Verdeso

6 ADVERSE REACTIONS The most common adverse reactions (>1%) are upper respiratory tract infection, cough, application site burning, headache, viral infection, and increased blood pressure. ( 6.1 ) In post-marketing reports, the most common adverse reactions were application site irritation followed by application site erythema. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Almirall at 1-866-665-2782 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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 clinical practice. In a controlled clinical trial of 581 subjects aged 3 months to 17 years, adverse reactions occurred at the application site in 6% of subjects treated with VERDESO Foam and 14% of subjects treated with vehicle foam. Other commonly reported adverse reactions for VERDESO Foam and vehicle foam are noted in Table 1 . Table 1. Adverse Reactions in the Clinical Trial Adverse Reaction VERDESO Foam (N = 387) Vehicle (N = 194) Upper respiratory tract infection 37 (10%) 12 (6%) Cough 14 (4%) 3 (2%) Application site burning 11 (3%) 15 (8%) Viral infection 6 (2%) 0 (0%) Elevated blood pressure 6 (2%) 1 (1%) Headache 7 (2%) 1 (1%) Asthma 3 (1%) 0 (0%) Irritability 2 (1%) 0 (0%) Pharyngitis 2 (1%) 0 (0%) Application site atrophy 5 (1%) 0 (0%) Application site reactions (including atrophy, striae, telangiectasia and pigmentation changes) 3 (1%) 6 (3%) Other local adverse events occurred at rates less than 1.0%. The majority of adverse reactions were transient and mild to moderate in severity, and they were not affected by age, race, or gender. The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria. 6.2 Post-marketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post-approval use of VERDESO Foam: application site irritation, application site erythema, skin reactions, and swelling face. Ophthalmic adverse reactions of blurred vision, cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported with the use of topical corticosteroids.

4 CONTRAINDICATIONS None. None. ( 4 )

11 DESCRIPTION VERDESO Foam is a white to off-white petrolatum-based emulsion aerosol foam containing the active ingredient desonide, a low-potency topical corticosteroid. Chemically, desonide is (11,16)-11,21-dihydroxy-16,17-[(1-methylethylidene)-bis(oxy)]-pregna-1,4-diene-3,20-dione. The structural formula of desonide is represented below: Desonide has a molecular formula of C 24 H 32 O 6 and a molecular weight of 416.51. Desonide is a white powder or crystal that is practically insoluble in water, sparingly soluble in ethanol and in acetone, and soluble in chloroform. Each gram of VERDESO Foam contains 0.5 mg desonide. The foam also contains anhydrous citric acid, cetyl alcohol, cyclomethicone, isopropyl myristate, light mineral oil, white petrolatum, polyoxyl 20 cetostearyl ether, potassium citrate (monohydrate), propylene glycol, purified water, sorbitan monolaurate, and phenoxyethanol as a preservative. VERDESO Foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/butane) propellant. Chemical Structure

2 DOSAGE AND ADMINISTRATION VERDESO Foam is not for oral, ophthalmic, or intravaginal use. A thin layer of VERDESO Foam should be applied to the affected area(s) twice daily. Shake the can before use. VERDESO Foam should be dispensed by inverting the can (upright actuation will cause loss of the propellant which may affect product delivery). Dispense the smallest amount of foam necessary to adequately cover the affected area(s) with a thin layer. The medication should not be dispensed directly on the face. Dispense in hands and gently massage into affected areas of the face until the medication disappears. For areas other than the face, the medication may be dispensed directly onto the affected area. Take care to avoid contact with the eyes or other mucous membranes. Therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, reassessment of diagnosis may be necessary. The safety and efficacy of VERDESO Foam has not been established beyond 4 weeks of use. Unless directed by a physician, VERDESO Foam should not be used with occlusive dressings. VERDESO Foam should be applied to the affected area(s) twice daily. ( 2 ) Discontinue therapy when control has been achieved. ( 2 ) If no improvement is seen within 4 weeks, reassess diagnosis. ( 2 ) Unless directed by a physician, do not use with occlusive dressings. ( 2 ) VERDESO Foam is not for oral, ophthalmic, or intravaginal use. ( 2 ) The safety and efficacy of VERDESO Foam has not been established beyond 4 weeks of use. ( 2 )

