HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1How Supplied Clobetasol Propionate Foam, 0.05% contains 0.5 mg of clobetasol propionate, USP per gram. The white emulsion aerosol foam is available as follows:NDC 0378-8055-5050 aluminum canNDC 0378-8055-01100 aluminum can. 16.2Storage and Handling Store at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature.]FLAMMABLE. AVOID FIRE, FLAME OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120F (49C).Keep out of reach of children.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE Clobetasol propionate foam is indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years and older.. oClobetasol propionate foam is corticosteroid indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients aged 12 years and older. (1). oClobetasol propionate foam is corticosteroid indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients aged 12 years and older. (1).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: oEffects on Endocrine System [see Warnings and Precautions (5.1)] oOphthalmic Adverse Reactions [see Warnings and Precautions (5.3)] oEffects on Endocrine System [see Warnings and Precautions (5.1)] oOphthalmic Adverse Reactions [see Warnings and Precautions (5.3)] oThe most common adverse reactions (incidence >= 1%) are application site atrophy and application site reaction. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. oThe most common adverse reactions (incidence >= 1%) are application site atrophy and application site reaction. (6.1). 6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.In controlled clinical trials involving 821 subjects exposed to clobetasol propionate foam and vehicle foam, the pooled incidence of local adverse reactions in trials for atopic dermatitis and psoriasis with clobetasol propionate foam was 1.9% for application site atrophy and 1.6% for application site reaction. Most local adverse events were rated as mild to moderate and they were not affected by age, race, or gender. 6.2Postmarketing Experience Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.The following adverse reactions have been identified during post-approval use of clobetasol formulations: erythema, pruritus, burning, alopecia, and dryness.The following additional 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 clobetasol propionate.Cushings syndrome has been reported in infants and adults as result of prolonged use of topical clobetasol propionate formulations.Ophthalmic adverse reactions may include cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate foam or clobetasol propionate. In 90-day repeat-dose toxicity study in rats, topical administration of clobetasol propionate foam at dose concentrations from 0.001% to 0.1% or from 0.03 to 0.3 mg/kg/day of clobetasol propionate resulted in 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. 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 for carcinogenesis.Clobetasol propionate was non-mutagenic in the Ames test, the mouse lymphoma test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli WP2 fluctuation test. In the in vivo mouse micronucleus test, positive finding was observed at 24 hours, but not at 48 hours, following oral administration at dose of 2,000 mg/kg. Studies in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and decrease in the number of living fetuses at the highest dose.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Corticosteroids play role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in corticosteroid-responsive dermatoses is unknown.. 12.2 Pharmacodynamics In trial evaluating the potential for HPA axis suppression, using the cosyntropin stimulation test, clobetasol propionate foam demonstrated reversible adrenal suppression after two weeks of twice-daily use in subjects with atopic dermatitis of at least 30% body surface area (BSA). The proportion of subjects aged 12 years and older demonstrating HPA axis suppression was 16.2% (6 out of 37). In this trial HPA axis suppression was defined as serum cortisol level <=18 mcg/dL 30 minutes post cosyntropin stimulation. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested weeks post treatment [see Warnings and Precautions (5.1), Use in Specific Populations (8.4)].. 12.3 Pharmacokinetics Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation and the integrity of the epidermal barrier. Occlusion, inflammation, and/or other disease processes in the skin may increase percutaneous absorption. The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids may be necessary due to the fact that circulating levels are often below the level of detection. Once absorbed through the skin, topical corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.Following twice-daily application of clobetasol propionate foam for one week to 32 adult subjects with mild to moderate plaque-type psoriasis, mean peak plasma concentrations (+-SD) of 59 +- 36 pg/mL of clobetasol were observed at around hours post dose on Day 8.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES In randomized trial of subjects 12 years and older with moderate to severe atopic dermatitis, 251 subjects were treated with clobetasol propionate foam and 126 subjects were treated with vehicle foam. Subjects were treated twice daily for weeks. At the end of treatment, 131 of 251 subjects (52%) treated with clobetasol propionate foam compared with 18 of 126 subjects (14%) treated with vehicle foam achieved treatment success. Treatment success was defined by an Investigators Static Global Assessment (ISGA) score of clear (0) or almost clear (1) with at least grades improvement from baseline, and scores of absent or minimal (0 or 1) for erythema and induration/papulation.In an additional randomized trial of subjects 12 years and older with mild to moderate plaque-type psoriasis, 253 subjects were treated with clobetasol propionate foam and 123 subjects were treated with vehicle foam. Subjects were treated twice daily for weeks. At the end of treatment, 41 of 253 subjects (16%) treated with clobetasol propionate foam compared with of 123 subjects (4%) treated with vehicle foam achieved treatment success. Treatment success was defined by an ISGA score of clear (0) or almost clear (1) with at least grades improvement from baseline, scores of none or faint/minimal (0 or 1) for erythema and scaling, and score of none (0) for plaque thickness.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS None.. None. (4).

