HOW SUPPLIED SECTION.

HOW SUPPLIED. Diflorasone Diacetate Ointment USP, 0.05% is available in 15 gram (NDC 51672-1295-1), 30 gram (NDC 51672-1295-2) and 60 gram (NDC 51672-1295-3) tubes.. Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Topical corticosteroids are indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. 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 approximate decreasing order of occurrence:BurningItchingIrritationDrynessFolliculitisHypertrichosisAcneiform eruptionsHypopigmentationPerioral dermatitisAllergic contact dermatitisMaceration of the skinSecondary infectionSkin atrophyStriaeMiliaria. Burning. Itching. Irritation. Dryness. Folliculitis. Hypertrichosis. Acneiform eruptions. Hypopigmentation. Perioral dermatitis. Allergic contact dermatitis. Maceration of the skin. Secondary infection. Skin atrophy. Striae. Miliaria.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, 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.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Topical corticosteroids share anti-inflammatory, antipruritic 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 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 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. 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.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Topical steroids are contraindicated in those patients with history of hypersensitivity to any of the components of the preparation.

DESCRIPTION SECTION.

DESCRIPTION. Each gram of diflorasone diacetate ointment contains 0.5 mg diflorasone diacetate in an ointment base.Chemically, diflorasone diacetate is 6,9-difluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione 17,21-diacetate. The structural formula is represented below:molecular formula: C26H32F2O7 molecular weight: 494.54Each gram of diflorasone diacetate ointment contains 0.5 mg diflorasone diacetate in an ointment base of glyceryl monostearate, propylene glycol and white petrolatum.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Diflorasone diacetate ointment should be applied to the affected area as thin film from one to three times daily depending on the severity or resistant nature 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 initiated.

GENERAL PRECAUTIONS SECTION.

General. Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushings 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 large dose of potent topical steroid applied to 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 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.Pediatric patients 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 favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

INFORMATION FOR PATIENTS SECTION.

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 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.. 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 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.

LABORATORY TESTS SECTION.

Laboratory Tests. The following tests may be helpful in evaluating the HPA axis suppression: Urinary free cortisol test ACTH stimulation test. Urinary free cortisol test. ACTH stimulation test.

MECHANISM OF ACTION SECTION.

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 recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.

NURSING MOTHERS SECTION.

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 deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to nursing woman.

OVERDOSAGE SECTION.

OVERDOSAGE. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 30 Tube Carton. NDC 51672-1295-230 gDiflorasone Diacetate Ointment USP, 0.05%FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC USE.Rx onlyKeep this and all medications out of the reach of children.TARO. PRINCIPAL DISPLAY PANEL 30 Tube Carton.

PEDIATRIC USE SECTION.

Pediatric Use. Safety and effectiveness of diflorasone diacetate ointment in pediatric patients have not been established. Because of higher ratio of skin surface area to body mass, pediatric 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 withdrawal of treatment and of Cushings syndrome while on treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in pediatric patients.HPA axis suppression, Cushings syndrome, and intracranial hypertension have been reported in pediatric 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.

PHARMACOKINETICS SECTION.

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 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. 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.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushings 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 large dose of potent topical steroid applied to 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 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.Pediatric patients 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 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 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.. 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 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.. Laboratory Tests. The following tests may be helpful in evaluating the HPA axis suppression: Urinary free cortisol test ACTH stimulation test. Urinary free cortisol test. ACTH stimulation test. Carcinogenesis, Mutagenesis, 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 deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to nursing woman.. Pediatric Use. Safety and effectiveness of diflorasone diacetate ointment in pediatric patients have not been established. Because of higher ratio of skin surface area to body mass, pediatric 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 withdrawal of treatment and of Cushings syndrome while on treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in pediatric patients.HPA axis suppression, Cushings syndrome, and intracranial hypertension have been reported in pediatric 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.

PREGNANCY SECTION.

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.

SPL UNCLASSIFIED SECTION.

Rx onlyFor Topical Use Only Not for Ophthalmic Use.

STORAGE AND HANDLING SECTION.

Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].