No information provided.
Clobetasol propionate is a highly potent topical
corticosteroid that has been shown to suppress the HPA axis at the lowest doses
Systemic absorption of topical corticosteroids has caused
reversible adrenal suppression with the potential for glucocorticosteroid
insufficiency after withdrawal of treatment. Manifestations of Cushing's
syndrome, hyperglycemia, and glucosuria can also be produced in some patients
by systemic absorption of topical corticosteroids while on treatment.
Conditions which increase systemic absorption include the
application of the more potent steroids, use over large surface areas,
prolonged use, and the addition of occlusive dressings. Therefore, patients
applying a topical steroid to a large surface area or to areas under occlusion
should be evaluated periodically for evidence of adrenal suppression (see laboratory
tests below). If adrenal suppression is noted, an attempt should be made to
withdraw the drug, to reduce the frequency of application, or to substitute a
less potent steroid. Recovery of HPA
axis function is generally prompt upon
discontinuation of topical corticosteroids. Infrequently, signs and symptoms of
glucocorticosteroid insufficiency may occur requiring supplemental systemic
corticosteroids. For information on systemic supplementation, see prescribing
information for those products.
The effect of CLOBEX® Lotion, 0.05% on HPA axis
function was compared to clobetasol propionate cream 0.05% (Temovate E®
Emollient, 0.05%) in adults in two studies, one for psoriasis and one for
atopic dermatitis. In total, 8 of 10 evaluable patients with moderate to severe
plaque psoriasis experienced adrenal suppression following 4 weeks of CLOBEX® Lotion, 0.05% therapy (treatment beyond 4 consecutive weeks is not
recommended in moderate to severe plaque psoriasis). In follow-up testing, 1 of
2 patients remained suppressed after 8 days. In this comparative study, for
clobetasol propionate cream, 0.05% there were 3 of 10 evaluable patients with
HPA axis suppression. Furthermore, 5 of 9 evaluable patients with moderate to
severe atopic dermatitis experienced adrenal suppression following 2 weeks of
CLOBEX® Lotion, 0.05% therapy (treatment beyond 2 consecutive weeks
is not recommended in moderate to severe atopic dermatitis). Of the 3 patients
that had follow-up testing, one patient failed to recover adrenal function 7
days post-treatment. For patients treated with clobetasol propionate cream,
0.05%, 4 of 9 evaluable patients experienced adrenal suppression following 2
weeks of treatment. Of the 2 patients that had follow-up testing, both
recovered adrenal function 7 days post-treatment. The proportion of subjects
suppressed may be underestimated because the adrenal glands were stimulated
weekly with cosyntropin in these studies.
The potential increase in systemic exposure does not
correlate with any proven benefit, but may lead to an increased potential for
hypothalamic-pituitary-adrenal (HPA) axis suppression. Patients with acute
illness or injury may have increased morbidity and mortality with intermittent
HPA axis suppression. Patients should be instructed to use CLOBEX® Lotion,
0.05% for the minimum amount of time necessary to achieve the desired results
(See INDICATIONS AND USAGE).
If irritation develops, CLOBEX® Lotion, 0.05%
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.
In the presence of dermatological infections, the use of an
appropriate antifungal or antibacterial agent should be instituted. If a
favorable response does not occur promptly, use of CLOBEX® Lotion,
0.05% should be discontinued until the infection has been adequately
CLOBEX® Lotion, 0.05% should not be used in
the treatment of rosacea or perioral dermatitis, and should not be used on the
face, groin, or axillae.
Information for Patients
Patients using topical corticosteroids should receive the
following information and instructions:
- This medication is to be used as directed by the physician
and should not be used longer than the prescribed time period.
- This medication should not be used for any disorder other
than that for which it was prescribed.
- The treated skin area should not be bandaged, otherwise
covered, or wrapped so as to be occlusive unless directed by the physician.
- Patients should wash their hands after applying the
- Patients should report any signs of local or systemic
adverse reactions to the physician.
- Patients should inform their physicians that they are using
CLOBEX® (clobetasol propionate) Lotion, 0.05% if surgery is
- This medication is for external use only. It should not be
used on the face, underarms, or groin area, and avoid contact with the eyes and
- As with other corticosteroids, therapy should be
discontinued when control is achieved. If no improvement is seen within 2
weeks, contact the physician.
- Patients should be informed to not use more than 50 g (50 mL
or 1.75 fl.oz.) per week of CLOBEX® Lotion, 0.05%.
