Halonate

Like other topical corticosteroids, halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of the anti- inflammatory activity of the topical corticosteroids, in general, is unclear However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocorins It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier Occlusive dressings with hydrocortisone for up to 24 hours have not bean demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Human and animal studies indicate that less than 6% of the applied dose of halobetasol propionate enters the circulation within 96 hours following topical administration of the ointment.

Studies performed with Halobetasol Propionate Ointment indicate that it is in the super-high range of potency as compared with other topical corticosteroids.

Halonate Halobetasol Propionate Ointment, 0.05% contains halobetasol propionate, a synthetic corticosteroid for topical dermatological use. The corticosteroids constitute a class of primarily synthetic steroids used topically as an anti-inflammatory and anti-pruritic agent.  Chemically halobetasol propionate is 21-chloro-6α, 9-difluoro-11β,17-dihydroxy-16β-methylpregna-1, 4-diene-3-20-dione, 17-propionate, C25H31ClF2O5. It has the following structural formula:

Halobetasol propionate has the molecular weight of 485. It is a white crystalline powder insoluble in water.  Each gram of Halobetasol Propionate Ointment contains 0.5 mg/g of halobetasol propionate in a
base of aluminum stearate, beeswax, pentaerythritol cocoate, petrolatum, propylene glycol, sorbitan sesquioleate, and stearyl citrate.

General:  Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.

Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free-cortisol tests.  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.

Halobetasol Propionate Ointment produced HPA axis suppression when used in divided doses at 7 grams per day for one week in patients with psoriasis. These effects were reversible upon discontinuation of treatment.

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 corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see PRECAUTIONS: Pediatric Use).

If irritation develops, Halobetasol Propionate Ointment should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing. If concomitant skin infections are present or develop, an appropriate antifungal or anti-bacterial agent should be used. If a favorable response does not occur promptly, use of Halobetasol Propionate Ointment should be discontinued until the infection has been adequately controlled.

Halobetasol Propionate Ointment 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.

Patients using topical corticosteroids should receive the following information and instructions:

1) The medication is to be used as directed by the physician. It is for external use only. Avoid contact
with the eyes.

2) The 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 unless directed by the physician.

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

The following tests may be helpful in evaluating patients for HPA axis suppression: ACTH-stimulation test; A.M. plasma cortisol test; Urinary freecortisol test.

Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol propionate.

Positive mutagenicity effects were observed in two genotoxicity assays. Halobetasol propionate was positive in a Chinese hamster micronucleus test, and in a mouse lymphoma gene mutation assay in vitro.

Studies in the rat following oral administration at dose levels up to 50 μg/kg/day indicated no impairment of fertility or general reproductive performance.

In other genotoxicity testing, halobetasol propionate was not found to be genotoxic in the Ames/Salmonella assay, in the sister chromatid exchange test in somatic cells of the Chinese hamster, in chromosome aberration studies of germinal and somatic cells of rodents, and in a mammalian spot test to determine point mutations.

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

Halonate™ is supplied in the following:

(NDC 68712-042-01) one 50 g tube of halobetasol propionate ointment 0.05% packaged with one
4 oz can of ammonium lactate mousse 12%

STORAGE: Store between 15°C and 30°C (59°F and 86°F).

Manufactured by:

G and W Laboratories, Inc.
South Plainfield, NJ  07080


Manufactured for:

Innocutis Holdings LLC
Charleston, SC  29401
1-800-499-4468
www.innocutis.com

Halonate PAC  halobetasol ointment

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68712-042 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HALOBETASOL PROPIONATE (HALOBETASOL ) HALOBETASOL PROPIONATE 0.5 mg  in 1 g

Inactive Ingredients Ingredient Name Strength ALUMINUM STEARATE   YELLOW WAX   PENTAERYTHRITOL   PETROLATUM   PROPYLENE GLYCOL

Packaging # Item Code Package Description 1 NDC:68712-042-01 50 g in 1 TUBE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077721 05/01/2010

Labeler - Innocutis Holdings LLC (071501252)

Establishment
Name	Address	ID/FEI	Operations
G &W Laboratories Inc.		001271188	manufacture

Revised: 11/2011   Innocutis Holdings LLC