Verdeso (Page 2 of 4)

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 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.

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.

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:

Chemical Structure
(click image for full-size original)

Desonide has a molecular formula of C24 H32 O6 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.

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.

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.

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