READY F GET OR clearer skin IN TWELVE WEEKS Individual results may vary.

Not an actual patient.

Approved Uses TAZORAC® (tazarotene) Cream 0.1% is used to treat acne. TAZORAC® (tazarotene) Gel 0.1% is used to treat people with mild to moderate facial acne vulgaris. IMPORTANT SAFETY INFORMATION WARNINGS Retinoids may cause fetal harm when administered to a pregnant female. Do not use TAZORAC Cream and Gel if you are pregnant, attempting to become pregnant or at high risk of pregnancy. Consult your physician for adequate birth control measures if you are a female of child-bearing potential. To help assure that you are not pregnant when you begin use, your doctor will need to perform a pregnancy test within 2 weeks prior to starting use of TAZORAC Cream or Gel and/or begin taking TAZORAC Cream or Gel during a normal menstrual period. To report an adverse event, side effect, or product complaint, call or email: Phone: 1-866-665-2782; Fax: 510-595-8183; Email: [email protected]. Please see additional Important Safety Information on next page. Time for TAZORAC® (tazarotene) cream and gel 0.1%!

Set TAZORAC where you’ll see 3 steps to clearer skin: it every night and remember:

1. CLEANSE More doesn’t mean better. Gently wash face with warm water and a mild You don’t need a ton of TAZORAC for it to work, and cleanser, then pat skin dry. using more won’t give you clearer skin any faster—it may just irritate your skin. 2. MOISTURIZE Apply a moisturizer before TAZORAC. Moisturizing is a key step before applying 3. TREAT TAZORAC, so don’t forget it or skip it! Spread 1 pea-sized drop, once a day in the It may seem weird to use a moisturizer if your face is evening, over the affected areas of the face. Avoid naturally oily, but dermatologists agree even oily skin eyes, eyelids, and mouth. Wash hands thoroughly. needs to be moisturized.

IMPORTANT SAFETY INFORMATION (continued) WARNINGS (continued) TAZORAC Cream and Gel 0.1% should not be used if you are allergic to any of its ingredients. Please see complete Information for Patients for a list of ingredients. PRECAUTIONS TAZORAC Cream and Gel should not be used if you are also taking other drugs that increase your sensitivity to sunlight (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides). Inform your physician if you are taking any other medications. Use protective clothing and sunscreens of at least SPF 15 during the day when using TAZORAC Cream and Gel. Do not use TAZORAC Cream and Gel if you have sunburn, eczema, or other continuing skin condition. Use TAZORAC Cream and Gel with caution if you are using other topical products that might dry or irritate the skin.

Please see additional Important Safety Information on next page. Clearer skin is possible as early as 4 weeks

StickTolerability to your new skinTolerability care routine and youTolerability may notice an improvementTolerability in just 4 weeks, with full results at 12 weeks

Baseline Week 12 Baseline Week 12

Actual, unretouched photos of TAZORAC® (tazarotene) Cream and Gel 0.1% patients from clinical trials. In clinical trials, TAZORAC improved acne with 12 weeks of use. Actual results may vary. IMPORTANT SAFETY INFORMATION (continued) ADVERSE REACTIONS TAZORAC Cream and Gel 0.1% may cause serious side effects, including: • Skin irritation and allergic reactions (hypersensitivity). Tell your doctor if you develop hives, or itching, burning, redness, or peeling of your skin during treatment.

Please see full Prescribing Information and Patient Information. LEARER SKIN 2. Place TAZORAC® (tazarotene) C Cream or Gel 0.1% where you won’t miss it. Don’t let your busy schedule get in the way of treating is coming your acne. Keep the medication ! where you’ll remember to use it IN TWELVE WEEKS every night. Individual results may vary. 3. Remind yourself. Set a reminder 3 things to remember: on your phone or ask your parents to help you remember to use 1. Take selfies every week. Progress pics will help you and TAZORAC every single night. your doctor see how far you’ve come. Questions or concerns about treatment? Call your doctor. He or she wants you to succeed as much as you do.

IMPORTANT SAFETY INFORMATION WARNINGS Retinoids may cause fetal harm when administered to a pregnant female. Do not use TAZORAC Cream and Gel if you are pregnant, attempting to become pregnant or at high risk of pregnancy. Consult your physician for adequate birth control measures if you are a female of child-bearing potential. To help assure that you are not pregnant when you begin use, your doctor will need to perform a pregnancy test within 2 weeks prior to starting use of TAZORAC Cream or Gel and/or begin taking TAZORAC Cream or Gel during a normal menstrual period. Please see full Prescribing Information and Patient Information.

TAZORAC® is a registered trademark of Almirall, LLC. © Almirall, LLC. Exton, PA 19341. www.almirall.us. All rights reserved. US-TAZ-2000018 04-2020 HIGHLIGHTS OF PRESCRIBING INFORMATION ------WARNINGS AND PRECAUTIONS ------These highlights do not include all the information needed to use TAZORAC® Gel • Embryofetal Toxicity: TAZORAC Gel contains tazarotene, which is a teratogen. safely and effectively. See full prescribing information for TAZORAC® Gel. TAZORAC Gel is contraindicated in pregnancy. Females of child-bearing potential TAZORAC® (tazarotene) gel, 0.05% and 0.1%, for topical use should have a negative pregnancy test within 2 weeks prior to initiating treatment and Initial U.S. Approval: 1997 use an effective method of contraception during treatment. (5.1) ------INDICATIONS AND USAGE ------• Local Irritation: Excessive pruritus, burning, skin redness or peeling can occur. If these reactions occur, discontinue until the integrity of the skin has been restored, or • TAZORAC® Gel, 0.05% and 0.1% is a retinoid indicated for the topical treatment of consider reducing dosing frequency or in the case of psoriasis, consider switching to plaque psoriasis of up to 20% body surface area involvement. (1.1) the lower concentration. TAZORAC Gel should not be used on eczematous skin, as it • TAZORAC Gel, 0.1% is indicated for the topical treatment of mild to moderate facial may cause severe irritation. (5.2) acne vulgaris. (1.2) • Photosensitivity and Risk for Sunburn: Avoid exposure to sunlight, sunlamps, and Limitations of Use weather extremes. Wear sunscreen daily. TAZORAC Gel should be administered with caution if the patient is also taking drugs known to be photosensitizers. (5.3) • The safety of TAZORAC Gel use on more than 20% body surface area has not been established. (1.3) ------ADVERSE REACTIONS ------DOSAGE AND ADMINISTRATION ------• Plaque Psoriasis: Most common adverse reactions occurring in 10 to 30% of patients are pruritus, burning/stinging, erythema, worsening of psoriasis, irritation, and skin • Apply a thin layer of TAZORAC Gel only to the affected area once daily in the evening. pain. (6.1) (2.1, 2.2) • Acne Vulgaris: Most common adverse reactions occurring in 10 to 30% of patients are • Not for ophthalmic, oral, or intravaginal use. (2.2) desquamation, burning/stinging, dry skin, erythema and pruritus. (6.1) • If contact with eyes occurs, rinse thoroughly with water. (2.2) To report SUSPECTED ADVERSE REACTIONS, contact Allergan, Inc. at 1-800-678-1605 or ------DOSAGE FORMS AND STRENGTHS ------FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Gel, 0.05% and 0.1% (3) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. ------CONTRAINDICATIONS ------Revised: 08/2019 • Pregnancy (4, 8.1) • Hypersensitivity (4)

