ADVERSE REACTIONS SECTION.

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 Padagis at 1-866-634-9120 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 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 weeks. total of 149 subjects applied desoximetasone topical spray.Adverse reactions that occurred in >= 1% of subjects treated with desoximetasone topical spray are presented in Table 1.Table 1. Number (%) of Subjects with Adverse Reactions Occurring in >= 1%Desoximetasone Topical Spray, 0.25%b.i.d.(N 149)Vehicle sprayb.i.d.(N 135)Number of Subjects with Adverse Reactions13 (8.7%)18 (13.3%)Application site dryness4 (2.7%)7 (5.2%)Application site irritation4 (2.7%)5 (3.7%)Application site pruritus3 (2.0%)5 (3.7%)Another less common adverse reaction (<1% but >0.1%) was folliculitis.. 6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Postmarketing reports for local adverse reactions to topical corticosteroids included atrophy, striae, telangiectasias, itching, dryness, hypopigmentation, perioral dermatitis, secondary infection, and miliaria.Ophthalmic adverse reactions of cataracts, glaucoma, and increased intraocular pressure have been reported during use of topical corticosteroids.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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 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 toxicity profile consistent with long-term exposure to corticosteroids, including adrenal atrophy and histopathological changes in several organ systems indicative of severe immune suppression. 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/m2/day) in Sprague-Dawley rats.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Corticosteroids play role in cellular signaling, immune function, inflammation and protein regulation; however, the precise mechanism of action in psoriasis is unknown.. 12.2 Pharmacodynamics. Vasoconstrictor AssayVasoconstrictor 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.Hypothalamic-Pituitary Adrenal (HPA) Axis SuppressionThe potential for hypothalamic-pituitary-adrenal (HPA) axis suppression was evaluated in two trials. Desoximetasone topical spray was applied twice day for 28 days and HPA axis suppression was defined as serum cortisol level <=18 mcg/dL 30-min post cosyntropin stimulation.In the first trial, out of 24 adult subjects with moderate to severe plaque psoriasis, 21 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 10-15% of body surface area (BSA), and 22.2% (2 out of 9) in subjects having psoriasis involvement of >15% of their BSA. In the subjects with available follow-up values, suppression reversed 28 days after the end of treatment.In another trial, the HPA axis suppression was evaluated in 106 pediatric subjects with moderate to severe plaque psoriasis. One hundred subjects had evaluable serum cortisol levels. The proportion of subjects demonstrating HPA axis suppression was 35.0% (21 out of 60) in Cohort (12 years to less than 18 years of age, with mean baseline BSA involvement of 16%), and 43.3% (13 out of 30) in Cohort (6 years to less than 12 years of age, with mean baseline BSA involvement of 19%). Trial enrollment in the youngest cohort (2 years to less than years of age) was discontinued early due to high incidence of HPA axis suppression observed in the two oldest cohorts (6 years to less than 18 years of age).The overall HPA axis suppression rate was 36% in pediatric subjects years to less than 18 yearsof age. Due to high incidence of HPA axis suppression observed from this trial, desoximetasonetopical spray is not recommended for use in pediatric patients less than 18 years of age [see Use in Specific Populations (8.4)].. 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.In the pediatric HPA axis suppression trial, plasma concentrations of desoximetasone were measured in subset of subjects in Cohorts and [see Clinical Pharmacology (12.2)]. High inter subject variability in plasma concentrations was observed in both cohorts. The mean (% Coefficient of Variation) maximum concentration on Day 29 was 1881 pg/mL (127%) in Cohort (n=11) and 1116 pg/mL (94%) in Cohort (n=8).

CLINICAL STUDIES SECTION.

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 weeks. Enrolled subjects had minimum body surface area of involvement of 10%, and Physicians Global Assessment score (PGA) of (moderate) or (severe).Efficacy was assessed at Week as the proportion of subjects who were considered Clinical Success (clear (0) or almost clear (1) according to the PGA scale). Table presents the efficacy results.Table 2. Number of Subjects (%) with Clinical Success (scored as clear or almost clear) at Week 4.ParameterTrial 1Trial 2Desoximetasone Topical Spray, N= 59VehicleN= 60Desoximetasone Topical SprayN= 60VehicleN= 60Clinical Success18 (30.5%)3 (5.0%)32 (53.3%)11 (18.3%).

