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1 INDICATIONS AND USAGE Desoximetasone Topical Spray is a corticosteroid indicated for the treatment of plaque psoriasis in patients 18 years of age or older. Desoximetasone Topical Spray is a corticosteroid indicated for the treatment of plaque psoriasis in patients 18 years of age or older ( 1 ).

2 DOSAGE 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 )

5 WARNINGS AND PRECAUTIONS 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 ) 5.1 Effect 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) ] 5.2 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.

ly 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.

6 ADVERSE 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 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%)

<table width="75%"><caption>Table 1. Number (%) of Subjects with Adverse Reactions Occurring in &#x2265; 1%</caption><col width="40%" align="left" valign="middle"/><col width="30%" align="center" valign="middle"/><col width="30%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule" valign="top">Desoximetasone Topical Spray, 0.25% <content styleCode="italics">b.i.d.</content> (N = 149) </th><th styleCode="Rrule" valign="top">Vehicle spray <content styleCode="italics">b.i.d.</content> (N = 135) </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Number of Subjects with Adverse Reactions</td><td styleCode="Rrule">13 (8.7%)</td><td styleCode="Rrule">18 (13.3%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Application site dryness</td><td styleCode="Rrule">4 (2.7%)</td><td styleCode="Rrule">7 (5.2%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Application site irritation</td><td styleCode="Rrule">4 (2.7%)</td><td styleCode="Rrule">5 (3.7%)</td></tr><tr><td styleCode="Lrule Rrule">Application site pruritus</td><td styleCode="Rrule">3 (2.0%)</td><td styleCode="Rrule">5 (3.7%)</td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 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) ] 8.5 Geriatric 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.

8.1 Pregnancy 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.

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) ]

8.5 Geriatric 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.

11 DESCRIPTION Desoximetasone Topical Spray, 0.25% contains desoximetasone as the active ingredient. Desoximetasone is a corticosteroid with the chemical name of pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 21-dihydroxy-16-methyl-, (11β,16α)-. Desoximetasone has the molecular formula of 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: Each gram of Desoximetasone Topical Spray contains 2.5 mg of desoximetasone in a clear, colorless liquid with the following inactive ingredients: glyceryl oleate, isopropyl alcohol (23.4%), isopropyl myristate, L-menthol, and mineral oil. Desoximetasone Topical Spray is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing to patients. Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Corticosteroids play a role in cellular signaling, immune function, inflammation and protein regulation; however, the precise mechanism of action in psoriasis is unknown. 12.2 Pharmacodynamics Vasoconstrictor studies performed with Desoximetasone Topical Spray in healthy subjects indicate that it is in the high to super-high range of potency as compared with other topical corticosteroids. The potential for hypothalamic-pituitary-adrenal (HPA) axis suppression was evaluated in a study of 24 adult subjects with moderate to severe plaque psoriasis. Desoximetasone Topical Spray was applied twice a day for 28 days. Twenty-one subjects had evaluable serum cortisol levels. The proportion of subjects demonstrating HPA axis suppression was 8.3% (1 out of 12) in subjects having psoriasis involvement of 10 to 15% of body surface area (BSA), and 22.2% (2 out of 9) in subjects having psoriasis involvement of > 15% of their BSA. In this study HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30-min post cosyntropin stimulation. In the 2 subjects with available follow-up values, suppression reversed 28 days after the end of treatment. 12.3 Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Plasma concentrations of desoximetasone were measured at two single random time points in the HPA axis suppression trial in 24 subjects with psoriasis [ see Clinical Pharmacology (12.2) ]. The mean (% Coefficient of Variation) concentration of desoximetasone was 449 pg/mL (86%) at Day 14 and 678 pg/mL (135%) at Day 28. The concentration time profile following application of Desoximetasone Topical Spray is not known.

12.2 Pharmacodynamics Vasoconstrictor studies performed with Desoximetasone Topical Spray in healthy subjects indicate that it is in the high to super-high range of potency as compared with other topical corticosteroids. The potential for hypothalamic-pituitary-adrenal (HPA) axis suppression was evaluated in a study of 24 adult subjects with moderate to severe plaque psoriasis. Desoximetasone Topical Spray was applied twice a day for 28 days. Twenty-one subjects had evaluable serum cortisol levels. The proportion of subjects demonstrating HPA axis suppression was 8.3% (1 out of 12) in subjects having psoriasis involvement of 10 to 15% of body surface area (BSA), and 22.2% (2 out of 9) in subjects having psoriasis involvement of > 15% of their BSA. In this study HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30-min post cosyntropin stimulation. In the 2 subjects with available follow-up values, suppression reversed 28 days after the end of treatment.

