Halobetasol propionate

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression and Other Adverse Endocrine Effects [see Warnings and Precautions (5.1) ] Allergic Contact Dermatitis [see Warnings and Precautions (5.5) ] The most commonly reported adverse reactions (≥1%) are application site pain and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 practice. In randomized, multicenter, vehicle-controlled clinical trials, 351 adults with plaque psoriasis were treated with Halobetasol Propionate Topical Foam twice daily for up to two weeks (up to approximately 50 grams per week). Table 1 presents selected adverse reactions that occurred in at least 1% of subjects. Table 1: Adverse Reactions Occurring in ≥ 1% of Subjects through Week 2 HBP Foam N=351 Vehicle Foam N=353 Adverse Reaction % % Skin atrophy (n=1) and telangiectasia (n=2) were reported with Halobetasol Propionate Topical Foam, but not with vehicle foam. Application site burning/stinging 12% 15% Application site pain 1% <1% Headache 1% <1% 6.2 Postmarketing Experience Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following local adverse reactions have been reported with topical corticosteroids: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, irritation, striae, and miliaria. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, such as halobetasol propionate.

4 CONTRAINDICATIONS None. None.

11 DESCRIPTION Halobetasol Propionate Topical Foam is a hydroethanolic aerosol foam that contains a corticosteroid, halobetasol propionate intended for topical use. The chemical name of 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 C 25 H 31 ClF 2 O 5 . It has the following structural formula: It is practically insoluble in water and freely soluble in dichloromethane and in acetone. Each gram of Halobetasol Propionate Topical Foam contains 0.5 mg of halobetasol propionate in a white to off-white foam base consisting of alcohol (specially denatured alcohol [SDA]), benzoic acid, cetostearyl alcohol, emulsifying wax, polyoxyl 20 cetostearyl ether, propylene glycol and purified water. Halobetasol Propionate Topical Foam is dispensed from an aluminum can pressurized with a hydrocarbon (isobutane and propane) propellant. Chemical Structure

2 DOSAGE AND ADMINISTRATION Shake can prior to use. Apply Halobetasol Propionate Topical Foam as a thin uniform film to the affected skin twice daily for up to two weeks. Rub in gently. Wash hands after applying the product. Discontinue therapy when control is achieved. If no improvement is seen within two weeks, reassessment of the diagnosis may be necessary. Treatment beyond two weeks is not recommended and the total dosage should not exceed 50 grams per week because of the potential for the drug to suppress the hypothalamic-pituitary­ adrenal (HPA) axis [see Warnings and Precautions (5.1) ]. Do not use with occlusive dressings unless directed by a physician. Avoid use on the face, groin, or axillae. Avoid contact with eyes. Halobetasol Propionate Topical Foam is for topical use only. Halobetasol Propionate Topical Foam is not for ophthalmic, oral, or intravaginal use. Shake before use. ( 2 ) Apply Halobetasol Propionate Topical Foam as a thin uniform film to the affected skin twice daily for up to two weeks. Rub in gently. ( 2 ) Do not use more than 50 grams per week. ( 2 ) Discontinue Halobetasol Propionate Topical Foam when control is achieved. ( 2 ) If no improvement is seen within 2 weeks, reassess diagnosis. ( 2 ) Treatment beyond 2 consecutive weeks is not recommended. ( 2 ) Do not use with occlusive dressings unless directed by a physician. ( 2 ) Avoid use on the face, groin, or axillae. ( 2 ) Halobetasol Propionate Topical Foam is not for ophthalmic, oral, or intravaginal use. ( 2 )

1 INDICATIONS AND USAGE Halobetasol Propionate Topical Foam is indicated for the topical treatment of plaque psoriasis in patients 12 years of age and older. Halobetasol Propionate Topical Foam is a corticosteroid indicated for the topical treatment of plaque psoriasis in patients twelve (12) years of age and older. ( 1 )

10 OVERDOSAGE Topically applied Halobetasol Propionate Topical Foam can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1) ].

12 CLINICAL PHARMACOLOGY 12.1 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. 12.2 Pharmacodynamics Vasoconstrictor Assay A vasoconstrictor assay in healthy patients with Halobetasol Propionate Topical Foam indicated that the formulation is in the super-high 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 hypothalamic-pituitary adrenal axis (HPA-axis) suppression was evaluated in the following two studies. In both studies, the criteria for HPA-axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter 30 minutes after stimulation with cosyntropin (adrenocorticotropic hormone, ACTH). In the first study, Halobetasol Propionate Topical Foam was applied to 25 adult subjects with moderate to severe plaque psoriasis involving a mean body surface area of 18.4%. A mean dose of 3.7 g of Halobetasol Propionate Topical Foam was applied twice daily for two weeks and produced laboratory evidence of HPA axis suppression in 6 of 25 (24%) subjects. All subjects returned to normal HPA axis function at follow-up at least 4 weeks after stopping the treatment. In the second study, Halobetasol Propionate Topical Foam was applied to 24 subjects 12 to less than 18 years of age with stable plaque psoriasis with a mean percent BSA of 15.1% (range of 11% to 23%). The mean dose of Halobetasol Propionate Topical Foam used was 3.1 grams, which was applied twice daily for two weeks. In the study, 24 subjects completed the study, and 23 subjects had evaluable ACTH stimulation tests. HPA axis suppression was observed in 6 of the 23 subjects (26.1%), and all subjects returned to normal HPA axis function at follow-up at least 4 weeks after stopping the treatment. 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) C max concentration for HBP on Day 14 was 199.7 ± 217.3 pg/mL, with the corresponding median T max 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.

