DIFLORASONE DIACETATE ointment

Diflorasone Diacetate by

Drug Labeling and Warnings

Diflorasone Diacetate by is a Prescription medication manufactured, distributed, or labeled by Rising Pharmaceuticals, Inc., Lyne Laboratories, Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

DESCRIPTION

Each gram of diflorasone diacetate ointment contains 0.5 mg diflorasone diacetate in an ointment base. Chemically, diflorasone diacetate is 6α,9-difluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3, 20-dione 17,21-diacetate. The structural formula is represented below:

C26H32F2O7 MW = 494.54

Each gram of diflorasone diacetate ointment contains 0.5 mg diflorasone diacetate in an ointment base of propylene glycol, glyceryl monostearate and white petrolatum.

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 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. 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.

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

Topical steroids 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.

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 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 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

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

Pediatric Use

Safety and effectiveness of diflorasone diacetate ointment in pediatric patients have not been established.

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 when they are treated with topical corticosteroids. They are, therefore, also at greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing's syndrome while on treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in pediatric patients.

HPA axis suppression, Cushing's 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.

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:

1. Burning
2. Itching
3. Irritation
4. Dryness
5. Folliculitis
6. Hypertrichosis
7. Acneiform eruptions
8. Hypopigmentation
9. Perioral dermatitis
10. Allergic contact dermatitis
11. Maceration of the skin
12. Secondary infection
13. Skin atrophy
14. Striae
15. Miliaria

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

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

DOSAGE AND ADMINISTRATION

Diflorasone diacetate ointment should be applied to the affected area as a 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.

HOW SUPPLIED

Diflorasone Diacetate Ointment USP, 0.05% is available in 15 gram, 30 gram, 45 gram and 60 gram tubes.

• 15 gram tube: NDC: 64980-124-15
• 30 gram tube: NDC: 64980-124-03
• 45 gram tube: NDC: 64980-124-45
• 60 gram tube: NDC: 64980-124-60

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

Keep this and all medications out of the reach of children.

Mfd. By:
Lyne Laboratories, Inc.
Brockton, MA 02301

Mfd. For:
Rising Pharmaceuticals, Inc.
East Brunswick, NJ 08816
R2-03/23
PIR12460-01

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Carton - 15g

Tube - 15 g

INGREDIENTS AND APPEARANCE

DIFLORASONE DIACETATE 
diflorasone diacetate ointment

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 64980-124
Route of Administration	TOPICAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
DIFLORASONE DIACETATE (UNII: 7W2J09SCWX) (DIFLORASONE - UNII:T2DHJ9645W)	DIFLORASONE DIACETATE	0.5 mg  in 1 g

Inactive Ingredients
Ingredient Name	Strength
PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
PETROLATUM (UNII: 4T6H12BN9U)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 64980-124-15	1 in 1 CARTON	02/27/2017
1		15 g in 1 TUBE; Type 0: Not a Combination Product
2	NDC: 64980-124-03	1 in 1 CARTON	02/27/2017
2		30 g in 1 TUBE; Type 0: Not a Combination Product
3	NDC: 64980-124-45	1 in 1 CARTON	02/27/2017
3		45 g in 1 TUBE; Type 0: Not a Combination Product
4	NDC: 64980-124-60	1 in 1 CARTON	02/27/2017
4		60 g in 1 TUBE; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA207440	02/27/2017

Labeler - Rising Pharma Holdings, Inc. (116880195)

Establishment
Name	Address	ID/FEI	Business Operations
Lyne Laboratories, Inc.		053510459	MANUFACTURE(64980-124)