12.3 Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Plasma concentrations of desoximetasone were measured at two single random time points in the HPA axis suppression trial in 24 subjects with psoriasis [ see Clinical Pharmacology (12.2) ]. The mean (% Coefficient of Variation) concentration of desoximetasone was 449 pg/mL (86%) at Day 14 and 678 pg/mL (135%) at Day 28. The concentration time profile following application of Desoximetasone Topical Spray is not known.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of Desoximetasone Topical Spray. In a 13-week repeat-dose toxicity study in rats, topical administration of desoximetasone spray at concentrations of 0.001, 0.005 and 0.02% BID (which corresponds to dose levels of 0.01, 0.05, or 0.2 mg/kg/dose BID, respectively) resulted in a toxicity profile consistent with long-term exposure to corticosteroids, including adrenal atrophy and histopathological changes in several organ systems indicative of severe immune suppression. A no observable adverse effect level (NOAEL) could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk for carcinogenesis. Desoximetasone revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster ovary cell chromosome aberration assay) and one in vivo genotoxicity test (mouse bone marrow micronucleus assay). No evidence of impairment of male or female fertility was observed at subcutaneous desoximetasone doses up to 0.1 mg/kg/day (0.6 mg/m 2 /day) in Sprague-Dawley rats.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of Desoximetasone Topical Spray. In a 13-week repeat-dose toxicity study in rats, topical administration of desoximetasone spray at concentrations of 0.001, 0.005 and 0.02% BID (which corresponds to dose levels of 0.01, 0.05, or 0.2 mg/kg/dose BID, respectively) resulted in a toxicity profile consistent with long-term exposure to corticosteroids, including adrenal atrophy and histopathological changes in several organ systems indicative of severe immune suppression. A no observable adverse effect level (NOAEL) could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk for carcinogenesis. Desoximetasone revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster ovary cell chromosome aberration assay) and one in vivo genotoxicity test (mouse bone marrow micronucleus assay). No evidence of impairment of male or female fertility was observed at subcutaneous desoximetasone doses up to 0.1 mg/kg/day (0.6 mg/m 2 /day) in Sprague-Dawley rats.

14 CLINICAL STUDIES Two multi-center, randomized, double-blind, vehicle-controlled clinical trials were conducted in 239 subjects aged 18 years and older with moderate to severe plaque psoriasis of the body. In both trials, randomized subjects applied Desoximetasone Topical Spray or vehicle spray to the affected areas twice daily for 4 weeks. Enrolled subjects had a minimum body surface area of involvement of 10%, and a Physician's Global Assessment score (PGA) of 3 (moderate) or 4 (severe). Efficacy was assessed at Week 4 as the proportion of subjects who were considered a Clinical Success ("clear" (0) or "almost clear" (1) according to the PGA scale). Table 2 presents the efficacy results. Table 2. Number of Subjects (%) with Clinical Success (scored as clear or almost clear) at Week 4. Parameter Trial 1 Trial 2 Desoximetasone Vehicle Desoximetasone Vehicle N=59 N=60 N=60 N=60 Clinical Success 18 (30.5%) 3 (5.0%) 32 (53.3%) 11 (18.3%)

<table width="75%"><caption>Table 2. Number of Subjects (%) with Clinical Success (scored as clear or almost clear) at Week 4.</caption><col width="20%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Parameter</th><th colspan="2" styleCode="Botrule Rrule">Trial 1</th><th colspan="2" styleCode="Botrule Rrule">Trial 2</th></tr><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">Desoximetasone</th><th styleCode="Rrule">Vehicle</th><th styleCode="Rrule">Desoximetasone</th><th styleCode="Rrule">Vehicle</th></tr><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">N=59</th><th styleCode="Rrule">N=60</th><th styleCode="Rrule">N=60</th><th styleCode="Rrule">N=60</th></tr></thead><tbody><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Clinical Success</content></td><td styleCode="Rrule">18 (30.5%)</td><td styleCode="Rrule">3 (5.0%)</td><td styleCode="Rrule">32 (53.3%)</td><td styleCode="Rrule">11 (18.3%)</td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied/Storage Desoximetasone Topical Spray, 0.25% is a clear colorless liquid supplied in white, opaque bottles with white, opaque screw caps in the following sizes: 30 mL 50 mL 100 mL (2-50 mL bottles) 100 mL (NDC 51672-1396-3) (NDC 51672-1396-4) (NDC 51672-1396-6) (NDC 51672-1396-7) Store at controlled room temperature between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature] Spray is flammable; avoid heat, flame or smoking when using this product. Each unit is co-packaged with a manual spray pump for installation by the pharmacist. 16.2 Instructions for the Pharmacist Remove the spray pump from the wrapper Remove and discard the cap from the bottle Keeping the bottle vertical, insert the spray pump into the bottle and turn clockwise until well-fastened Dispense the bottle with the spray pump inserted Label the bottle with "discard the product 30 days after dispensing"

