General
Clobetasol propionate is a highly potent topical corticosteroid that has
been shown to suppress the HPA axis at the lowest doses tested.
In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA)
axis suppression, using the Cosyntropin Stimulation Test, CLOBEX® (clobetasol
propionate) Spray, 0.05% demonstrated rates of suppression that were comparable
after 2 and 4 weeks of twice-daily use (19% and 15-20%, respectively), in adult
patients with moderate to severe plaque psoriasis ( ≥ 20%BSA). In these studies,
HPA axis suppression was defined as serum cortisol level ≤ 18 µg/dL
30-min post cosyntropin stimulation. (See CLINICAL PHARMACOLOGY).
Patients with acute illness or injury may have increased morbidity and mortality
with intermittent HPA axis suppression. Patients should be instructed to use
CLOBEX® (clobetasol propionate) Spray, 0.05% for the minimum amount of time
necessary to achieve the desired results (see INDICATIONS).
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.
HPA axis suppression has not been evaluated in psoriasis patients treated with
CLOBEX® (clobetasol propionate) Spray, 0.05% who are less than 18 years
old. 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). 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.
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 (seelaboratory 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.
If irritation develops, CLOBEX® (clobetasol propionate) Spray, 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® (clobetasol propionate) Spray, 0.05% should be discontinued until the infection has been adequately controlled.
CLOBEX® (clobetasol propionate) Spray, 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.
Instructions to the Pharmacist
- Remove the spray pump from the wrapper
- Remove and discard the cap from the bottle
- Keeping the bottle vertical, insert the spray pump into the bottle and turn
clockwise until well-fastened
- Dispense the bottle with the spray pump inserted
Laboratory Tests
The cosyntropin stimulation test may be helpful in evaluating patients for
HPA axis suppression.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic
potential of clobetasol propionate.
Clobetasol propionate was negative in the in vitro mammalian chromosomal
aberration test and in the in vivo mammalian erythrocyte micronucleus
test.
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 with fluid. 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.
Pregnancy
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.
The effect of clobetasol propionate on pregnancy outcome and development of
offspring was studied in the rat. Clobetasol propionate was administered subcutaneously
to female rats twice daily (0, 12.5, 25, and 50 µg/kg/day) from day 7
of presumed gestation through day 25 of lactation or day 24 presumed gestation
for those rats that did not deliver a litter. The maternal NOEL for clobetasol
propionate was less than 12.5 µg/kg/day due to reduced body weight gain
and feed consumption during the gestation period. The reproductive NOEL in the
dams was 25 µg/kg/day (ratio of animal dose to proposed human dose of
0.07 on a mg/m2/day basis) based on prolonged delivery at a higher
dose level. The no-observed-adverse-effect-level (NOAEL) for viability and growth
in the offspring 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 incidence of stillbirths,
reductions in pup body weights on days 1 and 7 of lactation, increased pup mortality,
increases in the incidence of umbilical hernia, and increases in the incidence
of pups with cysts on the kidney at higher dose levels during the preweaning
period. The weights of the epididymides and testes were significantly reduced
at higher dosages. Despite these changes, there were no effects on the mating
and fertility of the offspring.
There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. CLOBEX® (clobetasol propionate) Spray, 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 CLOBEX® (clobetasol propionate) Spray, 0.05% is administered
to a nursing woman.
Pediatric Use
Use in patients under 18 years of age is not recommended, because safety has
not been established and because numerically high rates of HPA axis suppression
were seen with other clobetasol propionate topical formulations. Safety and
effectiveness in pediatric patients treated with CLOBEX® (clobetasol propionate)
Spray, 0.05% have not been established (see PRECAUTIONS: General).
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 glucocortisteroid insufficiency during and/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.
Geriatric Use
Clinical studies of CLOBEX® (clobetasol propionate) Spray, 0.05% did not
include sufficient numbers of patients aged 65 and over to adequately determine
whether they respond differently than younger patients. In the two Phase 3 studies,
21 of the 240 patients (9%) were over the age of 65. 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.
Last updated on RxList: 11/26/2008
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