DESCRIPTION SECTION.

11 DESCRIPTION Clobetasol propionate foam, is white to off-white petrolatum-based emulsion aerosol foam, containing the active ingredient clobetasol propionate, USP, synthetic corticosteroid for topical dermatologic use. Clobetasol, an analog of prednisolone, has high degree of glucocorticoid activity and slight degree of mineralocorticoid activity.Clobetasol propionate is 21-chloro-9-fluoro-11ss,17-dihydroxy-16ss-methylpregna-1,4-diene-3,20-dione 17-propionate, with the empirical formula C25H32ClFO5, and molecular weight of 466.97.The following is the chemical structure:Clobetasol propionate is white to almost white crystalline powder, practically insoluble in water.Each gram of clobetasol propionate foam contains 0.5 mg clobetasol propionate, USP. The foam also contains anhydrous citric acid, cetyl alcohol, cyclomethicone, isopropyl myristate, light mineral oil, polyoxyl 20 cetostearyl ether, potassium citrate monohydrate, propylene glycol, purified water, sorbitan monolaurate, white petrolatum, and phenoxyethanol as preservative.Clobetasol propionate foam is dispensed from an aluminum can pressurized with hydrocarbon (propane/butane) propellant.. Clobetasol Propionate Structural Formula.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION oApply thin layer of clobetasol propionate foam to the affected area(s) twice daily, morning and evening, for up to consecutive weeks; therapy should be discontinued when control has been achieved. oThe maximum weekly dose should not exceed 50 or an amount greater than 21 capfuls per week. oFor proper dispensing of foam, shake the can, hold it upside down, and depress the actuator.oDispense small amount of foam (about capful) and gently massage the medication into the affected areas (excluding the face, groin, and axillae) until the foam is absorbed. oClobetasol propionate foam is not for oral, ophthalmic, or intravaginal use.oAvoid contact with the eyes.oAvoid use on face, axillae, and groin, or if skin atrophy is present at the treatment site. oWash hands after each application.. oApply thin layer of clobetasol propionate foam to the affected area(s) twice daily, morning and evening, for up to consecutive weeks; therapy should be discontinued when control has been achieved. oThe maximum weekly dose should not exceed 50 or an amount greater than 21 capfuls per week. oFor proper dispensing of foam, shake the can, hold it upside down, and depress the actuator.. oDispense small amount of foam (about capful) and gently massage the medication into the affected areas (excluding the face, groin, and axillae) until the foam is absorbed. oClobetasol propionate foam is not for oral, ophthalmic, or intravaginal use.. oAvoid contact with the eyes.. oAvoid use on face, axillae, and groin, or if skin atrophy is present at the treatment site. oWash hands after each application.. Clobetasol propionate foam is not for oral, ophthalmic, or intravaginal use. (2)oApply clobetasol propionate foam to the affected area(s) twice daily, morning and evening, for up to consecutive weeks. The maximum weekly dose should not exceed 50 g. (2)oAvoid use on face, axillae, and groin, or if skin atrophy is present at the treatment site. (2). oApply clobetasol propionate foam to the affected area(s) twice daily, morning and evening, for up to consecutive weeks. The maximum weekly dose should not exceed 50 g. (2). oAvoid use on face, axillae, and groin, or if skin atrophy is present at the treatment site. (2).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS Clobetasol Propionate Foam, 0.05% contains 0.5 mg of clobetasol propionate, USP per gram. Foam, 0.05%. (3).