12.1 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.

12.2 Pharmacodynamics Vasoconstrictor Assay A vasoconstrictor assay in healthy patients with Halobetasol Propionate Topical Foam indicated that the formulation is in the super-high 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 hypothalamic-pituitary adrenal axis (HPA-axis) suppression was evaluated in the following two studies. In both studies, the criteria for HPA-axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter 30 minutes after stimulation with cosyntropin (adrenocorticotropic hormone, ACTH). In the first study, Halobetasol Propionate Topical Foam was applied to 25 adult subjects with moderate to severe plaque psoriasis involving a mean body surface area of 18.4%. A mean dose of 3.7 g of Halobetasol Propionate Topical Foam was applied twice daily for two weeks and produced laboratory evidence of HPA axis suppression in 6 of 25 (24%) subjects. All subjects returned to normal HPA axis function at follow-up at least 4 weeks after stopping the treatment. In the second study, Halobetasol Propionate Topical Foam was applied to 24 subjects 12 to less than 18 years of age with stable plaque psoriasis with a mean percent BSA of 15.1% (range of 11% to 23%). The mean dose of Halobetasol Propionate Topical Foam used was 3.1 grams, which was applied twice daily for two weeks. In the study, 24 subjects completed the study, and 23 subjects had evaluable ACTH stimulation tests. HPA axis suppression was observed in 6 of the 23 subjects (26.1%), and all subjects returned to normal HPA axis function at follow-up at least 4 weeks after stopping the treatment.

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) C max concentration for HBP on Day 14 was 199.7 ± 217.3 pg/mL, with the corresponding median T max 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.

20230810

7

3 DOSAGE FORMS AND STRENGTHS Halobetasol Propionate Topical Foam is a white to off-white topical foam. Each gram of Halobetasol Propionate Topical Foam, 0.05% contains 0.5 mg of halobetasol propionate. Topical foam: 0.05% (0.5 mg/g). ( 3 )

Halobetasol propionate Halobetasol propionate Halobetasol propionate Halobetasol ALCOHOL Propylene Glycol POLAWAX POLYSORBATE Polyoxyl 20 Cetostearyl Ether Cetostearyl Alcohol WATER Benzoic Acid

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 Halobetasol Propionate Topical Foam 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.

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 Halobetasol Propionate Topical Foam 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.

NDA210566

Halobetasol propionate

Halobetasol propionate

51862-606

HUMAN PRESCRIPTION DRUG

TOPICAL

PRINCIPAL DISPLAY PANEL - 50 g Canister Carton NDC 51862-606-50 Halobetasol Propionate Topical Foam, 0.05% For topical use only. Rx ONLY Net Wt. 50 g mayne pharma PRINCIPAL DISPLAY PANEL - 50 g Canister Carton

Indication and Usage ( 1 ) 05/2021

Rx Only Distributed by: Mayne Pharma Raleigh, NC 27609 U.S. Patent 10,857,159 and 11,020,407 Revised: 03/2023

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 Halobetasol Propionate Topical Foam 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.

INSTRUCTIONS FOR USE HALOBETASOL PROPIONATE (hal-oh-BAY-ta-sol PRO-pee-oh-nate) Topical Foam, 0.05% Read the Patient Information and Instructions for Use before you use Halobetasol Propionate Topical Foam. Important information : Halobetasol Propionate Topical Foam is for skin use only. Do not get Halobetasol Propionate Topical Foam in your mouth, eyes, or vagina. Parts of the Halobetasol Propionate Topical Foam can: Step 1 : Before applying Halobetasol Propionate Topical Foam for the first time, remove cap and break the small tab at the base of the actuator by gently pushing the actuator away from the tab as shown. Do not break the hinge on the actuator. Step 2: Shake the can well before use. Step 3: Turn the can completely upside down. Step 4 : Press down on the actuator to dispense a small amount of the foam into the palm of your hand. Step 5 : Apply a thin layer of Halobetasol Propionate Topical Foam to the affected skin area. Gently rub Halobetasol Propionate Topical Foam into the affected skin until the foam disappears. Repeat Steps 4 and 5 to all the affected areas as prescribed by your healthcare provider. Step 6 : After applying Halobetasol Propionate Topical Foam, put the cap back on the can. Step 7: Wash your hands after applying Halobetasol Propionate Topical Foam unless you are using the medicine to treat your hands. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Distributed by: Mayne Pharma Raleigh, NC 27609 U.S. Patent 10,857,159 and 11,020,407 Revised: 03/2023 Figure Figure Figure Figure Figure Figure

14 CLINICAL STUDIES Halobetasol Propionate Topical Foam 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 Halobetasol Propionate Topical Foam 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 HBP Foam N=75 Vehicle Foam N=76 HBP Foam N=205 Vehicle Foam N=204 Overall Treatment Success 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. 19 (25%) 3 (4%) 63 (31%) 15 (7%) Plaque Elevation 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. 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%)

8.5 Geriatric Use Clinical studies with Halobetasol Propionate Topical Foam included 131 subjects aged 65 years and over. No overall differences in safety or effectiveness were observed between these subjects and those younger than 65 years.

