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  • 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

    For the treatment of corticosteroid-responsive dermatoses, including atopic dermatitis, localized vitiligo, eczema, phimosis, lichen planus, and localized bullous pemphigoid.
    Topical dosage (cream or ointment)
    Adults

    Apply a thin layer topically to the affected skin area(s) once or twice daily (Max: 50 g/week). If no response is seen within 2 weeks, reassess treatment options.

    Children and Adolescents 12 years and older

    Apply a thin layer topically to the affected skin area(s) once or twice daily (Max: 50 g/week). If no response is seen within 2 weeks, reassess treatment options.

    Children 5 to 11 years†

    Apply a thin layer topically to the affected skin area(s) twice daily (Max: 50 g/week). If no response is seen within 2 weeks, reassess treatment options. In a pediatric study (age 5 to 15 years), halobetasol cream was applied in a thin layer topically to the affected area(s) once daily in the morning, and halobetasol ointment was applied in a thin layer topically once daily in the evening for 14 days. Efficacy was documented in more than 90% with no systemic adverse events. Safety and efficacy have not been established in pediatric patients; FDA-labeling does not recommend use in those less than 12 years of age.  

    For the treatment of moderate to severe chronic plaque-type psoriasis.
    Topical dosage (cream or ointment)
    Adults

    Apply a thin layer of cream or ointment to the affected skin area(s) once or twice daily; rub in gently and completely. Max: 50 grams/week; do not use for longer than 2 consecutive weeks. Discontinue when control is achieved. If no improvement in 2 weeks, reassess. Do not use with occlusive dressings.

    Children† and Adolescents† 5 years and older

    Safety and efficacy have not been established; however, off-label use for localized plaque psoriasis is reported. Apply topically twice daily to the affected skin area(s). Max: 50 grams/week; do not use for longer than 2 weeks; do not use with occlusive dressings. In a pediatric study (age 5 to 15 years), halobetasol cream was applied in a thin layer to the affected area(s) once daily in the morning, and halobetasol ointment was applied in a thin layer once daily in the evening for 14 days. Occlusion was not used. Success was documented in more than 90% with no systemic adverse events.

    Topical dosage (Ultravate lotion only)
    Adults

    Apply a thin layer to the affected skin area(s) twice daily. Limit treatment to 2 consecutive weeks. Max: 50 grams/week. Discontinue when control is achieved. If no improvement in 2 weeks, reassess.

    Children and Adolescents 12 years and older

    Apply a thin layer to the affected skin area(s) twice daily. Limit treatment to 2 consecutive weeks. Max: 50 grams/week. Discontinue when control is achieved. If no improvement in 2 weeks, reassess.

    Topical dosage (Bryhali Lotion only)
    Adults

    Apply a thin layer to the affected skin area(s) once daily. Limit treatment to 8 consecutive weeks. Max: 50 grams/week. Discontinue if control is achieved before 8 weeks. If no improvement in 8 weeks, reassess.

    Topical dosage (foam)
    Adults

    Apply a thin layer topically to the affected skin area(s) twice daily for up to 2 weeks. Limit treatment to 2 consecutive weeks. Max: 50 grams/week. Discontinue when control is achieved. If no improvement in 2 weeks, reassess.

    Children and Adolescents 12 years and older

    Apply a thin layer topically to the affected skin area(s) twice daily for up to 2 weeks. Limit treatment to 2 consecutive weeks. Max: 50 grams/week. Discontinue when control is achieved. If no improvement in 2 weeks, reassess.

    For the treatment of cutaneous T-cell lymphoma (CTCL)† (also known as mycosis fungoides†).
    Topical dosage (cream or ointment)
    Adults and Adolescents 14 years and older

    Apply thoroughly and vigorously only to the lesioned skin areas twice daily. One study (n = 79) demonstrated complete remission in 88% of patients (age 14 to 84 years) with patch-stage mycosis fungoides treated with corticosteroids. Treatment was continued of 2 to 3 months before determining efficacy, and was continued for 1 month following clearing. The very high potency compounds studied, including halobetasol, were most effective. Thirteen percent of patients experienced reversible serum cortisol depression, but none had clinical symptoms. One patient discontinued therapy due to skin atrophy.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    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.

    Geriatric

    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.

    Adolescents

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

    Children

    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.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    Topical 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.

