No information provided.
General: Systemic absorption of topical corticosteroids can produce
reversible hypothalamic-pituitary-adrenal (HPA) axis 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 cor-ticosteroids while on treatment.
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 or urinary
free cortisol tests.
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
steroid. Recovery of HPA axis function is generally prompt and complete upon
discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal
may occur, requiring supplemental systemic corti-costeroids. 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, Pandel (hydrocortisone probutate cream) Cream,
0.1% 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 observed with most topical
products not containing corticosteroids.
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 Pandel (hydrocortisone probutate cream) Cream, 0.1% should
be discontinued until the infection has been adequately controlled.
The following tests may be helpful in evaluating if HPA axis suppression does
ACTH stimulation test
A.M.plasma cortisol test
Urinary free cortisol test
Carcinogenesis, Mutagenesis and Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic
potential or the effect on fertility of topical corticosteroids.
In two mutagenicity experiments using hydrocortisone probutate, negative responses
were observed in the occurrence of micronuclei in the bone marrow of mice and
in the Ames reverse mutation test bacterial assay - with and without metabolic
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.
Hydrocortisone probutate has not been tested for teratogenicity when applied
topically; however, it is absorbed percutaneously, and studies in Wistar rats
using the subcutaneous route resulted in teratogenicity at dose levels equal
to or greater than 1 mg/kg. This dose is approximately 12 times the human average
topical dose of Pandel (hydrocortisone probutate cream) Cream, 0.1% assuming 3% absorption and an application
of 30 g/day on a 70 kg individual. Abnormalities seen included delayed ossification
of the caudal vertebrae and other skeletal variations, cleft palate, umbilical
hernia, edema, and exencephalia.
In rabbits, hydrocortisone probutate given by the subcutaneous route was teratogenic
at doses equal to or greater than 0.1 mg/kg. This dose is approximately 2 times
the human average topical dose of Pandel (hydrocortisone probutate cream) Cream, 0.1% assuming 3% absorption
and an application of 30 g/day on a 70 kg individual. Abnormalities seen included
delayed ossification of the cau-dal vertebrae and other skeletal abnormalities,
cleft palate and increased fetal mortality.
The differences between the doses used in animal studies and the proposed human
dose may not fully predict the human outcome. The animals received a bolus subcutaneous
dose, whereas humans receive a dermal application, where absorption is lower
and highly dependent on various factors (e.g., vehicle, integrity of epidermal
There are no adequate and well-controlled studies of the teratogenic potential
of hydrocortisone probutate in pregnant women. Although human epidemiological
studies do not indicate an increased incidence of teratogenicity with the use
of topical corticosteroids, Pandel (hydrocortisone probutate cream) Cream 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 quantities
in human milk. Because many drugs are excreted in human milk, caution should
be exercised when Pandel (hydrocortisone probutate cream) Cream, 0.1% is administered
to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
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 a greater risk of adrenal 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.
Hypothalamic-pituitary-adrenal (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 an
absence of response to ACTH stimulation. Manifestations of intracranial hypertension
include bulging fontanelles, headaches, and bilateral papilledema.