Bryhali
(halobetasol propionate)Dosage & Administration
Bryhali Prescribing Information
BRYHALI® (halobetasol propionate) lotion, 0.01% is indicated for the topical treatment of plaque psoriasis in adults.
Apply a thin layer of BRYHALI Lotion to affected areas once daily. Rub in gently. Wash hands after each application, unless BRYHALI Lotion is for treatment of the hands.
BRYHALI Lotion treatment beyond 8 weeks is not recommended, and the total dosage should not exceed approximately 50 g per week. Discontinue treatment if control is achieved before 8 weeks. Do not use with occlusive dressings unless directed by a physician.
BRYHALI Lotion should not be used on the face, groin, or in the axillae.
BRYHALI Lotion is not for oral, ophthalmic, or intravaginal use.
Lotion, 0.01%
Each gram of BRYHALI Lotion contains 0.1 mg (0.01%) halobetasol propionate in a white to off-white lotion.
Pregnancy
Risk Summary
There are no available data on BRYHALI Lotion use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
In animal reproduction studies, increased malformations, including cleft palate and omphalocele, were observed after oral administration of halobetasol propionate during organogenesis to pregnant rats and rabbits. The available data do not support relevant comparisons of systemic halobetasol propionate exposures achieved in the animal studies to exposures observed in humans after topical use of BRYHALI Lotion.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Halobetasol propionate has been shown to cause malformations in rats and rabbits when given orally during organogenesis at doses of 0.04 to 0.1 mg/kg/day in rats and 0.01 mg/kg/day in rabbits. 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.
Lactation
Risk Summary
There are no data on the presence of halobetasol propionate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production after treatment with BRYHALI Lotion.
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.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BRYHALI Lotion and any potential adverse effects on the breastfed child from BRYHALI Lotion.
Clinical Considerations
Advise breastfeeding women not to apply BRYHALI Lotion directly to the nipple and areola to avoid direct infant exposure.
Pediatric Use
Safety and effectiveness of BRYHALI Lotion in pediatric patients under the age of 18 years have not been evaluated.
Because of higher skin-surface-area-to-body-mass ratios, 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 reactions including striae have been reported with use of topical corticosteroids in infants and children [see Warnings and Precautions (5.1)].
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 [see Warnings and Precautions (5.1)].
Geriatric Use
Of 284 subjects exposed to BRYHALI Lotion in clinical trials, 61 subjects were 65 years or older. Clinical trials of BRYHALI Lotion did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.
None.
Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression
BRYHALI Lotion has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis.
Systemic effects of topical corticosteroids may include reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of treatment with the topical corticosteroid.
The potential for hypothalamic-pituitary-adrenal (HPA) axis suppression with BRYHALI Lotion was evaluated in a study of 19 adult subjects with moderate to severe plaque psoriasis involving ≥20% of their body surface area (BSA). HPA axis suppression was reported for 1 (5.6%) subject at Week 4 and for 3 (15.8%) subjects at Week 8. All 3 subjects had normal HPA axis suppression test with discontinuation of treatment [see Clinical Pharmacology (12.2)].
Because of the potential for systemic absorption, use of topical corticosteroids, including BRYHALI Lotion, may require that patients be evaluated periodically for evidence of HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent corticosteroids, use over large surface areas, occlusive use, use on an altered skin barrier, concomitant use of multiple corticosteroid-containing products, liver failure, and young age. An adrenocorticotropic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression.
If HPA axis suppression is documented, attempt to gradually withdraw the drug, reduce the frequency of application, or substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.
Systemic effects of topical corticosteroids may also include Cushing’s syndrome, hyperglycemia, and glucosuria. Use of more than one corticosteroid-containing product at the same time may increase the total systemic exposure to corticosteroids. Pediatric patients may be more susceptible than adults to systemic toxicity from the use of topical corticosteroids due to their larger surface-to-body-mass ratios [see Use in Specific Populations (8.4)].
Local Adverse Reactions
Local adverse reactions from topical corticosteroids may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. These may be more likely with occlusive use, prolonged use, or use of higher potency corticosteroids, including BRYHALI Lotion. Some local adverse reactions may be irreversible.
Ophthalmic Adverse Reactions
Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in postmarketing experience with the use of topical corticosteroid products. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.
Concomitant Skin Infections
Use an appropriate antimicrobial agent if a skin infection is present or develops. If a favorable response does not occur promptly, discontinue use of BRYHALI Lotion until the infection has been adequately treated.
Allergic Contact Dermatitis
Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Consider confirmation of a clinical diagnosis of allergic contact dermatitis by appropriate patch testing. Discontinue BRYHALI Lotion if allergic contact dermatitis occurs.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In randomized, double-blind, multicenter, vehicle-controlled clinical trials, 426 adults with plaque psoriasis were treated with BRYHALI Lotion and had post-baseline safety data. Subjects applied BRYHALI Lotion once daily for up to 8 weeks. Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with BRYHALI Lotion and more frequently than in vehicle-treated subjects.
