PREDNICARBATE
DESCRIPTION:
FOR DERMATOLOGIC USE ONLY.
NOT FOR USE IN EYES.
Dermatop(R) Emollient Cream (prednicarbate emollient cream) 0.1% contains
prednicarbate, a synthetic corticosteroid for topical dermatologic use. The
chemical name of prednicarbate is 11beta, 17,21-trihydroxypregna-1,4-diene-
3,20-dione 17-(ethyl carbonate) 21-propionate. Prednicarbate has the empirical
formula C27H36O8 and a molecular weight of 488.58. Topical corticosteroids
constitute a class of primarily synthetic steroids used topically as anti-
inflammatory and antipruritic agents.
Prednicarbate is a practically odorless white to yellow-white powder insoluble
to practically insoluble in water and freely soluble in ethanol.
Each gram of Dermatop(R) Emollient Cream 0.1% contains 1.0 mg of prednicarbate
in a base consisting of white petrolatum USP, purified water USP, isopropyl
myristate NF, lanolin alcohols NF, mineral oil USP, cetostearyl alcohol NF,
aluminum stearate, edetate disodium USP, lactic acid USP, and magnesium stearate
DAB 9.
ACTIONS/CLINICAL PHARMACOLOGY:
In common with other topical corticosteroids, prednicarbate has anti-
inflammatory, antipruritic, and vasoconstrictive properties. In general, the
mechanism of the anti-inflammatory activity of topical steroids is unclear.
However, corticosteroids are thought to act by the induction of phospholipase A2
inhibitory proteins, collectively called lipocortins. It is postulated that
these proteins control the biosynthesis of potent mediators of inflammation such
as prostaglandins and leukotrienes by inhibiting the release of their common
precursor arachidonic acid. Arachidonic acid is released from membrane
phospholipids by phospholipase A2.
PHARMACOKINETICS
The extent of percutaneous absorption of topical corticosteroids is determined
by many factors, including the vehicle and the integrity of the epidermal
barrier. Use of occlusive dressings with hydrocortisone for up to 24 hours have
not been shown to increase penetration; however, occlusion of hydrocortisone for
96 hours does markedly enhance penetration. Topical corticosteroids can be
absorbed from normal intact skin. Inflammation and/or other disease processes in
the skin increase percutaneous absorption.
Studies performed with Dermatop(R) Emollient Cream (prednicarbate emollient
cream) 0.1% indicate that the drug product is in the medium range of potency
compared with other topical corticosteroids.
INDICATIONS AND USAGE:
Dermatop(R) Emollient Cream 0.1% is a medium- potency corticosteroid indicated
for the relief of the inflammatory and pruritic manifestations of
corticosteroid-responsive dermatoses. Dermatop(R) Emollient Cream 0.1% may be
used with caution in pediatric patients 1 year of age or older. The safety and
efficacy of drug use for longer than 3 weeks in this population have not been
established. Since safety and efficacy of Dermatop(R) Emollient Cream 0.1% have
not been established in pediatric patients below 1 year of age, its use in this
age group is not recommended.
CONTRAINDICATIONS:
Dermatop(R) Emollient Cream 0.1% is contraindicated in those patients with a
history of hypersensitivity to any of the components in the preparations.
PRECAUTIONS:
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 corticosteroids 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, AM plasma cortisol,
and urinary free cortisol tests.
Dermatop(R) Emollient Cream (prednicarbate emollient cream) 0.1% did not produce
significant HPA-axis suppression when used at a dose of 30g/day for a week in 10
adult patients with extensive psoriasis or atopic dermatitis. Dermatop(R)
Emollient Cream 0.1% did not produce HPA-axis suppression in any of 59 pediatric
patients with extensive atopic dermatitis when applied BID for 3 weeks to >20%
of the body surface (See PRECAUTIONS, PEDIATRIC USE.)
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
corticosteroid. 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.
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, Dermatop(R) Emollient 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. Such an observation should be corroborated with
appropriate diagnostic patch testing.
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 Dermatop(R) Emollient Cream 0.1% should be discontinued until
the infection has been adequately controlled.
INFORMATION FOR PATIENTS
Patients using topical corticosteroids should receive the following information
and instructions:
1. This medication is to be used as directed by the physician. It is for
external use only. Avoid contact with the eyes.
2. This medication should not be used for any disorder other than that for which
it was prescribed.
3. The treated skin area should not be bandaged, otherwise covered or wrapped so
as to be occlusive, unless directed by the physician.
4. Patients should report to their physician any signs of local adverse
reactions.
5. Parents of pediatric patients should be advised not to use this medication
in the treatment of diaper dermatitis. This medication should not be applied
in the diaper area as diapers or plastic pants may constitute occlusive
dressing. (See DOSAGE AND ADMINISTRATION.)
6. This medication should not be used on the face, underarms, or groin areas.
7. As with other corticosteroids, therapy should be discontinued when control
is achieved. If no improvement is seen within two weeks, contact the physician.
LABORATORY TESTS
The following tests may be helpful in evaluating patients for HPA-axis
suppression:
ACTH stimulation test
AM plasma cortisol test
Urinary free cortisol test
CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
In a study of the effect of prednicarbate on fertility, pregnancy, and postnatal
development in rats, no effect was noted on the fertility or pregnancy of the
parent animals or postnatal development of the offspring after administration of
up to 0.80 mg/kg of prednicarbate subcutaneously.
Prednicarbate has been evaluated in the Salmonella reversion test (Ames test)
over a wide range of concentrations in the presence and absence of an S-9 liver
microsomal fraction, and did not demonstrate mutagenic activity. Similarly,
prednicarbate did not produce any significant changes in the numbers of
micronuclei seen in erythrocytes when mice were given doses ranging from 1 to
160 mg/kg of the drug.