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None. None (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Desoximetasone Topical Spray, 0.25% for dermatologic use contains desoximetasone as the active ingredient.Desoximetasone is corticosteroid with the chemical name of pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 21-dihydroxy-16-methyl-, (11ss,16)-. Desoximetasone has the molecular formula of C22H29FO4 and 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 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 manual spray pump for installation by the pharmacist prior to dispensing to patients.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Apply desoximetasone topical spray as thin film to the affected skin areas twice daily. Rub in gently.Do not bandage or otherwise cover or wrap the treated skin unless directed by the physician.Discontinue treatment when control is achieved.Treatment beyond 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.. oApply thin film to the affected skin areas twice daily. Rub in gently. (2)oDiscontinue treatment when control is achieved. (2)oTreatment beyond weeks is not recommended. (2)oDo not use if atrophy is present at the treatment site. (2)oDo not use with occlusive dressings, unless directed by the physician. (2)oAvoid use on the face, axilla or groin. (2)oNot for oral, ophthalmic, or intravaginal use. (2). oApply thin film to the affected skin areas twice daily. Rub in gently. (2). oDiscontinue treatment when control is achieved. (2). oTreatment beyond weeks is not recommended. (2). oDo not use if atrophy is present at the treatment site. (2). oDo not use with occlusive dressings, unless directed by the physician. (2). oAvoid use on the face, axilla or groin. (2). oNot for oral, ophthalmic, or intravaginal use. (2).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Topical Spray, 0.25%. Each gram of desoximetasone topical spray contains 2.5 mg of desoximetasone in clear, colorless liquid.. Spray, 0.25% w/w (3).

GERIATRIC USE SECTION.

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.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied/Storage. Desoximetasone Topical Spray, 0.25% is clear colorless liquid supplied in white, opaque bottles with white, opaque screw caps in the following size:o100 mL (NDC 45802-807-98)Store at controlled room temperature between 20C to 25C (68F to 77F), excursions permitted to 15C to 30C (59F to 86F) [see USP Controlled Room Temperature]. Spray is flammable; avoid heat, flame or smoking when using this product.Each unit is co-packaged with manual spray pump for installation by the pharmacist.. o100 mL (NDC 45802-807-98). 16.2 Instructions for the Pharmacist. 1. Remove the spray pump from the wrapper2. Remove and discard the cap from the bottle3. Keeping the bottle vertical, puncture seal, insert the spray pump into the bottle and turn clockwise until well-fastened4. Dispense the bottle with the spray pump inserted5. Label the bottle with discard the product 30 days after dispensing.

INDICATIONS & USAGE SECTION.

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

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. See FDA-approved patient labeling (Patient Information and Instructions for Use) Inform patients of the following:oUse this medication as directed by the physician. Do not use this medication for any disorder other than that for which it was prescribed.oDesoximetasone topical spray is for external use only. oAvoid contact with eyes and use on the face, axilla or groin.oTo minimize the risk of adverse reactions:odo not bandage or otherwise cover or wrap the treated skin so as to be occlusive.odiscontinue therapy when control is achieved. If no improvement is seen within weeks, contact the physician.odo not use other corticosteroid-containing products with desoximetasone topical spray without first consulting with the physician.oAdvise patients that desoximetasone topical spray may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. [see Warnings and Precautions (5.1)].oAdvise women to use desoximetasone topical spray on the smallest area of skin and for the shortest duration possible while pregnant or breastfeeding. Advise breastfeeding woman not to apply desoximetasone topical spray directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.1 and 8.2)]. oReport any signs of local or systemic adverse reactions including any visual symptoms to the physician.oThis medication is flammable; avoid heat, flame, or smoking when applying this product.oDiscard this product 30 days after dispensed by pharmacist.Made in IsraelManufactured By PadagisYeruham, IsraelDistributed ByPadagisAllegan, MI 49010 www.padagis.comRev 11-217Y200 RC J3. oUse this medication as directed by the physician. Do not use this medication for any disorder other than that for which it was prescribed.. oDesoximetasone topical spray is for external use only. oAvoid contact with eyes and use on the face, axilla or groin.. oTo minimize the risk of adverse reactions:odo not bandage or otherwise cover or wrap the treated skin so as to be occlusive.odiscontinue therapy when control is achieved. If no improvement is seen within weeks, contact the physician.odo not use other corticosteroid-containing products with desoximetasone topical spray without first consulting with the physician.. odo not bandage or otherwise cover or wrap the treated skin so as to be occlusive.. odiscontinue therapy when control is achieved. If no improvement is seen within weeks, contact the physician.. odo not use other corticosteroid-containing products with desoximetasone topical spray without first consulting with the physician.. oAdvise patients that desoximetasone topical spray may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. [see Warnings and Precautions (5.1)].. oAdvise women to use desoximetasone topical spray on the smallest area of skin and for the shortest duration possible while pregnant or breastfeeding. Advise breastfeeding woman not to apply desoximetasone topical spray directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.1 and 8.2)]. oReport any signs of local or systemic adverse reactions including any visual symptoms to the physician.. oThis medication is flammable; avoid heat, flame, or smoking when applying this product.. oDiscard this product 30 days after dispensed by pharmacist.

