BETAMETHASONE DIPROPIONATE OINTMENT USP (AUGMENTED*), 0.05% (potency expressed as betamethasone) *Vehicle augments the penetration of the steroid For Dermatologic Use Only- Not for Ophthalmic Use Rx Only

betamethasone dipropionate (Betamethasone Dipropionateointment 
[Actavis Mid Atlantic LLC]

DESCRIPTION

Betamethasone Dipropionate Ointment USP (Augmented) contains betamethasone dipropionate USP, a synthetic adrenocorticosteroid, for dermatologic use. Betamethasone, an analog of prednisolone, has a high degree of corticosteroid activity and a slight degree of mineralocorticoid activity. Betamethasone dipropionate is the 17,21-dipropionate ester of betamethasone.

Chemically, betamethasone dipropionate is 9-Fluoro-11ß, 17,21-trihydroxy-16ß-methylpregna- 1,4-diene-3,20-dione 17,21-dipropionate, with the molecular formula C28H37FO7, a molecular weight of 504.60, and the following structural formula:

Image from Drug Label Content

It is a white to creamy-white, odorless powder insoluble in water; freely soluble in acetone and in chloroform; sparingly soluble in alcohol.

Each gram of Betamethasone Dipropionate Ointment 0.05% contains: 0.643 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone), in a vehicle of propylene glycol, propylene glycol stearate, white wax and white petrolatum.

CLINICAL PHARMACOLOGY

The corticosteroids are a class of compounds comprising steroid hormones secreted by the adrenal cortex and their synthetic analogs. In pharmacologic doses, corticosteroids are used primarily for their anti-inflammatory and/or immunosuppressive effects.

Topical corticosteroids, such as betamethasone dipropionate, are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, antipruritic, and vasoconstrictive actions. However, while the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in each disease are uncertain. Betamethasone dipropionate, a corticosteroid, has been shown to have topical (dermatologic) and systemic pharmacologic and metabolic effects characteristic of this

class of drugs.

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. (See DOSAGE AND ADMINISTRATIONsection.)

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. (See DOSAGE AND ADMINISTRATIONsection.)

Once absorbed through the skin, topical corticosteroids enter pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees, 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.

Studies performed with betamethasone dipropionate ointment (augmented), 0.05% indicate that it is in the super-high range of potency as compared with other topical corticosteroids.

INDICATIONS AND USAGE

Betamethasone Dipropionate Ointment (Augmented), 0.05% is a super-high potency corticosteroid indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years and older. The total dose should not exceed 50 g per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis.

CONTRAINDICATIONS

Betamethasone Dipropionate Ointment (Augmented), 0.05% is contraindicated in patients who are hypersensitive to betamethasone dipropionate, to other corticosteroids, or to any ingredient in this preparation.

PRECAUTIONS

General

Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and glycosuria in some patients. Conditions which augment systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure. (See DOSAGE AND ADMINISTRATIONsection.)

Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area 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, 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. Patients should not be treated with amounts of betamethasone dipropionate ointment (augmented), 0.05% greater than 50 g per week because of the potential for the drug to suppress HPA axis.  Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time and only small areas should be treated at any one time due to the increased risk of HPA suppression.

At 14 g per day betamethasone dipropionate ointment (augmented), 0.05% was shown to depress the plasma levels of adrenal cortical hormones following repeated application to diseased skin in patients with psoriasis.

These effects were reversible upon discontinuation of treatment. At 7 g per day betamethasone dipropionate ointment (augmented), 0.05% was shown to cause minimal inhibition of the HPA axis when applied 2 times daily for 2 to 3 weeks in healthy patients and in patients with psoriasis and exzematous disorders.

With 6 to 7 g of betamethasone dipropionate ointment (augmented), 0.05% applied once daily for 3 weeks, no signigicant inhibition of the HPA axis was observed in patients with psoriasis and atopic dermatitis, as measured by plasma cortisol and 24 –hour urinary 17-hydroxy-corticosteroid levels. 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. Betamethasone dipropionate ointment (augmented), 0.05% should not be used in the treatment of rosacea or perioral dermatitis, and it should not be used on the face, groin, or in the axillae.

Information for Patients

Patients using topical corticosteroids should receive the following information and instructions.  This information is intended to aid in the safe and effective use of this medication.  It is not a disclosure of all possible adverse or intended effects.

  1. This medication is to be used as directed by the physician and should not be used longer than the prescribed time period. It is for external use only. Avoid contact with the eyes.

  2. This medication should not be used for any disorder other than that for which it was prescribed.

  3. The treated skin area should not be bandaged, otherwise covered or wrapped, so as to be occlusive (See DOSAGE AND ADMINISTRATION section).