FULL PRESCRIBING INFORMATION: CONTENTS* 8 USE IN SPECIFIC POPULATIONS 1 INDICATIONS AND USAGE 8.1 Pregnancy 1.1 Plaque Psoriasis 8.2 Lactation 1.2 Acne Vulgaris 8.3 Females and Males of Reproductive Potential 1.3 Limitations of Use 8.4 Pediatric Use 2 DOSAGE AND ADMINISTRATION 8.5 Geriatric Use 2.1 Psoriasis 10 OVERDOSAGE 2.2 Acne 11 DESCRIPTION 3 DOSAGE FORMS AND STRENGTHS 12 CLINICAL PHARMACOLOGY 4 CONTRAINDICATIONS 12.1 Mechanism of Action 5 WARNINGS AND PRECAUTIONS 12.2 Pharmacodynamics 5.1 Embryofetal Toxicity 12.3 Pharmacokinetics 5.2 Local Irritation and Hypersensitivity Reactions 13 NONCLINICAL TOXICOLOGY 5.3 Photosensitivity and Risk for Sunburn 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 6 ADVERSE REACTIONS 14 CLINICAL STUDIES 6.1 Clinical Trials Experience 16 HOW SUPPLIED/STORAGE AND HANDLING 6.2 Postmarketing Experience 17 PATIENT COUNSELING INFORMATION 7 DRUG INTERACTIONS * Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Plaque Psoriasis TAZORAC® (tazarotene) Gel, 0.05% and 0.1% are indicated for the topical treatment of patients with plaque psoriasis of up to 20% body surface area involvement. 1.2 Acne Vulgaris TAZORAC (tazarotene) Gel, 0.1% is also indicated for the topical treatment of patients with facial acne vulgaris of mild to moderate severity. The efficacy of TAZORAC Gel in the treatment of acne previously treated with other retinoids or resistant to oral antibiotics has not been established. 1.3 Limitations of Use The safety of TAZORAC Gel use on more than 20% body surface area has not been established in psoriasis or acne [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. 2 DOSAGE AND ADMINISTRATION TAZORAC Gel is for topical use only. TAZORAC Gel is not for ophthalmic, oral, or intravaginal use. Avoid accidental transfer of TAZORAC Gel 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. 2.1 Psoriasis It is recommended that treatment starts with TAZORAC Gel, 0.05%, with strength increased to 0.1% if tolerated and medically indicated. Apply a thin film (2 mg/cm2) of TAZORAC Gel once per day, in the evening, to cover only the psoriatic lesions on no more than 20% of body surface area. If a bath or shower is taken prior to application, the skin should be dry before applying the gel. If emollients are used, they should be applied at least an hour before application of TAZORAC Gel. Because unaffected skin may be more susceptible to irritation, application of tazarotene to these areas should be carefully avoided. TAZORAC Gel was investigated for up to 12 months during clinical trials for psoriasis. 2.2 Acne Cleanse the face gently. After the skin is dry, apply a thin layer (2 mg/cm2) of TAZORAC Gel 0.1% once per day, in the evening, to the skin where acne lesions appear. Use enough to cover the entire affected area. TAZORAC Gel was investigated for up to 12 weeks during clinical trials for acne. Use effective sunscreens and wear protective clothing while using TAZORAC Gel [see Warnings and Precautions (5.3)]. 3 DOSAGE FORMS AND STRENGTHS Gel, 0.05% and 0.1%, in 30 g and 100 g tubes. Each gram of TAZORAC Gel, 0.05% and 0.1% contains 0.5 mg and 1 mg of tazarotene, respectively in a translucent, aqueous gel. 4 CONTRAINDICATIONS TAZORAC Gel 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)]. 5 WARNINGS AND PRECAUTIONS 5.1 Embryofetal Toxicity Based on data from animal reproduction studies, retinoid pharmacology and the potential for systemic absorption, TAZORAC Gel may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Tazarotene elicits malformations and developmental effects associated with retinoids after topical and oral administration to pregnant rats and rabbits during organogenesis. Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically over sufficient body surface area, exposure could be in the same order of magnitude as in orally treated animals. Although there may be less systemic exposure in the treatment of acne of the face alone due to less surface area for application, tazarotene is a teratogenic substance and causes fetal malformations in animals, and it is not known what level of exposure is required for teratogenicity in humans [see Clinical Pharmacology (12.3)]. There were thirteen reported pregnancies in subjects who participated in the clinical trials for topical tazarotene. Nine of the subjects had been treated with topical tazarotene, and the other four had been treated with vehicle. One of the subjects who was treated with tazarotene cream elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during the clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown. Females of Child-bearing Potential Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when TAZORAC Gel is used. The possibility that a female of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test should be obtained within 2 weeks prior to TAZORAC Gel therapy. TAZORAC Gel therapy should begin during a normal menstrual period [see Use in Specific Populations (8.1)]. 5.2 Local Irritation and Hypersensitivity Reactions Application of TAZORAC Gel may cause excessive irritation in the skin of certain sensitive individuals. Local reactions (including blistering and skin desquamation, pruritus, burning, erythema) and hypersensitivity adverse reactions (including urticaria) have been observed with topical tazarotene. If these adverse reactions occur, consider discontinuing the medication or reducing the dosing frequency, as appropriate, until the integrity of the skin is restored. Alternatively, patients with psoriasis who are being treated with the 0.1% concentration can be switched to the lower concentration. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. Therapy can be resumed, or the drug concentration or frequency of application can be increased as the patient becomes able to tolerate treatment. Concomitant topical medications and cosmetics that have a strong drying effect should be avoided. It is also advisable to "rest" a patient's skin until the effects of such preparations subside before treatment with TAZORAC Gel is initiated. TAZORAC Gel, should not be used on eczematous skin, as it may cause severe irritation. Weather extremes, such as wind or cold, may be more irritating to patients using TAZORAC Gel. 5.3 Photosensitivity and Risk for Sunburn Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided unless deemed medically necessary, and in such cases, exposure should be minimized during the use of TAZORAC Gel. Patients must be warned to use sunscreens and protective clothing when using TAZORAC Gel. Patients with sunburn should be advised not to use TAZORAC Gel until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using TAZORAC Gel. TAZORAC Gel should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. 6 ADVERSE REACTIONS 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)] 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. Psoriasis A total of 439 subjects 14 to 87 years of age were treated with TAZORAC Gel, 0.05% and 0.1% in two controlled clinical trials. The most frequent adverse events reported with TAZORAC Gel, 0.05% and 0.1% occurring in 10 to 30% of subjects, in descending order, included pruritus, burning/stinging, erythema, worsening of psoriasis, irritation, and skin pain. Reactions occurring in 1 to 10% of subjects included rash, desquamation, irritant contact dermatitis, skin inflammation, fissuring, bleeding, and dry skin. Increases in “psoriasis worsening” and “sun-induced erythema” were noted in some subjects over the 4th to 12th months of treatment as compared to the first three months of a 1 year study. In general, the incidence of adverse events with TAZORAC Gel 0.05% was 2 to 5% lower than that seen with TAZORAC Gel 0.1%. Acne A total of 596 subjects 12 to 44 years of age were treated with TAZORAC Gel, 0.05% and 0.1% in two controlled clinical trials. The most frequent adverse events reported during clinical trials with TAZORAC Gel, 0.1% in the treatment of acne occurring in 10 to 30% of subjects, in descending order, included desquamation, burning/stinging, dry skin, erythema and pruritus. Reactions occurring in 1 to 10% of subjects included irritation, skin pain, fissuring, localized edema and skin discoloration. 6.2 Postmarketing Experience 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. The following adverse reactions have been identified during postapproval use of tazarotene. 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. 7 DRUG INTERACTIONS No formal drug-drug interaction studies were conducted with TAZORAC Gel. In a trial of 27 healthy female subjects between the ages of 20–55 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 Cmax and AUC0-24 of tazarotenic acid were 28.9 ± 9.4 ng/mL and 120.6 ± 28.5 ng•hr/mL, respectively) 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. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, TAZORAC Gel may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Safety in pregnant females has not been established. The potential risk to the fetus outweighs the potential benefit to the mother from TAZORAC Gel during pregnancy; therefore, TAZORAC Gel should be discontinued as soon as pregnancy is recognized [see Contraindications (4), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)]. Limited case reports of pregnancy in females enrolled in clinical trials for TAZORAC Gel have not established a clear association with tazarotene and major birth defects or miscarriage risk. Because the exact timing and extent of exposure in relation to the gestational age are not certain, the significance of these findings is unknown. In animal reproduction studies with pregnant rats, tazarotene dosed topically during organogenesis at 0.5 times the maximum systemic exposure in subjects treated with the maximum recommended human dose (MRHD) of tazarotene gel, 0.1% resulted in reduced fetal body weights and reduced skeletal ossification. In animal reproduction studies with pregnant rabbits dosed topically with tazarotene gel at 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, there were single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. In animal reproduction studies with pregnant rats and rabbits, tazarotene dosed orally during organogenesis at 0.5 and 13 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1% resulted in malformations, fetal toxicity, developmental delays, and/or behavioral delays. In pregnant rats, tazarotene dosed orally prior to mating through early gestation resulted in decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations at doses approximately 2 times higher than the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1% [see Data]. The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In rats, a tazarotene gel, 0.05% formulation dosed topically during gestation days 6 through 17 at 0.25 mg/kg/day, which represented 0.5 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1% (i.e., 2 mg/cm2 over a 20% body surface area), resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel, which represented 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. When tazarotene was given orally to animals, developmental delays were seen in rats, and malformations and post-implantation loss were observed in rats and rabbits at doses producing 0.5 and 13 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%. In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, which represented 2 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, classic developmental effects of retinoids were observed including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights. A low incidence of retinoid-related malformations was observed at that dose. In a pre- and postnatal development toxicity study, topical administration of tazarotene gel (0.125 mg/kg/day) to pregnant female rats from gestation day 16 through lactation day 20 reduced pup survival, but did not affect the reproductive capacity of the offspring. Based on data from another study, the maximum systemic exposure in the rat would be 0.3 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%. 8.2 Lactation Risk Summary There is no information regarding the presence of tazarotene in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of 14C-tazarotene gel to the skin of lactating rats, radioactivity was detected in rat milk. The lack of clinical data during lactation precludes a clear determination of the risk of TAZORAC Gel to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TAZORAC Gel and any potential adverse effects on the breastfed child from TAZORAC Gel or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential within 2 weeks prior to initiating TAZORAC Gel therapy which should begin during a menstrual period. Contraception Females Based on animal studies, TAZORAC Gel may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with TAZORAC Gel. 8.4 Pediatric Use The safety and efficacy of TAZORAC Gel have not been established in pediatric patients with psoriasis or acne under the age of 12 years. 8.5 Geriatric Use Of the total number of subjects in clinical trials of TAZORAC Gel for plaque psoriasis, 163 were over the age of 65. Subjects over 65 years of age experienced more adverse events and lower treatment success rates after 12 weeks of use of TAZORAC Gel compared with those 65 years of age and younger. Currently there is no other clinical experience on the differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Tazarotene gel for the treatment of acne has not been clinically evaluated in persons over the age of 65. 10 OVERDOSAGE Excessive topical use of TAZORAC Gel, 0.05% and 0.1% may lead to marked redness, peeling, or discomfort [see Warnings and Precautions (5.2)]. TAZORAC Gel 0.05% and 0.1% are not for oral use. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other retinoids. If oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary. 11 DESCRIPTION TAZORAC (tazarotene) Gel, 0.05% and 0.1% is for topical use and contains the active ingredient, tazarotene. Each gram of TAZORAC Gel, 0.05% and 0.1% contains 0.5 and 1 mg of tazarotene, respectively in a translucent, aqueous gel. Tazarotene is a member of the acetylenic class of retinoids. Chemically, tazarotene is ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. The compound has an empirical formula of C21H21NO2S and molecular weight of 351.46. The structural formula is shown below: O

