DESOXIMETASONE: 11,635 Adverse Event Reports & Safety Profile

DESCRIPTION Desoximetasone cream USP, 0.05%, desoximetasone cream USP, 0.25%, and desoximetasone gel USP, 0.05% contain the active synthetic corticosteroid desoximetasone. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents. Each gram of desoximetasone cream USP, 0.05% contains 0.5 mg of desoximetasone in an emollient cream base consisting of cetostearyl alcohol, edetate disodium, isopropyl myristate, lanolin alcohol, mineral oil, purified water, and white petrolatum. Each gram of desoximetasone cream USP, 0.25% contains 2.5 mg of desoximetasone in an emollient cream base consisting of cetostearyl alcohol, isopropyl myristate, lanolin alcohol, mineral oil, purified water, and white petrolatum. Each gram of desoximetasone gel USP, 0.05% contains 0.5 mg of desoximetasone in a gel base consisting of carbomer 940, docusate sodium, edetate disodium, isopropyl myristate, purified water, SDAG-3 95% alcohol, and trolamine. The chemical name of desoximetasone is Pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 21-dihydroxy-16-methyl-,(11ß,16α)-. Desoximetasone has the molecular formula C 22 H 29 FO 4 and a molecular weight of 376.47. The CAS Registry Number is 382-67-2. The structural formula is: Chemical Structure

AND USAGE Desoximetasone topical spray, 0.25% is a corticosteroid indicated for the treatment of plaque psoriasis in patients 18 years of age or older ( 1 ). Desoximetasone topical spray, 0.25% is a corticosteroid indicated for the treatment of plaque psoriasis in patients 18 years of age or older.

AND ADMINISTRATION Apply Desoximetasone Topical Spray as a thin film to the affected skin areas twice daily. Rub in gently. The treated skin area should not be bandaged or otherwise covered or wrapped unless directed by the physician.

Desoximetasone Topical

Spray should be discontinued when control is achieved. Treatment beyond 4 weeks is not recommended. Do not use if atrophy is present at the treatment site. Avoid use on the face, axilla or groin.

Desoximetasone Topical

Spray is for external use only. It is not for oral, ophthalmic, or intravaginal use. Apply a thin film to the affected skin areas twice daily. Rub in gently. ( 2 )

Desoximetasone Topical

Spray should be discontinued when control is achieved. ( 2 ) Treatment beyond 4 weeks is not recommended. ( 2 ) Do not use if atrophy is present at the treatment site. ( 2 ) Do not use with occlusive dressings, unless directed by the physician ( 2 ) Avoid use on the face, axilla or groin. ( 2 )

Desoximetasone Topical

Spray is not for oral, ophthalmic, or intravaginal use. ( 2 )

CONTRAINDICATIONS Desoximetasone cream USP, 0.05%, desoximetasone cream USP, 0.25%, and desoximetasone gel USP, 0.05% are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

REACTIONS 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 Lupin Pharmaceuticals, Inc. at 1-800-399-2561 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, 0.25% or vehicle spray twice daily for 4 weeks. A total of 149 subjects applied desoximetasone topical spray, 0.25%. Adverse reactions that occurred in ≥ 1% of subjects treated with desoximetasone topical spray, 0.25% are presented in Table 1.

Table

1. Number (%) of Subjects with Adverse Reactions Occurring in ≥ 1% Another less common adverse reaction (<1% but >0.1%) was folliculitis.

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%) Another less common adverse reaction (<1% but >0.1%) was folliculitis.

6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Postmarketing reports for local adverse reactions to topical corticosteroids included atrophy, striae, telangiectasias, itching, dryness, hypopigmentation, perioral dermatitis, secondary infection, and miliaria. Ophthalmic adverse reactions of cataracts, glaucoma, and increased intraocular pressure have been reported during use of topical corticosteroids.

AND PRECAUTIONS Effect on Endocrine System: Desoximetasone topical spray, 0.25% 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. Safety and effectiveness have not been established in pediatric patients and use in pediatric patients is not recommended. ( 5.1 , 8.4 )

Ophthalmic Adverse

Reactions: Topical corticosteroid products may increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. ( 5.3 .). Flammability: Desoximetasone topical spray, 0.25% is flammable; keep away from heat or flame. ( 5.6 )

5.1 Effect on Endocrine System Desoximetasone topical spray, 0.25% 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 &gt;15% of BSA after treatment with desoximetasone topical spray, 0.25% twice a day for 28 days. <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.2 )]</span> 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&apos;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. Use in patients under 18 years of age is not recommended due to numerically high rates of HPA axis suppression (the safety and effectiveness of desoximetasone topical spray, 0.25% have not been established in pediatric patients) <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.4 ) and Clinical Pharmacology ( 12.2 )]</span>

5.2 Local 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 Ophthalmic Adverse Reactions Use of topical corticosteroids, including Desoximetasone topical spray, 0.25%, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported with the postmarketing use of topical corticosteroid products <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span> . Avoid contact of Desoximetasone topical spray, 0.25% with eyes. Desoximetasone topical spray, 0.25% may cause eye irritation. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

5.4 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.

5.5 Concomitant Skin Infections Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, desoximetasone topical spray, 0.25% should be discontinued until the infection has been adequately treated.

5.6 Flammability Desoximetasone topical spray, 0.25% is flammable; keep away from heat or flame.

PRECAUTIONS General Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. 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 more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure. 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.

Local 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.

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.

Concomitant Skin Infections

Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, desoximetasone cream USP, 0.05%, desoximetasone cream USP, 0.25%, or desoximetasone gel USP, 0.05% should be discontinued until the infection has been adequately treated. Information for the Patient Patients using topical corticosteroids should receive the following information and instructions: This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. Patients should report any signs of local adverse reactions, especially under occlusive dressings. Other corticosteroid-containing products should not be used with desoximetasone cream USP, 0.05%, desoximetasone cream USP, 0.25%, or desoximetasone gel USP, 0.05% without first consulting with the physician. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician.

Laboratory Tests

The following tests may be helpful in evaluating the hypothalamic-pituitary-adrenal (HPA) axis suppression: Urinary free cortisol test ACTH stimulation test Carcinogenesis, Mutagenesis, and Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Desoximetasone was nonmutagenic in the Ames test.

Pregnancy Teratogenic Effects Pregnancy

Category C 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. Desoximetasone has been shown to be teratogenic and embryotoxic in mice, rats, and rabbits when given by subcutaneous or dermal routes of administration in doses 3 to 30 times the human dose of desoximetasone cream USP, 0.25% and 15 to 150 times the human dose of desoximetasone cream USP, 0.05%, or desoximetasone gel USP, 0.05%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, desoximetasone cream USP, 0.05%, desoximetasone cream USP, 0.25%, or desoximetasone gel USP, 0.05%, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

Nursing

Mothers It is not known whether topical administration of corticosteroids could 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, caution should be exercised when topical corticosteroids are administered to a nursing woman.

Pediatric Use

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio. Hypothalamic-pituitary-adrenal (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 absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of pediatric patients.