CLASSES

Plain Topical Corticosteroids

DEA CLASS

Rx

DESCRIPTION

Very high-potency fluorinated topical corticosteroid
Used for moderate to severe corticosteroid-responsive dermatoses, including psoriasis
Generally use for short durations due to potential for systemic effects

COMMON BRAND NAMES

BRYHALI, LEXETTE, Ultravate

HOW SUPPLIED

BRYHALI/Ultravate Topical Lotion: 0.01%, 0.05%
Halobetasol Propionate/LEXETTE Topical Foam: 0.05%
Halobetasol Propionate/Ultravate Topical Cream: 0.05%
Halobetasol Propionate/Ultravate Topical Ointment: 0.05%

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

50 grams/week topically; no more than 2 weeks per treatment cycle for all products except Bryhali lotion, which is no more than 8 weeks per treatment cycle.

50 grams/week topically; no more than 2 weeks per treatment cycle for all products except Bryhali lotion, which is no more than 8 weeks per treatment cycle.

50 grams/week topically; no more than 2 weeks per treatment cycle.

12 years: 50 grams/week topically; no more than 2 weeks per treatment cycle (Ultravate lotion, Lexette topical foam, and halobetasol cream and ointment).
5 to 11 years: Safety and efficacy have not been established; off-label short-term use reported; do not exceed 50 grams/week; use for 2 weeks or less per treatment cycle.
1 to 5 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

For topical dermatologic use only. Not for ophthalmic, oral, or vaginal use.
Avoid contact with the eyes. Halobetasol is not recommended for use on the face, scalp, groin, or in the axillae.

STORAGE

BRYHALI:
- Protect from freezing
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
LEXETTE:
- Do not freeze
- Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
- Flammable, keep away from heat and flame
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Ultravate:
- Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Halobetasol is contraindicated in any patient with a history of hypersensitivity to any ingredients in the preparation; use with caution in patients with a history of severe corticosteroid hypersensitivity reactions to other corticosteroids. Halobetasol cream and ointment should not be used with an occlusive dressing. Do not use the foam or lotion with occlusive dressings unless directed by a physician.

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions that increase systemic absorption include the application of very high-potency corticosteroids (such as halobetasol), use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of an occlusive dressing. Patients receiving large doses of a potent topical corticosteroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression using ACTH stimulation, AM plasma cortisol, and urinary free cortisol 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 corticosteroid. HPA axis suppression has been reported in psoriasis patients using 7 grams/day of halobetasol for 1 week of treatment. In one study, 5 out of 20 (25%) adults with moderate to severe plaque psoriasis (involving 20% or more of their body) receiving treatment with Ultravate lotion (mean dose of 3.5 grams applied twice daily for 2 weeks) developed HPA axis suppression. In this study, suppression was defined as serum cortisol concentration less than or equal to 18 mcg/dL 30 minutes after stimulation with cosyntropin. Recovery of HPA axis function was noted upon retest 4 weeks after therapy discontinuation. In another clinical study, 16 adolescent patients (12 to less than 17 years old) with moderate to severe plaque psoriasis involving a mean 11.5% (range 10% to 14%) of their body surface area (BSA) applied a mean dose of 3.6 grams of Ultravate lotion twice daily to the affected areas for 2 weeks. Of the 14 subjects evaluated for HPA axis suppression, adrenal suppression occurred in 1 subject (7%) which recovered upon retest 4 weeks after discontinuation of therapy. In a study with 19 adult subjects with moderate to severe plaque psoriasis involving 20% or more of their BSA, an approximate dose of 7 grams of Bryhali lotion was applied once daily for 8 weeks. HPA axis suppression was reported for 1 (5.6%) subject at Week 4 and for 3 (15.8%) subjects at Week 8. All subjects had normal HPA axis suppression test with discontinuation of treatment. Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids. Due to the potential for glucose alterations, halobetasol should be used cautiously in patients with diabetes mellitus.

Use halobetasol with caution in children. Administration of halobetasol cream and ointment to pediatric patients 12 years and older should be limited to the least amount compatible with an effective therapeutic regimen. The safety and efficacy of halobetasol cream and ointment in neonates, infants, and children less than 12 years of age have not been established, although off-label use has been reported in pediatric patients 5 years and older. The safety and effectiveness of halobetasol 0.01% lotion (Bryhali) in patients younger than 18 years of age have not been established. The safety and effectiveness of halobetasol 0.05% lotion (Ultravate) and halobetasol foam in patients younger than 12 years of age have not been established. Children may absorb proportionally larger amounts of topical corticosteroids due to a larger skin surface area to body weight ratio, and therefore are more susceptible to developing systemic toxicity, especially with very-high-potency products. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, growth inhibition (linear growth retardation and delayed weight gain), and increased intracranial pressure have been reported in children receiving topical corticosteroids. If children are being treated with topical corticosteroids in the diaper area, tight-fitting diapers or plastic pants should be avoided as these garments may act as an occlusive dressing and increase systemic absorption of the drug.