PREGNANCY: TERATOGENIC EFFECTS: PREGNANCY CATEGORY C.
Corticosteroids have been shown to be teratogenic in laboratory animals when
administered systematically at relatively low dosage levels. Some
corticosteroids have been shown to be teratogenic after dermal application in
laboratory animals.
Prednicarbate has been shown to be teratogenic and embryotoxic in Wistar rats
and Himalayan rabbits when given subcutaneously during gestation at doses 1900
times and 45 times the recommended topical human dose, assuming a percutaneous
absorption of approximately 3%.
In the rats, slightly retarded fetal development and an incidence of thickened
and wavy ribs higher than the spontaneous rate were noted.
In rabbits, increased liver weights and slight increase in the fetal
intrauterine death rate were observed. The fetuses that were delivered exhibited
reduced placental weight, increased frequency of cleft palate, ossification
disorders in the sternum, omphalocele, and anomalous posture of the forelimbs.
There are no adequate and well-controlled studies in pregnant women on
teratogenic effects of prednicarbate. Dermatop(R) Emollient Cream (prednicarbate
emollient cream) 0.1% 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 human milk. Because many drugs are excreted in human
milk, caution should be exercised when Dermatop(R) Emollient Cream 0.1% is
administered to a nursing woman.
PEDIATRIC USE
Dermatop(R) Emollient Cream 0.1% may be used with caution in pediatric patients
1 year of age or older, although the safety and efficacy of drug use longer than
3 weeks have not been established. The use of Dermatop(R) Emollient Cream
(prednicarbate emollient cream) 0.1% is supported by results of a three-week,
uncontrolled study in 59 pediatric patients between the ages of 4 months and 12
years of age with atopic dermatitis. None of the 59 pediatric patients showed
evidence of HPA-axis suppression. Safety and efficacy of Dermatop(R) Emollient
Cream 0.1% in pediatric patients below 1 year of age have not been established,
therefore use in this age group 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 HPA-axis suppression and Cushing's syndrome when they are treated with
topical corticosteroids. They are therefore also at greater risk of adrenal
insufficiency during and/or after withdrawal of treatment. In an uncontrolled
study in pediatric patients with atopic dermatitis, the incidence of adverse
reactions possibly or probably associated with the use of Dermatop(R) Emollient
Cream 0.1% was limited. Mild signs of atrophy developed in 5 patients (5/59, 8%)
during the clinical trial, with 2 patients exhibiting more than one sign. Two
patients (2/59, 3%) developed shininess, and 2 patients (2/59, 3%) developed
thinness. Three patients (3/59, 5%) were observed with mild telangectasia. It is
unknown whether prior use of topical corticosteroids was a contributing factor
in the development of telangectasia in 2 of the patients. Adverse effects
including striae have also been reported with inappropriate use of topical
corticosteroids in infants and children. Pediatric patients applying topical
corticosteroids to greater than 20% of body surface are at higher risk for HPA-
axis suppression.
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.
Dermatop(R) Emollient Cream 0.1% should not be used in the treatment of diaper
dermatitis.
ADVERSE REACTIONS:
In controlled adult clinical studies, the incidence of adverse reactions
probably or possibly associated with the use of Dermatop(R) Emollient Cream 0.1%
was approximately 4%. Reported reactions included mild signs of skin atrophy in
1% of treated patients, as well as the following reactions which were reported
in less than 1% of patients: pruritus, edema, paresthesia, urticaria, burning,
allergic contact dermatitis and rash.
In an uncontrolled study in pediatric patients with atopic dermatitis, the
incidence of adverse reactions possibly or probably associated with the use of
Dermatop(R) Emollient Cream 0.1% was limited. Mild signs of atrophy developed in
5 patients (5/59, 8%) during the clinical trial, with 2 patients exhibiting more
than one sign. Two patients (2/59, 3%) developed shininess, and 2 patients
(2/59, 3%) developed thinness. Three patients (3/59, 5%) were observed with mild
telangectasia. It is unknown whether prior use of topical corticosteroids was a
contributing factor in the development of telangectasia in 2 of the patients
(See PRECAUTIONS, PEDIATRIC USE.)
The following additional local adverse reactions have been reported infrequently
with topical corticosteroids, but may occur more frequently with the use of
occlusive dressings. These reactions are listed in an approximate decreasing
order of occurrence: folliculitis, acneiform eruptions, hypopigmentation,
perioral dermatitis, secondary infection, striae and miliaria.
OVERDOSAGE:
Topically applied corticosteroids can be absorbed in sufficient amounts to
produce systemic effects (See PRECAUTIONS.)
DOSAGE AND ADMINISTRATION:
Apply a thin film of Dermatop(R) Emollient Cream (prednicarbate emollient cream)
0.1% to the affected skin areas twice daily. Rub in gently.
Dermatop(R) Emollient Cream 0.1% may be used in pediatric patients 1 year of age
or older. Safety and efficacy of Dermatop(R) Emollient Cream 0.1% in pediatric
patients for more than 3 weeks of use have not been established. Use in
pediatric patients under 1 year of age is not recommended.
As with other corticosteroids, therapy should be discontinued when control is
achieved. If no improvement is seen within 2 weeks, reassessment of the
diagnosis may be necessary.
Dermatop(R) Emollient Cream 0.1% should not be used with occlusive dressings
unless directed by the physician. Dermatop(R) Emollient Cream 0.1% should not be
applied in the diaper area if the child still requires diapers or plastic pants
as these garments may constitute occlusive dressing.
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