Instructions Brihali lotion 0.01% tube 100 g
Composition
active ingredient: halobetasol propionate;
1 g of lotion contains halobetasol propionate 0.10 mg;
Excipients: diethyl sebacate, light mineral oil, sorbitan oleate, methylparaben, propylparaben, disodium edetate dihydrate, carbomer copolymer type B (Pemulen TR-1), carbomer homopolymer type A (Carbopol 981), sodium hydroxide, purified water, sorbitol solution, 70%.
Dosage form
Lotion.
Main physicochemical properties: white or almost white lotion.
Pharmacotherapeutic group
Corticosteroids for use in dermatology. Active corticosteroids (group III). ATC code D07AC21.
Pharmacological properties
Mechanism of action.
Corticosteroids play a role in cell signaling, immune function, inflammation, and regulation of protein synthesis; however, the precise mechanism of their action in plaque psoriasis is unknown.
Clinical efficacy and safety.
BRIHALI™ Lotion was evaluated in 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 included 430 subjects 18 years of age and older with moderate to severe psoriasis, with 3% to 12% of the body surface area (BSA) affected, excluding the face, scalp, palms, soles, axillae, and intertriginous areas. Disease severity was assessed using a five-point Investigator Global Assessment (IGA) scale. Patients applied BRIHALItm lotion or placebo to all affected areas once daily for 8 weeks. Patients were evaluated 4 weeks after the end of treatment (week 12) for safety and efficacy.
The primary efficacy endpoint was the proportion of patients with treatment success at week 8, defined as at least a 2-point improvement from baseline in the IGA, and an IGA score of “clear” or “almost clear.” Table 1 presents the primary efficacy results for Studies 1 and 2. Secondary efficacy endpoints assessed treatment success at 12, 6, 4, and 2 weeks, respectively. Figure 1 shows the primary and secondary efficacy results over time.
Table 1. Primary efficacy results in patients with moderate to severe plaque psoriasis at 8 weeks
| Research 1 | | Study 2 | |
| BRICHALITM | Placebo | BRICHALITM | Placebo |
| Treatment success according to the IGA scale at 8 weeks* | N=143 | N=74 | N=142 | N=71 |
*Treatment success was defined as at least a 2-grade improvement from baseline. IGA is an IGA score that is equivalent to “clear” or “almost clear.” “Clear” = no symptoms of psoriasis: erythema, no elevation of plaques above the level of healthy skin. “Almost clear” = isolated plaques with red scales, mild pink/light red erythema on most plaques, slight or barely noticeable elevation of plaques above the level of healthy skin.
Fig. 1. Effectiveness of treatment results* over 12 weeks
| % of subjects with treatment success | % of patients with successful |
| Vehicle | Placebo |
| Weeks | Weeks |
| Trial 1 | Research 1 |
| Trial 2 | Study 2 |
| No treatment (4 Week follow-up) | Without treatment (observation for 4 weeks) |
*The treatment difference at 2 weeks in Study 2 was not statistically significant.
Pharmacodynamics.
A vasoconstrictor study in healthy subjects using BRIHALItm Lotion showed that the drug has a range of potent to superpotent activity compared to other topical corticosteroids. However, such performance does not necessarily imply therapeutic equivalence.
The potential for hypothalamic-pituitary-adrenal axis suppression was evaluated in a study of 19 adults with moderate to severe plaque psoriasis, involving at least 20% of the PTP. The approximate dose of BRIHALitm lotion was 7 grams, applied once daily for 8 weeks.
Abnormal results of the hypothalamic-pituitary-adrenal axis suppression test, as evidenced by a 30-minute post-stimulation cortisol level of 8 μg/dL, were reported in 1 (5.6%) subject at week 4 and in 3 (15.8%) subjects at week 8. The subject who had hypothalamic-pituitary-adrenal axis suppression at week 4 also had this symptom at week 8. These effects were reversible, as recovery of hypothalamic-pituitary-adrenal axis function generally occurred rapidly after discontinuation of treatment.
Pharmacokinetics.
In an open-label, randomized pharmacokinetic study, 23 patients 18 years of age and older with moderate to severe plaque psoriasis applied approximately 7 grams of BRIHALI™ Lotion with a mean CRP of 27.7 ± 11.3% once daily for 28 days. Systemic concentrations reached steady state by day 14. Only 5 of 20 subjects had one or more quantifiable systemic halobetasol propionate concentrations at day 14. The mean ± standard deviation for the maximum systemic concentration (Cmax) on day 14 was 31.2 ± 62.2 μg/mL. The mean area under the concentration-time curve (AUC) could not be reliably estimated due to the insufficient number of time points measured.
