Included as part of the PRECAUTIONS section.
Effects On The Endocrine System
IMPOYZ Cream can cause reversible
hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for
glucocorticosteroid insufficiency. This may occur during treatment or after
withdrawal of treatment. Because of the potential for systemic absorption, use
of topical corticosteroids, including IMPOYZ Cream, may require that patients
be evaluated periodically for evidence of HPA axis suppression. Factors that
predispose a patient to HPA axis suppression include the use of high-potency steroids,
large treatment surface areas, prolonged use, use of occlusive dressings,
altered skin barrier, liver failure, and young age.
Evaluation for HPA axis suppression may be done by using
the adrenocorticotropic hormone (ACTH) stimulation test. In a trial evaluating
the effects of IMPOYZ Cream on the HPA axis, subjects with plaque psoriasis
applied IMPOYZ Cream twice daily to at least 20% of involved Body Surface Area (BSA)
for 15 days. Abnormal ACTH stimulation tests suggestive of HPA axis suppression
were seen in 3 of 24 (12.5%) subjects on IMPOYZ Cream [see CLINICAL
PHARMACOLOGY]. In another trial to evaluate the effects of IMPOYZ Cream on
the HPA axis, subjects with moderate to severe plaque psoriasis applied IMPOYZ
Cream twice daily to at least 25% of involved BSA for 28 consecutive days. Abnormal
ACTH stimulation test suggestive of HPA axis suppression was seen in 8 of 26
(30.8%) of subjects on IMPOYZ Cream.
If HPA axis suppression is documented, gradually withdraw
the drug, reduce the frequency of application, or substitute with a less potent
corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental
systemic corticosteroids may be required. Recovery of HPA axis function is generally
prompt and complete upon discontinuation of topical corticosteroids.
Systemic effects of topical corticosteroids may also
manifest as Cushing's syndrome, hyperglycemia, and glucosuria. These
complications are rare and generally occur after prolonged exposure to larger than
recommended doses, particularly with high-potency topical corticosteroids.
Use of more than one corticosteroid-containing product at
the same time may increase the total systemic exposure to topical
Minimize the unwanted risks from endocrine effects by
mitigating risk factors favoring increased systemic bioavailability and by
using the product as recommended [see DOSAGE AND ADMINISTRATION].
Pediatric patients may be more susceptible to systemic
toxicity because of their larger skin surface to body mass ratios [see Use In
Local Adverse Reactions With Topical Corticos teroids
Local adverse reactions from topical corticosteroids may
include atrophy, striae, telangiectasias, burning, itching, irritation,
dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis,
allergic contact dermatitis, secondary infection, and miliaria. These may be
more likely to occur with occlusive use, prolonged use, or use of higher
potency corticosteroids, including IMPOYZ Cream. Some local adverse reactions
may be irreversible.
Concomitant Skin Infections
Use an appropriate antimicrobial agent if a skin
infection is present or develops. If a favorable response does not occur
promptly, discontinue use of IMPOYZ Cream until the infection has been
Allergic Contact Dermatitis
Allergic contact dermatitis with corticosteroids is
usually diagnosed by observing failure to heal rather than noting a clinical
exacerbation. Such an observation should be corroborated with appropriate diagnostic
patch testing. If irritation develops, discontinue the topical corticosteroid
and institute appropriate therapy.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION)
Advise pregnant women of the potential risk to a fetus
and to use IMPOYZ Cream on the smallest area of skin and for the shortest
duration possible [see Use In Specific Populations].
Advise a woman to use IMPOYZ cream on the smallest area
of skin and for the shortest duration possible while breastfeeding. Advise
breastfeeding women not to apply IMPOYZ Cream directly to the nipple and areola
to avoid direct infant exposure [see Use In Specific Populations].
Important Administration Instructions
Instruct patients to discontinue IMPOYZ Cream when
psoriasis is controlled. IMPOYZ Cream should not be used for longer than 2
weeks. Advise patients to contact the physician if no improvement is seen within
2 weeks. Inform patients that total dosage should not exceed 50 grams per week [see
DOSAGE AND ADMINISTRATION].
Instruct patients to avoid bandaging, wrapping or
otherwise occluding the treatment area(s), unless directed by physician. Advise
patients to avoid use on the face, scalp, groin, or axillae [see DOSAGE AND
Inform patients that IMPOYZ Cream is for external use
only. Advise patients that IMPOYZ Cream is not for ophthalmic, oral, or
intravaginal use. Patients should wash their hands after applying the
medication [see DOSAGE AND ADMINISTRATION].
Do not use other corticosteroid-containing products while
using IMPOYZ Cream.
Effects On Endocrine System
IMPOYZ Cream may cause HPA axis suppression. Advise patients
that use of topical corticosteroids, including IMPOYZ Cream, may require
periodic evaluation for HPA axis suppression. Topical corticosteroids may have
other endocrine effects. Concomitant use of multiple corticosteroidcontaining products
may increase the total systemic exposure to topical corticosteroids. Patients
should inform their physician(s) that they are using IMPOYZ Cream if surgery is
contemplated [see WARNINGS AND PRECAUTIONS].
