Included as part of the "PRECAUTIONS" Section
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].
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].
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.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all administration instructions or all possible adverse or unintended effects.
Advise patients using BRYHALI Lotion of the following information and instructions:
Important Administration Instructions
Instruct patients to discontinue BRYHALI Lotion when psoriasis is controlled. Inform patients that BRYHALI Lotion is to be used as directed by the physician and should not be used for longer than the prescribed time period. Total dosage should not exceed 50 grams per week [see DOSAGE AND ADMINISTRATION].
Instruct patients to avoid bandaging, wrapping or otherwise occluding the treatment area(s), unless directed by physician. Advise patients to avoid use on the face, groin, or axillae [see DOSAGE AND ADMINISTRATION].
Inform patients that BRYHALI Lotion is for external use only. Advise patients that BRYHALI Lotion is not for oral, ophthalmic, or intravaginal use [see DOSAGE AND ADMINISTRATION].
Breastfeeding women should not apply BRYHALI Lotion directly to the nipple and areola to avoid directly exposing the infant [see Use In Specific Populations].
Effects On Endocrine System
BRYHALI Lotion may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including BRYHALI Lotion, may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. Concomitant use of multiple corticosteroid-containing products may increase the total systemic exposure to topical corticosteroids [see WARNINGS AND PRECAUTIONS].
Local Adverse Reactions
Inform patients that BRYHALI Lotion may cause local adverse reactions. These reactions may be more likely to occur with occlusive use or prolonged use of BRYHALI Lotion [see WARNINGS AND PRECAUTIONS].
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.
Use In Specific Populations
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.
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.
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.
Advise breastfeeding women not to apply BRYHALI Lotion directly to the nipple and areola to avoid direct infant exposure.
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].
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].
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.