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of halobetasol propionate.
Halobetasol propionate was not genotoxic in the Ames test, the Chinese hamster somatic cell sister chromatid exchange test, the rodent germline and somatic cell chromosomal aberration assay, and the mammalian spot test. Positive mutagenic effects were observed in the in vitro mouse lymphoma gene mutation test and the Chinese hamster micronucleus test.
Studies in rats following oral administration of halobetasol propionate at doses up to 0.05 mg/kg/day indicated no impairment of fertility or general reproductive function.
Indication
Topical treatment of plaque psoriasis in adults.
Contraindication
Hypersensitivity to the active substance or to other corticosteroids or to any of the excipients included in the medicinal product.
Rosacea, acne, perioral dermatitis.
Perianal and genital itching.
Untreated skin infections.
Skin lesions caused by viruses (herpes simplex virus, chickenpox). Skin lesions primarily infected with fungi or bacteria.
Tuberculosis of the skin.
Untreated skin infections.
Interaction with other medicinal products and other types of interactions
Not described.
Application features
Suppression of the hypothalamic-pituitary-adrenal system.
During the use of BRIHALItm lotion, suppression of the hypothalamic-pituitary-adrenal system was observed.
Systemic effects of topical corticosteroids may include reverse suppression of the hypothalamic-pituitary-adrenal axis with possible glucocorticosteroid insufficiency. This may occur during or after discontinuation of topical corticosteroids.
The potential for hypothalamic-pituitary-adrenal axis suppression with BRIHALITm Lotion was evaluated in a study of 19 adult patients with moderate to severe plaque psoriasis with ≤20% skin involvement. Hypothalamic-pituitary-adrenal axis suppression was observed in 1 (5.6%) patient at 4 weeks and in 3 (15.8%) patients at 8 weeks. Hypothalamic-pituitary-adrenal axis suppression tests were normal in all 3 patients after discontinuation of treatment.
Because of the potential for systemic absorption with topical corticosteroids, including BRIHALITm Lotion, patients should be periodically evaluated for evidence of hypothalamic-pituitary-adrenal axis suppression. Factors that predispose patients to hypothalamic-pituitary-adrenal axis suppression in patients receiving corticosteroids include: use of active corticosteroids, application to large areas of skin, use of occlusive dressings, use on areas with compromised skin barrier, concurrent use of multiple corticosteroid-containing products, hepatic impairment, and young age. An adrenocorticotropic hormone (ACTH) stimulation test may be useful in assessing the degree of hypothalamic-pituitary-adrenal axis suppression in patients.
If hypothalamic-pituitary-adrenal axis suppression is confirmed, the drug should be gradually discontinued by reducing the frequency of application or by changing to a less potent corticosteroid. Manifestations of adrenal insufficiency may necessitate the use of additional systemic corticosteroids.
Restoration of hypothalamic-pituitary-adrenal system function usually occurs rapidly and completely after discontinuation of topical corticosteroids.
Systemic effects of topical corticosteroids may also include Cushing's syndrome, hyperglycemia, and glycosuria. Concurrent use of more than one corticosteroid-containing product may increase the overall systemic exposure.
Children, compared with adults, may be more susceptible to systemic side effects from topical corticosteroids, as a result of their larger skin surface area to body weight ratio.
In case of diabetes, liver and adrenal gland diseases, you should inform your doctor.
Vision disorders.
The use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma.
If you experience symptoms such as blurred vision or other disturbances, you should see an ophthalmologist to identify possible causes, which may include cataracts, glaucoma, or rare diseases such as central serous chorioretinopathy.
In the event of the presence or development of a skin infection, an appropriate antibacterial agent should be used. If improvement is not immediately observed, the use of BRlHALI™ Lotion should be discontinued until the infection has been adequately treated.
Allergic contact dermatitis.
Allergic contact dermatitis that occurs with corticosteroid use is usually diagnosed by delayed healing rather than clinical exacerbation. Confirmation of the clinical diagnosis of allergic contact dermatitis by appropriate patch testing should be considered. Use of Blxali™ Lotion should be discontinued if allergic contact dermatitis occurs.
Children.
Because of their higher skin surface area to body mass ratio, children are at greater risk than adults of hypothalamic-pituitary-adrenal axis suppression and Cushing's syndrome during treatment with topical corticosteroids. Children are at greater risk of developing adrenal insufficiency during or after treatment discontinuation. Adverse reactions, including striae, have been reported with topical corticosteroids in infants and children.