<table width="75%" styleCode="Noautorules"><col width="50%" align="left" valign="top"/><col width="50%" align="left" valign="top"/><tbody><tr><td><list listType="unordered" styleCode="Disc"><item>30 mL</item><item>50 mL</item><item>100 mL (2-50 mL bottles)</item><item>100 mL</item></list></td><td><list listType="unordered"><item>(NDC 51672-1396-3)</item><item>(NDC 51672-1396-4)</item><item>(NDC 51672-1396-6)</item><item>(NDC 51672-1396-7)</item></list></td></tr></tbody></table>

Store at controlled room temperature between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature] Spray is flammable; avoid heat, flame or smoking when using this product. Each unit is co-packaged with a manual spray pump for installation by the pharmacist.

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling ( Patient Information and Instructions for Use ) Inform patients of the following: Use this medication as directed by the physician. Desoximetasone Topical Spray is for external use only. Avoid use on the face, axilla or groin. Do not to use this medication for any disorder other than that for which it was prescribed. Do not bandage or otherwise cover or wrap the treated skin so as to be occlusive. Report any signs of local or systemic adverse reactions to the physician. Do not use other corticosteroid-containing products with Desoximetasone Topical Spray without first consulting with the physician. Discontinue therapy when control is achieved. If no improvement is seen within 4 weeks, contact the physician. This medication is flammable; avoid heat, flame, or smoking when applying this product. Discard this product 30 days after dispensed by pharmacist.

Instructions for Use Desoximetasone (des ox'' i met' a sone) Topical Spray Important information: Desoximetasone Topical Spray is for use on skin only. Do not get Desoximetasone Topical Spray near or in your mouth, eyes or vagina. Read the Instructions for Use that comes with Desoximetasone Topical Spray before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. Parts of Desoximetasone Topical Spray bottle (See Figure A ) Figure A How to apply Desoximetasone Topical Spray: Step 1: Remove the cap from the pump top. Step 2: Hold the bottle in an upright position while pointing the opening of the pump top in the direction of the affected area. To spray, push down on the pump top. Apply Desoximetasone Topical Spray to the affected area as instructed by your doctor. ( See Figure B ) Figure B Step 3: Spray only enough Desoximetasone Topical Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Desoximetasone Topical Spray gently. Figure C Repeat Steps 2 and 3 to apply Desoximetasone Topical Spray to other affected areas as instructed by your doctor. Step 4: After applying Desoximetasone Topical Spray, place the cap back onto the pump top. ( See Figure D ) This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1 Dist. by: Taro Pharmaceuticals U.S.A., Inc. , Hawthorne, NY 10532 Issued: April, 2018 PPK-8768-0 167 Figure A Figure B Figure C Figure D