GERIATRIC USE SECTION.

8.5 Geriatric Use A limited number of subjects aged 65 years or older have been treated with clobetasol propionate foam (n 58) in U.S. clinical trials. While the number of subjects is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger subjects. Based on available data, no adjustment of dosage of clobetasol propionate foam in geriatric patients is warranted.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information)Effects on Endocrine SystemClobetasol propionate foam may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including clobetasol propionate foam, 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. Patients should inform their physician(s) that they are using clobetasol propionate foam if surgery is contemplated [see Warnings and Precautions (5.1)]. Ophthalmic Adverse ReactionsAdvise patients to report any visual symptoms to their healthcare providers [see Warnings and Precautions (5.3)].Local Adverse ReactionsReport any signs of local adverse reactions to the physician. Advise patients that local reactions and skin atrophy are more likely to occur with occlusive use or prolonged use [see Warnings and Precautions (5.2)].PregnancyAdvise pregnant woman that use of clobetasol propionate foam may cause fetal harm and to use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible [see Use in Specific Populations (8.1)]. LactationAdvise woman to use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply clobetasol propionate foam directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.2)]. Important Administration InstructionsPatients using topical corticosteroids should receive the following information and instructions:oThis medication is to be used as directed by the physician. It is for external use only. Unless directed by the prescriber, it should not be used on the face or in skin-fold areas, such as the underarms or groin. Avoid contact with the eyes or other mucous membranes. Wash hands after use. oAs with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within weeks, contact the physician. oDo not use for more than 50 grams per week of clobetasol propionate foam, or an amount greater than 21 capfuls per week. [see Dosage and Administration (2).]oThis medication is flammable; avoid heat, flame, or smoking when applying this product.. oThis medication is to be used as directed by the physician. It is for external use only. Unless directed by the prescriber, it should not be used on the face or in skin-fold areas, such as the underarms or groin. Avoid contact with the eyes or other mucous membranes. Wash hands after use. oAs with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within weeks, contact the physician. oDo not use for more than 50 grams per week of clobetasol propionate foam, or an amount greater than 21 capfuls per week. [see Dosage and Administration (2).]. oThis medication is flammable; avoid heat, flame, or smoking when applying this product.

LACTATION SECTION.

8.2 Lactation Risk Summary. There is no information regarding the presence of clobetasol propionate in breast milk or its effects on the breastfed infant or on milk production. 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 clobetasol propionate 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 mothers clinical need for clobetasol propionate foam and any potential adverse effects on the breastfed infant from clobetasol propionate foam or from the underlying maternal condition. Clinical Considerations. To minimize potential exposure to the breastfed infant via breast milk, use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply clobetasol propionate foam directly to the nipple and areola to avoid direct infant exposure.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action Corticosteroids play role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in corticosteroid-responsive dermatoses is unknown.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate foam or clobetasol propionate. In 90-day repeat-dose toxicity study in rats, topical administration of clobetasol propionate foam at dose concentrations from 0.001% to 0.1% or from 0.03 to 0.3 mg/kg/day of clobetasol propionate resulted in 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. 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 for carcinogenesis.Clobetasol propionate was non-mutagenic in the Ames test, the mouse lymphoma test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli WP2 fluctuation test. In the in vivo mouse micronucleus test, positive finding was observed at 24 hours, but not at 48 hours, following oral administration at dose of 2,000 mg/kg. Studies in the rat following subcutaneous administration of clobetasol propionate at dosage levels up to 0.05 mg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and decrease in the number of living fetuses at the highest dose.

OVERDOSAGE SECTION.