Hypothalamic-pituitary-adrenal axis suppression, Cushing's syndrome, growth retardation, reduced 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 unresponsiveness to ACTH stimulation. Manifestations of intracranial hypertension include bulging parietal lobe, headache, and bilateral optic disc edema.
Use during pregnancy or breastfeeding
Pregnancy.
There are no data available on the use of BRlHALI™ Lotion in pregnant women to inform about the drug-associated risks of serious birth defects, miscarriages, or adverse maternal or fetal outcomes.
In animal reproduction studies, an increased incidence of malformations, including cleft palate and omphalocele, was observed in pregnant rats and rabbits following oral administration of halobetasol propionate during organogenesis. The available data do not support appropriate comparisons of systemic effects of halobetasol propionate obtained in animal studies with those observed in humans following topical application of BRlHALI™ Lotion.
The background risk of major birth defects and miscarriage in this population is unknown. In the 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.
in accordance.
Data obtained during animal studies.
Halobetasol propionate has been shown to cause developmental defects in female rats and rabbits when administered orally during organogenesis at doses of 0.04-0.1 mg/kg/day in rats and 0.01 mg/kg/day in rabbits. Halobetasol propionate was embryotoxic in rabbits but not in rats. Omphalocele was observed in both rats and rabbits.
Breast-feeding.
There is no data on: the presence of halobetasol propionate or its metabolites in breast milk; the effect on breastfeeding infants; the effect on milk production after treatment with BRlHALI™ lotion.
Systemically administered corticosteroids appear in human milk and may suppress growth, inhibit endogenous corticosteroid production, or cause other adverse effects. It is not known whether topical corticosteroids would result in systemic absorption that would result in measurable amounts of the drug in human milk. The benefits of breastfeeding to fetal development and health should be considered along with the mother's clinical need for BRlHALI™ Lotion and any potential adverse effects on the breastfed infant.
Breastfeeding women should not apply BRlHALI™ lotion directly to the nipple and areola area to avoid direct exposure to the breastfed infant.
Ability to influence reaction speed when driving or operating other mechanisms
No effect.
Method of administration and doses
The lotion should be applied in a thin layer to the affected areas of the skin once a day until the condition improves. It is necessary to wash hands after each application. If BRIHALItm lotion is intended for treatment of the skin of the hands, washing hands is not necessary. As with the use of other highly active corticosteroids, after achieving control of the disease, the application should be stopped.
It is not recommended to continue treatment with BRIHALYTM lotion for more than 8 weeks, and the total dose should not exceed 50 g per week. Treatment should be discontinued if the therapeutic effect has been achieved by week 8. Do not use with occlusive dressings unless prescribed by a physician.
Avoid using BRIHALI™ lotion on the face, groin, or underarms.
BRIXALI™ Lotion is not intended for oral, ophthalmic, or intravaginal use.
Children.
The safety and effectiveness of BRIHALI™ Lotion in patients under 18 years of age have not been evaluated.
Overdose
The probability of an acute overdose is very small. In case of chronic overdose or misuse, signs of hypercorticism may occur, requiring a reduction in the frequency of application or gradual discontinuation of the use of topical corticosteroids, which should be carried out under medical supervision, taking into account the risk of adrenal insufficiency.
Side effects
Local adverse reactions: atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acne, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, suppuration. They may be more likely with the use of occlusive dressings, prolonged use, or use of highly potent corticosteroids, including BRIHALI™ Lotion. Some local adverse reactions may be irreversible.
3 sides of the endocrine system: suppression of the hypothalamic-pituitary-adrenal system: Cushing's syndrome, growth retardation and weight gain in children, hyperglycemia, glucosuria, decreased endogenous cortisol levels.
Visual impairment: blurred vision (see section "Special instructions") glaucoma, cataract.
Respiratory tract: upper respiratory tract infections.
Expiration date
36 months.
Storage conditions
Store at a temperature of 20 °C to 25 °C. Tolerance is 15 °C to 30 °C. Protect from freezing. Keep out of the reach of children.
Packaging
100 g in a tube, 1 tube in a cardboard box.
Vacation category
According to the recipe.
Producer
Bausch Health Company Inc.
Location of the manufacturer and address of its place of business.
2150 Art. Elzar Boulevard West Laval, Quebec, Canada H7L 4A8, Canada.
