CALCIPOTRIENE AND BETAMETHASONE DIPROPIONATE

Calcipotriene and betamethasone dipropionate topical suspension contains calcipotriene and betamethasone dipropionate. It is for topical use only. Calcipotriene is a synthetic vitamin D 3 analog. Calcipotriene Calcipotriene is a vitamin D analog and has the chemical name (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1(alpha),3(beta),24-triol, with the empirical formula C 27 H 40 O 3 , a molecular weight of 412.3, and the following structural formula (calcipotriene is a white to almost white, crystalline compound): 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)-(11ß,16ß), 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): Calcipotriene and Betamethasone Dipropionate Topical Suspension Each gram of calcipotriene and betamethasone dipropionate topical suspension contains 50 mcg of calcipotriene and 0.643 mg of betamethasone dipropionate (equivalent to 0.5 mg of betamethasone) in a base of hydrogenated castor oil, mineral oil and polyoxypropylene stearyl ether. Calcipotriene and betamethasone dipropionate topical suspension is an odorless clear to slightly off-white suspension. Calcipotriene Chemical Structure Betamethasone Chemical Structure

Calcipotriene and betamethasone dipropionate topical suspension is indicated for the topical treatment of plaque psoriasis of the scalp in patients 12 years and older and plaque psoriasis of the scalp and body in patients 18 years and older. Additional pediatric use information is approved for LEO Pharma A/S’s Taclonex® (calcipotriene and betamethasone dipropionate) Topical Suspension. However, due to LEO Pharma A/S’s marketing exclusivity rights, this drug product is not labeled with that information. Calcipotriene and betamethasone dipropionate topical suspension is a combination of calcipotriene, a vitamin D analog, and betamethasone dipropionate, a corticosteroid, indicated for the topical treatment of plaque psoriasis of the scalp in patients 12 years and older and plaque psoriasis of the scalp and body in patients age 18 years and older. ( 1 )

Instruct patients to shake bottle prior to using calcipotriene and betamethasone dipropionate topical suspension. Apply calcipotriene and betamethasone dipropionate topical suspension to affected areas on the scalp and body once daily for up to 8 weeks. Calcipotriene and betamethasone dipropionate topical suspension should be discontinued when control is achieved. Instruct patients to wash their hands after applying the product. Inform patients that they should not take a bath or shower or wash their hair right after application of calcipotriene and betamethasone dipropionate topical suspension. Patients 12 to 17 years should not use more than 60 grams per week and patients 18 years and older should not use more than 100 grams per week. Calcipotriene and betamethasone dipropionate topical suspension should not be: Used with occlusive dressings unless directed by a healthcare provider. Used on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Applied to the scalp in the 12 hours before or after any chemical treatments to the hair. Calcipotriene and betamethasone dipropionate topical suspension is not for oral, ophthalmic, or intravaginal use. Shake bottle before use. ( 2 ) Apply calcipotriene and betamethasone dipropionate topical suspension to affected areas on the scalp and body once daily for up to 8 weeks. Discontinue therapy when control is achieved. ( 2 ) Patients age 12 to 17 years should not use more than 60 grams per week. ( 2 ) Adult patients should not use more than 100 grams per week. ( 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 )

The most common adverse reactions (≥ 1%) are folliculitis and burning sensation of skin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Additional pediatric use information is approved for LEO Pharma A/S’s Taclonex ® (calcipotriene and betamethasone dipropionate) Topical Suspension. However, due to LEO Pharma A/S’s marketing exclusivity rights, this drug product is not labeled with that information . 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 of the Scalp The rates of adverse reactions described below were from randomized, multicenter, vehicle- and/or active controlled clinical trials in adult subjects with psoriasis of the scalp [see Clinical Studies ( 14 )] . Subjects applied study product once daily for 8 weeks, and the median weekly dose was 12.6 grams. Adverse reactions that occurred in ≥1% of subjects treated with calcipotriene and betamethasone dipropionate topical suspension and at a rate higher than in subjects treated with vehicle are presented in Table 1. Table 1. Number and Percentage of Subjects with Adverse Reactions in Scalp Psoriasis Trials (Events Reported by ≥1% of Subjects and for Which a Relationship is Possible) Calcipotriene and betamethasone dipropionate topical suspension N=1,953 Betamethasone Dipropionate in vehicle N=1,214 Calcipotriene in vehicle N=979 Vehicle N=173 Event # of subjects (%) Folliculitis 16 (1%) 12 (1%) 5 (1%) 0 (0%) Burning sensation of skin 13 (1%) 10 (1%) 29 (3%) 0 (0%) Other less common adverse reactions (<1% but >0.1%) were, in decreasing order of incidence: acne, exacerbation of psoriasis, eye irritation, and pustular rash. In a 52-week trial, adverse reactions that were reported by >1% of subjects treated with calcipotriene and betamethasone dipropionate topical suspension were pruritus (3.6%), psoriasis (2.4%), erythema (2.1%), skin irritation (1.4%), and folliculitis (1.2%). Clinical Trials Conducted in Subjects 18 years and older with Psoriasis of the Body In randomized, multicenter, vehicle- and/or active controlled clinical trials in adult subjects with plaque psoriasis on non-scalp areas, 824 subjects applied calcipotriene and betamethasone dipropionate topical suspension once daily for 8 weeks [see Clinical Studies ( 14 )] . The median weekly dose was 22.6 grams. There were no adverse reactions that occurred in ≥1% of subjects treated with calcipotriene and betamethasone dipropionate topical suspension and at a rate higher than in subjects treated with vehicle. Other less common adverse reactions (<1% but >0.1%) were, in decreasing order of incidence: rash and folliculitis. Clinical Trials Conducted in Subjects 12 to 17 years with Psoriasis of the Scalp In two uncontrolled clinical trials, 109 subjects aged 12 to 17 years with plaque psoriasis of the scalp applied calcipotriene and betamethasone dipropionate topical suspension once daily for up to 8 weeks. The median weekly dose was 40 grams. Adverse reactions included acne, acneiform dermatitis and application site pruritus (0.9% each) [see Use in Specific Populations ( 8.4 ) and Clinical Pharmacology ( 12.2 )] . Additional pediatric use information is approved for LEO Pharma A/S’s Taclonex® (calcipotriene and betamethasone dipropionate) Topical Suspension. However, due to LEO Pharma A/S’s marketing exclusivity rights, this drug product is not labeled with that information. 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 topical corticosteroids included atrophy, striae, telangiectasias, itching, dryness, hypopigmentation, perioral dermatitis, secondary infection, and miliaria. Ophthalmic adverse reactions of cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported during use of topical corticosteroids, including topical betamethasone products.