of the body at a time should be considered.

Children: Children may be more susceptible to systemic toxicity from equivalent doses due to larger skin surface to body mass ratios (see Children below).

Topical corticosteroids, particularly the more potent ones, should be used with caution on lesions close to the eye because systemic absorption may cause increased intraocular pressure, glaucoma, or cataracts.

Prolonged use of topical corticosteroid preparations may produce striae or atrophy of the skin or subcutaneous tissue. Topical corticosteroids should be used with caution on lesions of the face, groin and axillae as these areas are more prone to atrophic changes than other areas of the body. Frequent observation is important if these areas are to be treated. If skin atrophy is observed, treatment should be discontinued.

If irritation develops, desoximetasone cream should be discontinued and appropriate therapy instituted. Allergic contact dermatitis from corticosteroids is usually diagnosed by observing ‘failure to heal’ rather than clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

Suitable precautions should be taken when using topical corticosteroids in patients with stasis dermatitis and other skin diseases with impaired circulation.

If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of desoximetasone cream should be discontinued until the infection has been adequately controlled.

Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.

Pregnancy: Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage. Desoximetasone has been shown to be teratogenic after topical (dermal) or s.c. application of human therapeutic doses. Desoximetasone cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, particularly in the first trimester of pregnancy. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for hypoadrenalism.

Lactation: Systemically administered corticosteroids are secreted into human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause untoward effects. Caution should be exercised when desoximetasone cream is administered to a nursing mother.

Children: Safety and effectiveness of desoximetasone in children and infants have not been established. Because of the higher ratio of skin surface area to body mass, children are at a greater risk than adults for HPA axis suppression when treated with topical corticosteroids. They are also at greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment. Adverse effects including striae have been reported with use of topical corticosteroids in infants and children. 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 ACT stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches and bilateral papilloedema.

Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

Carcinogenesis, Mutagenicity, Reproduction: Long-term animal studies have not been performed to evaluate carcinogenic potential of topical corticosteroids.

Reproduction and teratology studies have been performed in mice, rats and rabbits.

Desoximetasone, given s.c. at the dose of 1 600 g/kg to pregnant mice during gestational days 7 to 15, induced a depression of body weight gain and an expected slight increase in the incidence of cleft palate in the fetuses.

Both desoximetasone and dexamethasone produced an inhibitory effect on the weight gain of adult male and female rats during the premating period. The fertility of rats was not affected by desoximetasone, however, a higher than normal number of resorptions was observed in rats given 100 µg/kg of dexamethasone. Lower dose-dependent birth weights of pups as compared to controls were seen in treated animals, especially in those given dexamethasone.

Administered s.c. to pregnant rats during gestational days 8 to 16, desoximetasone produced, at the doses of 400 and 100 g/kg, depression of body weight gain in the dams during the treatment period. A retardation of ossification of the odontoid process and an increased incidence of lumbar ribs were also noted.

Topical application of 0.25% desoximetasone ointment to the intact skin of rats during gestational days 7 to 16 and of rabbits during gestational days 7 to 19 produced typical corticosteroid effects in treated animals. The dams showed decreased weight gain, increased rate of abortion and ‘in utero’ fetal death. Delivered fetuses exhibited varying degrees of growth retardation and corticosteroid-induced malformations which were dose-dependent.

Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results. Desoximetasone was not mutagenic in the Ames microbial mutagen test, with or without metabolic activation.

Adverse Reactions:

In controlled clinical trials in adults the total incidence of adverse reactions associated with desoximetasone cream 0.25% was approximately 0.8%. These adverse reactions were usually not severe and included burning, folliculitis and folliculo-pustular lesions. Similarly, for desoximetasone cream 0.05%, the total incidence of adverse reactions was also 0.8% and included pruritus, erythema, vesiculation and burning sensation.

The following additional local adverse reactions have been reported with topical cortiocsteroids and may occur more frequently with use of occlusive dressings. These reactions are listed in 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 and miliaria. In addition, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction or discontinuation of potent topical corticosteroid products.

Symptoms And Treatment Of Overdose :

Symptoms: Topically applied desoximetasone cream can be absorbed systemically. Percutaneous absorption is enhanced when large amounts of corticosteroid are applied, when used under occlusive dressings, or when used chronically. Toxic effects of hypercorticism and adrenal suppression may appear. Should toxic effects occur, the dosage of desoximetasone cream should be discontinued slowly, consistent with accepted procedures for discontinuation of chronic steroid therapy. The restoration of hypothalamic-pituitary axis may be slow; during periods of pronounced physical stress (severe infections, trauma, surgery) a supplement with systemic steroids may need to be considered. Toxic effect may include ecchymosis of skin, striae, discoloration or atrophy of the skin, peptic ulceration, hypertension, aggravation of infection, hirsutism, acne, edema, hypokalemia, subcapsular cataracts, muscle weakness and wastage due to protein depletion.Treatment

Treatment: Treatment of a patient with systemic toxic manifestations consists of assuring and maintaining a patent airway and supporting ventilation using oxygen and assisted or controlled respiration as required. This usually will be sufficient in the management of most reactions. Should circulatory depression occur, vasopressors and i.v. fluids may be used. Should a convulsion persist despite oxygen therapy, small increments of ultra-short acting barbiturate (pentobarbital or secobarbital) may be given i.v. Allergic reactions are characterized by cutaneous lesions, urticaria, edema, or anaphylactoid reactions.

Dosage And Administration:

Apply a thin film of cream to the affected skin areas twice daily. Rub in gently and completely.

Total weekly dose should not exceed 45 g in adults. Therapy should be limited to 2 weeks. If a symptomatic response is not noted within a few days to a week, the local applications of corticosteroid should be discontinued and the patient re-evaluated. Therapy should be discontinued as soon as lesions heal. The patient should be kept under close observation if treated with large amounts of topical corticosteroid or with the occlusive technique or with use over a prolonged period of time.

Availability And Storage:

0.05%: Each g of white cream used for topical application contains: desoximetasone 0.5 mg. Nonmedicinal ingredients: cetostearyl alcohol, isopropyl myristate, lactic acid (pH adjustment), lanolin alcohol, mineral oil, sodium edetate, water and white petrolatum. Tubes of 20 and 60 g.

0.25%: Each g of white cream used for topical application contains: desoximetasone 2.5 mg. Nonmedicinal ingredients: cetostearyl alcohol, isopropyl myristate, lanolin alcohol, mineral oil, water and white petrolatum. Tubes of 20 and 60 g.

Store at controlled room temperature, 15 to 25°C.

TARO-DESOXIMETASONE Taro Desoximetasone Topical Corticosteroid

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