10 OVERDOSAGE Topically applied clobetasol propionate foam can be absorbed in sufficient amounts to produce systemic effects.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 0.05% NDC 0378-8055-50ClobetasolPropionateFoam0.05%EmulsionFormulationFOR TOPICAL USE ONLY.NOT FOR OPHTHALMIC, ORAL,OR INTRAVAGINAL USE.Shake can before use.Invert canand thenpress firmlyto dispense.Description: Each gram of ClobetsolPropionate Foam contains 0.5 mgclobetasol propionate, USP.The foam also contains anhydrouscitric acid, cetyl alcohol,cyclomethicone, isopropyl myristate,light mineral oil, polyoxyl 20cetostearyl ether, potassium citratemonohydrate, propylene glycol,purified water, sorbitan monolaurate,white petrolatum, and phenoxyethanolas preservative, and is pressurizedwith hydrocarbon (propane/butane)propellant.Usual Dosage: Use only asprescribed by your physician. Seeaccompanying prescribinginformation.Warning: FLAMMABLE. AVOID FIRE,FLAME, OR SMOKING DURING ANDIMMEDIATELY FOLLOWINGAPPLICATION.Contents under pressure. Do notpuncture or incinerate. Do notexpose to heat or store attemperatures above 120F (49C).Avoid contact with eyes or othermucous membranes. Keep this andall medication out of the reach ofchildren.Store at 20 to 25C (68 to 77F).[See USP Controlled RoomTemperature.]CFC FREEManufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.Manufactured by: DPT Laboratories, Ltd. San Antonio, TX 78215 U.S.A.For more information, callMylan Pharmaceuticals Inc. at1-877-446-3679 (1-877-4-INFO-RX).DPT:8055:50:1C:R1117492-0917Mylan.com. Carton Label Invert Can Clobetasol Propionate Foam 0.05% Carton Label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use Use in pediatric patients younger than 12 years is not recommended because of the risk of HPA axis suppression.After two weeks of twice-daily treatment with clobetasol propionate foam, of 15 subjects (47%) aged to 11 years demonstrated HPA axis suppression. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested weeks post-treatment.In 92 subjects aged 12 to 17 years, safety was similar to that observed in the adult population. Based on these data, no adjustment of dosage of clobetasol propionate foam in adolescent patients aged 12 to 17 years is warranted [see Warnings and Precautions (5.1)]. Because of higher ratio of skin surface area to body mass, pediatric patients are at greater risk than adults of HPA axis suppression and Cushings syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment.HPA axis suppression, Cushings 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 (in infants), headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.Adverse effects, including striae, have been reported with inappropriate use of topical corticosteroids in infants and children.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics In trial evaluating the potential for HPA axis suppression, using the cosyntropin stimulation test, clobetasol propionate foam demonstrated reversible adrenal suppression after two weeks of twice-daily use in subjects with atopic dermatitis of at least 30% body surface area (BSA). The proportion of subjects aged 12 years and older demonstrating HPA axis suppression was 16.2% (6 out of 37). In this trial HPA axis suppression was defined as serum cortisol level <=18 mcg/dL 30 minutes post cosyntropin stimulation. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested weeks post treatment [see Warnings and Precautions (5.1), Use in Specific Populations (8.4)].

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation and the integrity of the epidermal barrier. Occlusion, inflammation, and/or other disease processes in the skin may increase percutaneous absorption. The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids may be necessary due to the fact that circulating levels are often below the level of detection. Once absorbed through the skin, topical corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.Following twice-daily application of clobetasol propionate foam for one week to 32 adult subjects with mild to moderate plaque-type psoriasis, mean peak plasma concentrations (+-SD) of 59 +- 36 pg/mL of clobetasol were observed at around hours post dose on Day 8.

PREGNANCY SECTION.