1 INDICATIONS AND USAGE VERDESO ® (desonide) Foam, 0.05% is indicated for the treatment of mild to moderate atopic dermatitis in patients 3 months of age and older. Patients should be instructed to use VERDESO Foam for the minimum amount of time necessary to achieve the desired results because of the potential for VERDESO Foam to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Treatment should not exceed 4 consecutive weeks. VERDESO Foam is a corticosteroid indicated for the topical treatment of mild to moderate atopic dermatitis in patients 3 months of age and older. ( 1 )

10 OVERDOSAGE Topically applied VERDESO Foam can be absorbed in sufficient amounts to produce systemic effects. 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.

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 the treatment of atopic dermatitis is unknown. The contribution to efficacy by individual components of the vehicle has not been established. 12.2 Pharmacodynamics In an HPA axis suppression trial, three of 75 (4%) pediatric subjects with mild to moderate atopic dermatitis covering at least 25% body surface area, who applied VERDESO Foam twice daily, experienced reversible suppression of the adrenal glands (as indicated by a 30-minute post-stimulation cortisol level 18 mcg/dL) following 4 weeks of therapy. [See also Hypothalamic-Pituitary-Adrenal Axis Suppression ( 5.1 ) and Pediatric Use ( 8.4 )]. 12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation, the integrity of the epidermal barrier, and age. Occlusion, inflammation, and/or other disease processes in the skin may also increase percutaneous absorption. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized primarily in the liver and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.

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 the treatment of atopic dermatitis is unknown. The contribution to efficacy by individual components of the vehicle has not been established.

12.2 Pharmacodynamics In an HPA axis suppression trial, three of 75 (4%) pediatric subjects with mild to moderate atopic dermatitis covering at least 25% body surface area, who applied VERDESO Foam twice daily, experienced reversible suppression of the adrenal glands (as indicated by a 30-minute post-stimulation cortisol level 18 mcg/dL) following 4 weeks of therapy. [See also Hypothalamic-Pituitary-Adrenal Axis Suppression ( 5.1 ) and Pediatric Use ( 8.4 )].

12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation, the integrity of the epidermal barrier, and age. Occlusion, inflammation, and/or other disease processes in the skin may also increase percutaneous absorption. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized primarily in the liver and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.

20210801

7

3 DOSAGE FORMS AND STRENGTHS Foam, 0.05%. Each gram of VERDESO Foam contains 0.5 mg of desonide in a white to off-white petrolatum-based emulsion aerosol foam. Foam, 0.05% ( 3 )

Verdeso desonide DESONIDE DESONIDE ANHYDROUS CITRIC ACID CETYL ALCOHOL CYCLOMETHICONE ISOPROPYL MYRISTATE LIGHT MINERAL OIL PETROLATUM POLYOXYL 20 CETOSTEARYL ETHER POTASSIUM CITRATE PROPYLENE GLYCOL WATER SORBITAN MONOLAURATE PHENOXYETHANOL