There are no available data on halobetasol use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Halobetasol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids, including halobetasol, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women. Guidelines recommend mild to moderate potency agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birth weight have been reported with the use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. Corticosteroids have been shown to be teratogenic after dermal, oral, and subcutaneous administration in animal studies. Halobetasol has greater potency, and thus greater teratogenic potential, than other topical corticosteroids. After systemic halobetasol propionate administration to pregnant rats and rabbits at doses of 0.04 to 0.1 mg/kg/day and 0.01 mg/kg/day, respectively, increased malformations, such as cleft palate, were observed. Omphalocele was also seen in rats and halobetasol was found to be embryotoxic in rabbits.  

It is not known whether topical administration of halobetasol could result in sufficient systemic absorption to produce detectable quantities in breast milk. Use of low to mid-potency topical corticosteroids is recommended in this patient population. However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast, nipple, and areola.   Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

The normal inflammatory response to local infections can be masked by halobetasol. Application of topical corticosteroids to areas of infection, including tuberculosis of the skin, dermatologic fungal infection, and cutaneous or systemic viral infection (i.e., measles or varicella), should be initiated or continued only if the appropriate antiinfective treatment is instituted. Herpes infection may be transmitted to other sites, including the eye. If the infection does not respond to the antimicrobial therapy, the concurrent use of the topical corticosteroid should be discontinued until the infection is controlled. Topical corticosteroids may delay the healing of non-infected wounds, such as venous stasis ulcers.

As with other potent fluorinated topical corticosteroids, halobetasol should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis. Halobetasol may aggravate these conditions. Halobetasol preparations should not be applied to the face, groin, or axillae. Care should be taken to avoid the use of highly potent corticosteroids, such as halobetasol, around the eyes; ocular exposure should be avoided. Topical corticosteroid therapy may increase the risk of posterior subcapsular cataracts and glaucoma. Visual impairment, ocular hypertension, cataracts, and glaucoma have been reported with topical corticosteroid therapy. Instruct patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.[48615] [60291] [63282]

Topical corticosteroids, including halobetasol, should be used for brief periods or under close medical supervision in patients with evidence of pre-existing skin atrophy. Geriatric patients may be more likely to have preexisting skin atrophy secondary to aging. Purpura and skin lacerations that may raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the use of topical corticosteroids in geriatric patients. Use halobetasol preparations cautiously in patients with markedly impaired circulation or peripheral vascular disease due to the potential for skin ulcers. Use of lower potency topical corticosteroids also may be necessary in some patients.

The foam formulation of halobetasol is flammable. Avoid use of the foam near a fire or flame, including tobacco smoking, during or immediately after application.[63282]

ADVERSE REACTIONS

skin atrophy / Delayed / 1.0-1.0
increased intracranial pressure / Early / Incidence not known
papilledema / Delayed / Incidence not known
visual impairment / Early / Incidence not known
ocular hypertension / Delayed / Incidence not known

hyperglycemia / Delayed / 1.0-1.0
erythema / Early / Incidence not known
Cushing's syndrome / Delayed / Incidence not known
hypertension / Early / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
glycosuria / Early / Incidence not known
adrenocortical insufficiency / Delayed / Incidence not known
hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
cataracts / Delayed / Incidence not known
impaired wound healing / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
withdrawal / Early / Incidence not known
tolerance / Delayed / Incidence not known

xerosis / Delayed / 0-4.4
pruritus / Rapid / 0-4.4
skin irritation / Early / 1.6-4.4
telangiectasia / Delayed / 1.0-1.0
skin hypopigmentation / Delayed / 0.1-1.0
headache / Early / 0-1.0
pharyngitis / Delayed / 0.1-1.0
influenza / Delayed / 0.1-1.0
striae / Delayed / Incidence not known
hypertrichosis / Delayed / Incidence not known
miliaria / Delayed / Incidence not known
infection / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
folliculitis / Delayed / Incidence not known
rash / Early / Incidence not known
acneiform rash / Delayed / Incidence not known
purpura / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known

DRUG INTERACTIONS

There are no drug interactions associated with Halobetasol products.

PREGNANCY AND LACTATION

There are no available data on halobetasol use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Halobetasol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids, including halobetasol, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women. Guidelines recommend mild to moderate potency agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birth weight have been reported with the use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. Corticosteroids have been shown to be teratogenic after dermal, oral, and subcutaneous administration in animal studies. Halobetasol has greater potency, and thus greater teratogenic potential, than other topical corticosteroids. After systemic halobetasol propionate administration to pregnant rats and rabbits at doses of 0.04 to 0.1 mg/kg/day and 0.01 mg/kg/day, respectively, increased malformations, such as cleft palate, were observed. Omphalocele was also seen in rats and halobetasol was found to be embryotoxic in rabbits.  

It is not known whether topical administration of halobetasol could result in sufficient systemic absorption to produce detectable quantities in breast milk. Use of low to mid-potency topical corticosteroids is recommended in this patient population. However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast, nipple, and areola.   Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

MECHANISM OF ACTION

Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme that causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes, and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation, and scaling of the affected skin.

PHARMACOKINETICS

Halobetasol is administered topically to the skin; a variety of formulations are available for topical use. Once in the systemic circulation, halobetasol is metabolized in the liver, but systemic metabolism has not been fully quantified. Excretion of halobetasol and its metabolites occurs via the urine and bile.