LEXETTE (Page 3 of 4)
12.3 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 the HPA-axis and pharmacokinetic study, as described above in Clinical Pharmacology (12.2) , pharmacokinetics was evaluated in a subgroup of 23 adult subjects with moderate to severe plaque psoriasis following twice daily treatment for 14 days. Plasma concentration of halobetasol propionate (HBP) was measurable in all subjects and steady state was achieved by Day 14. The mean (± standard deviation) Cmax concentration for HBP on Day 14 was 199.7 ± 217.3 pg/mL, with the corresponding median Tmax value of 1 hour (range 0 – 12 hours); mean area under the halobetasol propionate concentration versus time curve over the dosing interval (AUCt ) was 1434.9 ± 1310.6 pg∙h/mL.
In the HPA axis study in subjects 12 to less than 18 years [see Clinical Pharmacology (12.2)], trough plasma concentrations of HBP were measured on Day 8 and Day 15 in 23 subjects following twice daily treatment for 14 days. On Day 8, nine (9) of the 23 evaluable subjects had morning trough concentrations of halobetasol propionate in plasma that were above the quantifiable limit (≥20.0 pg/mL); mean halobetasol concentration was 154.6 ± 308.67 pg/mL. Similarly, on Day 15, nine (9) of the 23 evaluable subjects had morning trough concentrations of halobetasol propionate above the quantifiable limit; mean halobetasol concentration was 59.9 ± 90.15 pg/mL. Of the 9 subjects with quantifiable plasma concentrations at Day 15, seven (7) also had quantifiable plasma concentrations at Day 8.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol propionate.
In a 90-day repeat-dose toxicity study in rats, topical administration of LEXETTE at dose concentrations from 0.005% to 0.05% or from 0.011 to 0.11 mg/kg/day of halobetasol propionate resulted in a toxicity profile consistent with long-term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression, and opportunistic fungal and bacterial infections. A no observable adverse effect level could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk of carcinogenesis.
Halobetasol propionate was not found to be genotoxic in the Ames/Salmonella assay, in the Chinese hamster CHO/HGPRT assay, in the mouse micronucleus test, in the sister chromatid exchange test in somatic cells of the Chinese hamster, or in the chromosome aberration test in somatic cells of Chinese hamsters. Positive mutagenicity effects were observed in two genotoxicity assays: Chinese hamster nuclear anomaly test and mouse lymphoma gene mutation assay in vitro.
Studies in the rat following oral administration at dose levels up to 0.05 mg/kg/day indicated no impairment of fertility or general reproductive performance.
14 CLINICAL STUDIES
LEXETTE was evaluated for the treatment of moderate to severe plaque psoriasis in two multicenter, randomized, double-blind, vehicle-controlled studies (Study 1 [NCT02368210] and Study 2 [NCT02742441]).
These studies were conducted in 560 subjects 18 years of age and older with plaque psoriasis involving between 2% and 12% body surface area. Baseline disease severity was determined using a static, five-level Investigator’s Global Assessment (IGA) scale, on which a subject scored either moderate or severe. Overall, approximately 60% of subjects were male and approximately 90% were Caucasian.
Subjects applied LEXETTE or vehicle to all affected areas twice daily for up to 14 consecutive days.
The primary measure of efficacy was Overall Treatment Success, defined as the proportion of subjects who were cleared or almost cleared with at least a two-grade improvement from baseline at Week 2 (end of treatment) based on the IGA. The studies also evaluated treatment success for the individual signs of psoriasis (plaque elevation, scaling, and erythema) at the end of treatment. Table 2 presents these results.
Study 1 | Study 2 | |||
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LEXETTEN=75 | Vehicle FoamN=76 | LEXETTEN=205 | Vehicle FoamN=204 | |
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Overall Treatment Success * | 19 (25%) | 3 (4%) | 63 (31%) | 15 (7%) |
Plaque Elevation † | 20/75 (27%) | 3/76 (4%) | 71/202 (35%) | 20/203 (10%) |
Scaling † | 21/75 (28%) | 4/76 (5%) | 68/201 (34%) | 20/204 (10%) |
Erythema † | 16/75 (21%) | 2/76 (3%) | 59/205 (29%) | 17/204 (8%) |
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
LEXETTE, 0.05% is a white to off-white foam. It is supplied in aluminum cans of:
50 grams (NDC 51862-604-50)
100 grams (2 cans of 50 grams) (NDC 51862-604-02)
16.2 Storage
Store at 20°-25°C (68°-77°F); excursions permitted to 15ºC and 30ºC (59ºF to 86ºF). Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C). Do not freeze.
16.3 Handling
LEXETTE is flammable; avoid heat, flame, or smoking when using this product.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
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.
Inform patients of the following:
Important Administration Instructions:
- Total dosage should not exceed 50 grams (one can) per week [see Dosage and Administration (2)].
- Advise patients to avoid use on the face, groin, or axillae. Avoid contact with eyes [see Dosage and Administration (2)].
- Inform patients that topical corticosteroids may cause HPA axis suppression and local adverse reactions [see Warnings and Precautions (5.1)].
- Breastfeeding women should not apply LEXETTE directly to the nipple and/or areola to avoid direct exposure to the infant [see Use in Specific Populations (8.2)].
- This product is flammable; avoid heat, flame, or smoking during and immediately following application of this product.
Rx Only
Distributed by: Mayne Pharma Raleigh, NC 27609
U.S. Patent 10,857,159 and 11,020,407
Revised: 03/2023
PATIENT INFORMATIONLEXETTE® (lex-et)(halobetasol propionate) Topical Foam, 0.05% | |
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This Patient Information has been approved by the U.S. Food and Drug Administration. | Revised: 03/2023 |
Important: LEXETTE is for use on the skin only. Do not apply LEXETTE near or in your eyes, mouth, or vagina. | |
What is LEXETTE? LEXETTE is a prescription corticosteroid medicine used on the skin to treat plaque psoriasis in people 12 years of age and older. It is not known if LEXETTE is safe and effective in children under 12 years of age. | |
Before using LEXETTE, tell your healthcare provider about all of your medical conditions, including if you:
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How should I use LEXETTE?See the “Instructions for Use” for detailed information about the right way to apply LEXETTE.
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What should I avoid while using LEXETTE? LEXETTE is flammable. Avoid heat, flame, or smoking during and right after applying LEXETTE to your skin. | |
What are the possible side effects of LEXETTE? LEXETTE may cause serious side effects, including:
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How should I store LEXETTE?
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General information about the safe and effective use of LEXETTE. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use LEXETTE for a condition for which it was not prescribed. Do not give LEXETTE to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about LEXETTE that is written for health professionals. | |
What are the ingredients in LEXETTE? Active ingredient: halobetasol propionateInactive ingredients: alcohol (specially denatured alcohol [SDA]), benzoic acid, cetostearyl alcohol, emulsifying wax, polyoxyl 20 cetostearyl ether, propylene glycol, and purified water. LEXETTE is dispensed from an aluminum can pressurized with a hydrocarbon propellant containing isobutane and propane. Distributed by: Mayne Pharma Raleigh, NC 27609 U.S. Patent 10,857,159 and 11,020,407For more information call: 1-844-825-8500 |
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