INSTRUCTIONS FOR USE SECTION.

Instructions for Use. Instructions for UseDesoximetasone (des-oks-i-MET-a-sone) Topical Spray, 0.25%Important information:Desoximetasone topical spray is for use on skin (topical) only.Do not get desoximetasone topical spray near or in your mouth, eyes or vagina.Read the Instructions for Use before you start using desoximetasone topical spray and each time you get 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).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).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 to the affected area.Repeat Steps and 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).How should store desoximetasone topical sprayoStore desoximetasone topical spray at room temperature between 68F to 77F (20C to 25C). oThrow away (discard) unused desoximetasone topical spray 30 days after it has been opened. oDesoximetasone topical spray is flammable. Keep away from heat, flames or smoke.Keep desoximetasone topical spray and all medicines out of the reach of children.This Instructions for Use has been approved by the U.S. Food and Drug Administration.. oStore desoximetasone topical spray at room temperature between 68F to 77F (20C to 25C). oThrow away (discard) unused desoximetasone topical spray 30 days after it has been opened. oDesoximetasone topical spray is flammable. Keep away from heat, flames or smoke.. Figure A. Figure B. Figure C. Figure D.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere is no information on the presence of topically administered desoximetasone in human milk, the effects on the breastfed infant, or the effects on milk production. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for desoximetasone topical spray and any potential adverse effects on the breastfed infant from desoximetasone topical spray or from the underlying maternal condition.Clinical ConsiderationsTo minimize potential exposure to the breastfed infant via breast milk, use desoximetasone topical spray on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply desoximetasone topical spray directly to the nipple and areola to avoid direct infant exposure [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Corticosteroids play role in cellular signaling, immune function, inflammation and protein regulation; however, the precise mechanism of action in psoriasis is unknown.

NONCLINICAL TOXICOLOGY SECTION.

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 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 toxicity profile consistent with long-term exposure to corticosteroids, including adrenal atrophy and histopathological changes in several organ systems indicative of severe immune suppression. 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/m2/day) in Sprague-Dawley rats.

OVERDOSAGE SECTION.

