HYDROCORTISONE 17-BUTYRATE
DESCRIPTION:
LOCOID(R) cream, ointment and topical solution contain the topical
corticosteroid, hydrocortisone butyrate, a non-fluorinated hydrocortisone ester.
It has the chemical name: pregn-4-ene-3,20-dione, 11,21-dihydroxy- 17-((1-
oxobutyl)oxy-,(11beta); the molecular formula: C25H36O6; the molecular weight:
432.54 and the CAS registry number: 13609-67-1.
LOCOID(R) CREAM 0.1%
Each gram of LOCOID(R) cream contains 1 mg of hydrocortisone butyrate in a
hydrophilic base consisting of cetostearyl alcohol, ceteth-20, mineral oil,
white petrolatum, citric acid, sodium citrate, propylparaben and butylparaben
(preservatives) and purified water.
ACTIONS/CLINICAL PHARMACOLOGY:
Topical corticosteroids share anti-inflammatory, anti-pruritic and
vasoconstrictive actions.
The mechanism of anti-inflammatory activity of the topical corticosteroids is
unclear. Various laboratory methods, including vasoconstrictor assays, are used
to compare and predict potencies and/or clinical efficacies of the topical
corticosteroids. There is some evidence to suggest that a recognizable
correlation exists between vasoconstrictor potency and therapeutic efficacy in
man.
PHARMACOKINETICS
The extent of percutaneous absorption of topical corticosteroids is determined
by many factors including the vehicle, the integrity of the epidermal barrier,
and the use of occlusive dressings.
Topical corticosteroids can be absorbed from normal intact skin. Inflammation
and/or other disease processes in the skin increase percutaneous absorption.
Occlusive dressings substantially increase the percutaneous absorption of
topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic
adjunct for treatment of resistant dermatoses. (See DOSAGE AND ADMINISTRATION.)
Once absorbed through the skin, topical corticosteroids are handled through
pharmacokinetic pathways similar to systemically administered corticosteroids.
Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids
are metabolized primarily in the liver and are then excreted by the kidneys.
Some of the topical corticosteroids and their metabolites are also excreted into
the bile.
INDICATIONS AND USAGE:
LOCOID(R) cream 0.1% and ointment 0.1% (hydrocortisone butyrate) are indicated
for the relief of the inflammatory and pruritic manifestations of
corticosteroid-responsive dermatoses.
LOCOID(R) solution 0.1% (hydrocortisone butyrate) is indicated for the relief of
the inflammatory and pruritic manifestations of seborrheic dermatitis.
CONTRAINDICATIONS:
Topical corticosteroids are contraindicated in those patients with a history of
hypersensitivity to any of the components of the preparation.
PRECAUTIONS:
GENERAL: Systemic absorption of topical corticosteroids has produced reversible
hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of
Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions
which augment 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 receiving a large dose of a potent topical steroid applied
to a large surface area or under an occlusive dressing should be evaluated
periodically for evidence of HPA axis suppression by using the urinary free
cortisol and ACTH stimulation 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 corticosteroids.
Children may absorb proportionally larger amounts of topical corticosteroids and
thus be more susceptible to systemic toxicity. (See PRECAUTIONS--PEDIATRIC USE.)
If irritation develops, topical corticosteroids should be discontinued and
appropriate therapy instituted. 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, the corticosteroid
should be discontinued until the infection has been adequately controlled.
INFORMATION FOR THE PATIENT
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. Patients should be advised not to use this medication for any disorder other
than for which it was prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped
as to be occlusive unless directed by the physician.
4. Patients should report any signs of local adverse reactions especially under
occlusive dressing.
5. Parents of pediatric patients should be advised not to use tight-fitting
diapers or plastic pants on a child being treated in the diaper area, as these
garments may constitute occlusive dressings.
LABORATORY TESTS
The following tests may be helpful in evaluating the HPA axis suppression:
Urinary free cortisol test
ACTH stimulation 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.
Studies to determine mutagenicity with prednisolone and hydrocortisone have
revealed negative results.
PREGNANCY CATEGORY C
Corticosteroids are generally teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. The more potent
corticosteroids have been shown to be teratogenic after dermal application in
laboratory animals. There are no adequate and well-controlled studies in
pregnant women on teratogenic effects from topically applied corticosteroids.
Therefore, topical corticosteroids should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus. Drugs of this class
should not be used extensively on pregnant patients, in large amounts, or for
prolonged periods of time.
NURSING MOTHERS
It is not known whether topical administration of corticosteroids could result
in sufficient systemic absorption to produce detectable quantities in breast
milk. Systemically administered corticosteroids are secreted into breast milk,
in quantities not likely to have a deleterious effect on the infant.
Nevertheless, caution should be exercised when topical corticosteroids are
administered to a nursing woman.
PEDIATRIC USE
Pediatric patients may demonstrate greater susceptibility to topical
corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature
patients because of a larger skin surface area to body weight ratio.
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and
intracranial hypertension have been reported in children receiving topical
corticosteroids. Manifestations of adrenal suppression in children include
linear growth retardation, delayed weight gain, low plasma cortisol levels, and
absence of response to ACTH stimulation. Manifestations of intracranial
hypertension include bulging fontanelles, headaches, and bilateral papilledema.
Administration of topical corticosteroids to children should be limited to the
least amount compatible with an effective therapeutic regimen. Chronic
corticosteroid therapy may interfere with the growth and development of
children.
ADVERSE REACTIONS:
The following local adverse reactions are 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: burning, itching, irritation, dryness, folliculitis, hypertrichosis,
acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact
dermatitis, maceration of the skin, secondary infection, skin atrophy, striae,
miliaria.
OVERDOSAGE:
Topically applied corticosteroids can be absorbed in sufficient amounts to
produce systemic effects. (See PRECAUTIONS.)
DOSAGE AND ADMINISTRATION:
LOCOID(R) cream 0.1% or LOCOID(R) ointment 0.1% (hydrocortisone butyrate) should
be applied to the affected area as a thin film two to three times daily
depending on the severity of the condition.
Occlusive dressings may be used for the management of psoriasis or recalcitrant
conditions.
If an infection develops, the use of occlusive dressings should be discontinued
and appropriate antimicrobial therapy instituted. LOCOID(R) solution 0.1%
(hydrocortisone butyrate) should be applied to the affected area as a thin film
from two to three times daily depending on the severity of the condition.
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