Browse the corpus

1 INDICATIONS AND USAGE FABIOR ® (tazarotene) Foam, 0.1% is indicated for the topical treatment of acne vulgaris in patients 12 years of age or older. FABIOR Foam is a retinoid indicated for the topical treatment of acne vulgaris in patients 12 years of age or older. ( 1 )

2 DOSAGE AND ADMINISTRATION FABIOR Foam is for topical use only. FABIOR Foam is not for oral, ophthalmic, or intravaginal use. FABIOR Foam should be applied once daily in the evening after washing with a mild cleanser and fully drying the affected area. Dispense a small amount of foam into the palm of the hand. Using fingertips, apply only enough foam to lightly cover the entire affected areas of the face and/or upper trunk with a thin layer; gently massage the foam into the skin until the foam disappears. Avoid the eyes, lips, and mucous membranes. Wash hands after application. Patients may use moisturizer as needed. If undue irritation (redness, peeling, or discomfort) occurs, patients should reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides. Treatment should be discontinued if irritation persists. Apply a thin layer to the entire affected areas of the face and/or upper trunk once daily in the evening. Avoid the eyes, lips, and mucous membranes. Wash hands after application. ( 2 )

4 CONTRAINDICATIONS FABIOR Foam is contraindicated in pregnancy. FABIOR Foam may cause fetal harm when administered to a pregnant woman. Tazarotene elicits teratogenic and developmental effects associated with retinoids after topical or systemic administration in rats and rabbits [see Use in Specific Populations (8.1) ]. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient apprised of the potential hazard to the fetus [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ]. Pregnancy. ( 4 , 8.1 )

5 WARNINGS AND PRECAUTIONS Fetal Risk: FABIOR Foam contains tazarotene, which is a teratogenic substance. FABIOR Foam is contraindicated in pregnancy. Females of childbearing 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 ) Local Irritation: Use with caution in patients with a history of local tolerability reactions or local hypersensitivity. ( 5.2 ) Potential Irritant Effect with Concomitant Topical Medications: Use with caution because a cumulative irritant effect may occur. ( 5.3 ) Photosensitivity and Risk for Sunburn: Avoid exposure to sunlight, sunlamps, and weather extremes. Wear sunscreen daily. ( 5.4 ) Contents are flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. ( 5.5 ) 5.1 Fetal Risk 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. Tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans [see Clinical Pharmacology (12) ] . There were 5 reported pregnancies in subjects who participated in clinical trials for topical tazarotene foam. One of the subjects was found to have been treated with topical tazarotene for 25 days, 2 were treated with vehicle foam, and the other 2 did not receive either tazarotene foam or vehicle foam. The subjects were discontinued from the trials when their pregnancy was reported. The one pregnant woman who was inadvertently exposed to topical tazarotene during the clinical trial delivered a full-term healthy infant. Females of Childbearing Potential: Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when tazarotene foam is used. The possibility of pregnancy should be considered in females of child-bearing potential at the time of institution of therapy. A negative serum or urine result for pregnancy test having a sensitivity down to at least 25 mIU/mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to therapy with FABIOR Foam, which should begin during a normal menstrual period for females of childbearing potential. Advise patients of the need to use an effective method of contraception to avoid pregnancy [see Use in Specific Populations (8.1) ] . 5.2 Local Irritation FABIOR Foam should be used with caution in patients with a history of local tolerability reactions or local hypersensitivity. Retinoids should not be used on abraded or eczematous skin, as they may cause severe irritation. Contact with the mouth, eyes, and mucous membranes should be avoided. In case of accidental contact, rinse well with water. Some individuals may experience skin redness, peeling, burning or excessive pruritus. 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. Weather extremes, such as wind or cold, may be more irritating to patients using FABIOR Foam.

hould 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. Weather extremes, such as wind or cold, may be more irritating to patients using FABIOR Foam. 5.3 Potential Irritant Effect with Concomitant Topical Medications Concomitant topical acne therapy should be used with caution because a cumulative irritant effect may occur. If irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. Treatment should be discontinued if the irritation persists. 5.4 Photosensitivity and Risk for Sunburn Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided. Patients must be warned to use sunscreens and protective clothing when using FABIOR Foam. Patients with sunburn should be advised not to use FABIOR Foam 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 FABIOR Foam and ensure that the precautions are observed [see FDA-approved patient labeling ]. Due to the potential for photosensitivity resulting in greater risk for sunburn, FABIOR Foam should be used with caution in patients with a personal or family history of skin cancer. FABIOR Foam 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. 5.5 Flammability The propellant in FABIOR Foam is flammable. Instruct the patient to avoid fire, flame, and/or smoking during and immediately following application.

