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.

Table 2: Efficacy Results at Week 2 in Subjects with Plaque Psoriasis
Study 1 Study 2
LEXETTEN=75 Vehicle FoamN=76 LEXETTEN=205 Vehicle FoamN=204
*
Subjects whose condition was cleared or almost cleared of all signs of psoriasis and with at least a two-grade improvement from baseline based on the IGA.
Subjects who were cleared or almost cleared of the designated clinical sign with at least a two-grade improvement from baseline. Individual signs were rated by severity using a five-point scale ranging from 0 (clear) to 4 (severe). Subjects with baseline value of 0 or 1 were excluded.
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%
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:
  • have had irritation or other skin reaction to a steroid medicine in the past.
  • have a skin infection. You may need medicine to treat the skin infection before using LEXETTE.
  • have diabetes.
  • have adrenal gland problems.
  • have liver problems.
  • plan to have surgery.
  • are pregnant or plan to become pregnant. It is not known if LEXETTE will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if LEXETTE passes into your breast milk. If you use LEXETTE and breastfeed, do not apply LEXETTE to your nipple or areola to avoid getting LEXETTE into your baby’s mouth.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other corticosteroid medicines by mouth, or injection, or use other products on your skin that contain corticosteroid.
How should I use LEXETTE?See the “Instructions for Use” for detailed information about the right way to apply LEXETTE.
  • Use LEXETTE exactly as your healthcare provider tells you to use it.
  • Apply a thin layer of LEXETTE to the affected skin areas 2 times each day.
  • You should not use more than 50 grams of LEXETTE in 1 week.
  • Avoid using LEXETTE on your face, underarms (armpits), or groin areas.
  • Do not bandage, cover, or wrap the treated skin area unless your healthcare provider tells you to.
  • Talk to your healthcare provider if your skin does not improve after 2 weeks of treatment with LEXETTE.
  • Do not use LEXETTE longer than 2 continuous weeks unless advised to do so by your prescriber.
  • Wash your hands after using LEXETTE unless you are using the medicine to treat your hands.
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:
  • LEXETTE can pass through your skin. Too much LEXETTE passing through your skin can cause adrenal glands to stop working.
  • Cushing’s syndrome , a condition that happens when your body is exposed to too much of the hormone cortisol.
  • High blood sugar (hyperglycemia).
  • Vision problems. LEXETTE may increase your chance of developing cataract(s) and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with LEXETTE.
  • Skin reactions at the treated skin site. Tell your healthcare provider if you get any skin reactions or skin infections.
  • Effects on growth and weight in children.
Your healthcare provider may do certain blood tests to check for side effects.The most common side effect of LEXETTE is mild to moderate pain at the treated site. These are not all of the possible side effects of LEXETTE.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store LEXETTE?
  • Store LEXETTE at room temperature between 68°F to 77°F (20°C to 25°C).
  • Do not puncture or burn LEXETTE can.
  • Do not store LEXETTE next to heat or store at temperatures above120°F (49°C).
  • Do not freeze LEXETTE.
Keep LEXETTE and all medicines out of the reach of children.
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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