10 OVERDOSAGE. Desoximetasone topical spray can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1)].

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Package/Label Display Panel 100 mL Carton. Rx OnlyNDC 45802-807-98Desoximetasone Topical Spray, 0.25%For Topical Use OnlyNot For Oral, Ophthalmic, or Intravaginal Use100 mLThe following image is placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.. carton. serialization-template.jpg.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of desoximetasone topical spray have not been established in pediatric patients for the treatment of plaque psoriasis. Desoximetasone topical spray is not recommended for use in patients less than 18 years of age due to the high incidence of HPA axis suppression observed [see Warnings and Precautions (5.1)].Hypothalamic-Pituitary Adrenal (HPA) Axis SuppressionThe HPA axis suppression potential of desoximetasone topical spray was assessed in an open-label, sequential cohort, safety trial in 129 subjects years to less than 18 years of age with moderate to severe plaque psoriasis defined as Physician Global Assessment (PGA) score of >=3 with involvement of at least 10% of their body surface area (excluding the face and scalp). In total, 100 pediatric subjects were evaluated for HPA axis function via cosyntropin stimulation testing at baseline and following weeks of twice daily application of desoximetasone topical spray. Overall, 36% of pediatric subjects years to less than 18 years of age demonstrated HPA axis suppression defined as serum cortisol level <= 18 mcg/dL 30-minutes post cosyntropin stimulation. The proportion of subjects demonstrating HPA axis suppression was 35.0% in Cohort (12 years to less than 18 years of age) and 43.3% in Cohort (6 years to less than 12 years of age). Trial enrollment in the youngest cohort (2 years to less than years of age) was discontinued early due to high incidence of HPA axis suppression observed in the two oldest cohorts (6 years to less than 18 years of age) [see Clinical Pharmacology (12.2)].Because of higher ratio of skin surface area to body mass, pediatric patients are at greater risk than adults of HPA axis suppression and Cushings 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 reactions including striae have been reported with inappropriate use of topical corticosteroids in infants and children.HPA axis suppression, Cushings 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.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Vasoconstrictor AssayVasoconstrictor 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.Hypothalamic-Pituitary Adrenal (HPA) Axis SuppressionThe potential for hypothalamic-pituitary-adrenal (HPA) axis suppression was evaluated in two trials. Desoximetasone topical spray was applied twice day for 28 days and HPA axis suppression was defined as serum cortisol level <=18 mcg/dL 30-min post cosyntropin stimulation.In the first trial, out of 24 adult subjects with moderate to severe plaque psoriasis, 21 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 10-15% of body surface area (BSA), and 22.2% (2 out of 9) in subjects having psoriasis involvement of >15% of their BSA. In the subjects with available follow-up values, suppression reversed 28 days after the end of treatment.In another trial, the HPA axis suppression was evaluated in 106 pediatric subjects with moderate to severe plaque psoriasis. One hundred subjects had evaluable serum cortisol levels. The proportion of subjects demonstrating HPA axis suppression was 35.0% (21 out of 60) in Cohort (12 years to less than 18 years of age, with mean baseline BSA involvement of 16%), and 43.3% (13 out of 30) in Cohort (6 years to less than 12 years of age, with mean baseline BSA involvement of 19%). Trial enrollment in the youngest cohort (2 years to less than years of age) was discontinued early due to high incidence of HPA axis suppression observed in the two oldest cohorts (6 years to less than 18 years of age).The overall HPA axis suppression rate was 36% in pediatric subjects years to less than 18 yearsof age. Due to high incidence of HPA axis suppression observed from this trial, desoximetasonetopical spray is not recommended for use in pediatric patients less than 18 years of age [see Use in Specific Populations (8.4)].

PHARMACOKINETICS SECTION.

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.In the pediatric HPA axis suppression trial, plasma concentrations of desoximetasone were measured in subset of subjects in Cohorts and [see Clinical Pharmacology (12.2)]. High inter subject variability in plasma concentrations was observed in both cohorts. The mean (% Coefficient of Variation) maximum concentration on Day 29 was 1881 pg/mL (127%) in Cohort (n=11) and 1116 pg/mL (94%) in Cohort (n=8).

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThere are no available data on desoximetasone use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Observational studies suggest maternal use of high to super-high potency topical steroids, including desoximetasone topical spray, may be associated with an increased risk of low birthweight infants (see Data). Advise pregnant woman that desoximetasone topical spray may increase the potential risk of low birth weight infants and to use desoximetasone topical spray on the smallest area of skin and for the shortest duration possible. Desoximetasone has been shown to cause malformations and be embryotoxic in mice, rats, and rabbits when given by subcutaneous or dermal routes of administration at doses to 30 times the human dose of desoximetasone topical spray based on body surface area comparison.The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.DataHuman DataAvailable observational studies in pregnant women did not identify drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency. However, when the dispensed amount of high to super-high potency topical corticosteroids exceeded 300g during the entire pregnancy, maternal use was associated with an increased risk of low birth weight in infants.

SPL PATIENT PACKAGE INSERT SECTION.

