Desoximetasone

Desoximetasone Topical Spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1) Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1) Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. (5.1) Modify use if HPA axis suppression develops. (5.1) High potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure and young age may predispose patients to HPA axis suppression. (5.1) Pediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. (5.1, 8.4) Desoximetasone Topical Spray is flammable; keep away from heat or flame. (5.5)

5.1Effect on Endocrine System Desoximetasone Topical

Spray is a topical corticosteroid that has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. In a study including 21 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, adrenal suppression was identified in 1 out of 12 subjects having involvement of 10 to 15% of body surface area (BSA) and 2 out of 9 subjects having involvement of >15% of BSA after treatment with Desoximetasone Topical Spray twice a day for 28 days. [see Clinical Pharmacology (12.2)] Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of high potency steroids, larger treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure and young age. An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure. Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. [see Use in Specific Populations (8.4)]

5.2Local Adverse Reactions with Topical Corticosteroids

Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. 5.3 Allergic Contact Dermatitis with Topical Corticosteroids Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing. 5.4 Concomitant Skin Infections Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, Desoximetasone Topical Spray should be discontinued until the infection has been adequately treated. 5.5 Flammable Contents Desoximetasone Topical Spray is flammable; keep away from heat or flame.

The most common adverse reactions (≥ 1%) are application site dryness, application site irritation and application site pruritus. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals, U.S.A., Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In randomized, multicenter, prospective vehicle-controlled clinical trials, subjects with moderate to severe plaque psoriasis of the body applied Desoximetasone Topical Spray or vehicle spray twice daily for 4 weeks. A total of 149 subjects applied Desoximetasone Topical Spray. Adverse reactions that occurred in ≥ 1% of subjects treated with Desoximetasone Topical Spray were application site dryness (2.7%), application site irritation (2.7%) and application site pruritus (2.0%). Another less common adverse reaction (<1% but >0.1%) was folliculitis. Table 1. Number (%) of Subjects with Adverse Reactions Occurring in ≥ 1% Desoximetasone Topical Spray, 0.25% b.i.d. (N = 149) Vehicle spray b.i.d. (N = 135) Number of Subjects with Adverse Reactions 13 (8.7%) 18 (13.3%) Application site dryness 4 (2.7%) 7 (5.2%) Application site irritation 4 (2.7%) 5 (3.7%) Application site pruritus 3 (2.0%) 5 (3.7%)

8.1Pregnancy Teratogenic Effects: Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Desoximetasone Topical Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Desoximetasone has been shown to be teratogenic and embryotoxic in mice, rats, and rabbits when given by subcutaneous or dermal routes of administration at doses 3 to 30 times the human dose of Desoximetasone Topical Spray based on a body surface area comparison. 8.3 Nursing Mothers Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, caution should be exercised when Desoximetasone Topical Spray is administered to a nursing woman. If used during lactation, Desoximetasone Topical Spray should not be applied on the chest to avoid accidental ingestion by the infant. 8.4 Pediatric Use Safety and effectiveness of Desoximetasone Topical Spray in patients younger than 18 years of age have not been studied; therefore use in pediatric patients is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. [see Warnings and Precautions (5.1)] HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. [see Warnings and Precautions (5.1)]

8.5Geriatric

Use Clinical studies of Desoximetasone Topical Spray did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.