TAZAROTENE

Tazarotene cream, 0.1% is for topical use and contains the active ingredient, tazarotene. Each gram of tazarotene cream, 0.1% contains 1 mg of tazarotene in a white cream base. Tazarotene is a member of the acetylenic class of retinoids. Chemically, tazarotene is ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl] nicotinate. The compound has an empirical formula of C 21 H 21 NO 2 S and molecular weight of 351.46. The structural formula is shown below: Tazarotene Cream contains the following inactive ingredients: carbomer copolymer type B, carbomer homopolymer type B, edetate disodium, medium-chain triglycerides, mineral oil, purified water, sodium hydroxide (to adjust pH), sodium thiosulfate, and sorbitan monooleate. Chemical Structure

Tazarotene cream, 0.1% is indicated as an adjunctive agent for use in the mitigation (palliation) of facial fine wrinkling, facial mottled hyper-and hypopigmentation, and benign facial lentigines in patients who use comprehensive skin care and sunlight avoidance programs. Tazarotene cream, 0.1% is a retinoid indicated as an adjunctive agent for use in the mitigation (palliation) of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines in patients who use comprehensive skin care and sunlight avoidance programs. ( 1 ) Limitations of Use: Does not eliminate or prevent wrinkles or restore more youthful skin. ( 1 ) Does not repair sun damaged skin or reverse photoaging. ( 1 ) Safety and effectiveness for the prevention or treatment of actinic keratoses, skin neoplasms, or lentigo maligna have not been established. ( 1 , 5.4 ) Limitations of Use: Tazarotene cream does not eliminate or prevent wrinkles or restore more youthful skin. Tazarotene cream does not reverse photoaging or repair sun damaged skin; tazarotene cream does not mitigate coarse or deep wrinkling, tactile roughness, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, or dermal elastosis. The safety and the effectiveness of tazarotene cream for the prevention or treatment of actinic keratoses, skin neoplasms, or lentigo maligna have not been established.

Apply a pea-sized amount of tazarotene cream to lightly cover the entire face once daily at bedtime. ( 2 ) If contact with eyes occurs, rinse thoroughly with water. ( 2 ) Not for ophthalmic, oral, or intravaginal use. ( 2 ) 2.1 Assessment Prior to Treatment Initiation Obtain a pregnancy test within 2 weeks prior to tazarotene cream therapy. Initiate tazarotene cream therapy during a menstrual period [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , 8.3) ] . Carefully assess facial pigmented lesions of concern by a qualified physician (e.g., dermatologist) before application of tazarotene cream [see Warnings and Precautions (5.4) ] . 2.2 Important Administration Instructions Avoid accidental transfer of tazarotene cream into eyes, mouth, or other mucous membranes. If contact with mucous membranes occurs, rinse thoroughly with water [see Warnings and Precautions (5.2) ] . Wash hands thoroughly after application. Emollients or moisturizers can be applied either before or after applying tazarotene cream. However, ensure that the first cream or lotion has absorbed into the skin and has dried completely before subsequent cream or lotion application. Use facial moisturizers as frequently as desired [see Warnings and Precautions (5.2) ]. Tazarotene cream is for topical use only. Tazarotene cream is not for ophthalmic, oral, or intravaginal use. Use effective sunscreens and wear protective clothing while using tazarotene cream [see Warnings and Precautions (5.3) ]. 2.3 Dosage and Administration Instructions Remove any makeup before applying tazarotene cream to the face. Dry the skin before applying the cream after face washing, bathing, or showering. Apply a pea-sized amount once a day at bedtime to lightly cover the entire face, including the eyelids, if desired. Wash hands thoroughly after application.

Tazarotene cream is contraindicated in: Pregnancy. Retinoids may cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1 , 8.3) ] . Individuals who have known hypersensitivity to any of its components. [see Warnings and Precautions (5.2) ]. Pregnancy. ( 4 , 8.1 ) Known Hypersensitivity. ( 4 )

The following serious adverse reactions are discussed in more detail in other sections of the labeling: Embryofetal toxicity [see Warnings and Precautions (5.1) ] Photosensitivity and Risk of Sunburn [see Warnings and Precautions (5.3) ] Most common adverse events (occurring in ≥10% of patients) are desquamation, erythema, burning sensation, dry skin, skin irritation, and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 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 clinical practice. The most frequent adverse reactions reported with tazarotene cream, 0.1% that occurred in greater than 10% of subjects, included desquamation, erythema, burning sensation, and dry skin (in descending order). Reactions that occurred in 1 to 10% of subjects, included skin irritation, pruritus, irritant contact dermatitis, stinging, rash, and cheilitis (in descending order). Common adverse events that occurred at a rate of at least 1% and at a higher rate in the tazarotene cream group than in the vehicle group in the clinical trials are presented in the following table. TABLE OF ADVERSE EVENTS SEEN IN 24-WEEK CLINICAL TRIALS WITH TAZAROTENE CREAM 0.1% Adverse Event Tazarotene Cream, 0.1% N=567 Vehicle N=564 Desquamation 40% 3% Erythema 34% 3% Burning Sensation 26% <1% Dry Skin 16% 3% Irritation Skin 10% 1% Pruritus 10% 1% Irritant Contact Dermatitis 8% 1% Stinging 3% <1% Rash 3% 1% Cheilitis 1% 0% A few subjects reported adverse events at Week 0; however, for patients who were treated with tazarotene cream, the highest number of new reports for each adverse event was at Week 2. When combining data from the two trials, 5.3% of subjects in the tazarotene cream group and 0.9% of subjects in the vehicle group discontinued because of adverse events. Overall, 20/567 (3.5%) subjects in the tazarotene cream group and 16/564 (2.8%) subjects in the vehicle group reported adverse events (including edema, irritation, and inflammation) directly related to the eye or eyelid. The majority of these conditions were mild. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of tazarotene. Because these 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. Skin and subcutaneous tissue disorders: blister, dermatitis, urticaria, skin exfoliation, skin discoloration (including skin hyperpigmentation or skin hypopigmentation), swelling at or near application sites, and pain.

No formal drug-drug interaction studies were conducted with tazarotene cream. In a trial of 27 healthy female subjects between the ages of 20 to 55 years receiving a combination oral contraceptive tablet containing 1 mg norethindrone and 35 mcg ethinyl estradiol, concomitant use of tazarotene administered as 1.1 mg orally (mean ± SD C max and AUC 0-24 of tazarotenic acid were 28.9 ± 9.4 ng/mL and 120.6 ± 28.5 ng*h/mL) did not affect the pharmacokinetics of norethindrone and ethinyl estradiol over a complete cycle. The impact of tazarotene on the pharmacokinetics of progestin only oral contraceptives (i.e., minipills) has not been evaluated.

Storage: Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].