Patient Information. PATIENT INFORMATIONDesoximetasone (des-oks-i-MET-a-sone) Topical Spray, 0.25%Important information: Desoximetasone topical spray is for use on skin (topical) only.Do not get desoximetasone topical spray near or in your mouth, eyes or vagina.What is desoximetasone topical sprayDesoximetasone topical spray is prescription corticosteroid medicine used to treat plaque psoriasis of the body in people 18 years of age and older.It is not known if desoximetasone topical spray is safe and effective in children under 18 years of age. Desoximetasone topical spray is not recommended for use in children under 18 years of age.Before you use desoximetasone topical spray, tell your doctor about all of your medical conditions, including if you:ohave had irritation or other skin reaction to steroid medicine in the past.ohave skin infection. You may need medicine to treat the skin infection before you use desoximetasone topical spray.ohave thinning of the skin (atrophy) at the treatment siteohave adrenal gland problemsohave diabetesoliver problemsoare pregnant or plan to become pregnant. It is not known if desoximetasone topical spray will harm your unborn baby. Desoximetasone topical spray may increase your chance of having low birthweight baby. If you use desoximetasone topical spray during pregnancy, use desoximetasone topical spray on the smallest area of the skin and for the shortest time needed.oare breastfeeding or plan to breastfeed. It is not known if desoximetasone passes into your breast milk. If you use desoximetasone topical spray and breastfeed, use desoximetasone topical spray on the smallest area of the skin and for the shortest time needed. Do not apply desoximetasone topical spray directly to the nipple and areola to avoid contact with your baby.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. Do not use other products containing corticosteroid medicine while using desoximetasone topical spray without talking to your doctor first.What should avoid while using desoximetasone topical sprayDesoximetasone topical spray is flammable. Avoid heat, flames or smoking while applying desoximetasone topical spray to your skin.How should use desoximetasone topical spraySee the Instructions for Use for detailed information about the right way to apply desoximetasone topical spray.oUse desoximetasone topical spray exactly as your doctor tells you to use it.oYour doctor should tell you how much desoximetasone topical spray to use and where to use it.oApply desoximetasone topical spray to the affected skin areas times day and rub it in gently.oDo not bandage, cover, or wrap the treated skin area, unless your doctor tells you to.oUse desoximetasone topical spray for the shortest amount of time needed to treat your plaque psoriasis. Tell your doctor if your skin condition is not getting better after weeks of using desoximetasone topical spray. You should not use desoximetasone topical spray for longer than weeks.oDo not use desoximetasone topical spray on your face, armpits or groin.oDo not use desoximetasone topical spray if you have thinning of your skin (atrophy) at the treatment site. oWash your hands after applying desoximetasone topical spray.What are the possible side effects of desoximetasone topical sprayDesoximetasone topical spray may cause serious side effects, including:oSymptoms of disorder where the adrenal gland does not make enough of certain hormones (adrenal insufficiency) during treatment or after stopping treatment with desoximetasone topical spray. Your doctor may do blood tests to check for adrenal gland problems. oCushings syndrome, condition that happens when your body is exposed to large amounts of the hormone cortisol. Your doctor may do tests to check for this. oHigh blood sugar (hyperglycemia) or diabetes mellitus that has not been diagnosed can happen when treated with desoximetasone topical spray. Your doctor may do tests to check for this. oSkin reactions at the treated skin site. Tell your doctor if you get any skin reactions or skin infections. oEye problems. Using desoximetasone topical spray may increase your chance of getting cataracts and glaucoma. Do not get desoximetasone topical spray in your eyes because it may cause eye irritation. Tell your doctor if you have blurred vision or other vision problems during treatment with desoximetasone topical spray.The most common side effects of desoximetasone topical spray include dryness, irritation and itching of skin at the treated site.These are not all the possible side effects of desoximetasone topical spray.