For Dermatological Use Only. Not for Ophthalmic Use.
Ultravate® (halobetasol propionate
ointment) 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 antipruritic
Chemically halobetasol propionate is 21-chloro-6α, 9-difluoro-11β,
17-dihydroxy-16β-methylpregna-1, 4-diene-3-20-dione, 17-propionate,
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 Ultravate 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.
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 lipocortins. 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.
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 been 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 Ultravate Ointment indicate that it is in
the super-high range of potency as compared with other topical corticosteroids.
INDICATIONS AND USAGE
Ultravate Ointment 0.05% is a super-high potency corticosteroid
indicated for the relief of the inflammatory and pruritic manifestations of
corticosteroid-responsive dermatoses. Treatment beyond two consecutive weeks
is not recommended, and the total dosage should not exceed 50 g/week
because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal
(HPA) axis. Use in children under 12 years of age is not recommended.
As with other highly active corticosteroids, therapy should be
discontinued when control has been achieved. If no improvement is seen within
2 weeks, reassessment of the diagnosis may be necessary.
Ultravate Ointment is contraindicated in those patients with a
history of hypersensitivity to any of the components of the preparation.
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
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.
Ultravate 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, Ultravate 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
If concomitant skin infections are present or develop, an appropriate
antifungal or antibacterial agent should be used. If a favorable response
does not occur promptly, use of Ultravate Ointment should be discontinued
until the infection has been adequately controlled.
Ultravate 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
Information for Patients
Patients using topical corticosteroids should receive the following
information and instructions:
The medication is to be used as directed by
the physician. It is for external use only. Avoid contact with the eyes.
The medication should not be used for any disorder
other than that for which it was prescribed.
The treated skin area should not be bandaged,
otherwise covered or wrapped, so as to be occlusive unless directed by the
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
Carcinogenesis, Mutagenesis and Impairment of Fertility
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
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.
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.
Halobetasol propionate has been shown to be teratogenic in SPF
rats and chinchilla-type rabbits when given systemically during gestation
at doses of 0.04 to 0.1 mg/kg in rats and 0.01 mg/kg in rabbits. These doses
are approximately 13, 33 and 3 times, respectively, the human topical dose
of Ultravate Ointment. Halobetasol propionate was embryotoxic in rabbits but
not in rats.
Cleft palate was observed in both rats and rabbits. Omphalocele
was seen in rats, but not in rabbits.
There are no adequate and well-controlled studies of the teratogenic
potential of halobetasol propionate in pregnant women. Ultravate Ointment
should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
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 Ultravate Ointment is administered
to a nursing woman.
Safety and effectiveness of Ultravate Ointment in pediatric patients
have not been established and use in pediatric patients under 12 is not recommended.
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 and Cushing's syndrome
when they are treated with topical corticosteroids. They are therefore also
at greater risk of adrenal insufficiency during or after withdrawal of treatment.
Adverse effects including striae have been reported with inappropriate use
of topical corticosteroids in infants and children.
HPA axis suppression, Cushing's syndrome, linear growth retardation,
delayed weight gain and intracranial hypertension have been reported in children
receiving topical corticosteroids. Manifestations of adrenal suppression in
children include low plasma cortisol levels and an absence of response to
ACTH stimulation. Manifestations of intracranial hypertension include bulging
fontanelles, headaches, and bilateral papilledema.
Of approximately 850 patients treated with Ultravate® Ointment
in clinical studies, 21% were 61 years and over and 6% were 71 years and over.
No overall differences in safety or effectiveness were observed between these
patients and younger patients; and other reported clinical experience has
not identified differences in responses between the elderly and younger patients,
but greater sensitivity of some older individuals cannot be ruled out.
In controlled clinical trials, the most frequent adverse events
reported for Ultravate Ointment included stinging or burning in 1.6% of the
patients. Less frequently reported adverse reactions were pustulation, erythema,
skin atrophy, leukoderma, acne, itching, secondary infection, telangiectasia,
urticaria, dry skin, miliaria, paresthesia, and rash.
The following additional local adverse reactions are reported infrequently
with topical corticosteroids, and they may occur more frequently with high
potency corticosteroids, such as Ultravate Ointment. These reactions are listed
in an approximate decreasing order of occurrence: folliculitis, hypertrichosis,
acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact
dermatitis, secondary infection, striae and miliaria.
Topically applied Ultravate Ointment can be absorbed in sufficient
amounts to produce systemic effects (see PRECAUTIONS).
DOSAGE AND ADMINISTRATION
Apply a thin layer of Ultravate Ointment to the affected skin once
or twice daily, as directed by your physician, and rub in gently and completely.
Ultravate (halobetasol propionate ointment) Ointment is a super-high
potency topical corticosteroid; therefore, treatment should be limited to
two weeks, and amounts greater than 50 g/wk should not be used. 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
Ultravate Ointment should not be used with occlusive dressings.
Ultravate® (halobetasol propionate
ointment) Ointment, 0.05% is supplied in the following tube sizes:
15 g (NDC 0072-1450-15)
50 g (NDC 0072-1450-50)
Store between 15°C and 30°C (59°F and 86°F).
U.S. Patent No. 4,619,921
Distributed by: Bristol-Myers
Squibb Company Princeton, NJ 08543 USA 51-022864-01 Revised
halobetasol propionate ointment
HUMAN PRESCRIPTION DRUG
Item Code (Source)
Route of Administration
Name (Active Moiety)
halobetasol propionate (halobetasol)
0.5 MILLIGRAM In 1 GRAM
contains a TUBE
This package is contained within the CARTON (0072-1450-15)
contains a TUBE
This package is contained within the CARTON (0072-1450-50)