8.4 Pediatric Use The safety and effectiveness of Halobetasol Propionate Topical Foam in patients younger than 12 years of age have not been established; therefore, use in children younger than 12 years is not recommended. The safety and effectiveness of Halobetasol Propionate Topical Foam for the treatment of stable plaque psoriasis in subjects 12 to less than 18 years of age is supported by evidence from adequate and well-controlled studies in adults and from one open-label safety study in 24 subjects aged 12 to less than 18 years. Subjects 12 to less than 18 years with stable plaque psoriasis covering a minimum of 10% of the total body surface area at baseline were treated twice daily for 2 weeks with Halobetasol Propionate Topical Foam. Hypothalamic-pituitary adrenal (HPA) axis function (ACTH stimulation test) was evaluated in a subset of 23 subjects. After 2 weeks of treatment, 6 of 23 subjects (26.1%) experienced laboratory evidence of adrenal suppression (i.e., cortisol serum level of ≤18 µg/dL) that recovered upon retesting after at least 4 weeks of stopping the treatment [see Clinical Pharmacology (12.2) ]. 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) ] .

8.1 Pregnancy Risk Summary There are no available data on Halobetasol Propionate Topical Foam use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published data report an increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. 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. No comparisons of animal exposure with human exposure may be calculated due to minimal systemic exposure in humans after topical administration of Halobetasol Propionate Topical Foam [see Clinical Pharmacology (12.3) ]. The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data Multiple observational studies found no significant associations between maternal use of topical corticosteroids of any potency and congenital malformations, preterm delivery, or fetal mortality. However, when the dispensed amount of potent or very potent topical corticosteroid exceeded 300 g during the entire pregnancy, use was associated with an increase in low birth weight infants. 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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on Halobetasol Propionate Topical Foam use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published data report an increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. 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. No comparisons of animal exposure with human exposure may be calculated due to minimal systemic exposure in humans after topical administration of Halobetasol Propionate Topical Foam [see Clinical Pharmacology (12.3) ]. The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data Multiple observational studies found no significant associations between maternal use of topical corticosteroids of any potency and congenital malformations, preterm delivery, or fetal mortality. However, when the dispensed amount of potent or very potent topical corticosteroid exceeded 300 g during the entire pregnancy, use was associated with an increase in low birth weight infants. 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. 8.2 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 topical application to women who are breastfeeding. 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 Halobetasol Propionate Topical Foam and any potential adverse effects on the breastfed infant from Halobetasol Propionate Topical Foam or from the underlying maternal condition. Clinical Considerations Advise breastfeeding women not to apply Halobetasol Propionate Topical Foam directly to the nipple and/or areola to avoid direct infant exposure. 8.4 Pediatric Use The safety and effectiveness of Halobetasol Propionate Topical Foam in patients younger than 12 years of age have not been established; therefore, use in children younger than 12 years is not recommended. The safety and effectiveness of Halobetasol Propionate Topical Foam for the treatment of stable plaque psoriasis in subjects 12 to less than 18 years of age is supported by evidence from adequate and well-controlled studies in adults and from one open-label safety study in 24 subjects aged 12 to less than 18 years. Subjects 12 to less than 18 years with stable plaque psoriasis covering a minimum of 10% of the total body surface area at baseline were treated twice daily for 2 weeks with Halobetasol Propionate Topical Foam. Hypothalamic-pituitary adrenal (HPA) axis function (ACTH stimulation test) was evaluated in a subset of 23 subjects. After 2 weeks of treatment, 6 of 23 subjects (26.1%) experienced laboratory evidence of adrenal suppression (i.e., cortisol serum level of ≤18 µg/dL) that recovered upon retesting after at least 4 weeks of stopping the treatment [see Clinical Pharmacology (12.2) ]. 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) ] . 8.5 Geriatric Use Clinical studies with Halobetasol Propionate Topical Foam included 131 subjects aged 65 years and over. No overall differences in safety or effectiveness were observed between these subjects and those younger than 65 years.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Halobetasol Propionate Topical Foam, 0.05% is a white to off-white foam. It is supplied in aluminum cans of: 50 grams (NDC 51862-606-50) 100 grams (2 cans of 50 grams) (NDC 51862-606-02) 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 Halobetasol Propionate Topical Foam is flammable; avoid heat, flame, or smoking when using this product.

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.