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store desoximetasone topical sprayoStore desoximetasone topical spray at room temperature between 68F to 77F (20C to 25C).oThrow away (discard) unused desoximetasone topical spray after 30 days. 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.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use desoximetasone topical spray for condition for which it was not prescribed. Do not give desoximetasone topical spray to other people, even if they have the same symptoms you have. It may harm them. 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 sprayActive ingredient: desoximetasoneInactive ingredients: glyceryl oleate, isopropyl alcohol, isopropyl myristate, L-menthol, and mineral oilMade in IsraelManufactured By PadagisYeruham, IsraelDistributed ByPadagisAllegan, MI 49010 www.padagis.comRev 11-217Y200 RC J3This Patient Information has been approved by the U.S. Food and Drug Administration.. ohave had irritation or other skin reaction to steroid medicine in the past.. ohave skin infection. You may need medicine to treat the skin infection before you use desoximetasone topical spray.. ohave thinning of the skin (atrophy) at the treatment site. ohave adrenal gland problems. ohave diabetes. oliver problems. oare pregnant or plan to become pregnant. It is not known if desoximetasone topical spray will harm your unborn baby. Desoximetasone topical spray may increase your chance of having low birthweight baby. If you use desoximetasone topical spray during pregnancy, use desoximetasone topical spray on the smallest area of the skin and for the shortest time needed.. oare breastfeeding or plan to breastfeed. It is not known if desoximetasone passes into your breast milk. If you use desoximetasone topical spray and breastfeed, use desoximetasone topical spray on the smallest area of the skin and for the shortest time needed. Do not apply desoximetasone topical spray directly to the nipple and areola to avoid contact with your baby.. oUse desoximetasone topical spray exactly as your doctor tells you to use it.. oYour doctor should tell you how much desoximetasone topical spray to use and where to use it.. oApply desoximetasone topical spray to the affected skin areas times day and rub it in gently.. oDo not bandage, cover, or wrap the treated skin area, unless your doctor tells you to.. oUse desoximetasone topical spray for the shortest amount of time needed to treat your plaque psoriasis. Tell your doctor if your skin condition is not getting better after weeks of using desoximetasone topical spray. You should not use desoximetasone topical spray for longer than weeks.. oDo not use desoximetasone topical spray on your face, armpits or groin.. oDo not use desoximetasone topical spray if you have thinning of your skin (atrophy) at the treatment site. oWash your hands after applying desoximetasone topical spray.. oSymptoms of disorder where the adrenal gland does not make enough of certain hormones (adrenal insufficiency) during treatment or after stopping treatment with desoximetasone topical spray. Your doctor may do blood tests to check for adrenal gland problems. oCushings syndrome, condition that happens when your body is exposed to large amounts of the hormone cortisol. Your doctor may do tests to check for this. oHigh blood sugar (hyperglycemia) or diabetes mellitus that has not been diagnosed can happen when treated with desoximetasone topical spray. Your doctor may do tests to check for this. oSkin reactions at the treated skin site. Tell your doctor if you get any skin reactions or skin infections. oEye problems. Using desoximetasone topical spray may increase your chance of getting cataracts and glaucoma. Do not get desoximetasone topical spray in your eyes because it may cause eye irritation. Tell your doctor if you have blurred vision or other vision problems during treatment with desoximetasone topical spray.. oStore desoximetasone topical spray at room temperature between 68F to 77F (20C to 25C).. oThrow away (discard) unused desoximetasone topical spray after 30 days.