6 ADVERSE REACTIONS Most common adverse reactions reported at an incidence ≥6% are application site irritation, application site dryness, application site erythema, and application site exfoliation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data reflect exposure to FABIOR Foam in 744 subjects with acne vulgaris. Subjects were aged 12 to 45 years and were treated once daily in the evening for 12 weeks. Adverse reactions reported in ≥ 1% of subjects treated with FABIOR Foam are presented in Table 1. Most adverse reactions were mild to moderate in severity. Severe adverse reactions represented 3.0% of the subjects treated. Overall, 2.7% (20/744) of subjects discontinued FABIOR Foam because of local skin reactions. Table 1. Incidence of Adverse Reactions in ≥1 % of Subjects Treated with FABIOR Foam FABIOR Foam N = 744 Vehicle Foam N = 741 Patients with any adverse reaction, n (%) 163 (22) 19 (3) Application site irritation 107 (14) 9 (1) Application site dryness 50 (7) 8 (1) Application site erythema 48 (6) 3 (<1) Application site exfoliation 44 (6) 3 (<1) Application site pain 9 (1) 0 Application site photosensitivity (including sunburn) 8 (1) 3 (<1) Application site pruritus 7 (1) 3 (<1) Application site dermatitis 6 (1) 1 (<1) Additional adverse reactions that were reported in <1% of subjects treated with FABIOR Foam included application site reactions (including discoloration, discomfort, edema, rash, and swelling), dermatitis, impetigo, and pruritus. Local skin reactions, dryness, erythema, and peeling actively assessed by the investigator and burning/stinging and itching reported by the subject were evaluated at baseline, during treatment, and end of treatment. During the 12 weeks of treatment, each local skin reaction peaked at Week 2 and gradually reduced thereafter with the continued use of FABIOR Foam.

<table width="75%"><caption>Table 1. Incidence of Adverse Reactions in &#x2265;1 % of Subjects Treated with FABIOR Foam</caption><col width="60%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">FABIOR Foam N = 744 </th><th styleCode="Rrule">Vehicle Foam N = 741 </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Patients with any adverse reaction, n (%)</td><td styleCode="Rrule">163 (22)</td><td styleCode="Rrule">19 (3)</td></tr><tr><td styleCode="Lrule Rrule">Application site irritation</td><td styleCode="Rrule">107 (14)</td><td styleCode="Rrule">9 (1)</td></tr><tr><td styleCode="Lrule Rrule">Application site dryness</td><td styleCode="Rrule">50 (7)</td><td styleCode="Rrule">8 (1)</td></tr><tr><td styleCode="Lrule Rrule">Application site erythema</td><td styleCode="Rrule">48 (6)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site exfoliation</td><td styleCode="Rrule">44 (6)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site pain</td><td styleCode="Rrule">9 (1)</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule">Application site photosensitivity (including sunburn)</td><td styleCode="Rrule">8 (1)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site pruritus</td><td styleCode="Rrule">7 (1)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site dermatitis</td><td styleCode="Rrule">6 (1)</td><td styleCode="Rrule">1 (&lt;1)</td></tr></tbody></table>

7 DRUG INTERACTIONS No formal drug-drug interaction studies were conducted with FABIOR Foam. Concomitant dermatologic medications and cosmetics that have a strong drying effect should be avoided. It is recommended to postpone treatment until the effects of these products subside before use of FABIOR Foam is started. Concomitant use with oxidizing agents, such as benzoyl peroxide, may cause degradation of tazarotene and may reduce the clinical efficacy of tazarotene. If combination therapy is required, they should be applied at different times of the day (e.g., one in the morning and the other in the evening). The impact of tazarotene on the pharmacokinetics of progestin-only oral contraceptives (i.e., minipills) has not been evaluated. 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 did not affect the pharmacokinetics of norethindrone and ethinyl estradiol over a complete cycle. Avoid concomitant dermatologic medications and cosmetics that have a strong drying effect. ( 7 )