Local Adverse Reactions
Inform patients that topical corticosteroids may cause
local adverse reactions, some of which may be irreversible. These reactions may
be more likely to occur with occlusive use, prolonged use or use of higher
potency corticosteroids, including IMPOYZ Cream [see WARNINGS AND
PRECAUTIONS]. Patients should report any signs of local or systemic adverse
reactions to their physician.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term animal studies have not been performed to
evaluate the carcinogenic potential of clobetasol propionate cream.
In a 13-week repeat dose toxicity study in rats, topical
administration of clobetasol propionate cream, 0.001, 0.005 and 0.025 % at
corresponding doses of 0.004, 0.02 and 0.1 mg/kg/day resulted in corticosteroid
class-related systemic effects such as reductions in body weight gain,
reductions in total leukocytes and individual white cells, decrease in weight
of adrenals, thymus, spleen, liver and lung. Histologically, there were
decreased hematopoiesis in the bone marrow, thymic atrophy and mast cell infiltration
of the mesenteric lymph nodes. All these effects were indicative of severe
immune suppression consistent with long-term exposure to corticosteroids. A no
observable adverse effect level (NOAEL) was determined to be clobetasol
propionate cream, 0.001% (0.004 mg/kg/day) in male rats while a NOAEL could not
be determined in females. The clinical relevance of the findings in animals to
humans is not clear, but sustained glucocorticoid-related immune suppression
may increase the risk of infection and possibly the risk of carcinogenesis.
Clobetasol propionate was not mutagenic in three
different test systems: the Ames test, the Saccharomyces cerevisiae gene
conversion assay, and the E. coli B WP2 fluctuation test.
Fertility studies conducted in the rat following
subcutaneous administration of clobetasol propionate at dosage levels up to
0.05 mg/kg/day revealed that females exhibited an increase in the number of resorbed
embryos and a decrease in the number of living fetuses at the highest dose.
Use In Specific Populations
There are no available data on IMPOYZ Cream in pregnant
women to inform a drug-associated risk for adverse developmental outcomes.
Published data report a significantly increased risk of low birthweight with
the use of greater than 300 grams of potent or very potent topical
corticosteroid during a pregnancy. Advise pregnant women of the potential risk
to a fetus and to use IMPOYZ Cream on the smallest area of skin and for the
shortest duration possible (see Data). In animal reproduction studies,
increased malformations, such as cleft palate and skeletal abnormalities, were
observed after subcutaneous administration of clobetasol propionate to pregnant
mice and rabbits. No comparisons of animal exposure with human exposure are
provided due to minimal systemic exposure noted after topical administration of
IMPOYZ Cream [see CLINICAL PHARMACOLOGY].
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 background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%,
Multiple observational studies found no significant
associations between maternal use of topical corticosteroids of any potency and
congenital malformations, preterm delivery, or fetal mortality. However, when
the dispensed amount of potent or very potent topical corticosteroid exceeded
300 g during the entire pregnancy, use was associated with an increase in low
birth weight infants [adjusted RR, 7.74 (95% CI, 1.49–40.11)]. In addition, a
small cohort study, in which 28 sub-Saharan women using potent topical
corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during
pregnancy, noted a higher incidence of low birth weight infants in the exposed
group. The majority of exposed subjects treated large areas of the body (a mean
quantity of 60 g/month (range, 12– 170g) over long periods of time.
In an embryofetal development study in mice, subcutaneous
administration of clobetasol propionate resulted in fetotoxicity at the highest
dose tested (1 mg/kg) and malformations at the lowest dose tested (0.03 mg/kg).
Malformations seen included cleft palate and skeletal abnormalities. In an
embryofetal development study in rabbits, subcutaneous administration of
clobetasol propionate resulted in malformations at doses of 0.003 and 0.01
mg/kg. Malformations seen included cleft palate, cranioschisis, and other
There is no information regarding the presence of
clobetasol propionate in breast milk or its effects on the breastfed infant or
on milk production. 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 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 IMPOYZ Cream and any potential adverse effects on the breastfed infant
from IMPOYZ Cream or from the underlying maternal condition.
To minimize potential exposure to the breastfed infant
via breast milk, use IMPOYZ Cream on the smallest area of skin and for the
shortest duration possible while breastfeeding. Advise breastfeeding women not
to apply IMPOYZ Cream directly to the nipple and areola to avoid direct infant
The safety and effectiveness of IMPOYZ Cream in patients
younger than 18 years of age have not been established; therefore, use in
children younger than 18 years is not recommended. Because of a higher ratio of
skin surface area to body mass, pediatric patients are at a greater risk than
adults of systemic toxicity, including HPA axis suppression, when treated with
topical drugs [see WARNINGS AND PRECAUTIONS].
Rare systemic toxicities such as Cushing's syndrome,
linear growth retardation, delayed weight gain, and intracranial hypertension
have been reported in pediatric patients, especially those with prolonged exposure
to large doses of high potency topical corticosteroids.
Local adverse reactions including striae and skin atrophy
have also been reported with use of topical corticosteroids in pediatric
Avoid use of IMPOYZ Cream in the treatment of diaper
Clinical studies of IMPOYZ Cream did not include
sufficient numbers of subjects aged 65 and over to determine whether they
respond differently from younger subjects. Other reported clinical experience with
topical corticosteroids has not identified differences in responses between the
elderly and younger patients.