SPL UNCLASSIFIED SECTION.

5.1 Effect on Endocrine System. Desoximetasone topical spray is 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 study including 21 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, adrenal suppression was identified in out of 12 subjects having involvement of 10 to 15% of body surface area (BSA) and out of subjects having involvement of >15% of BSA after treatment with desoximetasone topical spray twice 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 patient using 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 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.Cushings syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. Use in patients under 18 years of age is not recommended due to numerically high rates of HPA axis suppression (the safety and effectiveness of desoximetasone topical spray have not been established in pediatric patients) [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.2)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryThere are no available data on desoximetasone use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Observational studies suggest maternal use of high to super-high potency topical steroids, including desoximetasone topical spray, may be associated with an increased risk of low birthweight infants (see Data). Advise pregnant woman that desoximetasone topical spray may increase the potential risk of low birth weight infants and to use desoximetasone topical spray on the smallest area of skin and for the shortest duration possible. Desoximetasone has been shown to cause malformations and be embryotoxic in mice, rats, and rabbits when given by subcutaneous or dermal routes of administration at doses to 30 times the human dose of desoximetasone topical spray based on body surface area comparison.The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.DataHuman DataAvailable observational studies in pregnant women did not identify drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency. However, when the dispensed amount of high to super-high potency topical corticosteroids exceeded 300g during the entire pregnancy, maternal use was associated with an increased risk of low birth weight in infants.. 8.2 Lactation. Risk SummaryThere is no information on the presence of topically administered desoximetasone in human milk, the effects on the breastfed infant, or the effects on milk production. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for desoximetasone topical spray and any potential adverse effects on the breastfed infant from desoximetasone topical spray or from the underlying maternal condition.Clinical ConsiderationsTo minimize potential exposure to the breastfed infant via breast milk, use desoximetasone topical spray on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply desoximetasone topical spray directly to the nipple and areola to avoid direct infant exposure [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].. 8.4 Pediatric Use. The safety and effectiveness of desoximetasone topical spray have not been established in pediatric patients for the treatment of plaque psoriasis. Desoximetasone topical spray is not recommended for use in patients less than 18 years of age due to the high incidence of HPA axis suppression observed [see Warnings and Precautions (5.1)].Hypothalamic-Pituitary Adrenal (HPA) Axis SuppressionThe HPA axis suppression potential of desoximetasone topical spray was assessed in an open-label, sequential cohort, safety trial in 129 subjects years to less than 18 years of age with moderate to severe plaque psoriasis defined as Physician Global Assessment (PGA) score of >=3 with involvement of at least 10% of their body surface area (excluding the face and scalp). In total, 100 pediatric subjects were evaluated for HPA axis function via cosyntropin stimulation testing at baseline and following weeks of twice daily application of desoximetasone topical spray. Overall, 36% of pediatric subjects years to less than 18 years of age demonstrated HPA axis suppression defined as serum cortisol level <= 18 mcg/dL 30-minutes post cosyntropin stimulation. The proportion of subjects demonstrating HPA axis suppression was 35.0% in Cohort (12 years to less than 18 years of age) and 43.3% in Cohort (6 years to less than 12 years of age). Trial enrollment in the youngest cohort (2 years to less than years of age) was discontinued early due to high incidence of HPA axis suppression observed in the two oldest cohorts (6 years to less than 18 years of age) [see Clinical Pharmacology (12.2)].Because of higher ratio of skin surface area to body mass, pediatric patients are at greater risk than adults of HPA axis suppression and Cushings 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 reactions including striae have been reported with inappropriate use of topical corticosteroids in infants and children.HPA axis suppression, Cushings 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.. 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oEffect on Endocrine System: Desoximetasone topical spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1)oCushings syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1)oBecause of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. (5.1)oModify use if HPA axis suppression develops. (5.1)oHigh 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)oPediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. Safety and effectiveness have not been established in pediatric patients and use in pediatric patients is not recommended. (5.1, 8.4)oOphthalmic Adverse Reactions: Topical corticosteroid products may increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. (5.3).oFlammability: Desoximetasone topical spray is flammable; keep away from heat or flame. (5.6). oEffect on Endocrine System: Desoximetasone topical spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1). oCushings syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1). oBecause of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. (5.1). oModify use if HPA axis suppression develops. (5.1). oHigh 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). oPediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. Safety and effectiveness have not been established in pediatric patients and use in pediatric patients is not recommended. (5.1, 8.4). oOphthalmic Adverse Reactions: Topical corticosteroid products may increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. (5.3).. oFlammability: Desoximetasone topical spray is flammable; keep away from heat or flame. (5.6). 5.1 Effect on Endocrine System. Desoximetasone topical spray is 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 study including 21 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, adrenal suppression was identified in out of 12 subjects having involvement of 10 to 15% of body surface area (BSA) and out of subjects having involvement of >15% of BSA after treatment with desoximetasone topical spray twice 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 patient using 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 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.Cushings syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. Use in patients under 18 years of age is not recommended due to numerically high rates of HPA axis suppression (the safety and effectiveness of desoximetasone topical spray have not been established in pediatric patients) [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.2)].. 5.2 Local Adverse Reactions with Topical Corticosteroids. Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible.. 5.3 Ophthalmic Adverse Reactions Use of topical corticosteroids, including desoximetasone topical spray, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported with the postmarketing use of topical corticosteroid products [see Adverse Reactions (6.2)]. Avoid contact of desoximetasone topical spray with eyes. Desoximetasone topical spray may cause eye irritation. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.. 5.4 Allergic Contact Dermatitis with Topical Corticosteroids. Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by failure to heal rather than clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.. 5.5 Concomitant Skin Infections. Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, desoximetasone topical spray should be discontinued until the infection has been adequately treated.. 5.6 Flammability. Desoximetasone topical spray is flammable; keep away from heat or flame.