Each gram of FLORONE Cream contains 0.5 mg diflorasone diacetate in a cream base. Chemically, diflorasone diacetate is: 6a,9-Difluoro- 11b, 17, 21-trihydroxy-16b-methylpregna-1,4-diene- 3,20-dione 17,21-diacetate. FLORONE
diflorasone diacetate cream, USP
FPO
The structural formula is represented below:
O CH2OCCH3
C H
O O
OCCH3 CH3
CH
H H
F H
O
F H
FLORONE Cream contains diflorasone diacetate in an emulsified and hydrophilic cream base of pro- pylene glycol, stearic acid, polysorbate 60, sorbitan monostearate and monooleate, sorbic acid, citric acid and water. The corticosteroid is formulated as a solution in the vehicle using 15 percent propylene glycol to optimize drug delivery.
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 effi- cacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and thera- peutic efficacy in man.
The extent of percutaneous absorption of topical cor- ticosteroids 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 pro- cesses in the skin increase percutaneous absorp- tion. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable thera- peutic adjunct for treatment of resistant dermatoses. (See DOSAGE AND ADMINISTRATION.) Once absorbed through the skin, topical cortico- steroids are handled through pharmacokinetic path- ways similar to systemically administered cortico- steroids. Corticosteroids are bound to p lasma proteins in varying degrees. They 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.
Topical corticosteroids are indicated for relief of the inflammatory and pruritic manifestations of cortico- steroid responsive dermatoses.
Topical steroids are contraindicated in those patients with a history of hypersensitivity to any of the com- ponents of the preparation.
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, o r to substitute a l ess potent steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of t he drug. Infrequently, signs and symptoms of s teroid withdrawal may occur, requiring supplemental systemic corticosteroids. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible t o systemic toxicity. (See PRE- CAUTIONS--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 dis- continued until the infection has been adequately controlled.
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 con- tact with the eyes.
Patients should be advised not to use this med- ication 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 dressing.
Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on an infant or child being treated in the diaper area, as these garments may constitute occlusive dressings.
The following tests may be helpful in evaluating the HPA axis suppression: Urinary free cortisol test ACTH stimulation test
Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect of topical corticosteroids on fertility. Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results.
Corticosteroids are generally teratogenic in labora- tory animals when administered systemically at rela- tively low dosage levels. The more potent cortico- steroids 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 preg- nant patients, in large amounts, or for prolonged periods of time.
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 cortico- steroids are administered to a nursing woman.
Safety and effectiveness of FLORONE in pediatric patients have not been established. Because of a higher ratio of skin surface area to body mass, pedi- atric patients are at greater risk than adults of HPA- axis suppression when they are treated with topical corticosteroids. They are, therefore, also at greater risk of glucocorticosteroid insufficiency after with- drawal of treatment and of Cushing's syndrome while on treatment. Adverse effects including striae have been reported with inappropriate use of topical corti- costeroids in pediatric patients. HPA-axis suppression, Cushing's syndrome, and intracranial hypertension have been reported in pedi- atric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients 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.
FLORONE
brand of diflorasone diacetate cream, USP
0.05%
The following local adverse reactions have been reported 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
(continued below)
Allergic contact dermatitis Maceration of the skin Secondary infection Skin atrophy Striae Miliaria
Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)
Topical corticosteroids are generally applied to the affected area as a thin film from one to four times daily depending on the severity of the condition. Occlusive dressings may be used for the manage- ment of psoriasis or recalcitrant conditions. If an infection develops, the use of occlusive dress- ings should be discontinued and appropriate antimi- crobial therapy instituted.
FLORONE Cream is available in 30 gram and 60 gram collapsible tubes. Store at controlled room temperature 20deg to 25deg C (68deg to 77deg F) [see USP].
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only
Pharmacia & Upjohn Company A subsidiary of Pharmacia Corporation Kalamazoo, Michigan 49001 Revised May 2003 DAW123B