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy FABIOR Foam is contraindicated in pregnancy [see Contraindications (4) ]. There are no adequate and well-controlled studies with FABIOR Foam in pregnant women. FABIOR Foam is contraindicated in females who are or may become pregnant [see Contraindications (4) ]. Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when FABIOR Foam 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 serum or urine result for pregnancy test having a sensitivity down to at least 25 mIU/mL for hCG should be obtained within 2 weeks prior to therapy with FABIOR Foam, which should begin during a normal menstrual period for females of childbearing potential. In rats, tazarotene 0.05% gel administered topically during gestation days 6 through 17 at 0.25 mg/kg/day resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. Systemic exposure (AUC) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits were 15 and 166 times, respectively, the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. As with other retinoids, when tazarotene was administered orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at doses 13 and 325 times, respectively, the AUC to tazarotenic acid in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. In female rats orally administered 2 mg/kg/day tazarotene from 15 days before mating through gestation day 7, a number of 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 also observed. AUC in rats was 42 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. 8.3 Nursing Mothers After single topical doses of 14 C-tazarotene to the skin of lactating rats, radioactivity was detected in milk, suggesting that there would be transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. The safe use of FABIOR Foam during lactation has not been established. A decision should be made whether to discontinue breastfeeding or to discontinue therapy with FABIOR Foam taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. 8.4 Pediatric Use The safety and effectiveness of FABIOR Foam in pediatric patients younger than 12 years have not been established. Clinical studies of FABIOR Foam included 860 patients aged 12 to 17 years with acne vulgaris. 8.5 Geriatric Use FABIOR Foam for the treatment of acne has not been clinically evaluated in persons over the age of 65.

8.1 Pregnancy FABIOR Foam is contraindicated in pregnancy [see Contraindications (4) ]. There are no adequate and well-controlled studies with FABIOR Foam in pregnant women. FABIOR Foam is contraindicated in females who are or may become pregnant [see Contraindications (4) ]. Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when FABIOR Foam 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 serum or urine result for pregnancy test having a sensitivity down to at least 25 mIU/mL for hCG should be obtained within 2 weeks prior to therapy with FABIOR Foam, which should begin during a normal menstrual period for females of childbearing potential. In rats, tazarotene 0.05% gel administered topically during gestation days 6 through 17 at 0.25 mg/kg/day resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. Systemic exposure (AUC) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits were 15 and 166 times, respectively, the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. As with other retinoids, when tazarotene was administered orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at doses 13 and 325 times, respectively, the AUC to tazarotenic acid in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. In female rats orally administered 2 mg/kg/day tazarotene from 15 days before mating through gestation day 7, a number of 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 also observed. AUC in rats was 42 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area.

8.3 Nursing Mothers After single topical doses of 14 C-tazarotene to the skin of lactating rats, radioactivity was detected in milk, suggesting that there would be transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. The safe use of FABIOR Foam during lactation has not been established. A decision should be made whether to discontinue breastfeeding or to discontinue therapy with FABIOR Foam taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

8.4 Pediatric Use The safety and effectiveness of FABIOR Foam in pediatric patients younger than 12 years have not been established. Clinical studies of FABIOR Foam included 860 patients aged 12 to 17 years with acne vulgaris.

10 OVERDOSAGE Excessive topical application of FABIOR Foam may lead to marked redness, peeling, or discomfort. [see Warnings and Precautions (5.2) ]. Management of accidental ingestion or excessive application to the skin should be as clinically indicated.