8.1 Pregnancy Risk Summary. There are no available data on clobetasol propionate foam use in pregnant women to inform of drug associated risk for adverse developmental outcomes.Published data report significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during pregnancy. Advise pregnant women of the potential risk to fetus and to use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible (see Data ). In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits. No comparison of animal exposure with human exposure was computed.The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 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 during the entire pregnancy, use was associated with an increase in low birth weight infants (adjusted RR, 7.74 [95% CI, 1.49-40.11]). In addition, small cohort study, in which 28 sub-Saharan women using potent topical corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during pregnancy, noted higher incidence of low birth weight infants in the exposed group. The majority of exposed subjects treated large areas of the body (a mean quantity of 60 g/month [range, 12-170 g]) over long periods of time. Animal Data Embryofetal development studies conducted with clobetasol propionate in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and malformations at all dose levels tested down to 0.03 mg/kg. Malformations seen included cleft palate and skeletal abnormalities.In an embryofetal development study in rabbits, subcutaneous administration of clobetasol propionate resulted in malformations at doses of 0.003 and 0.01 mg/kg. Malformations seen included cleft palate, cranioschisis, and other skeletal abnormalities.

RECENT MAJOR CHANGES SECTION.

Warnings and Precautions, Ophthalmic Adverse Reactions (5.3) 5/2018.

RISKS.

Risk Summary. There are no available data on clobetasol propionate foam use in pregnant women to inform of drug associated risk for adverse developmental outcomes.Published data report significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during pregnancy. Advise pregnant women of the potential risk to fetus and to use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible (see Data ). In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits. No comparison of animal exposure with human exposure was computed.The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATION Clobetasol Propionate FoamImportant: For skin use only. Do not get clobetasol propionate foam in your eyes, mouth, or vagina.What is clobetasol propionate foamClobetasol propionate foam is prescription corticosteroid medicine used on the skin (topical) to treat people 12 years of age and older with certain skin conditions that cause red, flaky, and itchy skin.Clobetasol propionate foam is not recommended for use in children under 12 years of age. Clobetasol propionate foam should not be used:oon your face, underarms, or groin area oif you have skin thinning (atrophy) at the treatment areaYou should not use clobetasol propionate foam for longer than weeks in row.You should not use more than 50 grams or 21 capfuls of clobetasol propionate foam in week.Before using clobetasol propionate foam, tell your healthcare provider about all of your medical conditions, including if you:ohave had irritation or other skin reaction to steroid medicine in the past.ohave skin infection. You may need medicine to treat the skin infection before using clobetasol propionate foam.ohave diabetes. ohave adrenal gland problems.ohave liver problems. oplan to have surgery. oare pregnant or plan to become pregnant. It is not known if clobetasol propionate foam will harm your unborn baby. If you use clobetasol propionate foam during pregnancy, use clobetasol propionate foam on the smallest area of skin and for the shortest time needed. oare breastfeeding or plan to breastfeed. It is not known if clobetasol propionate passes into your breast milk. If you use clobetasol propionate foam while breastfeeding, use clobetasol propionate foam on the smallest area of skin and for the shortest time needed. Do not apply clobetasol propionate foam directly to the nipple and areola to avoid getting clobetasol propionate foam into your babys mouth. Tell your healthcare provider about all the medicine you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Do not use other products containing corticosteroid medicine during treatment with clobetasol propionate foam without talking to your healthcare provider first.How should use clobetasol propionate foamSee the Instructions for Use for detailed information about the right way to apply clobetasol propionate foam. oUse clobetasol propionate foam exactly as your healthcare provider tells you to use it. oApply thin layer of clobetasol propionate foam to the affected area times each day, time in the morning and time at night, or as directed by your healthcare provider. oDo not bandage, wrap or cover your treated area unless your healthcare provider tells you to. oTalk to your healthcare provider if your skin does not improve after weeks of treatment with clobetasol propionate foam. Wash your hands after using clobetasol propionate foam.What should avoid while using clobetasol propionate foamClobetasol propionate foam is flammable. Avoid heat, flame, or smoking during and right after you apply clobetasol propionate foam to your skin.What are the possible side effects of clobetasol propionate foamClobetasol propionate foam may cause serious side effects, including:oClobetasol propionate foam can pass through your skin. Too much clobetasol propionate foam passing through your skin can cause adrenal glands to stop working. oCushings syndrome, condition that happens when the body is exposed to too much of the hormone cortisol. oHigh blood sugar (hyperglycemia)oVision problems. Clobetasol propionate foam may increase your chance of developing vision problems such as cataract(s) and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during your treatment with clobetasol propionate foam. oSkin reactions at the treated site. Tell your healthcare provider if you get any skin reactions or skin infections. oEffects on growth and weight in children.Your healthcare provider may do certain blood tests to check for side effects. The most common side effects of clobetasol propionate foam include:othinning of skin oburning orednessoitching odrynessThese are not all the side effects of clobetasol propionate foam. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store clobetasol propionate foamoStore clobetasol propionate foam at room temperature between 68 to 77F (20 to 25C). oDo not break through (puncture) clobetasol propionate foam can. oNever throw the can into fire, even if the can is empty.oDo not store clobetasol propionate foam near heat or at temperatures above 120F (49C).Keep clobetasol propionate foam and all medicines out of the reach of children. General information about the safe and effective use of clobetasol propionate foamMedicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use clobetasol propionate foam for condition for which it was not prescribed. Do not give clobetasol propionate foam to other people, even if they have the same condition that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about clobetasol propionate foam that is written for health professionals.What are the ingredients in clobetasol propionate foamActive ingredient: clobetasol propionateInactive ingredients: anhydrous citric acid, cetyl alcohol, cyclomethicone, isopropyl myristate, light mineral oil, polyoxyl 20 cetostearyl ether, potassium citrate monohydrate, propylene glycol, purified water, sorbitan monolaurate, white petrolatum, and phenoxyethanol as preservative, pressurized with hydrocarbon (propane/butane) propellant.Manufactured for: Mylan Pharmaceuticals Inc.,Morgantown, WV 26505 U.S.A.For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX).INSTRUCTIONS FOR USEClobetasol Propionate FoamImportant information: Clobetasol propionate foam is for use on the skin only. Do not get clobetasol propionate foam in your eyes, mouth, or vagina; if contact happens, rinse well with water.How to apply clobetasol propionate foamFigure AStep 1: Before applying clobetasol propionate foam for the first time, break the tiny plastic piece at the base of the cans rim by gently pushing back (away from the piece) on the nozzle. (See Figure A).Figure BStep 2: Shake the can of clobetasol propionate foam before use. (See Figure B).Figure CStep 3: Turn the can of clobetasol propionate foam upside down and press the nozzle. See Figure C.Figure DStep 4: Press down on the actuator to dispense small amount of clobetasol propionate foam into the palm of your hand. (See Figure D).Figure EStep 5: Apply thin layer of clobetasol propionate foam to cover the affected area. Gently rub the foam into the affected area until the foam disappears. (See Figure E).Step 6: Wash your hands after applying clobetasol propionate foam.oThrow away any of the unused medicine that you dispensed out of the can.The Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.Manufactured by: DPT Laboratories, Ltd. San Antonio, TX 78215 U.S.A.140952-0518Revised: 5/2018DPT:ECLOBFOG:R2. oon your face, underarms, or groin area oif you have skin thinning (atrophy) at the treatment area. ohave had irritation or other skin reaction to steroid medicine in the past.. ohave skin infection. You may need medicine to treat the skin infection before using clobetasol propionate foam.. ohave diabetes. ohave adrenal gland problems.. ohave liver problems. oplan to have surgery. oare pregnant or plan to become pregnant. It is not known if clobetasol propionate foam will harm your unborn baby. If you use clobetasol propionate foam during pregnancy, use clobetasol propionate foam on the smallest area of skin and for the shortest time needed. oare breastfeeding or plan to breastfeed. It is not known if clobetasol propionate passes into your breast milk. If you use clobetasol propionate foam while breastfeeding, use clobetasol propionate foam on the smallest area of skin and for the shortest time needed. Do not apply clobetasol propionate foam directly to the nipple and areola to avoid getting clobetasol propionate foam into your babys mouth. oUse clobetasol propionate foam exactly as your healthcare provider tells you to use it. oApply thin layer of clobetasol propionate foam to the affected area times each day, time in the morning and time at night, or as directed by your healthcare provider. oDo not bandage, wrap or cover your treated area unless your healthcare provider tells you to. oTalk to your healthcare provider if your skin does not improve after weeks of treatment with clobetasol propionate foam. oClobetasol propionate foam can pass through your skin. Too much clobetasol propionate foam passing through your skin can cause adrenal glands to stop working. oCushings syndrome, condition that happens when the body is exposed to too much of the hormone cortisol. oHigh blood sugar (hyperglycemia). oVision problems. Clobetasol propionate foam may increase your chance of developing vision problems such as cataract(s) and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during your treatment with clobetasol propionate foam. oSkin reactions at the treated site. Tell your healthcare provider if you get any skin reactions or skin infections. oEffects on growth and weight in children.. othinning of skin oburning oredness. oitching odryness. oStore clobetasol propionate foam at room temperature between 68 to 77F (20 to 25C). oDo not break through (puncture) clobetasol propionate foam can. oNever throw the can into fire, even if the can is empty.. oDo not store clobetasol propionate foam near heat or at temperatures above 120F (49C).. oThrow away any of the unused medicine that you dispensed out of the can.. Instructions for Use Figure A. Instructions for Use Figure B. Instructions for Use Figure C. Instructions for Use Figure D. Instructions for Use Figure E.

SPL UNCLASSIFIED SECTION.

5.1Effects on Endocrine System Clobetasol propionate foam has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis.Systemic absorption of clobetasol propionate has caused reversible HPA axis suppression with the potential for clinical glucocorticoid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. Use of clobetasol propionate foam for longer than weeks may suppress the immune system [see Nonclinical Toxicology (13.1)].In trial including 37 subjects ages 12 years and older with atopic dermatitis of at least 30% body surface area (BSA), adrenal suppression was identified in out of 37 subjects (16.2%) after weeks of treatment with clobetasol propionate [see Clinical Pharmacology (12.2)].Because of the potential for systemic absorption, use of clobetasol propionate may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose patient using topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.An adrenocorticotrophic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute less potent steroid. Manifestations of adrenal insufficiency may require systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.Cushings syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.Use of more than corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.Pediatric patients may be more susceptible to systemic toxicity from equivalent doses because of their larger skin surface-to-body mass ratios [see Use in Specific Populations (8.4)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary. There are no available data on clobetasol propionate foam use in pregnant women to inform of drug associated risk for adverse developmental outcomes.Published data report significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during pregnancy. Advise pregnant women of the potential risk to fetus and to use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible (see Data ). In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits. No comparison of animal exposure with human exposure was computed.The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 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 during the entire pregnancy, use was associated with an increase in low birth weight infants (adjusted RR, 7.74 [95% CI, 1.49-40.11]). In addition, small cohort study, in which 28 sub-Saharan women using potent topical corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during pregnancy, noted higher incidence of low birth weight infants in the exposed group. The majority of exposed subjects treated large areas of the body (a mean quantity of 60 g/month [range, 12-170 g]) over long periods of time. Animal Data Embryofetal development studies conducted with clobetasol propionate in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and malformations at all dose levels tested down to 0.03 mg/kg. Malformations seen included cleft palate and skeletal abnormalities.In an embryofetal development study in rabbits, subcutaneous administration of clobetasol propionate resulted in malformations at doses of 0.003 and 0.01 mg/kg. Malformations seen included cleft palate, cranioschisis, and other skeletal abnormalities.. 8.2 Lactation Risk Summary. There is no information regarding the presence of clobetasol propionate in breast milk or its effects on the breastfed infant or on milk production. 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 clobetasol propionate 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 mothers clinical need for clobetasol propionate foam and any potential adverse effects on the breastfed infant from clobetasol propionate foam or from the underlying maternal condition. Clinical Considerations. To minimize potential exposure to the breastfed infant via breast milk, use clobetasol propionate foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply clobetasol propionate foam directly to the nipple and areola to avoid direct infant exposure.. 8.4 Pediatric Use Use in pediatric patients younger than 12 years is not recommended because of the risk of HPA axis suppression.After two weeks of twice-daily treatment with clobetasol propionate foam, of 15 subjects (47%) aged to 11 years demonstrated HPA axis suppression. The laboratory suppression was transient; in all subjects serum cortisol levels returned to normal when tested weeks post-treatment.In 92 subjects aged 12 to 17 years, safety was similar to that observed in the adult population. Based on these data, no adjustment of dosage of clobetasol propionate foam in adolescent patients aged 12 to 17 years is warranted [see Warnings and Precautions (5.1)]. Because of higher ratio of skin surface area to body mass, pediatric patients are at greater risk than adults of HPA axis suppression and Cushings syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment.HPA axis suppression, Cushings 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 (in infants), headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.Adverse effects, including striae, have been reported with inappropriate use of topical corticosteroids in infants and children.. 8.5 Geriatric Use A limited number of subjects aged 65 years or older have been treated with clobetasol propionate foam (n 58) in U.S. clinical trials. While the number of subjects is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger subjects. Based on available data, no adjustment of dosage of clobetasol propionate foam in geriatric patients is warranted.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oClobetasol propionate foam has been shown to suppress the HPA axis. Systemic absorption of clobetasol propionate foam may produce reversible HPA axis suppression, Cushings syndrome, hyperglycemia, and unmask latent diabetes. (5.1)oBecause of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. (5.1) oModify use should HPA axis suppression develop. (5.1) oHigh potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, and liver failure may predispose patients to HPA axis suppression. (5.1) oMay increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist for evaluation. (5.3)oPediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. (5.1, 8.4)oThe propellant in clobetasol propionate foam is flammable. Avoid fire, flame, or smoking during and immediately following application. (5.5). oClobetasol propionate foam has been shown to suppress the HPA axis. Systemic absorption of clobetasol propionate foam may produce reversible HPA axis suppression, Cushings syndrome, hyperglycemia, and unmask latent diabetes. (5.1). oBecause of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. (5.1) oModify use should HPA axis suppression develop. (5.1) oHigh potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, and liver failure may predispose patients to HPA axis suppression. (5.1) oMay increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist for evaluation. (5.3). oPediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. (5.1, 8.4). oThe propellant in clobetasol propionate foam is flammable. Avoid fire, flame, or smoking during and immediately following application. (5.5). 5.1Effects on Endocrine System Clobetasol propionate foam has been shown to suppress the hypothalamic-pituitary-adrenal (HPA) axis.Systemic absorption of clobetasol propionate has caused reversible HPA axis suppression with the potential for clinical glucocorticoid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. Use of clobetasol propionate foam for longer than weeks may suppress the immune system [see Nonclinical Toxicology (13.1)].In trial including 37 subjects ages 12 years and older with atopic dermatitis of at least 30% body surface area (BSA), adrenal suppression was identified in out of 37 subjects (16.2%) after weeks of treatment with clobetasol propionate [see Clinical Pharmacology (12.2)].Because of the potential for systemic absorption, use of clobetasol propionate may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose patient using topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.An adrenocorticotrophic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute less potent steroid. Manifestations of adrenal insufficiency may require systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.Cushings syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.Use of more than corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.Pediatric patients may be more susceptible to systemic toxicity from equivalent doses because of their larger skin surface-to-body mass ratios [see Use in Specific Populations (8.4)].. 5.2Local Adverse Reactions with Topical Corticosteroids Local adverse reactions may be more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible.Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by failure to heal rather than clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.If irritation develops, treatment with clobetasol propionate foam should be discontinued and appropriate therapy instituted.. 5.3Ophthalmic Adverse Reactions Use of topical corticosteroids, including clobetasol propionate foam, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing with the use of topical corticosteroids, including topical clobetasol products [see Adverse Reactions (6.2)]. Avoid contact of clobetasol propionate foam with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.. 5.4Concomitant Skin Infections Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, clobetasol propionate foam should be discontinued until the infection has been adequately treated.. 5.5Flammable Contents The propellant in clobetasol propionate foam is flammable. Avoid fire, flame, or smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120F (49C).