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of VERDESO Foam or desonide. In a 90-day repeat-dose toxicity study in rats, topical administration of VERDESO Foam at dose concentrations from 0.025% to 0.125% (providing 0.075 to 0.375 mg/kg/day of desonide) resulted in a toxicity profile consistent with long-term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression, and opportunistic fungal and bacterial infections. 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 of carcinogenesis. Desonide revealed no evidence of mutagenic potential based on the results of 2 in vitro genotoxicity tests (Ames assay, mouse lymphoma cell assay) and an in vivo genotoxicity test (mouse micronucleus assay). The effects of desonide on fertility have not been evaluated.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of VERDESO Foam or desonide. In a 90-day repeat-dose toxicity study in rats, topical administration of VERDESO Foam at dose concentrations from 0.025% to 0.125% (providing 0.075 to 0.375 mg/kg/day of desonide) resulted in a toxicity profile consistent with long-term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression, and opportunistic fungal and bacterial infections. 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 of carcinogenesis. Desonide revealed no evidence of mutagenic potential based on the results of 2 in vitro genotoxicity tests (Ames assay, mouse lymphoma cell assay) and an in vivo genotoxicity test (mouse micronucleus assay). The effects of desonide on fertility have not been evaluated.

NDA021978

Verdeso

desonide

16110-111

HUMAN PRESCRIPTION DRUG

TOPICAL

PRINCIPAL DISPLAY PANEL - NDC: 16110-111-00 - Can Label Can Label

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling ( Patient Information ). Important Administration Instructions Inform patients of the following: This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes or other mucous membranes. The medication should not be dispensed directly onto the face. Dispense in hands and gently massage into affected areas of the face until the medication disappears. For areas other than the face, the medication may be dispensed directly on the affected area. Wash hands after use. Advise patients to report any visual symptoms to their healthcare providers. This medication should not be used for any disorder other than that for which it was prescribed. The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician Patients should report any signs of local or systemic adverse reactions to the physician. Patients should inform their physicians that they are using VERDESO Foam if surgery is contemplated. Therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician. Do not use other corticosteroid-containing products while using VERDESO Foam without first consulting your physician. The propellant in VERDESO Foam is flammable. Avoid fire, flame or smoking during and immediately following application. Lactation Advise a woman to use VERDESO Foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women to wash off any VERDESO Foam that has been applied to the nipple and areola prior to breastfeeding to avoid direct infant exposure [see Use in Specific Populations ( 8.2 )] .

14 CLINICAL STUDIES In a double-blind, randomized trial of 581 subjects aged 3 months to 17 years, with mild to moderate atopic dermatitis, VERDESO Foam was applied twice daily for 4 weeks. Success was defined as the proportion of subjects who had all of the following: an Investigator’s Static Global Assessment (ISGA) score of clear or almost clear, a minimum improvement in the 5-point ISGA score of 2 grades from Baseline to Week 4, and a score of absent or minimal for both erythema and induration/papulation at Week 4. The results of this trial are presented in the following table . Table 2. Results of Clinical Trial in Subjects Aged 3 Months to 17 Years With Mild to Moderate Atopic Dermatitis VERDESO Foam Vehicle Foam Number of Patients 387 194 Patients Achieving Success 152 (39%) 18 (9%)

8.5 Geriatric Use Clinical trials of VERDESO Foam did not include any subjects aged 65 or over to determine whether they respond differently from younger subjects. 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.

8.4 Pediatric Use Safety and efficacy in pediatric patients younger than 3 months have not been established; therefore, the use of VERDESO Foam 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 also 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. 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 an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children. The effect of VERDESO Foam on HPA axis function was investigated in pediatric subjects, aged 6 months to 17 years in one trial. In this trial, subjects with atopic dermatitis covering at least 25% of their body applied VERDESO Foam twice daily for 4 weeks. Three out of 75 subjects (4%) displayed adrenal suppression after 4 weeks of use based on the ACTH stimulation test. The suppression was transient; all subjects’ cortisol levels had returned to normal when tested 4 weeks post-treatment.