<table width="100%" styleCode="Noautorules"><col width="100%" align="left" valign="middle"/><tbody><tr styleCode="Botrule"><td styleCode="Toprule Lrule Rrule"><content styleCode="bold">Important information: Desoximetasone Topical Spray is for use on skin only.</content>Do not get Desoximetasone Topical Spray near or in your mouth, eyes or vagina. </td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="100%" align="center" valign="middle"/><tbody><tr><td><content styleCode="bold">Parts of Desoximetasone Topical Spray bottle (See <linkHtml href="#figa">Figure A</linkHtml>) </content></td></tr><tr><td><renderMultiMedia ID="figa" referencedObject="MM2"/></td></tr><tr><td><content styleCode="bold">Figure A</content> </td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="25%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><tbody><tr><td><content styleCode="bold">Step 2:</content>Hold the bottle in an upright position while pointing the opening of the pump top in the direction of the affected area. To spray, push down on the pump top. Apply Desoximetasone Topical Spray to the affected area as instructed by your doctor. ( <content styleCode="bold">See <linkHtml href="#figb">Figure B</linkHtml></content>) </td><td align="center"><renderMultiMedia ID="figb" referencedObject="MM3"/> <content styleCode="bold">Figure B</content></td><td><content styleCode="bold">Step 3:</content>Spray only enough Desoximetasone Topical Spray to cover the affected area, for example, the elbow <content styleCode="bold">(See <linkHtml href="#figc">Figure C</linkHtml></content>). Rub in Desoximetasone Topical Spray gently. </td><td align="center"><renderMultiMedia ID="figc" referencedObject="MM4"/> <content styleCode="bold">Figure C</content></td></tr></tbody></table>

PATIENT INFORMATION Desoximetasone (des ox'' i met' a sone) Topical Spray Issued: April, 2018 PPK-8768-0 167 Important information: Desoximetasone Topical Spray is for use on skin only. Do not get Desoximetasone Topical Spray near or in your eyes, mouth or vagina. What is Desoximetasone Topical Spray? Desoximetasone Topical Spray is a prescription corticosteroid medicine used to treat plaque psoriasis of the body in people 18 years of age and older. You should not use Desoximetasone Topical Spray on your face, underarms (armpits), or groin areas. It is not known if Desoximetasone Topical Spray is safe and effective in children under 18 years of age. Desoximetasone Topical Spray should not be used in children under 18 years of age. Before you use Desoximetasone Topical Spray, tell your doctor if you: are allergic to any of the ingredients in Desoximetasone Topical Spray. See the end of this leaflet for a list of the ingredients in Desoximetasone Topical Spray. have a skin infection. You may need medicine to treat the skin infection before you use Desoximetasone Topical Spray. have thinning of the skin (atrophy) at the treatment site have any other medical conditions are pregnant or plan to become pregnant. It is not known if Desoximetasone Topical Spray will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Desoximetasone Topical Spray passes into your breast milk. Do not apply Desoximetasone Topical Spray to your chest area if you are breastfeeding. This will help to prevent your baby from accidentally getting Desoximetasone Topical Spray into the mouth. Tell your doctor about all the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Especially tell your doctor if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids. What should I avoid while using Desoximetasone Topical Spray? Desoximetasone Topical Spray is flammable. Avoid heat, flames or smoking while applying Desoximetasone Topical Spray to your skin. How should I use Desoximetasone Topical Spray? Use Desoximetasone Topical Spray exactly as your doctor tells you to use it. Apply Desoximetasone Topical Spray 2 times a day. Do not bandage, cover, or wrap the treated skin area. Desoximetasone Topical Spray should be used for the shortest amount of time needed to treat your plaque psoriasis. Tell your doctor if your skin condition is not getting better after 4 weeks of using Desoximetasone Topical Spray. You should not use Desoximetasone Topical Spray for longer than 4 weeks. Wash your hands after applying Desoximetasone Topical Spray. Safely throw away (discard) any unused Desoximetasone Topical Spray after 30 days. See the " Instructions for Use " at the end of the Patient Information for detailed information about the right way to apply Desoximetasone Topical Spray. What are the possible side effects of Desoximetasone Topical Spray? Desoximetasone Topical Spray may cause serious side effects, including: Desoximetasone Topical Spray can pass through your skin. Too much Desoximetasone Topical Spray passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check for adrenal gland problems. The most common side effects of Desoximetasone Topical Spray include dryness, irritation and itching of skin at the treated site.

your skin. Too much Desoximetasone Topical Spray passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check for adrenal gland problems. The most common side effects of Desoximetasone Topical Spray include dryness, irritation and itching of skin at the treated site. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Desoximetasone Topical Spray. For more information, ask your doctor. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov. How should I store Desoximetasone Topical Spray? Store Desoximetasone Topical Spray at room temperature between 68˚F to 77˚F (20˚C to 25˚C). Keep Desoximetasone Topical Spray and all medicines out of the reach of children. General information about the safe and effective use of Desoximetasone Topical Spray. Do not use Desoximetasone Topical Spray for a condition for which it was not prescribed. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Desoximetasone Topical Spray that is written for health professionals. What are the ingredients in Desoximetasone Topical Spray? Active ingredient: desoximetasone Inactive ingredients: glyceryl oleate, isopropyl alcohol, isopropyl myristate, L-menthol, and mineral oil Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1 Dist. by: Taro Pharmaceuticals U.S.A., Inc. , Hawthorne, NY 10532