N O CH3 H3C CH3

S

TAZAROTENE TAZORAC Gel contains the following inactive ingredients: benzyl alcohol 1%;ascorbic acid; butylated hydroxyanisole; butylated hydroxytoluene; carbomer homopolymer type B; edetate disodium; hexylene glycol; poloxamer 407; polyethylene glycol 400; polysorbate 40; purified water; and tromethamine. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tazarotene is a retinoid prodrug which is converted to its active form, the carboxylic acid of tazarotene, by deesterification. Tazarotenic acid binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARβ, and RARγ, but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings for the treatment of plaque psoriasis and facial acne vulgaris is unknown. 12.2 Pharmacodynamics The pharmacodynamics of TAZORAC Gel in the treatment of plaque psoriasis and facial acne vulgaris are unknown. 12.3 Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Little parent compound could be detected in the plasma. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways. The half-life of tazarotenic acid was approximately 18 hours, following topical application of tazarotene to normal, acne or psoriatic skin. The human in vivo studies described below were conducted with tazarotene gel applied topically at approximately 2 mg/cm2 and left on the skin for 10 to 12 hours. Both the peak plasma concentration (Cmax) and area under the plasma concentration time curve (AUC) refer to the active metabolite only. Two single, topical dose studies were conducted using 14C-tazarotene gel. Systemic absorption, as determined from radioactivity in the excreta, was less than 1% of the applied dose (without occlusion) in six subjects with psoriasis and approximately 5% of the applied dose (under occlusion) in six healthy subjects. One non-radiolabeled single-dose study comparing the 0.05% gel to the 0.1% gel in healthy subjects indicated that the Cmax and AUC were 40% higher for the 0.1% gel.

After 7 days of topical dosing with measured doses of tazarotene 0.1% gel on 20% of the total body surface without occlusion in 24 healthy subjects, the Cmax for tazarotenic acid was

0.72 ± 0.58 ng/mL (mean ± SD) occurring 9 hours after the last dose, and the AUC0-24hr for tazarotenic acid was 10.1 ± 7.2 ng·hr/mL. Systemic absorption was 0.91 ± 0.67% of the applied dose. In a 14-day study in five subjects with psoriasis, measured doses of tazarotene 0.1% gel were applied daily by nursing staff to involved skin without occlusion (8 to 18% of total body surface area; mean ± SD: 13 ± 5%). The Cmax for tazarotenic acid was 12.0 ± 7.6 ng/mL occurring 6 hours after the final dose, and the AUC0-24hr for tazarotenic acid was 105 ± 55 ng·hr/mL. Systemic absorption was 14.8 ± 7.6% of the applied dose. Extrapolation of these results to represent dosing on 20% of total body surface yielded estimates for tazarotenic acid with Cmax of

18.9 ± 10.6 ng/mL and AUC0-24hr of 172 ± 88 ng·hr/mL. An in vitro percutaneous absorption study, using radiolabeled drug and freshly excised human skin or human cadaver skin, indicated that approximately 4 to 5% of the applied dose was in the stratum corneum (tazarotene: tazarotenic acid = 5:1) and 2 to 4% was in the viable epidermis-dermis layer (tazarotene: tazarotenic acid = 2:1) 24 hours after topical application of the gel. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter-term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in the rat 0.3 times that seen in subjects treated with the MRHD of tazarotene gel, 0.1%. A long-term study with topical administration of up to 0.1% tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Systemic exposure at the highest dose was 2 times that seen in subjects treated with the MRHD of tazarotene gel, 0.1%. Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test. No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat at the highest dose was 0.3 times that observed in subjects treated with the MRHD of tazarotene gel, 0.1%. No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1 mg/kg/day tazarotene, which produced systemic exposure that was approximately equivalent to that observed in subjects treated with the MRHD of tazarotene gel, 0.1%. No impairment of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through gestation day 7 with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose, which produced systemic exposure 2 times that observed in subjects treated with the MRHD of tazarotene gel, 0.1% [see Use in Specific Populations (8.1)]. 14 CLINICAL STUDIES Psoriasis: In two large vehicle-controlled clinical trials, TAZORAC Gel, 0.05% and 0.1% applied once daily for 12 weeks was significantly more effective than vehicle in reducing the severity of the clinical signs of plaque psoriasis covering up to 20% of body surface area. In one of the studies, subjects were followed up for an additional 12 weeks following cessation of therapy with TAZORAC Gel. Mean baseline scores and changes from baseline (reductions) after treatment in these two trials are shown in Table 1. Table 1. Plaque Elevation, Scaling, and Erythema in Two Controlled Clinical Trials for Psoriasis

TAZORAC® 0.05% Gel TAZORAC® 0.1% Gel Vehicle Gel Trunk/Arm/Leg Knee/Elbow Trunk/Arm/Leg Knee/Elbow Trunk/Arm/Leg Knee/Elbow Lesions Lesions Lesions Lesions Lesions Lesions N=108 N=111 N=108 N=111 N=108 N=112 N=108 N=112 N=108 N=113 N=108 N=113 Plaque B* 2.5 2.6 2.6 2.6 2.5 2.6 2.6 2.6 2.4 2.6 2.6 2.6 Elevation C-12* -1.4 -1.3 -1.3 -1.1 -1.4 -1.4 -1.5 -1.3 -0.8 -0.7 -0.7 -0.6 C-24* -1.2 -1.1 -1.1 -1.0 -0.9 -0.7 Scaling B* 2.4 2.5 2.5 2.6 2.4 2.6 2.5 2.7 2.4 2.6 2.5 2.7 C-12* -1.1 -1.1 -1.1 -0.9 -1.3 -1.3 -1.2 -1.2 -0.7 -0.7 -0.6 -0.6 C-24* -0.9 -0.8 -1.0 -0.8 -0.8 -0.7 Erythema B* 2.4 2.7 2.2 2.5 2.4 2.8 2.3 2.5 2.3 2.7 2.2 2.5 C-12* -1.0 -0.8 -0.9 -0.8 -1.0 -1.1 -1.0 -0.8 -0.6 -0.5 -0.5 -0.5 C-24* -1.1 -0.7 -0.9 -0.8 -0.7 -0.6 Plaque elevation, scaling, and erythema scored on a 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe. B*=Mean Baseline Severity: C-12*=Mean Change from Baseline at end of 12 weeks of therapy: C-24*=Mean Change from Baseline at week 24 (12 weeks after the end of therapy). Global improvement over baseline at the end of 12 weeks of treatment in these two trials is shown in Table 2. Table 2. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Psoriasis

