General: Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g/day.
Systemic absorption of topical corticosteroids can produce reversible HPA axis
suppression with the potential for glucocorticosteroid insufficiency after withdrawal
from treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria
can also be produced in some patients by systemic absorption of topical corticosteroids
while on therapy.
Patients applying a topical steroid to a large surface area or to areas under
occlusion should be evaluated periodically for evidence of HPA axis suppression.
This may be done by using the ACTH stimulation, A.M. plasma Cortisol, and urinary
free Cortisol tests. Patients receiving super-potent corticosteroids should
not be treated for more than 2 weeks at a time, and only small areas shoufd
be treated at any one time due to the increased risk of HPA suppression.
If HPA axis suppression is noted, an attempt should be made to withdraw the
drug, to reduce the frequency of application, or to substitute a less potent
corticosteroid. Recovery of HPA axis function is generally prompt and complete
upon discontinuation of topical corticosteroids, infrequently, signs and symptoms
of glucocorticosteroid insufficiency may occur that require supplemental systemic
corticosteroids. For information on systemic supplementation, see prescribing
information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent
doses due to their larger skin surface to body mass ratios (see PRECAUTIONS:
Pediatric Use).
If irritation develops, TEMOVATE Gel should be discontinued and appropriate
therapy instituted. Allergic contact dermatitis with corticosteroids is usually
diagnosed by observing a failure to heal rather than noting a clinical exacerbation
as with most topical products not containing corticosteroids. Such an observation
should be corroborated with appropriate diagnostic patch testing.
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 Gel should be discontinued until the infection has been adequately controlled.
TEMOVATE Gel should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.
Laboratory Tests: The following tests may be helpful in evaluating patients
for HPA axis suppression:
ACTH stimulation test
A.M. plasma Cortisol test
Urinary free Cortisol test
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal
studies have not been performed to evaluate the carcinogenic potential of clobetasol
propionate.
Studies in the rat following subcutaneous administration at dosage levels up
to 50 mcg/kg per day revealed that the females exhibited an increase in the
number of resorbed embryos and a decrease in the number of living fetuses at
the highest dose.
Clobetasol propionate was nonmutagenic in 3 different test systems: the Ames
test, the Saccharomyces cerevisiae gene conversion assay, and the E
coli B WP2 fluctuation test.
Pregnancy. Teratogenic Effects: Pregnancy Category C. Corticosteroids
have been shown to be teratogenic in laboratory animals when administered systemicaliy
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 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 TEMOVATE Gel. 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 0.02 and 0.05 times, respectively, the human topical
dose of TEMOVATE Gel. Abnormalities seen included cleft palate, cranioschisis,
and other skeletal abnormalities.
There are no adequate and welt-controlled studies of the teratogenic potential
of clobetasol propionate in pregnant women. TEMOVATE Gel should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus.
Nursing Mothers: Systemicaliy 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 Gel is administered
to a nursing woman.
Pediatric Use: Safety and effectiveness of TEMOVATE Gel in children
and infants have not been established; therefore, use in children under 12 years
of age is not recommended. Because of a higher ratio of skin surface area to
body mass, children 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 adrenal 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 (see PRECAUTIONS).
HPA axis suppression, Cushing's syndrome, and intracranial hypertension have been repotted in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma Cortisol levels, and absence of response to ACTH stimulation.
Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
Geriatric Use: A limited number of patients at or above 65 years of
age (n = 37) have been treated with TEMOVATE Gel in US clinical trials. The
number of patients is too small to permit separate analysis of efficacy and
safety, and no adverse events were reported in geriatric patients. Based on
available data, no adjustment of dosage of TEMOVATE Gel in geriatric patients
is warranted.
Last updated on RxList: 3/24/2008
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