<table width="100%"><col width="100%" align="left" valign="middle"/><thead><tr><th align="center" styleCode="Lrule Rrule">PATIENT INFORMATION Desoximetasone (des ox&apos;&apos; i met&apos; a sone) Topical Spray </th></tr></thead><tfoot><tr><td align="left" colspan="1">Issued: April, 2018 PPK-8768-0 167 </td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Important information: Desoximetasone Topical Spray is for use on skin only.</content>Do not get Desoximetasone Topical Spray near or in your eyes, mouth or vagina. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">What is Desoximetasone Topical Spray?</content><list listType="unordered" styleCode="Disc"><item>Desoximetasone Topical Spray is a prescription corticosteroid medicine used to treat plaque psoriasis of the body in people 18 years of age and older.</item><item>You should not use Desoximetasone Topical Spray on your face, underarms (armpits), or groin areas.</item><item>It is not known if Desoximetasone Topical Spray is safe and effective in children under 18 years of age. Desoximetasone Topical Spray should not be used in children under 18 years of age.</item></list></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Before you use Desoximetasone Topical Spray, tell your doctor if you:</content><list listType="unordered" styleCode="Disc"><item>are allergic to any of the ingredients in Desoximetasone Topical Spray. See the end of this leaflet for a list of the ingredients in Desoximetasone Topical Spray.</item><item>have a skin infection. You may need medicine to treat the skin infection before you use Desoximetasone Topical Spray.</item><item>have thinning of the skin (atrophy) at the treatment site</item><item>have any other medical conditions</item><item>are pregnant or plan to become pregnant. It is not known if Desoximetasone Topical Spray will harm your unborn baby.</item><item>are breastfeeding or plan to breastfeed. It is not known if Desoximetasone Topical Spray passes into your breast milk. Do not apply Desoximetasone Topical Spray to your chest area if you are breastfeeding. This will help to prevent your baby from accidentally getting Desoximetasone Topical Spray into the mouth.</item></list></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Tell your doctor about all the medicines you take</content>including prescription and over-the-counter medicines, vitamins and herbal supplements. Especially tell your doctor if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids. </td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">What should I avoid while using Desoximetasone Topical Spray?</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Desoximetasone Topical Spray is flammable.</content>Avoid heat, flames or smoking while applying Desoximetasone Topical Spray to your skin.

tent styleCode="bold">What should I avoid while using Desoximetasone Topical Spray?</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Desoximetasone Topical Spray is flammable.</content>Avoid heat, flames or smoking while applying Desoximetasone Topical Spray to your skin. </td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">How should I use Desoximetasone Topical Spray?</content><list listType="unordered" styleCode="Disc"><item>Use Desoximetasone Topical Spray exactly as your doctor tells you to use it.</item><item>Apply Desoximetasone Topical Spray 2 times a day.</item><item>Do not bandage, cover, or wrap the treated skin area.</item><item>Desoximetasone Topical Spray should be used for the shortest amount of time needed to treat your plaque psoriasis. Tell your doctor if your skin condition is not getting better after 4 weeks of using Desoximetasone Topical Spray. You should not use Desoximetasone Topical Spray for longer than 4 weeks.</item><item>Wash your hands after applying Desoximetasone Topical Spray.</item><item>Safely throw away (discard) any unused Desoximetasone Topical Spray after 30 days.</item></list></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">See the &quot; <linkHtml href="#IFU">Instructions for Use</linkHtml>&quot; at the end of the Patient Information for detailed information about the right way to apply Desoximetasone Topical Spray. </content></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">What are the possible side effects of Desoximetasone Topical Spray?</content></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Desoximetasone Topical Spray may cause serious side effects, including:</content><list listType="unordered" styleCode="Disc"><item><content styleCode="bold">Desoximetasone Topical Spray can pass through your skin.</content>Too much Desoximetasone Topical Spray passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check for adrenal gland problems. </item></list></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">The most common side effects of Desoximetasone Topical Spray include</content>dryness, irritation and itching of skin at the treated site. </td></tr><tr><td styleCode="Lrule Rrule">Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Desoximetasone Topical Spray. For more information, ask your doctor.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <content styleCode="bold">For more information go to dailymed.nlm.nih.gov.</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How should I store Desoximetasone Topical Spray?</content><list listType="unordered" styleCode="Disc"><item>Store Desoximetasone Topical Spray at room temperature between 68&#x2DA;F to 77&#x2DA;F (20&#x2DA;C to 25&#x2DA;C).</item><item>Keep Desoximetasone Topical Spray and all medicines out of the reach of children.</item></list></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">General information about the safe and effective use of Desoximetasone Topical Spray.</content><list listType="unordered" styleCode="Disc"><item>Do not use Desoximetasone Topical Spray for a condition for which it was not prescribed. If you would like more information, talk with your doctor.