TAZORAC® 0.05% Gel TAZORAC® 0.1% Gel Vehicle Gel N=81 N=93 N=79 N=69 N=84 N=91 100% improvement 2 (2%) 1 (1%) 0 0 1 (1%) 0 ≥75% improvement 23 (28%) 17 (18%) 30 (38%) 17 (25%) 10 (12%) 9 (10%) ≥50% improvement 42 (52%) 39 (42%) 51 (65%) 36 (52%) 28 (33%) 21 (23%) 1-49% improvement 21 (26%) 32 (34%) 18 (23%) 23 (33%) 27 (32%) 32 (35%) No change or worse 18 (22%) 22 (24%) 10 (13%) 10 (14%) 29 (35%) 38 (42%) The 0.1% gel was more effective than the 0.05% gel, but the 0.05% gel was associated with less local irritation than the 0.1% gel [see Adverse Reactions (6.1)]. Acne: In two large vehicle-controlled trials, TAZORAC Gel, 0.1% applied once daily was significantly more effective than vehicle in the treatment of facial acne vulgaris of mild to moderate severity. Percent reductions in lesion counts after treatment for 12 weeks in these two trials are shown in Table 3. Table 3. Reduction in Lesion Counts after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne

TAZORAC® 0.1% Gel Vehicle Gel N=150 N=149 N=148 N=149 Noninflammatory lesions 55% 43% 35% 27% Inflammatory lesions 42% 47% 30% 28% Total lesions 52% 45% 33% 27%

Global improvement over baseline at the end of 12 weeks of treatment in these two trials is shown in Table 4. Table 4. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne

TAZORAC® 0.1% Gel Vehicle Gel N=105 N=117 N=117 N=110 100% improvement 1 (1%) 0 0 0 ≥75% improvement 40 (38%) 21 (18%) 23 (20%) 11 (10%) ≥50% improvement 71 (68%) 56 (48%) 47 (40%) 32 (29%) 1-49% improvement 23 (22%) 49 (42%) 48 (41%) 46 (42%) No change or worse 11 (10%) 12 (10%) 22 (19%) 32 (29%) 16 HOW SUPPLIED/STORAGE AND HANDLING TAZORAC (tazarotene) Gel is a translucent, aqueous gel, available in concentrations of 0.05% and 0.1%. It is available in a collapsible aluminum tube with a tamper-evident aluminum membrane over the opening and a white propylene screw cap, in 30 g and 100 g sizes. TAZORAC Gel 0.05% 30 g NDC 16110-833-30 TAZORAC Gel 0.05% 100 g NDC 16110-833-10 TAZORAC Gel 0.1% 30 g NDC 16110-042-30 TAZORAC Gel 0.1% 100 g NDC 16110-042-10 Storage: Store at 20°C to 25°C (68°F to 77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F). 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryofetal Toxicity Inform females of reproductive potential of the potential risk to a fetus. Advise these patients to use effective contraception during treatment with TAZORAC Gel. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. Photosensitivity and Risk of Sunburn Advise patients to avoid excessive sun exposure and to use of sunscreens and protective measures (hat, visor). Advise patients to avoid using TAZORAC Gel if also taking other medicines may increase sensitivity to sunlight. Important Administration Instructions Advise the patient of the following: 1. For the patient with psoriasis, apply TAZORAC Gel only to psoriasis skin lesions, avoiding uninvolved skin. 2. If undue irritation (redness, peeling, or discomfort) occurs, reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides [see Dosage and Administration (2.1)]. 3. Moisturizers may be used as frequently as desired. 4. Patients with psoriasis may use a cream or lotion to soften or moisten skin at least 1 hour before applying TAZORAC Gel. 5. Avoid contact with the eyes. If TAZORAC Gel gets in or near eyes, rinse thoroughly with water. Seek medical attention if eye irritation continues. 6. TAZORAC Gel is for topical use only. Do not apply to eyes, mouth, or other mucous membrane. Not for ophthalmic, oral, or intravaginal use. 7. Wash hands thoroughly after applying TAZORAC Gel.

Revised: 08/2019

Distributed by Almirall, LLC Exton, PA 19341 © 2019 Almirall, Inc. All rights reserved. All trademarks are the property of their respective owners.

US-TAZ-2000023 04/20 PATIENT INFORMATION TAZORAC® (TAZ-or-ac) (tazarotene) Gel, 0.05% and 0.1%

Important information: TAZORAC Gel is for use on skin only. Do not use TAZORAC Gel in your eyes, mouth, or vagina.

What is the most important information I should know about TAZORAC Gel? TAZORAC Gel may cause birth defects if used during pregnancy. • Females must not be pregnant when they start using TAZORAC Gel or become pregnant during treatment with TAZORAC Gel. • For females who can become pregnant: o Your doctor will order a pregnancy test for you within 2 weeks before you begin treatment with TAZORAC Gel to be sure that you are not pregnant. Your doctor will decide when to do the test. o Begin treatment with TAZORAC Gel during a normal menstrual period. o Use an effective form of birth control during treatment with TAZORAC Gel. Talk with your doctor about birth control options that may be used to prevent pregnancy during treatment with TAZORAC Gel. o Stop using TAZORAC Gel and tell your doctor right away if you become pregnant while using TAZORAC Gel.

What is TAZORAC Gel? • TAZORAC Gel 0.05% and 0.1% is a prescription medicine used on the skin (topical) to treat people with stable plaque psoriasis on up to 20% of your body surface. • TAZORAC Gel 0.1% is also used on the skin to treat people with mild to moderate facial acne vulgaris. It is not known if TAZORAC Gel is: • safe and effective for use in children under 12 years of age. • effective for the treatment of acne in people who have been treated with retinoid medicines or have acne that does not respond to treatment with oral antibiotics. • safe if used over more than 20% of your body for the treatment of psoriasis or acne.

Who should not use TAZORAC Gel? Do not use TAZORAC Gel if you: • are pregnant or plan to become pregnant. See “What is the most important information I should know about TAZORAC Gel?” at the beginning of this leaflet. • are allergic to tazarotene or any of the ingredients in TAZORAC Gel. See the end of this leaflet for a complete list of ingredients in TAZORAC Gel.

What should I tell my doctor before using TAZORAC Gel? Before you use TAZORAC Gel, tell your doctor about all of your medical conditions, including if you: • have eczema or any other skin problems • are breastfeeding or plan to breastfeed. It is not known if TAZORAC Gel passes into your breast milk. Talk to your doctor about using TAZORAC Gel while breastfeeding. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines, vitamins, or supplements may make your skin more sensitive to sunlight. Also, tell your doctor about any cosmetics you use, including moisturizers, creams, lotions, or products that can dry out your skin. Keep a list of your medicines to show to your doctor and pharmacist when you get a new medicine.

How should I use TAZORAC Gel? • Use TAZORAC Gel exactly as your doctor tells you to use it. • Apply TAZORAC Gel 1 time each day, in the evening. • Do not get TAZORAC Gel in your eyes, on your eyelids, or in your mouth. If TAZORAC Gel gets in or near your eyes, rinse them well with water. Call your doctor or get medical help if you have eye irritation that does not go away. • Wash your hands after applying TAZORAC Gel. Follow these instructions for applying TAZORAC Gel: • If you have psoriasis: o If you shower or bathe before applying TAZORAC Gel, your skin should be dry before applying the gel. o You may use a cream or lotion to soften or moisten your skin at least 1 hour before you apply TAZORAC Gel. o Apply a thin layer of TAZORAC Gel to cover only the psoriasis lesions. • If you have acne: o Gently wash and dry your face before applying TAZORAC Gel. o Apply a thin layer of TAZORAC Gel to cover only the acne lesions. • If you swallow TAZORAC Gel, call your doctor or go to the nearest hospital emergency room right away. What should I avoid while using TAZORAC Gel? • Avoid sunlight, including sunlamps, during treatment with TAZORAC Gel. TAZORAC Gel can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get a severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight. • Talk to your doctor if you get a sunburn during treatment with TAZORAC Gel. If you get a sunburn, do not use TAZORAC Gel until your sunburn is healed. • Avoid using cosmetics or topical medicines that may make your skin more sensitive to sunlight or make your skin dry. • Avoid using TAZORAC Gel on unaffected skin or skin with eczema because it may cause severe irritation.

What are the possible side effects of TAZORAC Gel? TAZORAC Gel may cause serious side effects, including: • Skin irritation and allergic reactions (hypersensitivity). TAZORAC Gel may cause increased skin irritation (including blistering and skin peeling) and allergic reactions (including hives). Tell your doctor if you develop itching, burning, redness, blistering or peeling of your skin during treatment with TAZORAC Gel. If you develop skin irritation or hives, your doctor may tell you to temporarily stop using TAZORAC Gel until your skin heals, tell you to use TAZORAC Gel less often, or change your TAZORAC Gel dose. Also, wind or cold weather may be more irritating to your skin while you are using TAZORAC Gel. • Sensitivity to sunlight and risk of sunburn. See “What should I avoid while using TAZORAC Gel?” The most common side effects of TAZORAC Gel in people with psoriasis include itching, burning, redness, worsening of psoriasis, irritation and skin pain. The most common side effects of TAZORAC Gel in people with acne include peeling, burning, dry skin, redness and itching. These are not all the possible side effects of TAZORAC Gel. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store TAZORAC Gel? • Store TAZORAC Gel at 68°F to 77°F (20°C to 25°C). • Keep TAZORAC Gel and all medicines out of the reach of children.

