ENSTILAR

Enstilar Foam contains calcipotriene hydrate and betamethasone dipropionate. It is for topical use only. Calcipotriene Hydrate Calcipotriene hydrate is a synthetic vitamin D analog and has the chemical name 9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol,24-cyclo-propyl-,monohydrate, (1α,3β,5Z,7E,22E,24S) with the empirical formula C 27 H 40 O 3 ∙H 2 O), a molecular weight of 430.6, and the following structural formula (calcipotriene hydrate is a white to almost white, crystalline compound): Chemical Structure Betamethasone Dipropionate Betamethasone dipropionate is a synthetic corticosteroid and has the chemical name pregna-1,4-diene-3,20-dione-9-fluoro-11-hydroxy-16-methyl-17,21-bis(1-oxypropoxy)-(11β,16β), with the empirical formula C 28 H 37 FO 7 , a molecular weight of 504.6, and the following structural formula (betamethasone dipropionate is a white to almost white, crystalline powder): Chemical Structure Enstilar ® Foam Each gram of Enstilar Foam contains 50 mcg of calcipotriene (equivalent to 52.2 mcg of calcipotriene hydrate) and 0.643 mg of betamethasone dipropionate (equivalent to 0.5 mg of betamethasone) in a base of white petrolatum, polyoxypropylene stearyl ether, mineral oil, all- rac -alpha-tocopherol, and butylhydroxytoluene. Enstilar Foam is a white to off-white opalescent liquid in a pressurized aluminum spray can with a continuous valve and actuator. The propellants used in Enstilar Foam are dimethyl ether and butane. At administration, the product is a white to off-white foam after evaporation of the propellants. Enstilar Foam has the appearance of a non-expanding foam that gradually collapses after spraying.

Enstilar ® (calcipotriene and betamethasone dipropionate) Foam is indicated for the topical treatment of plaque psoriasis in patients 12 years and older. Enstilar Foam is a combination of calcipotriene, a vitamin D analog, and betamethasone dipropionate, a corticosteroid, indicated for the topical treatment of plaque psoriasis in patients 12 years and older. ( 1 )

Shake can prior to using Enstilar Foam. Apply Enstilar Foam to affected areas once daily for up to 4 weeks. The maximum dose should not exceed 60 grams every 4 days. Rub in Enstilar Foam gently. Wash hands after applying the product. Discontinue Enstilar Foam when control is achieved. Enstilar Foam should not be used: with occlusive dressings unless directed by a healthcare provider. on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Enstilar Foam is not for oral, ophthalmic, or intravaginal use. Shake before use. Apply Enstilar Foam to affected area(s) once daily for up to 4 weeks. Discontinue therapy when control is achieved. Do not use more than 60 grams every 4 days. ( 2 ) Do not use with occlusive dressings unless directed by a healthcare provider. ( 2 ) Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 )

None. None. ( 4 )

Adverse reactions reported in < 1% of subjects included application site irritation, application site pruritus, folliculitis, skin hypopigmentation, hypercalcemia, urticaria, and exacerbation of psoriasis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LEO Pharma Inc. at 1-877-494-4536 or 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. Clinical Trials Conducted in Subjects 18 years and older with Psoriasis The rates of adverse reactions described below were from three randomized, multicenter, vehicle and/or active-controlled clinical trials in adult subjects with plaque psoriasis [see Clinical Studies (14) ] . Subjects applied study product once daily for 4 weeks, and the median weekly dose of Enstilar Foam was 25 grams. Adverse reactions reported in <1% of adult subjects treated with Enstilar Foam included: application site irritation, application site pruritus, folliculitis, skin hypopigmentation, hypercalcemia, urticaria, and exacerbation of psoriasis. Clinical Trials Conducted in Subjects 12 to 17 years with Psoriasis In one uncontrolled clinical trial, 106 subjects aged 12 to 17 years with plaque psoriasis of the scalp and body applied Enstilar Foam once daily for up to 4 weeks. The median weekly dose was 40 grams. Adverse reactions reported in <1% of adolescent subjects treated were acne, erythema, application site pain, and skin reactions [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.2) ]. 6.2 Postmarketing Experience Because adverse 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. Postmarketing reports for local adverse reactions to Enstilar Foam included application site burning. Postmarketing reports for local adverse reactions to topical corticosteroids included atrophy, striae, telangiectasia, dryness, perioral dermatitis, secondary infection, and miliaria. Ophthalmic adverse reactions of cataracts, glaucoma, and increased intraocular pressure have been reported with the use of topical corticosteroids, including topical betamethasone products.

16.2 Storage Store Enstilar Foam at 20°C - 25°C (68°F - 77°F); excursions permitted between 15°C - 30°C (59°F - 86°F). [See USP controlled room temperature]. 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. Unused product should be discarded six months after the can has been opened. Keep out of the reach of children. 16.3 Handling Enstilar Foam is flammable; avoid heat, flame or smoking when using this product.