DESONATE (Page 2 of 3)

8.4 Pediatric Use

Safety and effectiveness of DESONATE in pediatric patients less than 3 months of age have not been evaluated, and therefore its use in this age group is not recommended.

The effect of DESONATE on HPA axis function was investigated in pediatric subjects, with atopic dermatitis covering at least 35% of their body, who were treated with DESONATE twice daily for 4 weeks. One of 37 subjects (3%) displayed adrenal suppression after 4 weeks of use, based on the cosyntropin stimulation test [see Warnings and Precautions (5.1)].

In controlled clinical studies in subjects 3 months to 18 years of age, 425 subjects were treated with DESONATE and 157 subjects were treated with vehicle [see Adverse Reactions (6) and Clinical Studies (14)].

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 when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on 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 absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

8.5 Geriatric Use

Clinical studies of DESONATE did not include patients aged 65 and older to determine if they respond differently than younger patients. Treatment of this patient population should reflect the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

Topically applied DESONATE can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1)].

11 DESCRIPTION

DESONATE contains desonide [(pregna-1, 4-diene-3, 20-dione,11, 21-dihydroxy-16, 17-[(1-methylethylidene) bis(oxy)]-,(11β,16α)]- a synthetic nonfluorinated corticosteroid for topical dermatologic use. Chemically, desonide is C24 H32 O6 . It has the following structural formula:

Structural Formula
(click image for full-size original)

Desonide has the molecular weight of 416.52. It is a white to off-white odorless powder which is soluble in methanol and practically insoluble in water. Each gram of DESONATE contains 0.5 mg of desonide in an aqueous gel base of purified water, glycerin, propylene glycol, edetate disodium dihydrate, methylparaben, propylparaben, sodium hydroxide, and Carbopol® 981.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action of desonide is unknown.

12.2 Pharmacodynamics

In an HPA axis suppression study, one of 37 (3%) pediatric subjects, 6 months to 6 years old, with moderate to severe atopic dermatitis covering at least 35% body surface area who applied DESONATE experienced suppression of the adrenal glands following 4 weeks of therapy [see Warnings And Precautions (5.1) and Use In Specific Populations (8.4)]. A follow-up evaluation of the subject’s adrenal axis was not performed; it is unknown whether the suppression was reversible.

12.3 Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including product formulation and the integrity of the epidermal barrier. 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 then are 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

Systemic long-term animal studies have not been performed to evaluate the carcinogenic potential of desonide or its effect on fertility. In a 26-week dermal carcinogenicity study conducted in transgenic (Tg.AC) mice, once daily application of 0.005% to 0.05% DESONATE Gel significantly increased the incidence of papillomas at the treatment site in males and females compared to their respective control animals. The clinical relevance of these findings in animals to humans is not clear.

Desonide revealed no evidence of mutagenic potential based on the results of an in vitro genotoxicity test (Ames assay) and an in vivo genotoxicity test (mouse micronucleus assay). Desonide was positive without S9 activation and was equivocal with S9 activation in an in vitro mammalian cell mutagenesis assay (L5178YITK+ mouse lymphoma assay). A dose response trend was not noted in this assay.

14 CLINICAL STUDIES

In two randomized vehicle-controlled clinical studies, subjects 3 months to 18 years of age with mild to moderate atopic dermatitis were treated twice daily for 4 weeks with either DESONATE or vehicle. Treatment success was defined as achieving clear or almost clear on the Investigator’s Global Severity Score (IGSS) with at least a 2-point change (decrease) from the subject’s baseline IGSS when compared to the Week 4 IGSS. The results of the 2 clinical trials are summarized in Table 1:

Table 1: Subjects Achieving Treatment Success

Clinical Trial 1

DESONATE

N = 289

Vehicle

N = 92

128 (44%)

13 (14%)

Clinical Trial 2

DESONATE

N = 136

Vehicle

N = 65

38 (28%)

4 (6%)

16 HOW SUPPLIED/STORAGE AND HANDLING

DESONATE is a translucent to opaque gel supplied in a 60g tube (NDC 50222-504-60).

Storage:

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

Patients using topical corticosteroids should receive the following information and instructions:

•This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.

•This medication should not be used for any disorder other than that for which it was prescribed.

•Unless directed by the physician, the treated skin area should not be bandaged or otherwise covered or wrapped so as to be occlusive.

•Unless directed by a physician, this medication should not be used on the underarm or groin areas of pediatric patients.

•Parents of pediatric patients should be advised not to use DESONATE in the treatment of diaper dermatitis. DESONATE should not be applied in the diaper area, as diapers or plastic pants may constitute occlusive dressing [see Dosage and Administration (2)].

•Patients should report to their physician any signs of local adverse reactions.

•Other corticosteroid-containing products should not be used with DESONATE without first consulting with the physician.

•As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician.

DESONATE is a registered trademark of LEO Pharma A/S.

© 2018, LEO Pharma Inc. All rights reserved.

Manufactured for:

LEO Pharma Inc., Seven Giralda Farms, Madison, NJ 07940 USA

Manufactured by:

Contract Pharmaceuticals Limited, Mississauga, ON, Canada L5N 6L6

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