General information about the safe and effective use of TAZORAC Gel. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TAZORAC Gel for a condition for which it was not prescribed. Do not give TAZORAC Gel to other people, even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about TAZORAC Gel that is written for health professionals.

What are the ingredients in TAZORAC Gel? Active ingredient: tazarotene Inactive ingredients: ascorbic acid, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, carbomer homopolymer type B, edetate disodium, hexylene glycol, poloxamer 407, polyethylene glycol 400, polysorbate 40, purified water, and tromethamine Distributed by: Almirall, LLC. Exton, PA 19341 © 2019 Almirall. All rights reserved. All trademarks are the property of their respective owners.

For more information call 1-800-678-1605 or go to www.tazorac.com.

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: August 2019

US-TAZ-2000023 04/20 HIGHLIGHTS OF PRESCRIBING INFORMATION ------WARNINGS AND PRECAUTIONS------These highlights do not include all the information needed to use TAZORAC® Cream • Embryofetal Toxicity: TAZORAC Cream contains tazarotene, which is a teratogenic safely and effectively. See full prescribing information for TAZORAC® Cream. substance. TAZORAC Cream is contraindicated in pregnancy. Females of child-bearing TAZORAC® (tazarotene) cream, 0.05% and 0.1%, for topical use potential should have a negative pregnancy test within 2 weeks prior to initiating treatment and use an effective method of contraception during treatment. (5.1) Initial U.S. Approval: 1997 • Local Irritation: Some individuals may experience excessive pruritus, burning, skin ------INDICATIONS AND USAGE------redness or peeling. If these effects occur, discontinue until the integrity of the skin has • TAZORAC® Cream 0.05% and 0.1% is a retinoid indicated for the topical treatment of been restored, or reduce dosing interval, or in the case of psoriasis, may switch to the plaque psoriasis. (1.1) lower concentration. TAZORAC Cream should not be used on eczematous skin, as it may cause severe irritation. (5.2) • TAZORAC Cream 0.1% is indicated for the topical treatment of acne vulgaris. (1.2) • Photosensitivity and Risk for Sunburn: Avoid exposure to sunlight, sunlamps, and ------DOSAGE AND ADMINISTRATION ------weather extremes. Wear sunscreen daily. TAZORAC Cream should be administered • Apply a thin layer of TAZORAC Cream only to the affected area once daily in the with caution if the patient is also taking drugs known to be photosensitizers. (5.3) evening. (2.1, 2.2) ------ADVERSE REACTIONS------• Not for ophthalmic, oral, or intravaginal use. (2.2) • Plaque psoriasis: Most common adverse reactions occurring in 10 to 23% of patients • If contact with eyes occurs, rinse thoroughly with water. (2.2) are pruritus, erythema, and burning. (6.1) ------DOSAGE FORMS AND STRENGTHS------• Acne Vulgaris: Most common adverse reactions occurring in 10 to 30% of patients are Cream, 0.05% and 0.1%. (3) desquamation, dry skin, erythema, and burning sensation. (6.1) ------CONTRAINDICATIONS------To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. • Pregnancy (4, 8.1) • Hypersensitivity (4) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 08/2019

FULL PRESCRIBING INFORMATION: CONTENTS* 7 DRUG INTERACTIONS 1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS 1.1 Plaque Psoriasis 8.1 Pregnancy 1.2 Acne Vulgaris 8.2 Lactation 2 DOSAGE AND ADMINISTRATION 8.3 Females and Males of Reproductive Potential 2.1 Important Administration Instructions 8.4 Pediatric Use 2.2 Psoriasis 8.5 Geriatric Use 2.3 Acne 10 OVERDOSAGE 3 DOSAGE FORMS AND STRENGTHS 11 DESCRIPTION 4 CONTRAINDICATIONS 12 CLINICAL PHARMACOLOGY 5 WARNINGS AND PRECAUTIONS 12.1 Mechanism of Action 5.1 Embryofetal Toxicity 12.3 Pharmacokinetics 5.2 Local Irritation and Hypersensitivity Reactions 13 NONCLINICAL TOXICOLOGY 5.3 Photosensitivity and Risk for Sunburn 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 6 ADVERSE REACTIONS 14 CLINICAL STUDIES 6.1 Clinical Trials Experience 16 HOW SUPPLIED/STORAGE AND HANDLING 6.2 Postmarketing Experience 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Plaque Psoriasis TAZORAC® (tazarotene) Cream, 0.05% and 0.1% are indicated for the topical treatment of patients with plaque psoriasis. 1.2 Acne Vulgaris TAZORAC (tazarotene) Cream, 0.1% is also indicated for the topical treatment of patients with acne vulgaris. 2 DOSAGE AND ADMINISTRATION 2.1 Important Administration Instructions TAZORAC Cream is for topical use only. TAZORAC Cream is not for ophthalmic, oral, or intravaginal use. If contact with mucous membranes occurs, rinse thoroughly with water [see Warnings and Precautions (5.2)]. Wash hands thoroughly after application. 2.2 Psoriasis It is recommended that treatment starts with TAZORAC Cream, 0.05%, with strength increased to 0.1% if tolerated and medically indicated. Apply a thin film (2 mg/cm2) of TAZORAC Cream once per day, in the evening, to cover only the psoriatic lesions. If a bath or shower is taken prior to application, the skin should be dry before applying the cream. If emollients are used, they should be applied at least an hour before application of TAZORAC Cream. Because unaffected skin may be more susceptible to irritation, application of TAZORAC Cream to these areas should be carefully avoided. 2.3 Acne Cleanse the face gently. After the skin is dry, apply a thin layer (2 mg/cm2) of TAZORAC Cream 0.1% once per day, in the evening, to the skin areas where acne lesions appear. Use enough to cover the entire affected area. Use effective sunscreens and wear protective clothing while using TAZORAC Cream [see Warnings and Precautions (5.3)]. 3 DOSAGE FORMS AND STRENGTHS Cream, 0.05% and 0.1%. Each gram of TAZORAC Cream, 0.05% and 0.1% contains 0.5 mg and 1 mg of tazarotene, respectively in a white cream base. 4 CONTRAINDICATIONS TAZORAC 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)]. 5 WARNINGS AND PRECAUTIONS 5.1 Embryofetal Toxicity Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically over sufficient body surface area, exposure could be in the same order of magnitude as in orally treated animals. Although there may be less systemic exposure in the treatment of acne of the face alone due to less surface area for application, tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans [see Clinical Pharmacology (12.3)]. There were thirteen reported pregnancies in subjects who participated in the clinical trials for topical tazarotene. Nine of the subjects were found to have been treated with topical tazarotene, and the other four had been treated with vehicle. One of the subjects who was treated with tazarotene cream elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown. Females of Child-bearing Potential Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when TAZORAC Cream is used. The possibility that a female of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test should be obtained within 2 weeks prior to TAZORAC Cream therapy. TAZORAC Cream therapy should begin during a menstrual period [see Use in Specific Populations (8.1)]. 5.2 Local Irritation and Hypersensitivity Reactions Local tolerability reactions (including blistering and skin desquamation) and hypersensitivity adverse reactions (including urticaria) have been observed with topical tazarotene. Application of TAZORAC Cream may cause excessive irritation in the skin of certain sensitive individuals. Some individuals may experience excessive pruritus, burning, skin redness or peeling. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the dosing should be reduced to an interval the patient can tolerate. However, efficacy at reduced frequency of application has not been established. Alternatively, patients with psoriasis who are being treated with the 0.1% concentration can be switched to the lower concentration. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. Therapy can be resumed, or the drug concentration or frequency of application can be increased as the patient becomes able to tolerate treatment. Concomitant topical medications and cosmetics that have a strong drying effect should be avoided. It is also advisable to "rest" a patient's skin until the effects of such preparations subside before use of TAZORAC Cream is begun. TAZORAC Cream, should not be used on eczematous skin, as it may cause severe irritation. Weather extremes, such as wind or cold, may be more irritating to patients using TAZORAC Cream. 5.3 Photosensitivity and Risk for Sunburn Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided unless deemed medically necessary, and in such cases, exposure should be minimized during the use of TAZORAC Cream. Patients must be warned to use sunscreens and protective clothing when using TAZORAC Cream. Patients with sunburn should be advised not to use TAZORAC Cream until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using TAZORAC Cream. TAZORAC Cream should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. 6 ADVERSE REACTIONS 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)] 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. In human dermal safety trials, TAZORAC Cream, 0.05% and 0.1% did not induce allergic contact sensitization, phototoxicity, or photoallergy. Psoriasis The most frequent adverse reactions reported with TAZORAC Cream, 0.05% and 0.1% occurring in 10 to 23% of subjects, in descending order, included pruritus, erythema, and burning. Reactions occurring in greater than 1 to less than 10% of subjects, in descending order, included irritation, desquamation, stinging, contact dermatitis, dermatitis, eczema, worsening of psoriasis, skin pain, rash, hypertriglyceridemia, dry skin, skin inflammation, and peripheral edema. TAZORAC Cream, 0.1% was associated with a greater degree of local irritation than the 0.05% cream. The rates of irritation adverse reactions reported during psoriasis trials with TAZORAC Cream, 0.1% were 0.1-0.4% higher than those reported for TAZORAC Cream, 0.05%. Acne The most frequent adverse reactions reported during clinical trials with TAZORAC Cream 0.1% in the treatment of acne, occurring in 10-30% of subjects, in descending order included desquamation, dry skin, erythema, and burning sensation. Reactions occurring in 1 to 5% of subjects included pruritus, irritation, face pain, and stinging. 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. 7 DRUG INTERACTIONS No formal drug-drug interaction studies were conducted with TAZORAC Cream. In a trial of 27 healthy female subjects between the ages of 20–55 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 Cmax and AUC0-24 of tazarotenic acid were 28.9 ± 9.4 ng/mL and 120.6 ± 28.5 ng∙hr/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. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, TAZORAC Cream may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Safety in pregnant females has not been established. The potential risk to the fetus outweighs the potential benefit to the mother from TAZORAC Cream during pregnancy; therefore, TAZORAC Cream should be discontinued as soon as pregnancy is recognized [see Contraindications (4), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)]. Limited case reports of pregnancy in females enrolled in clinical trials for TAZORAC Cream have not established a clear association with tazarotene and major birth defects or miscarriage risk. Because the exact timing and extent of exposure in relation to the gestational age are not certain, the significance of these findings is unknown. In animal reproduction studies with pregnant rats, tazarotene dosed topically during organogenesis at 2 times the maximum systemic exposure in subjects treated with the maximum recommended human dose (MRHD) of tazarotene cream, 0.1% resulted in reduced fetal body weights and reduced skeletal ossification. In animal reproduction studies with pregnant rabbits dosed topically with tazarotene gel at 26 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%, there was a single incident of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. In animal reproduction studies with pregnant rats and rabbits, tazarotene dosed orally during organogenesis at 2 and 52 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% resulted in malformations, fetal toxicity, developmental delays, and/or behavioral delays. In pregnant rats, tazarotene dosed orally prior to mating through early gestation resulted in decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations at doses approximately 7 times higher than the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% [see Data]. The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In rats, a tazarotene gel, 0.05% formulation dosed topically during gestation days 6 through 17 at 0.25 mg/kg/day, which represented 2 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% (i.e., 2 mg/cm2 over a 15% body surface area), resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel, which represented 26 times the maximum systemic exposure in subjects treated with MRHD of tazarotene cream, 0.1%, during gestation days 6 through 18, had a single incident of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. When tazarotene was given orally to animals, developmental delays were seen in rats, and malformations and post-implantation loss were observed in rats and rabbits at doses representing 2 and 52 times, respectively, the maximum systemic exposure seen in subjects treated with the MRHD of tazarotene cream, 0.1%. In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, which represented 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%, classic developmental effects of retinoids were observed including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights. A low incidence of retinoid-related malformations was observed at that dose. In a pre- and postnatal development toxicity study, topical administration of tazarotene gel (0.125 mg/kg/day) to pregnant female rats from gestation day 16 through lactation day 20 reduced pup survival, but did not affect the reproductive capacity of the offspring. Based on data from another study, the maximum systemic exposure in the rat would be equivalent to the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%. 8.2 Lactation Risk Summary There is no information regarding the presence of tazarotene in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of 14C-tazarotene gel to the skin of lactating rats, radioactivity was detected in rat milk. The lack of clinical data during lactation precludes a clear determination of the risk of TAZORAC Cream to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TAZORAC Cream and any potential adverse effects on the breastfed child from TAZORAC Cream or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential within 2 weeks prior to initiating TAZORAC Cream therapy which should begin during a menstrual period. Contraception Females Based on animal studies, TAZORAC Cream may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with TAZORAC Cream. 8.4 Pediatric Use The safety and efficacy of TAZORAC Cream have not been established in patients with psoriasis under the age of 18 years, or in patients with acne under the age of 12 years. 8.5 Geriatric Use TAZORAC Cream for the treatment of acne has not been clinically tested in persons 65 years of age or older. Of the total number of subjects in clinical trials of TAZORAC Cream for plaque psoriasis, 120 were over the age of 65. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Currently there is no other clinical experience on the differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. 10 OVERDOSAGE Excessive topical use of TAZORAC Cream, 0.05% and 0.1% may lead to marked redness, peeling, or discomfort [see Warnings and Precautions (5.2)]. TAZORAC Cream, 0.05% and 0.1% are not for oral use. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other retinoids. If oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary. 11 DESCRIPTION TAZORAC (tazarotene) Cream, 0.05% and 0.1% is for topical use and contains the active ingredient, tazarotene. Each gram of TAZORAC Cream, 0.05% and 0.1% contains 0.5 and 1 mg of tazarotene, respectively in a white cream base. Tazarotene is a member of the acetylenic class of retinoids. Chemically, tazarotene is ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. The compound has an empirical formula of