"><content styleCode="bold">General information about the safe and effective use of Desoximetasone Topical Spray.</content><list listType="unordered" styleCode="Disc"><item>Do not use Desoximetasone Topical Spray for a condition for which it was not prescribed. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Desoximetasone Topical Spray that is written for health professionals.</item></list></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">What are the ingredients in Desoximetasone Topical Spray?</content></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Active ingredient:</content>desoximetasone </td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Inactive ingredients:</content>glyceryl oleate, isopropyl alcohol, isopropyl myristate, L-menthol, and mineral oil </td></tr><tr><td styleCode="Lrule Rrule">Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1</td></tr><tr><td styleCode="Lrule Rrule">Dist. by: <content styleCode="bold">Taro Pharmaceuticals U.S.A., Inc.</content>, Hawthorne, NY 10532 </td></tr></tbody></table>

For topical use only. Not for oral, ophthalmic, or intravaginal use. Rx only Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1 Dist. by: TaroPharma a division of Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532 Topicort ® and TaroPharma ® are registered trademarks of Taro Pharmaceuticals U.S.A., Inc. and/or its affiliates. Revised: April, 2015 PK-6692-3 64 0415-3

DESCRIPTION Topicort ® (desoximetasone ointment USP) 0.05% contains 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 Topicort ® (desoximetasone ointment USP) 0.05% contains 0.5 mg of desoximetasone in an ointment base consisting of mineral oil and white petrolatum. The chemical name of desoximetasone is Pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 21-dihydroxy- 16-methyl-,(11β,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

CLINICAL PHARMACOLOGY Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with Topicort ® (desoximetasone) Ointment 0.25% with tagged desoximetasone showed no detectable level (limit of sensitivity: 0.003 µg/mL) in 1 subject and 0.004 and 0.006 µg/mL in the remaining 2 subjects in the blood when it was applied topically on the back followed by occlusion for 24 hours. The extent of absorption for the ointment was 7% based on radioactivity recovered from urine and feces. Seven days after application, no further radioactivity was detected in urine or feces. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.

Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with Topicort ® (desoximetasone) Ointment 0.25% with tagged desoximetasone showed no detectable level (limit of sensitivity: 0.003 µg/mL) in 1 subject and 0.004 and 0.006 µg/mL in the remaining 2 subjects in the blood when it was applied topically on the back followed by occlusion for 24 hours. The extent of absorption for the ointment was 7% based on radioactivity recovered from urine and feces. Seven days after application, no further radioactivity was detected in urine or feces. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.

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, Topicort ® (desoximetasone ointment 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 that for which it was prescribed. The treated skin area should not be bandaged or otherwise covered or wrapped so 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 Topicort ® (desoximetasone ointment 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.

dressings. Other corticosteroid-containing products should not be used with Topicort ® (desoximetasone ointment 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 15 to 150 times the human dose of Topicort ® (desoximetasone ointment USP) 0.05%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, Topicort ® (desoximetasone ointment 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.

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.

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 that for which it was prescribed. The treated skin area should not be bandaged or otherwise covered or wrapped so 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 Topicort ® (desoximetasone ointment 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.

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 15 to 150 times the human dose of Topicort ® (desoximetasone ointment USP) 0.05%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, Topicort ® (desoximetasone ointment 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.

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 15 to 150 times the human dose of Topicort ® (desoximetasone ointment USP) 0.05%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, Topicort ® (desoximetasone ointment 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.

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.

ADVERSE REACTIONS The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate 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 controlled clinical studies the incidence of adverse reactions was low (0.2%) for Topicort ® (desoximetasone ointment USP) 0.05% and included mild burning sensation at the site of application.