8.1 Pregnancy Risk Summary There are no available data on VERDESO Foam use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, topical administration of a desonide cream, 0.05% formulation during organogenesis caused malformations characteristic of corticosteroids in rats and in rabbits (see Data ) . The available data do not allow the calculation of relevant comparisons between the systemic exposure of desonide observed in animal studies to the systemic exposure that would be expected in humans after topical use of VERDESO Foam. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a 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 2-4% and 15-20%, respectively. Data Animal Data Topical administration of a desonide cream, 0.05% formulation to pregnant rats (gestational days 6 to 15) and pregnant rabbits (gestational days 6 to 18) at 0.2, 0.6, and 2.0 g cream/kg/day was associated with maternal body weight loss at all dose levels in both species. Malformations characteristic of corticosteroids were observed in rats at topical doses of ≥0.6 g cream/kg/day and in rabbits at a topical dose of 2.0 g cream/kg/day. No malformations were observed at a topical dose of 0.2 g cream/kg/day in rats and at a topical dose of 0.6 g cream/kg/day in rabbits.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on VERDESO Foam use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, topical administration of a desonide cream, 0.05% formulation during organogenesis caused malformations characteristic of corticosteroids in rats and in rabbits (see Data ) . The available data do not allow the calculation of relevant comparisons between the systemic exposure of desonide observed in animal studies to the systemic exposure that would be expected in humans after topical use of VERDESO Foam. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a 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 2-4% and 15-20%, respectively. Data Animal Data Topical administration of a desonide cream, 0.05% formulation to pregnant rats (gestational days 6 to 15) and pregnant rabbits (gestational days 6 to 18) at 0.2, 0.6, and 2.0 g cream/kg/day was associated with maternal body weight loss at all dose levels in both species. Malformations characteristic of corticosteroids were observed in rats at topical doses of ≥0.6 g cream/kg/day and in rabbits at a topical dose of 2.0 g cream/kg/day. No malformations were observed at a topical dose of 0.2 g cream/kg/day in rats and at a topical dose of 0.6 g cream/kg/day in rabbits. 8.2 Lactation Risk Summary There are no data on the presence of desonide in human or animal milk, its effects on the breastfed infant, or its effects on milk production. It is not known whether topical administration of VERDESO Foam could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VERDESO Foam and any potential adverse effects on the breastfed infant from VERDESO Foam or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use VERDESO Foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women to wash off any VERDESO Foam that has been applied to the nipple and areola prior to breastfeeding to avoid direct infant exposure. 8.4 Pediatric Use Safety and efficacy in pediatric patients younger than 3 months have not been established; therefore, the use of VERDESO Foam 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 also 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. 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 an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children. The effect of VERDESO Foam on HPA axis function was investigated in pediatric subjects, aged 6 months to 17 years in one trial. In this trial, subjects with atopic dermatitis covering at least 25% of their body applied VERDESO Foam twice daily for 4 weeks. Three out of 75 subjects (4%) displayed adrenal suppression after 4 weeks of use based on the ACTH stimulation test. The suppression was transient; all subjects’ cortisol levels had returned to normal when tested 4 weeks post-treatment. 8.5 Geriatric Use Clinical trials of VERDESO Foam did not include any subjects aged 65 or over to determine whether they respond differently from younger subjects. 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.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied VERDESO Foam is a white to off-white aerosol foam supplied in 100-g (NDC 16110-111-00) aluminum cans. 16.2 Storage and Handling Store at USP controlled room temperature 68°F to 77°F (20°C to 25°C) with excursions permitted between 15°C (59°F) and 30°C (86°F). WARNING: FLAMMABLE. AVOID FIRE, FLAME, OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION. Contents under pressure. Do not puncture or incinerate. Do not expose containers to heat, and/or store at temperatures above 120°F (49°C). Avoid contact with eyes or other mucous membranes. Keep out of reach of children.

16.2 Storage and Handling Store at USP controlled room temperature 68°F to 77°F (20°C to 25°C) with excursions permitted between 15°C (59°F) and 30°C (86°F). WARNING: FLAMMABLE. AVOID FIRE, FLAME, OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION. Contents under pressure. Do not puncture or incinerate. Do not expose containers to heat, and/or store at temperatures above 120°F (49°C). Avoid contact with eyes or other mucous membranes. Keep out of reach of children.