    Cream/Ointment/Lotion Formulations

    Restrict application to the active lesions or affected areas and try to avoid normal surrounding skin.
    The amount of cream, lotion, or ointment needed to cover a certain area can be calculated. A 1 gram application of cream covers 100 cm2 of skin. The entire skin surface of the average size adult will be covered by 30 grams of topical steroid cream.
    Do not use cream or ointment with occlusive dressings. The lotion should only be used with occlusion under prescription order.
    Very high potency corticosteroids such as halobetasol are not recommended for use in the diaper area of infants. If halobetasol is medically necessary, do not use tight-fitting diapers or plastic pants on children, as these garments may constitute occlusive dressings.
    Apply sparingly in a thin film and rub gently into the affected area. Use gloves if required by universal precautions.
    Wash hands after application. Patients should wash their hands after application unless the product is being used to treat the hands.

    Other Topical Formulations

    Topical foam
    Prior to first application, remove cap and break the small tab at the base of the actuator; do not break the hinge on the actuator.
    Shake well prior to each use.
    Invert the can and dispense a small amount of the foam into the palm of the hand.
    Apply a thin layer to the affected area and rub in gently until foam disappears. Use gloves if required by universal precautions.
    Wash hands after application. Patients should wash their hands after application unless the foam is being used to treat the hands.
    This product is flammable; avoid heat, flame, or smoking during and immediately following application of the foam.

    STORAGE

    Generic:
    - 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
    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

    Corticosteroid hypersensitivity, occlusive dressing

    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.

    Cushing's syndrome, diabetes mellitus, hypothalamic-pituitary-adrenal (HPA) suppression, skin abrasion

    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.

    Children, growth inhibition, increased intracranial pressure, infants, neonates

    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.

    Pregnancy

    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.  

    Breast-feeding

    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.

    Fungal infection, herpes infection, infection, measles, tuberculosis, varicella, viral infection

    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.

    Acne rosacea, acne vulgaris, cataracts, glaucoma, ocular exposure, perioral dermatitis

    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]

    Geriatric, peripheral vascular disease, skin atrophy

    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.

    Tobacco smoking

    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

    Severe

    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

    Moderate

    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

    Mild

    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

    Pregnancy

    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.

    Topical Route

    The extent of percutaneous absorption of the topical corticosteroids is dependent on many factors, including the vehicle, integrity of the epidermis, and use of occlusive dressing. Absorption after topical application of halobetasol is increased in areas that have skin damage, inflammation, or occlusion, or in areas where the stratum corneum is thin such as the eyelids, genitalia, axillae, and face. The use of occlusive dressings with the application of halobetasol enhances penetration into the skin and may increase the chance of systemic absorption. Ointments have a hydrating effect, are lipophilic, and enhance the penetration of halobetasol into the skin. Anti-inflammatory effects are usually not seen for hours after halobetasol application, since the mechanism of action requires alterations in the synthesis of proteins. Because halobetasol is fluorinated and also contains a substituted 17-hydroxyl group, it is not metabolized in the skin. Repeated application results in a cumulative depot effect in the skin, which may lead to a prolonged duration of action and increased systemic absorption.
    cream and ointment: 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.
    lotion: The pharmacokinetics of halobetasol lotion (Ultravate) were evaluated in 12 adult patients with plaque psoriasis who applied 3.5 grams of halobetasol lotion (Ultravate) twice daily and all of the patients had detectable plasma concentrations on day 8 of therapy. On Day 8, the mean maximum systemic concentration (Cmax) was 201.1 +/- 157.5 pg/mL, the median time to maximum concentration (Tmax) was 3 hours (range 0 to 6 hours), and the mean AUC was 1,632 +/- 1,147 pg/hour/mL. In a pharmacokinetic study involving 23 adult subjects with plaque psoriasis who applied 7 grams of halobetasol lotion (Bryhali) over a mean body surface area (BSA) of 27.7 +/- 11.3% once daily for 28 days, steady-state concentrations were achieved by day 14. Only 5 out of 20 subjects had 1 or more quantifiable systemic concentrations of halobetasol propionate on day 14. The mean Cmax on Day 14 was 31.2 +/- 62.2 pg/mL. The mean AUC could not be reliably estimated due to an insufficient number of quantifiable timepoints.
    topical foam: In a study of 23 adults with moderate to severe plaque psoriasis receiving twice daily halobetasol foam for 14 days (mean dose of 7.4 grams/day), steady-state was achieved by day 14 with a mean Cmax of 199.7 +/- 217.3 pg/mL and a corresponding median time to maximum concentration (Tmax) of 1 hour (range 0 to 12 hours); mean AUC was 1,434 +/- 1,310.6 pg/hour/mL.