C21H21NO2S and molecular weight of 351.46. The structural formula is shown below: O

N O CH3 H3C CH3

S

TAZAROTENE TAZORAC Cream contains the following inactive ingredients: benzyl alcohol 1%; carbomer 1342; carbomer homopolymer type B; edetate disodium; medium chain triglycerides; mineral oil; purified water; sodium hydroxide; sodium thiosulfate; and sorbitan monooleate. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tazarotene is a retinoid prodrug which is converted to its active form, the carboxylic acid of tazarotene, by deesterification. Tazarotenic acid binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARβ, and RARγ, but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings is unknown. 12.3 Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Little parent compound could be detected in the plasma. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways. The half-life of tazarotenic acid was approximately 18 hours, following topical application of tazarotene to normal, acne or psoriatic skin. In a multiple dose trial with a once daily dose for 14 consecutive days in 9 psoriatic subjects (male=5; female=4), measured doses of TAZORAC Cream, 0.1% were applied by medical staff to involved skin without occlusion (5 to 35% of total body surface area: mean ± SD: 14 ± 11%). The Cmax of tazarotenic acid was 2.31 ± 2.78 ng/mL occurring 8 hours after the final dose, and the 2 AUC0-24h was 31.2 ± 35.2 ng∙hr/mL on day 15 in the five subjects who were administered clinical doses of 2 mg cream/cm . During clinical trials with TAZORAC Cream, 0.05% or 0.1% treatment for plaque psoriasis, three out of 139 subjects with their systemic exposure monitored had detectable plasma tazarotene concentrations, with the highest value at 0.09 ng/mL. Tazarotenic acid was detected in 78 out of 139 subjects (LLOQ = 0.05 ng/mL). Three subjects using tazarotene cream 0.1% had plasma tazarotenic acid concentrations greater than 1 ng/mL. The highest value was 2.4 ng/mL. However, because of the variations in the time of blood sampling, the area of psoriasis involvement, and the dose of tazarotene applied, actual maximal plasma levels are unknown.

