WARNINGS AND PRECAUTIONS
Effects on Endocrine System
OLUX-E Foam has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis.
Systemic absorption of OLUX-E has caused reversible HPA axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. Use of OLUX-E Foam for longer than 2 weeks may suppress the immune system. [see Nonclinical Toxicology (13.1
)].
In a trial including 37 subjects aged 12 years and older with at least 30% body surface area (BSA), adrenal suppression was identified in 6 out of 37 subjects (16.2%) after 2 weeks of treatment with OLUX-E. [see Clinical Pharmacology(12.2)].
Because of the potential for systemic absorption, use of OLUX-E may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.
An adrenocorticotrophic 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 systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.
Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.
Use of more than 1 corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses because of their larger skin surface- to-body mass ratios. [see Use in Specific Populations (
8.4
)].
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.
Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.
If irritation develops, treatment with OLUX-E Foam should be discontinued and appropriate therapy instituted.
Concomitant Skin Infections
Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, OLUX-E Foam should be discontinued until the infection has been adequately treated.
Flammable Contents
The propellant in OLUX-E Foam is flammable. Avoid fire, flame, 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).
USE IN SPECIFIC POPULATIONS
Pregnancy
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled trials of the teratogenic potential of clobetasol propionate in pregnant women. OLUX-E Foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.
Clobetasol propionate has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and when administered subcutaneously, it was a significant teratogen in both the rabbit and the mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.
Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of OLUX-E Foam based on body surface area comparisons. Abnormalities seen included cleft palate and skeletal abnormalities.
In rabbits, clobetasol propionate was teratogenic at doses of 0.003 and 0.01 mg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of OLUX-E Foam based on body surface area comparisons. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.
Nursing Mothers
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, caution should be exercised when OLUX-E Foam is administered to a nursing woman.
If used during lactation, OLUX-E Foam should not be applied on the chest to avoid accidental ingestion by the infant.
Pediatric Use
Use in pediatric patients younger than 12 years is not recommended because of the risk of HPA axis suppression.
After 2 weeks of twice-daily treatment with OLUX-E Foam, 7 of 15 subjects (47%) aged 6 to 11 years demonstrated HPA axis suppression. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested 4 weeks post-treatment.
In 92 subjects aged 12 to 17 years, safety was similar to that observed in the adult population. Based on these data, no adjustment of dosage of OLUX-E Foam in adolescent patients aged 12 to 17 years is warranted. [see Warnings and Precautions].
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.
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 (in infants), 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.
Adverse effects, including striae, have been reported with inappropriate use of topical corticosteroids in infants and children.
Geriatric Use
A limited number of subjects aged 65 years or older have been treated with OLUX-E Foam (n = 58) in US clinical trials. While the number of subjects is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger subjects. Based on available data, no adjustment of dosage of OLUX-E Foam in geriatric patients is warranted.
|
