Included as part of the "PRECAUTIONS" Section
Effects On The Endocrine System
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 can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression
with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the
In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, using the Cosyntropin Stimulation
Test, CLOBEX® 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].
Because of the potential for systemic absorption, use of topical corticosteroids 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 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
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]
Ophthalmic Adverse Reactions
Use of topical corticosteroids, including CLOBEX Spray, may increase the risks of glaucoma and posterior subcapsular cataract.
Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including
topical clobetasol products [see ADVERSE REACTIONS].
Avoid contact of CLOBEX Spray with eyes. Advise patients to report any visual symptoms and consider referral to an
ophthalmologist for evaluation.
Local Adverse Reactions With Topical Corticosteroids
The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently
with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions are listed
in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic
contact dermatitis, secondary infection, striae and miliaria.
Allergic Contact Dermatitis
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.
Concomitant Skin Infections
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® Spray, 0.05% should be discontinued until the infection has been
CLOBEX® Spray, 0.05% is flammable; keep away from heat or flame.
Patient Counseling Information
[See FDA-approved patient labeling (PATIENT INFORMATION)]
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.
- Do not use other corticosteroid-containing products while using CLOBEX® Spray, 0.05% unless directed by your physician.
- 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 medication.
- Advise patients to report any visual symptoms to their healthcare providers.
- Patients should report any signs of local or systemic adverse reactions to the physician.
- Patients should inform their physicians that they are using CLOBEX® Spray, 0.05% if surgery is contemplated.
- If you go to another doctor for illness, injury or surgery, tell that doctor you are using CLOBEX® Spray, 0.05%.
- This medication is for external use only. It should not be used on the face, underarms, or groin area. Also avoid contact with the eyes and lips.
- As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2
weeks, contact the physician.
- Advise a woman to use CLOBEX® Spray on the smallest area of skin and for the shortest duration possible while pregnant or
breastfeeding. Advise breastfeeding women not to apply CLOBEX® Spray directly to the nipple and areola to avoid direct
- Patients should not use more than 50 g (59 mL or 2 fl.oz.) per week of CLOBEX® Spray, 0.05%.
- Do not use more than 26 sprays per application or 52 sprays per day.
- This medication is flammable; avoid heat, flame or smoking when applying this product.
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
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.
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 NOAEL for paternal and maternal general toxicity based on decreased weight gain and for male reproductive toxicity based
on increased weights of fluid-filled seminal vesicles. The female reproductive NOAEL was 12.5 μg/kg/day 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
Use In Specific Populations
There are no available data on CLOBEX® Spray use in pregnant women to identify a drug-associated risk of major birth defects,
miscarriage, or adverse maternal or fetal outcomes.
Observational studies suggest an increased risk of low birthweight in infants with the maternal use of potent or very potent
topical corticosteroids (see Data). Advise pregnant women that CLOBEX® Spray may increase the risk of having a low birth
weight infant and to use CLOBEX® Spray on the smallest area of skin and for the shortest duration possible.
Animal reproduction studies have not been conducted with CLOBEX® Spray. In an animal reproduction study, subcutaneous
administration of clobetasol propionate to pregnant rats at doses greater than 12.5 μg/kg/day during the period of organogenesis
caused an increase in malformations (increased incidence of umbilical hernia) (see Data). The available data do not allow
calculation of relevant comparisons between the systemic exposure of clobetasol propionate in animal studies to the systemic
exposure that would be expected in humans after topical use of CLOBEX® Spray.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies
have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of
major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Available observational studies in pregnant women did not identify a drug-associated risk of major birth defects, preterm
delivery, or fetal mortality with the use of topical corticosteroids of any potency. However, when the dispensed amount of
potent or very potent topical corticosteroids exceeded 300 g during the entire pregnancy, maternal use was associated with an
increased risk of low birth weight in infants.
Clobetasol propionate is absorbed percutaneously, and when administered subcutaneously it caused malformations in both the
rabbit and the mouse.
Clobetasol propionate has greater potential for adverse developmental effects 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 noobserved-
adverse-effect-level (NOAEL) 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 NOAEL in the dams was 25 μg/kg/day based on prolonged
delivery at 50 μg/kg/day. The NOAEL for viability and growth in the offspring was 12.5 μg/kg/day 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 is no information regarding the presence of clobetasol propionate in human milk or its effects on the breastfed infant or on
milk production. It is not known whether topical administration of clobetasol propionate could result in sufficient systemic
absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be
considered along with the mother’s clinical need for CLOBEX® Spray and any potential adverse effects on the breastfed infant
from CLOBEX® Spray or from the underlying maternal condition.
To minimize potential exposure to the breastfed infant via breast milk, use CLOBEX® Spray on the smallest area of skin and for
the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply CLOBEX® Spray directly to the
nipple and areola to avoid direct infant exposure [see 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® Spray, 0.05% have not been established [see WARNINGS AND PRECAUTIONS].
Because of 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 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.
Clinical studies of CLOBEX® 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 two randomized, vehicle controlled clinical trials, 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.