TAZORAC Cream 0.1% was applied once daily to either the face (N=8) or to 15% of body surface area (N=10) of female subjects with moderate to severe acne vulgaris. The mean Cmax and AUC values of tazarotenic acid peaked at day 15 for both dosing groups during a 29 day treatment period. Mean Cmax and AUC0-24h values of tazarotenic acid from subjects in the 15% body surface area dosing group were more than 10 times higher than those from subjects in the face-only dosing group. The single highest Cmax throughout the trial period was 1.91 ng/mL on day 15 in the exaggerated dosing group. In the face-only group, the mean ± SD values of Cmax and AUC0-24h of tazarotenic acid on day 15 were 0.10 ± 0.06 ng/mL and 1.54 ± 1.01 ng∙hr/mL, respectively, whereas in the 15% body surface area dosing group, the mean ± SD values of Cmax and AUC0-24h of tazarotenic acid on day 15 were 1.20 ± 0.41 ng/mL and 17.01 ± 6.15 ng∙hr/mL, respectively. The steady state pharmacokinetics of tazarotenic acid had been reached by day 8 in the face-only and by day 15 in the 15% body surface area dosing groups. In a Phase 3 clinical trial, TAZORAC Cream, 0.1% was applied once daily for 12 weeks to each of 48 subjects (22 females and 26 males) with facial acne vulgaris. The mean ± SD values of plasma tazarotenic acid at weeks 4 and 8 were 0.078 ± 0.073 ng/mL (N=47) and 0.052 ± 0.037 ng/mL (N=42), respectively. The highest observed individual plasma tazarotenic acid concentration was 0.41 ng/mL at week 4 from a female subject. The magnitude of plasma tazarotenic acid concentrations appears to be independent of gender, age, and body weight. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in the rat equivalent to 0.6 times that seen in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/kg/cm2 over a 35% body surface area in a controlled pharmacokinetic study. This estimated systemic exposure in rats was 2 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% cream at 2 mg/cm2 over a 15% body surface area. A long-term topical application study of up to 0.1% of tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Systemic exposures at the highest dose was 3.9 times that seen in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm2 over a 35% body surface area in a controlled pharmacokinetic study, and 13 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm2 over a 15% body surface area. In evaluation of photo co-carcinogenicity, median time to onset of tumors was decreased, and the number of tumors increased in hairless mice following chronic topical dosing with intercurrent exposure to ultraviolet radiation at tazarotene concentrations of 0.001%, 0.005%, and 0.01% in a gel formulation for up to 40 weeks. Mutagenesis Tazarotene was found to be non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test. Impairment of Fertility No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat would be equivalent to 0.6 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm2 over a 35% body surface area in a controlled pharmacokinetic study, and 2 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm2 over a 15% body surface area. No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1 mg/kg/day tazarotene. That dose produced a systemic exposure that was 1.9 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm2 over a 35% body surface area, and 6.3 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm2 over a 15% body surface area. No impairment of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through gestation day 7 with oral doses up to 2 mg/kg/day of tazarotene. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose[see Use in Specific Populations (8.1)]. That dose produced a systemic exposure that was 3.4 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm2 over a 35% body surface area and 11 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm2 over a 15% body surface area. Reproductive capabilities of F1 animals, including F2 survival and development, were not affected by topical administration of tazarotene gel to female F0 parental rats from gestation day 16 through lactation day 20 at the maximum tolerated dose of 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat would be equivalent to 0.6 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm2 over a 35% body surface area, and 2 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm2 over a 15% body surface area. 14 CLINICAL STUDIES In two 12-week vehicle-controlled clinical trials, TAZORAC Cream, 0.05% and 0.1% was significantly more effective than vehicle in reducing the severity of stable plaque psoriasis. TAZORAC Cream, 0.1% and 0.05% demonstrated superiority over vehicle cream as early as 1 week and 2 weeks, respectively, after starting treatment. In these trials, the primary efficacy endpoint was “clinical success,” defined as the proportion of subjects with none, minimal, or mild overall lesional assessment at Week 12, and shown in Table 1. “Clinical success” was also significantly greater with TAZORAC Cream, 0.05% and 0.1% versus vehicle at most follow-up visits.

Table 1. Subject Numbers and Percentages for Overall Lesional Assessment Scores and “Clinical Success” at Baseline (BL), End of Treatment (Week 12) and 12 Weeks After Stopping Therapy (Week 24)# in Two Controlled Clinical Trials for Psoriasis TAZORAC Cream, 0.05% TAZORAC Cream, 0.1% Vehicle Cream Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 N=218 N=210 N=221 N=211 N=229 N=214 Score BL Wk 12 Wk 24 BL Wk 12 BL Wk 12 Wk 24 BL Wk 12 BL Wk 12 Wk 24 BL Wk 12 None (0) 0 1 1 0 2 0 0 0 0 6 0 0 1 0 1 (0.5%) (0.5%) (1%) (3%) (0.4%) (0.5%) Minimal (1) 0 11 12 0 7 0 12 14 0 11 0 7 6 0 1 (5%) (6%) (3%) (5%) (6%) (5%) (3%) (3%) (0.5%) Mild (2) 0 79 60 0 76 0 75 53 0 90 0 49 43 0 54 (36%) (28%) (36%) (34%) (24%) (43%) (21%) (19%) (25%) Moderate (3) 141 86 90 100 74 122 97 107 96 62 139 119 114 97 99 (65%) (39%) (41%) (48%) (35%) (55%) (44%) (48%) (45%) (29%) (61%) (52%) (50%) (45%) (46%) Severe (4) 69 39 51 80 36 91 36 46 86 29 81 51 61 93 47 (32%) (18%) (23%) (38%) (17%) (41%) (16%) (21%) (41%) (14%) (35%) (22%) (27%) (44%) (22%) Very Severe (5) 8 2 4 30 15 8 1 1 29 13 9 3 4 24 12 (4%) (0.9%) (2%) (14%) (7%) (4%) (0.5%) (0.5%) (14%) (6%) (4%) (1%) (2%) (11%) (6%) “Clinical Success” 0 91 73 0 85 0 87 67 0 107 0 56 50 0 56 (42%*) (33%*) (40%*) (39%*) (30%*) (51%*) (24%) (22%) (26%)

0 no plaque elevation above normal skin level; may have residual non-erythematous discoloration; no psoriatic scale 1 essentially flat with possible trace elevation; may have up to moderate erythema (red coloration); no psoriatic scale 2 slight but definite elevation of plaque above normal skin level; may have up to moderate erythema (red coloration); fine scales with some lesions partially covered 3 moderate elevation with rounded or sloped edges to plaque; moderate erythema (red coloration); somewhat coarser scales with most lesions partially covered 4 marked elevation with hard, sharp edges to plaque; severe erythema (very red coloration); thick scales with virtually all lesions covered and a rough surface 5 very marked elevation with very hard, sharp edges to plaque; very severe erythema (extreme red coloration); very coarse, thick scales with all lesions covered and a very rough surface Clinical Success defined as an overall lesional assessment score of none, minimal, or mild. # Trial 1 had post-treatment period observations for 12 weeks after stopping therapy, which were not part of Trial 2. * Denotes statistically significant difference for “Clinical Success” compared with vehicle. At the end of 12 weeks of treatment, TAZORAC Cream, 0.05% and 0.1% was consistently superior to vehicle in reducing the plaque thickness of psoriasis. Improvements in erythema and scaling were generally significantly greater with TAZORAC Cream, 0.05% and 0.1% than with vehicle. TAZORAC Cream, 0.1% was also generally more effective than TAZORAC Cream, 0.05% in reducing the severity of the individual signs of disease. However, TAZORAC Cream, 0.1% was associated with a greater degree of local irritation than TAZORAC Cream, 0.05%. Table 2. Mean Decreases in Plaque Elevation, Scaling and Erythema in Two Controlled Clinical Trials for Psoriasis TAZORAC Cream, 0.05% TAZORAC Cream, 0.1% Vehicle Cream Lesion Trunk/Arm/Leg Knee/Elbow All Treated Trunk/Arm/Leg Knee/Elbow All Treated Trunk/Arm/Leg Knee/Elbow All Treated lesions lesions lesions lesions lesions lesions

Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 N=218 N=210 N=218 N=210 N=218 N=210 N=221 N=211 N=221 N=211 N=221 N=211 N=229 N=214 N=229 N=214 N=229 N=214 Plaque B# 2.29 2.50 2.40 2.52 2.28 2.51 2.34 2.52 2.35 2.49 2.32 2.51 2.28 2.51 2.35 2.51 2.29 2.51 elevation C-12 -0.83* -0.98* -0.91* -1.04* -0.75* -0.90* -1.08* -1.25* -0.96* -1.21* -0.83* -1.08* -0.59 -0.69 -0.57 -0.68 -0.48 -0.61 C-24 -0.75* -0.73* -0.60* -0.87* -0.73* -0.63* -0.57 -0.49 -0.42 Scaling B# 2.26 2.45 2.47 2.60 2.32 2.47 2.37 2.45 2.40 2.57 2.36 2.53 2.34 2.46 2.45 2.61 2.31 2.53 C-12 -0.75 -0.90 -0.78* -0.98* -0.67* -0.80 -0.84* -1.06* -0.76* -1.13* -0.73* -1.03* -0.66 -0.79 -0.62 -0.76 -0.46 -0.70 C-24 -0.68 -0.62* -0.51* -0.79* -0.61* -0.59* -0.56 -0.45 -0.34 Erythema B# 2.26 2.51 2.17 2.40 2.23 2.48 2.25 2.53 2.17 2.42 2.21 2.51 2.24 2.47 2.17 2.34 2.24 2.47 C-12 -0.49 -0.65* -0.44 -0.66* -0.40 -0.62 -0.49 -0.82* -0.57* -0.82* -0.42* -0.78* -0.42 -0.46 -0.38 -0.44 -0.37 -0.47 C-24 -0.52 -0.44 -0.41 -0.55 -0.52* -0.39* -0.43 -0.34 -0.33

Plaque elevation, scaling and erythema scored on a 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe. B#=Mean Baseline Severity; C-12=Mean Change from Baseline at end of 12 weeks of therapy; C-24=Mean Change from Baseline at week 24 (12 weeks after the end of therapy). *Denotes statistically significant difference compared with vehicle. Acne: In two large vehicle-controlled trials, subjects age 12 years and over with facial acne vulgaris of a severity suitable for monotherapy with a topical agent were enrolled. After face cleansing in the evening, TAZORAC Cream, 0.1% was applied once daily to the entire face as a thin layer. TAZORAC Cream, 0.1% was significantly more effective than vehicle in the treatment of facial acne vulgaris. Efficacy results after 12 weeks of treatment are shown in Table 3:

Table 3. Efficacy Results after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne TAZORAC Cream, 0.1% Vehicle Cream Trial 1 Trial 2 Trial 1 Trial 2 N=218 N=206 N=218 N=205 Median Percent Reduction in • Noninflammatory lesions 46%* 41%* 27% 21% • Inflammatory lesions 41%* 44%* 27% 25% • Total lesions 44%* 42%* 24% 21% Percent of Subjects with No Acne or Minimal Acne 18%* 20%* 11% 6% Percent of Subjects with No Acne, Minimal Acne, or Mild Acne 55%* 53%* 36% 36% *Denotes statistically significant difference compared with vehicle. 16 HOW SUPPLIED/STORAGE AND HANDLING TAZORAC Cream is a white cream available in concentrations of 0.05% and 0.1%. It is supplied in a collapsible aluminum tube with a tamper-evident aluminum membrane over the opening and a white polypropylene screw cap, in 30 g and 60 g sizes.

