WARNINGS AND PRECAUTIONS
Effects on the Endocrine System
Clobetasol propionate is a highly potent topical corticosteroid that
has been shown to suppress the HPA axis at doses as low as 2 grams per day.
Systemic absorption of topical corticosteroids can produce reversible HPA axis
suppression with the potential for clinical glucocorticosteroid insufficiency.
This may occur during treatment or upon withdrawal of the topical corticosteroid.
Because of the potential for systemic absorption, use of topical corticosteroids may
require that patients be periodically evaluated for HPA axis suppression. In a study including
12 subjects ages 18 years and older with psoriasis or atopic dermatitis involving at least 30%
body surface area (BSA), adrenal suppression was identified in 3 out of 12 subjects (25%) following 1 week of treatment.
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 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.
Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes
mellitus can also result from systemic absorption of topical corticosteroids.
Use of more than one corticosteroid-containing product at the same time may
increase the total systemic corticosteroid exposure.
Pediatric patients may be more susceptible to systemic toxicity
from use of topical corticosteroids. [see Use in Specific Populations
]
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, hypertrichosis, perioral dermatitis, allergic contact dermatitis, secondary infection,
and miliaria. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with
acne vulgaris, rosacea or perioral dermatitis.
Allergic Contact Dermatitis
Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a
failure to heal
rather than noting a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be
confirmed with patch testing. If irritation develops, Temovate® E should be discontinued and appropriate therapy instituted.
Concomitant Skin Infections
If concomitant skin infections are present or develop, an appropriate antifungal or
antibacterial agent should be used. If a favorable response does not occur promptly, use of
Temovate® E should be discontinued until the infection has been adequately controlled.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women.
Therefore, Temovate® E 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 by this route; however, it is absorbed percutaneously,
and when administered subcutaneously it was a significant teratogen in both the rabbit and 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 0.33 and 0.01 times, respectively,
the human topical dose of Temovate® E. Abnormalities seen included cleft palate and skeletal abnormalities.
In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.001 and
0.003 times, respectively, the human topical dose of Temovate® E. 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 human milk. Because many drugs are
excreted in human milk, caution should be exercised when Temovate® E is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of Temovate® E in pediatric patients have not been established and its use in pediatric patients under
12 years of age is not recommended. In a study including 12 subjects ages 18 years and older with psoriasis or atopic
dermatitis involving at least 30% body surface area (BSA), adrenal suppression was identified in 3 out of 12 subjects (25%)
following 1 week of treatment. Four-week HPA axis suppression studies with Temovate® E Cream in pediatric subjects have not been conducted.
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 glucocorticosteroid insufficiency during 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 absence of response to ACTH stimulation. Manifestations of intracranial hypertension include
bulging fontanelles, headaches, and bilateral papilledema.
The use of Temovate® E for 4 consecutive weeks has not been studied in pediatric patients under 16 years of age.
Geriatric Use
Clinical studies of Temovate® E did not include sufficient numbers of subjects aged 65
and older to determine whether they respond differently from younger subjects.
In general, dose selection for an elderly patient should be cautious.
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