  4. Patients should report to their physician any signs of local adverse reactions.

  5. Patients should be advised not to use Betamethasone Dipropionate Ointment (Augmented), 0.05% in the treatment of diaper dermatitis. Betamethasone Dipropionate Ointment (Augmented), 0.05% should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing (See DOSAGE AND ADMINISTRATION).

  6. This medication should not be used on the face, underarms, or groin areas unless directed by the physician.

  7. As with other coticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.

  8. Other corticosteroid-containing products should not be used with Betamethasone Dipropionate Ointment (Augmented), 0.05%.

Laboratory Tests

The following tests may be helpful in evaluating HPA axis suppression:

ACTH stimulation test

Urinary free cortisol test

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of betamethasone dipropionate. Betamethasone was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in-vitro, human lymphocyte chromosome aberration assay, and equivocal in the in-vivo mouse bone marrow micronucleus assay.  This pattern of response is similar to that of dexamethasone and hydrocortisone. Studies in rabbits, mice and rats using intramuscular doses up to 1, 33 and 2 mg/kg, respectively, resulted in dose related increases in fetal resorptions in rabbits and mice.

Pregnancy

Teratogenic Effects

Pregnancy Category C: Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. Betamethasone dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. This dose is approximately 0.2 times the human topical dose of betamethasone dipropionate ointment (augmented), 0.05% in mg/m2 of body surface area, assuming 100% absorption and the use in a 60 kg person of 7 g per day. The abnormalities observed included umbilical hernias, cephalocele and cleft palate. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids.

Betamethasone dipropionate ointment (augmented), 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when betamethasone dipropionate ointment (augmented), 0.05% is administered to a nursing woman.

Pediatric Use

Use of betamethasone dipropionate ointment (augmented), 0.05% in pediatric patients 12 years of age and younger is not recommended. (See  CLINICAL PHARMACOLOGYandADVERSE REACTIONS  sections.)

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. Chronic corticosteroid therapy may interfere with the growth and development of children.

ADVERSE REACTIONS

The local adverse reactions were reported with betamethasone dipropionate ointment (augmented) 0.05% during controlled clinical studies were as follows: erythema,

folliculitis, pruritus and vesiculation each occurring in less than 1% of patients.

The following additional local adverse reactions have been reported with topical corticosteroids, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae and miliaria.

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.

OVERDOSAGE

Topically applied betamethasone dipropionate ointment (augmented) 0.05% can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)

DOSAGE AND ADMINISTRATION

Apply a thin film of Betamethasone Dipropionate Ointment (Augmented), 0.05% to the affected skin once or twice daily. Betamethasone Dipropionate Ointment (Augmented), 0.05% is a super-high potency topical corticosteroid. Treatment with Betamethasone Dipropionate Ointment (Augmented), 0.05% should be limited to 50 g per week.

As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Betamethasone Dipropionate Ointment (Augmented), 0.05% should not to be used with occlusive dressings.

Betamethasone Dipropionate Ointment (Augmented), 0.05% should not be applied to the diaper area if the patient requires diapers or plastic pants as these garments may constitute occlusive dressing.

HOW SUPPLIED

Betamethasone Dipropionate Ointment USP (Augmented), 0.05% is supplied in 15 g (0.53 oz) and 45 g (1.59 oz) tubes; boxes of one.

Store between 2° and 25°C (36° and 77°F).

Manufactured by:
Actavis Mid Atlantic LLC
1877 Kawai Road
Lincolnton, NC 28092 USA

FORM NO. 0382

Rev. 3/06

VC2797


Betamethasone Dipropionate (Betamethasone Dipropionate)
PRODUCT INFO
Product Code0472-0382Dosage FormOINTMENT
Route Of AdministrationTOPICALDEA Schedule
INGREDIENTS
Name (Active Moiety)TypeStrength
Betamethasone Dipropionate (Betamethasone) Active0.5 MILLIGRAM  In 1 GRAM
propylene glycolInactive 
propylene glycol stearateInactive 
white waxInactive 
white petrolatumInactive 
IMPRINT INFORMATION
CharacteristicAppearanceCharacteristicAppearance
ColorScore
ShapeSymbol
Imprint CodeCoating
Size
PACKAGING
#NDCPackage DescriptionMultilevel Packaging
10472-0382-151 TUBE In 1 CARTONcontains a TUBE
115 GRAM In 1 TUBEThis package is contained within the CARTON (0472-0382-15)
20472-0382-451 TUBE In 1 CARTONcontains a TUBE
245 GRAM In 1 TUBEThis package is contained within the CARTON (0472-0382-45)

Revised: 01/2008Actavis Mid Atlantic LLC