TAZORAC Cream, 0.05% TAZORAC Cream, 0.1% 30 g NDC 16110-915-30 NDC 16110-916-30 60 g NDC 16110-915-60 NDC 16110-916-60

Storage: Store at 20°C to 25°C (68°F to 77°F). Excursions permitted from -5°C to 30°C (23°F to 86°F). 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryofetal Toxicity Inform females of reproductive potential of the potential risk to a fetus. Advise these patients to use effective contraception during treatment with TAZORAC Cream. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. Photosensitivity and Risk of Sunburn Advise patients to avoid excessive sun exposure and to use of sunscreens and protective measures (hat, visor). Advise patients to avoid using TAZORAC if also taking other medicines may increase sensitivity to sunlight. Important Administration Instructions Advise the patient of the following: 1. For the patient with psoriasis, apply TAZORAC Cream only to psoriasis skin lesions, avoiding uninvolved skin. 2. If undue irritation (redness, peeling, or discomfort) occurs, reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides [see Dosage and Administration (2.1)]. 3. Moisturizers may be used as frequently as desired. 4. Patients with psoriasis may use a cream or lotion to soften or moisten skin at least 1 hour before applying TAZORAC Cream. 5. Avoid contact with the eyes. If TAZORAC Cream gets in or near eyes, rinse thoroughly with water. Seek medical attention if eye irritation continues. 6. TAZORAC Cream is for topical use only. Do not apply to eyes, mouth, or other mucous membrane. Not for ophthalmic, oral, or intravaginal use. 7. Wash hands thoroughly after applying TAZORAC Cream.

Distributed by Almirall, LLC Exton, PA 19341 © 2019 Almirall, Inc. All rights reserved. All trademarks are the property of their respective owners.

US-TAZ-2000024 04/20 PATIENT INFORMATION TAZORAC® (TAZ-or-ac) (tazarotene) Cream, 0.05% and 0.1%

Important information: TAZORAC Cream is for use on skin only. Do not use TAZORAC Cream in your eyes, mouth, or vagina.

What is the most important information I should know about TAZORAC Cream? TAZORAC Cream may cause birth defects if used during pregnancy. • Females must not be pregnant when they start using TAZORAC Cream or become pregnant during treatment with TAZORAC Cream. • For females who are able to get pregnant: o Your doctor will order a pregnancy test for you within 2 weeks before you begin treatment with TAZORAC Cream to be sure that you are not pregnant. Your doctor will decide when to do the test. o Begin treatment with TAZORAC Cream during a normal menstrual period. o Use an effective form of birth control during treatment with TAZORAC Cream. Talk with your doctor about birth control options that may be used to prevent pregnancy during treatment with TAZORAC Cream. o Stop using TAZORAC Cream and tell your doctor right away if you become pregnant while using TAZORAC Cream.

What is TAZORAC Cream? • TAZORAC Cream 0.05% and 0.1% is a prescription medicine used on the skin (topical) to treat people with plaque psoriasis. • TAZORAC Cream 0.1% is also used on the skin to treat people with acne vulgaris. • It is not known if TAZORAC Cream is safe and effective for: o the treatment of plaque psoriasis in children under 18 years of age o the treatment of acne vulgaris in children under 12 years of age

Who should not use TAZORAC Cream? Do not use TAZORAC Cream if you: • are pregnant or plan to become pregnant. See “What is the most important information I should know about TAZORAC Cream?” at the beginning of this leaflet. • are allergic to tazarotene or any of the ingredients in TAZORAC Cream. See the end of this leaflet for a complete list of ingredients in TAZORAC Cream.

What should I tell my doctor before using TAZORAC Cream? Before you use TAZORAC Cream, tell your doctor about all of your medical conditions, including if you: • have eczema or any other skin problems • are breastfeeding or plan to breastfeed. It is not known if TAZORAC Cream passes into your breast milk. Talk to your doctor about using TAZORAC Cream while breastfeeding. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines, vitamins, or supplements may make your skin more sensitive to sunlight. Also, tell your doctor about any cosmetics you use, including moisturizers, creams, lotions, or products that can dry out your skin.

How should I use TAZORAC Cream? • Use TAZORAC Cream exactly as your doctor tells you to use it. • Apply TAZORAC Cream 1 time each day, in the evening. • Do not get TAZORAC Cream in your eyes, on your eyelids, or in your mouth. If TAZORAC Cream gets in or near your eyes, rinse them well with water. Call your doctor or get medical help if you have eye irritation that does not go away. • Wash your hands after applying TAZORAC Cream. Follow these instructions for applying TAZORAC Cream: • If you have psoriasis: o If you shower or bathe before applying TAZORAC Cream, your skin should be dry before applying the cream. o You may use a cream or lotion to soften or moisten your skin at least 1 hour before you apply TAZORAC Cream. o Apply a thin layer of TAZORAC Cream to cover only the psoriasis lesions. • If you have acne: o Gently wash and dry your face before applying TAZORAC Cream. o Apply a thin layer of TAZORAC Cream to cover only the acne lesions. • If you swallow TAZORAC Cream, call your doctor or go to the nearest hospital emergency room right away. What should I avoid while using TAZORAC Cream? • Avoid sunlight, including sunlamps, during treatment with TAZORAC Cream. TAZORAC Cream can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get a severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight. • Talk to your doctor if you get a sunburn during treatment with TAZORAC Cream. If you get a sunburn, do not use TAZORAC Cream until your sunburn is healed. • Avoid using cosmetics or topical medicines that may make your skin more sensitive to sunlight or make your skin dry. • Avoid using TAZORAC Cream on unaffected skin or skin with eczema because it may cause severe irritation.

What are the possible side effects of TAZORAC Cream? TAZORAC Cream may cause serious side effects, including: • Skin irritation and allergic reactions (hypersensitivity). TAZORAC Cream may cause increased skin irritation and hives. Tell your doctor if you develop hives, or itching, burning, redness, or peeling of your skin during treatment with TAZORAC Cream. If you develop hives or skin irritation, your doctor may tell you to stop using TAZORAC Cream until your skin heals, tell you to use TAZORAC Cream less often, or change your TAZORAC Cream dose. Also, wind or cold weather may be more irritating to your skin while you are using TAZORAC Cream. • Sensitivity to sunlight and risk of sunburn. See “What should I avoid while using TAZORAC Cream?” The most common side effects of TAZORAC Cream in people with psoriasis include itching, redness and burning. The most common side effects of TAZORAC Cream in people with acne include peeling, dry skin, redness and burning. These are not all the possible side effects of TAZORAC Cream. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store TAZORAC Cream? • Store TAZORAC Cream at room temperature between 68°F to 77°F (20°C to 25°C). • Keep TAZORAC Cream and all medicines out of the reach of children.

General information about the safe and effective use of TAZORAC Cream. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TAZORAC Cream for a condition for which it was not prescribed. Do not give TAZORAC Cream to other people, even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about TAZORAC Cream that is written for health professionals.

What are the ingredients in TAZORAC Cream? Active ingredient: tazarotene Inactive ingredients: benzyl alcohol 1%, carbomer 1342, carbomer homopolymer type B, edetate disodium, medium chain triglycerides, mineral oil, purified water, sodium hydroxide, sodium thiosulfate, and sorbitan monooleate Distributed by: Almirall, LLC. Exton, PA 19341 © 2019 Almirall. All rights reserved. All trademarks are the property of their respective owners.

For more information call 1-800-678-1605 or go to www.tazorac.com.

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: August 2019

US-TAZ-2000024 04/20