HOW SUPPLIED Topicort ® (desoximetasone ointment USP) 0.05% is supplied in: 15 gram tubes (NDC 51672-5263-1), 30 gram tubes (NDC 51672-5263-2), 60 gram tubes (NDC 51672-5263-3) and 100 gram tubes (NDC 51672-5263-7). Store at controlled room temperature between 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]

For topical use only. Not for oral, ophthalmic, or intravaginal use. DESCRIPTION Desoximetasone cream, USP 0.05% contains 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, isopropyl myristate, lanolin alcohols, mineral oil, purified water and white petrolatum. The chemical name of desoximetasone is Pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 21-dihydroxy-16-methyl-, (11β, 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: structure

CLINICAL PHARMACOLOGY Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.

Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with desoximetasone cream, USP 0.25% with tagged desoximetasone showed a total of 5.2% ± 2.9% excretion in urine (4.1% ± 2.3%) and feces (1.1% ± 0.6%) and no detectable level (limit of sensitivity: 0.005 μg/mL) in the blood when it was applied topically on the back followed by occlusion for 24 hours. Seven days after application, no further radioactivity was detected in urine or feces. The half-life of the material was 15 ± 2 hours (for urine) and 17 ± 2 hours (for feces) between the third and fifth trial day.

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.

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% 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: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. 2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. 3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. 4. Patients should report any signs of local adverse reactions, especially under occlusive dressings. 5. Other corticosteroid-containing products should not be used with desoximetasone cream, 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.

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 Category C Teratogenic Effects 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 15 to 150 times the human dose of desoximetasone cream, 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% 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

ent 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.

ADVERSE REACTIONS The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate 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 controlled clinical studies the incidence of adverse reactions was low (0.8%) for desoximetasone cream, USP 0.05% and included pruritus, erythrema, vesiculation,and burning sensation. To report SUSPECTED ADVERSE REACTIONS, contact Saptalis Pharmaceuticals, LLC at 1-833-727-8254 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

HOW SUPPLIED Desoximetasone cream, USP 0.05% is supplied in 15 gram (NDC 71656-086-15) and 60 gram (NDC 71656-086-60) tubes. Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Distributed by: Saptalis Pharmaceuticals, LLC Hauppauge, NY 11788 MADE IN USA Rev. 03/2024 PPM-0073

DESCRIPTION Desoximetasone Cream USP, 0.25% contains the active synthetic corticosteroid desoximetasone. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and anti-pruritic agents. Each gram of Desoximetasone Cream USP, 0.25% contains 2.5 mg of desoximetasone in an emollient cream consisting of aluminum monostearate, cetostearyl alcohol, isopropyl myristate, lanolin alcohols, magnesium stearate, mineral oil, paraffin wax, purified water, and white petrolatum. The chemical name of desoximetasone is Pregna-1,4-diene-3,20-dione,9-fluoro-11,21-dihydroxy-16-methyl-,(11β,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 chemical structure is: structure

CLINICAL PHARMACOLOGY Topical corticosteroids share anti-inflammatory, anti-pruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. Pharmacokinetics - 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with desoximetasone cream 0.25% with tagged desoximetasone showed a total of 5.2% ± 2.9% excretion in urine (4.1% ± 2.3%) and feces (1.1% ± 0.6%) and no detectable level (limit of sensitivity: 0.005 µg/mL) in the blood when it was applied topically on the back followed by occlusion for 24 hours. Seven days after application, no further radioactivity was detected in urine or feces. The half-life of the material was 15 ± 2 hours (for urine) and 17 ± 2 hours (for feces) between the third and fifth trial day. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.

Pharmacokinetics - 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with desoximetasone cream 0.25% with tagged desoximetasone showed a total of 5.2% ± 2.9% excretion in urine (4.1% ± 2.3%) and feces (1.1% ± 0.6%) and no detectable level (limit of sensitivity: 0.005 µg/mL) in the blood when it was applied topically on the back followed by occlusion for 24 hours. Seven days after application, no further radioactivity was detected in urine or feces. The half-life of the material was 15 ± 2 hours (for urine) and 17 ± 2 hours (for feces) between the third and fifth trial day. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.

