5.1 Hypothalamic-Pituitary-Adrenal Axis Suppression

VERDESO Foam has been shown to reversibly suppress the HPA axis.

Topical application of VERDESO Foam may result in systemic absorption and effects including HPA axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, facial swelling, glycosuria, withdrawal, and growth retardation in children. Use of VERDESO Foam for longer than 4 weeks may suppress the immune system [see Nonclinical Toxicology (13.1)].

Conditions that augment systemic absorption include the application of topical corticosteroids over large body surface areas, prolonged use, or the addition of occlusive dressings. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression.

An adrenocorticotropic hormone (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.

The effect of VERDESO Foam on HPA axis function was investigated in pediatric subjects 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 cosyntropin stimulation test. The laboratory suppression was transient; all subjects had returned to normal when tested 4 weeks post-treatment.

Pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of VERDESO Foam due to their larger skin surface-to-body mass ratios. [see Use in Specific Populations (8.4)].

Concomitant therapy with topical corticosteroids should be used with caution because a cumulative effect may occur.

5.2 Skin Irritation

VERDESO Foam may cause local skin adverse reactions [see Adverse Reactions (6)]. If irritation develops, VERDESO Foam should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing.

5.3 Ophthalmic Adverse Reactions

Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in postmarketing experience with the use of topical corticosteroid products [see Adverse Reactions (6.2)].

Avoid contact of VERDESO Foam with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

5.4 Concomitant Skin Infections

If concomitant skin infections are present or develop, the use of an appropriate antifungal, antibacterial, or antiviral agent should be instituted. If a favorable response does not occur promptly, use of VERDESO Foam should be discontinued until the infection has been adequately controlled.

5.5 Flammable Contents

The contents of VERDESO Foam include alcohol and propane/butane, which are flammable. Avoid fire, flame, and/or smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

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.

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.

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.

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.

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.

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.