The following tests may be helpful in evaluating patients
for HPA axis suppression:
- Cosyntropin stimulation test
- AM plasma cortisol test
- Urinary free cortisol test
Carcinogenesis, Mutagenesis, Impairment of Fertility
Clobetasol propionate was not carcinogenic to rats when
topically applied for 2 years at concentrations up to 0.005% which corresponded
to doses up to 11 μg/kg/day (ratio of animal dose to proposed human dose
of 0.03 on a mg/m2/day basis).
Clobetasol propionate at concentrations up to 0.001% did not
increase the rate of formation of ultra violet light-induced skin tumors when
topically applied to hairless mice 5 days per week for a period of 40 weeks.
Clobetasol propionate was negative in the in vitro mammalian
chromosomal aberration test and in the in vivo mammalian erythrocyte
The effect of subcutaneously administered clobetasol
propionate on fertility and general reproductive toxicity was studied in rats
at doses of 0, 12.5, 25, and 50 μg/kg/day. Males were treated beginning 70
days before mating and females beginning 15 days before mating through day 7 of
gestation. A dosage level of less than 12.5 μg/kg/day clobetasol
propionate was considered to be the no-observed-effect-level (NOEL) for
paternal and maternal general toxicity based on decreased weight gain and for male
reproductive toxicity based on increased weights of the seminal vesicles. The
female reproductive NOEL was 12.5 μg/kg/day (ratio of animal dose to
proposed human dose of 0.03 on a mg/m²/day basis) based on reduction in the
numbers of estrous cycles during the pre-cohabitation period and an increase in
the number of nonviable embryos at higher doses.
Teratogenic effects: Pregnancy Category C.
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 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 CLOBEX® (clobetasol propionate) Lotion, 0.05%. Abnormalities seen included cleft
palate and skeletal abnormalities.
In rabbits, clobetasol propionate was teratogenic at doses
of 3 and 10 μg/kg. These doses are approximately 0.02 and 0.05 times,
respectively, the human topical dose of CLOBEX® (clobetasol
propionate) Lotion, 0.05%. Abnormalities seen included cleft palate,
cranioschisis, and other skeletal abnormalities.
A teratogenicity study in rats using the dermal route
resulted in dose related maternal toxicity and fetal effects from 0.05 to 0.5
mg/kg/day of clobetasol propionate. These doses are approximately 0.14 to 1.4
times, respectively, the human topical dose of CLOBEX® (clobetasol
propionate) Lotion, 0.05%. Abnormalities seen included low fetal weights,
umbilical herniation, cleft palate, reduced skeletal ossification, and other
There are no adequate and well-controlled studies of the
teratogenic potential of clobetasol propionate in pregnant women. CLOBEX® (clobetasol
propionate) Lotion, 0.05% should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
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 quanitities in breast milk. Because many drugs
are excreted in human milk, caution should be exercised when CLOBEX® Lotion,
0.05% is administered to a nursing woman.
Use of CLOBEX® Lotion, 0.05% in pediatric
patients is not recommended due to the potential for HPA axis suppression (see PRECAUTIONS:
The HPA axis suppression potential of CLOBEX® Lotion,
0.05% has been studied in adolescents (12 to 17 years of age) with moderate to
severe atopic dermatitis covering a minimum of 20% of the total body surface
area. In total 14 patients were evaluated for HPA axis function. Patients were
treated twice daily for 2 weeks with CLOBEX® Lotion, 0.05%. After 2
weeks of treatment, 9 out of 14 of the patients experienced adrenal
suppression. One out of 4 patients treated with CLOBEX® Lotion,
0.05% who were retested remained suppressed two weeks post-treatment. In
comparison, 2 of 10 of the patients treated with clobetasol propionate cream,
0.05% demonstrated HPA axis suppression. One patient who was retested
None of the patients who developed HPA axis suppression had
concomitant clinical signs of adrenal suppression and none of them was
discontinued from the study for reasons related to the safety or tolerability
of CLOBEX® Lotion, 0.05%. However patients with acute illness or
injury may have increased morbidity and mortality with intermittent HPA axis
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
and/or after withdrawal of treatment. Adverse effects including striae have
been reported with inappropriate use of topical corticosteroids in infants and
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.
Clinical studies of CLOBEX® (clobetasol
propionate) Lotion, 0.05% did not include sufficient numbers of patients aged
65 and over to determine whether they respond differently than younger
patients. In general, dose selection for an elderly patient should be made with
caution, 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.