PRECAUTIONS General - Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. 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 the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. (See PRECAUTIONS – Pediatric Use ). If irritation develops, topical corticosteroids 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 adequately controlled. Information for Patients Patients using topical corticosteroids should receive the following information and instructions: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. 2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. 3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. 4. Patients should report any signs of local adverse reactions, especially under occlusive dressing. 5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings. Laboratory Tests The following tests may be helpful in evaluating the HPA axis suppression: Urinary free cortisol test ACTH stimulation test Carcinogenesis, Mutagenesis, Impairment of Fertility - Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results. Desoximetasone did not show potential for mutagenic activity in vitro in the Ames microbial mutagen test with or without metabolic activation. Pregnancy: Teratogenic Effects: Pregnancy Category C - Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.

t metabolic activation. Pregnancy: Teratogenic Effects: Pregnancy Category C - Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent 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%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, Desoximetasone Cream USP, 0.25% 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. 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.

General - Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. 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 the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. (See PRECAUTIONS – Pediatric Use ). If irritation develops, topical corticosteroids 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 adequately controlled.

Information for Patients Patients using topical corticosteroids should receive the following information and instructions: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. 2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. 3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. 4. Patients should report any signs of local adverse reactions, especially under occlusive dressing. 5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings.

Carcinogenesis, Mutagenesis, Impairment of Fertility - Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results. Desoximetasone did not show potential for mutagenic activity in vitro in the Ames microbial mutagen test with or without metabolic activation.

Pregnancy: Teratogenic Effects: Pregnancy Category C - Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent 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%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, Desoximetasone Cream USP, 0.25% 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.

Teratogenic Effects: Pregnancy Category C - Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent 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%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, Desoximetasone Cream USP, 0.25% 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.

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. 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.

ADVERSE REACTIONS The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate 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, miliaria In controlled clinical studies, the incidence of adverse reactions was low (0.8%) for desoximetasone cream 0.25%, and included burning, folliculitis and folliculo-pustular lesions.

DESCRIPTION Desoximetasone ointment USP, 0.25% contains 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 ointment USP, 0.25% contains 2.5 mg of desoximetasone USP in an ointment base consisting of medium-chain triglycerides and white petrolatum. 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: structure

CLINICAL PHARMACOLOGY Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with desoximetasone ointment, 0.25% with tagged desoximetasone showed no detectable level (limit of sensitivity: 0.003 mcg/mL) in 1 subject and 0.004 and 0.006 mcg/mL in the remaining 2 subjects in the blood when it was applied topically on the back followed by occlusion for 24 hours. The extent of absorption for the ointment was 7% based on radioactivity recovered from urine and feces. Seven days after application, no further radioactivity was detected in urine or feces. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.

Pharmacokinetics 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 from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with desoximetasone ointment, 0.25% with tagged desoximetasone showed no detectable level (limit of sensitivity: 0.003 mcg/mL) in 1 subject and 0.004 and 0.006 mcg/mL in the remaining 2 subjects in the blood when it was applied topically on the back followed by occlusion for 24 hours. The extent of absorption for the ointment was 7% based on radioactivity recovered from urine and feces. Seven days after application, no further radioactivity was detected in urine or feces. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.

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 ointment, 0.25% 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: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. 2. Patients should be advised not to use this medication for any disorder other than that for which it was prescribed. 3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. 4. Patients should report any signs of local adverse reactions, especially under occlusive dressings. 5. Other corticosteroid-containing products should not be used with desoximetasone ointment, 0.25% 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.

er occlusive dressings. 5. Other corticosteroid-containing products should not be used with desoximetasone ointment, 0.25% 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 ointment, 0.25%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, desoximetasone ointment, 0.25% 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. Hypothalmic-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. Safety and effectiveness of desoximetasone ointment, 0.25% in pediatric patients below the age of 10 have not been established.

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 ointment, 0.25%. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, desoximetasone ointment, 0.25% 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.

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. Hypothalmic-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. Safety and effectiveness of desoximetasone ointment, 0.25% in pediatric patients below the age of 10 have not been established.

ADVERSE REACTIONS The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate 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 controlled clinical studies the incidence of adverse reactions was low (0.3%) for desoximetasone ointment, 0.25% and included mild burning sensation at the site of application.

HOW SUPPLIED Desoximetasone ointment USP, 0.25% is supplied as follows: 15 gram tubes NDC 68180-946-01 60 gram tubes NDC 68180-946-04 Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) – 454 775 India December 2024 ID#: 277874 Image