BRYHALI Lotion (N=284) | Vehicle Lotion (N=142) | |
Adverse Reaction | % | % |
Upper Respiratory Tract Infection | 2% | 1% |
Application Site Dermatitis | 1% | 0 |
Hyperglycemia | 1% | 0 |
BRYHALI (halobetasol propionate) lotion contains a corticosteroid, halobetasol propionate, as the active ingredient in a white to off-white lotion formulation intended for topical use.
Halobetasol propionate is a synthetic corticosteroid. The chemical name for halobetasol propionate is 21-chloro-6α, 9-difluoro-11β, 17-dihydroxy-16β-methylpregna-1, 4-diene-3, 20 –dione, 17-propionate. Halobetasol propionate is a white to off-white crystalline powder with a molecular weight of 484.96 and a molecular formula of C25H31ClF2O5. It is practically insoluble in water and freely soluble in dichloromethane and in acetone. The structural formula for halobetasol propionate is represented below:

Each gram of BRYHALI Lotion contains 0.1 mg (0.01%) halobetasol propionate in a white to off-white lotion base consisting of carbomer copolymer type B, carbomer homopolymer type A, diethyl sebacate, edetate disodium dihydrate, light mineral oil, methylparaben, propylparaben, purified water, sodium hydroxide, sorbitan monooleate and sorbitol solution, 70%.
Mechanism of Action
Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in plaque psoriasis is unknown.
Pharmacodynamics
Vasoconstrictor Assay
A vasoconstrictor assay in healthy subjects with BRYHALI Lotion indicated that the formulation is in the potent to superpotent range of potency as compared to other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.
Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression
The potential for HPA axis suppression was evaluated in 19 adult subjects with moderate to severe plaque psoriasis with at least 20% BSA involved. An approximate dose of 7 g BRYHALI Lotion was applied once daily for 8 weeks. An abnormal HPA axis suppression test, as indicated by a 30-minute post-stimulation cortisol level ≤18 mcg/dL, was reported for 1 (5.6%) subject at Week 4 and for 3 (15.8%) subjects at Week 8. The subject suppressed at Week 4 was also suppressed at Week 8. These effects were reversible as recovery of HPA axis function was generally prompt with the discontinuation of treatment. [See Warnings and Precautions (5.1).]
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. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
In an open-label, randomized, pharmacokinetic study, 23 subjects aged 18 years and older with moderate to severe plaque psoriasis applied approximately 7 grams of BRYHALI Lotion to a mean BSA of 27.7±11.3% once daily for 28 days. Systemic concentrations were at steady state by Day 14. Only 5 out of 20 subjects had one or more quantifiable systemic concentrations of halobetasol propionate on Day 14. The mean ± SD for maximum systemic concentration (Cmax) on Day 14 was 31.2±62.2 pg/mL. The mean area under the concentration versus time curve (AUC) could not be reliably estimated due to insufficient number of quantifiable timepoints.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol propionate.
Halobetasol propionate was not genotoxic in the Ames assay, in the sister chromatid exchange test in Chinese hamster somatic cells, in chromosome aberration studies of germinal and somatic cells of rodents, or in a mammalian spot test. Positive mutagenicity effects were observed in a mouse lymphoma gene mutation assay in vitro and in a Chinese hamster micronucleus test.
Studies in rats following oral administration of halobetasol propionate at dose levels up to 0.05 mg/kg/day indicated no impairment of fertility or general reproductive performance.
BRYHALI Lotion was evaluated for the treatment of moderate to severe plaque psoriasis in two prospective, multicenter, randomized, double-blind clinical trials (Trial 1 [NCT02514577] and Trial 2 [NCT02515097]). These trials were conducted in 430 subjects 18 years of age and older with moderate to severe plaque psoriasis that covered a body surface area (BSA) between 3% and 12% excluding the face, scalp, palms, soles, axillae, and intertriginous areas. Disease severity was determined by a 5-grade Investigator’s Global Assessment (IGA). Subjects applied BRYHALI Lotion or vehicle to all affected areas once daily for up to 8 weeks. Subjects had a follow-up visit 4 weeks after the end of treatment (Week 12) where safety and efficacy were evaluated.
The primary efficacy endpoint was the proportion of subjects with treatment success at Week 8, where treatment success was defined as at least a 2-grade improvement from baseline in IGA score and an IGA score equating to “clear” or “almost clear”. Table 2 lists the primary efficacy results for Trials 1 and 2. The secondary efficacy endpoints evaluated treatment success sequentially at Weeks 12, 6, 4, and 2. Figure 1 shows the primary and secondary efficacy results over time.
Trial 1 | Trial 2 | |||
---|---|---|---|---|
BRYHALI | Vehicle | BRYHALI | Vehicle | |
N=143 | N=74 | N=142 | N=71 | |
| ||||
IGA Treatment Success at Week 8 * | 37% | 8% | 38% | 12% |
*The treatment difference at Week 2 in Trial 2 was not statistically significant.
BRYHALI (halobetasol propionate) lotion, 0.01% is a white to off-white lotion supplied in a white aluminum tube as follows:
- •
- 60 g (NDC 0187-0002-60)
- •
- 100 g (NDC 0187-0002-01)
Storage and Handling Conditions
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.
Mechanism of Action
Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in plaque psoriasis is unknown.