Pramosone ® (hydrocortisone acetate 1% pramoxine hydrochloride 1%) Cream 1%Sebela Pharmaceuticals Inc.Ferndale Laboratories, Inc.Pramosone Creamhydrocortisone acetate and pramoxine hydrochlorideSTEARIC ACIDCETYL ALCOHOLISOPROPYL PALMITATEPOLYOXYL 40 STEARATEPROPYLENE GLYCOLPOTASSIUM SORBATESORBIC ACIDTRIETHANOLAMINE LAURYL SULFATEWATERHYDROCORTISONE ACETATEHYDROCORTISONEPRAMOXINE HYDROCHLORIDEPRAMOXINEDESCRIPTION: Pramosone ® Cream 1% is a topical preparation
containing hydrocortisone acetate 1% w/w and pramoxine hydrochloride 1% w/w in
a hydrophilic cream base containing stearic acid, cetyl alcohol, Aquaphor
®,
isopropyl palmitate, polyoxyl 40 stearate, propylene glycol, potassium sorbate,
sorbic acid, triethanolamine lauryl sulfate, and purified water.
Topical corticosteroids are anti-inflammatory and
anti-pruritic agents. The structural formula, the chemical name, molecular formula and molecular weight for active ingredients are presented below.hydrocortisone acetate
Pregn-4-ene-3,
20-dione, 21-(acetyloxy)-11, 17-dihydroxy-, (11-beta)-
C
23H
32O
6; mol.wt.: 404.50
pramoxine hydrochloride
4-(3-(p-butoxyphenoxy)propyl)morpholine
hydrochloride
C
17H
27NO
3.HCl; mol. wt.: 329.87
hydrocortisone acetatepramoxine hclCLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, anti-pruritic
and vasoconstrictive actions.
The mechanism of anti-inflammatory activity of 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.Pramoxine hydrochloride is a topical anesthetic agent which
provides temporary relief from itching and pain. It acts by stabilizing the
neuronal membrane of nerve endings with which it comes into contact.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: Topical corticosteroids are indicated for the relief of the
inflammatory and pruritic manifestations of corticosteroid-responsive
dermatoses.
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 and 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:
This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.Patients should be advised not to use this medication for any disorder other than for which it was prescribed.The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.Patients should report any signs of local adverse reactions especially under occlusive dressings.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: Teratogenic Effects: 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 amounts 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 fontanels, 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: