Clobetasol Propionate: Package Insert and Label Information (Page 2 of 3)

12.2 Pharmacodynamics

In a 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 4 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 5 hours post dose on 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 clobetasol propionate foam or clobetasol propionate.

In a 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 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 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 B WP2 fluctuation test. In the in vivo mouse micronucleus test, a positive finding was observed at 24 hours, but not at 48 hours, following oral administration at a 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 a decrease in the number of living fetuses at the highest dose.

14 CLINICAL STUDIES

In a 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 2 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 Investigator’s Static Global Assessment (ISGA) score of clear (0) or almost clear (1) with at least 2 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 2 weeks. At the end of treatment, 41 of 253 subjects (16%) treated with clobetasol propionate foam compared with 5 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 2 grades improvement from baseline, scores of none or faint/minimal (0 or 1) for erythema and scaling, and a score of none (0) for plaque thickness.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How 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 0378-8055-50
50 g aluminum can

NDC 0378-8055-01100 g aluminum can

16.2 Storage and Handling

Store at 20° to 25°C (68° to 77°F). [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 120°F (49°C).

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling (Patient Information)

Effects on Endocrine System

Clobetasol 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 Reactions

Advise patients to report any visual symptoms to their healthcare providers [see Warnings and Precautions (5.3)].

Local Adverse Reactions

Report 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)].

Pregnancy

Advise a 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)].

Lactation

Advise a 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 Instructions

Patients using topical corticosteroids should receive the following information and instructions:

•

This 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.

•

As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.

•

Do 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).]

•

This medication is flammable; avoid heat, flame, or smoking when applying this product.

PATIENT INFORMATION

Clobetasol Propionate Foam
Important: For skin use only. Do not get clobetasol propionate foam in your eyes, mouth, or vagina.
What is clobetasol propionate foam? Clobetasol propionate foam is a 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: • on your face, underarms, or groin area • if you have skin thinning (atrophy) at the treatment area You should not use clobetasol propionate foam for longer than 2 weeks in a row. You should not use more than 50 grams or 21 capfuls of clobetasol propionate foam in 1 week.
Before using clobetasol propionate foam, 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 clobetasol propionate foam. • 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 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. • are 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 baby’s 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 a corticosteroid medicine during treatment with clobetasol propionate foam without talking to your healthcare provider first.
How should I use clobetasol propionate foam? See the “Instructions for Use” for detailed information about the right way to apply clobetasol propionate foam. • Use clobetasol propionate foam exactly as your healthcare provider tells you to use it. • Apply a thin layer of clobetasol propionate foam to the affected area 2 times each day, 1 time in the morning and 1 time at night, or as directed by your healthcare provider. • Do not bandage, wrap or cover your treated 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 clobetasol propionate foam. Wash your hands after using clobetasol propionate foam.
What should I avoid while using clobetasol propionate foam? Clobetasol 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 foam? Clobetasol propionate foam may cause serious side effects, including: • Clobetasol propionate foam can pass through your skin. Too much clobetasol propionate foam passing through your skin can cause adrenal glands to stop working. • Cushing’s syndrome, a condition that happens when the body is exposed to too much of the hormone cortisol. • High blood sugar (hyperglycemia) • Vision 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. • Skin reactions at the treated 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 effects of clobetasol propionate foam include:
• thinning of skin • burning • redness	• itching • dryness
These 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 I store clobetasol propionate foam? • Store clobetasol propionate foam at room temperature between 68° to 77°F (20° to 25°C). • Do not break through (puncture) clobetasol propionate foam can. • Never throw the can into a fire, even if the can is empty. • Do not store clobetasol propionate foam near heat or at temperatures above 120°F (49°C). Keep clobetasol propionate foam and all medicines out of the reach of children.
General information about the safe and effective use of clobetasol propionate foam Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use clobetasol propionate foam for a 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 foam? Active ingredient: clobetasol propionate Inactive 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 a preservative, pressurized with a 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 USE Clobetasol Propionate Foam
Important 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 foam
Figure A	Step 1: Before applying clobetasol propionate foam for the first time, break the tiny plastic piece at the base of the can’s rim by gently pushing back (away from the piece) on the nozzle. (See Figure A).
Figure B	Step 2: Shake the can of clobetasol propionate foam before use. (See Figure B).
Figure C	Step 3: Turn the can of clobetasol propionate foam upside down and press the nozzle. See Figure C.
Figure D	Step 4: Press down on the actuator to dispense a small amount of clobetasol propionate foam into the palm of your hand. (See Figure D).
(click image for full-size original) Figure E	Step 5: Apply a 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. • Throw 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.

140952-0518

Revised: 5/2018
DPT:ECLOBFOG:R2