11 DESCRIPTION FABIOR (tazarotene) Foam, 0.1% contains the compound tazarotene, a member of the acetylenic class of retinoids. It is for topical use only. Chemically, tazarotene is ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. The structural formula is represented below: Molecular Formula: C 21 H 21 NO 2 S Molecular Weight: 351.46 Tazarotene is a pale yellow to yellow substance. FABIOR Foam contains tazarotene, 1 mg/g, in aqueous-based white to off-white foam vehicle consisting of butylated hydroxytoluene, ceteareth-12, citric acid anhydrous, diisopropyl adipate, light mineral oil, potassium citrate monohydrate, potassium sorbate, purified water, and sorbic acid. FABIOR Foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/n-butane/isobutane) propellant. Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tazarotene is a retinoid prodrug that is converted to its active form, the cognate carboxylic acid of tazarotene, by rapid deesterification in animals and man. Tazarotenic acid binds to all 3 members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ and RARγ and may modify gene expression. The clinical significance of these findings is unknown. The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene's therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and anti-inflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and cross- linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown. 12.2 Pharmacodynamics The pharmacodynamics of FABIOR Foam are unknown. 12.3 Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. 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. Systemic exposure following topical application of FABIOR Foam 0.1% was evaluated in one trial. Patients aged 15 years and older with moderate-to-severe acne applied approximately 3.7 grams of FABIOR Foam 0.1% (N = 13) to approximately 15% body surface area (face, upper chest, upper back, and shoulders) once daily for 22 days. On Day 22, the mean (±SD) tazarotenic acid C max was 0.43 (±0.19) ng/mL, the AUC 0 - 24h was 6.98 (±3.56) ng∙h/mL, and the half-life was 21.7 (±15.7) hours. The median T max was 6 hours (range: 4.4 to 12 hours). The AUC 0-24h for tazarotenic acid was approximately 50-fold higher compared with the parent compound tazarotene. The mean (±SD) half-life of tazarotene was 8.1 (±3.7) hours. Accumulation was observed upon repeated once-daily dosing as the tazarotenic acid predose concentrations were measurable in the majority of subjects. Steady state was attained within 22 days of daily application. Once-daily dosing resulted in little to no accumulation of tazarotene as predose concentrations were mostly below the quantitation limit throughout the study.

12.1 Mechanism of Action Tazarotene is a retinoid prodrug that is converted to its active form, the cognate carboxylic acid of tazarotene, by rapid deesterification in animals and man. Tazarotenic acid binds to all 3 members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ and RARγ and may modify gene expression. The clinical significance of these findings is unknown. The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene's therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and anti-inflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and cross- linked envelope formation in cultured human keratinocytes. 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. 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. Systemic exposure following topical application of FABIOR Foam 0.1% was evaluated in one trial. Patients aged 15 years and older with moderate-to-severe acne applied approximately 3.7 grams of FABIOR Foam 0.1% (N = 13) to approximately 15% body surface area (face, upper chest, upper back, and shoulders) once daily for 22 days. On Day 22, the mean (±SD) tazarotenic acid C max was 0.43 (±0.19) ng/mL, the AUC 0 - 24h was 6.98 (±3.56) ng∙h/mL, and the half-life was 21.7 (±15.7) hours. The median T max was 6 hours (range: 4.4 to 12 hours). The AUC 0-24h for tazarotenic acid was approximately 50-fold higher compared with the parent compound tazarotene. The mean (±SD) half-life of tazarotene was 8.1 (±3.7) hours. Accumulation was observed upon repeated once-daily dosing as the tazarotenic acid predose concentrations were measurable in the majority of subjects. Steady state was attained within 22 days of daily application. Once-daily dosing resulted in little to no accumulation of tazarotene as predose concentrations were mostly below the quantitation limit throughout the study.

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 risk. 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 rats approximately 2 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. A long-term topical application study 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 with vehicle control animals. AUC at the highest dose in mice was 49 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. In evaluation of photocarcinogenicity, median time to onset of tumors was decreased and the number of tumors increased in hairless mice following chronic topical dosing with 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 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 was observed 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 at the 0.125 mg/kg/day dose in rats would be equivalent to 7.6 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% 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. AUC at the highest dose in rats was 23 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. No effect on parameters 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 [see Pregnancy (8.1) ]. AUC at the highest dose in rats was 42 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% 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 AUC in rats would be equivalent to 7.6 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area.

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 risk. 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 rats approximately 2 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. A long-term topical application study 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 with vehicle control animals. AUC at the highest dose in mice was 49 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. In evaluation of photocarcinogenicity, median time to onset of tumors was decreased and the number of tumors increased in hairless mice following chronic topical dosing with 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 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 was observed 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 at the 0.125 mg/kg/day dose in rats would be equivalent to 7.6 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% 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. AUC at the highest dose in rats was 23 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. No effect on parameters 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 [see Pregnancy (8.1) ]. AUC at the highest dose in rats was 42 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% 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 AUC in rats would be equivalent to 7.6 times the AUC in acne patients treated with 2 mg/cm 2 of FABIOR Foam 0.1% over a 15% body surface area.

14 CLINICAL STUDIES In 2 multi-center, randomized, double-blind, vehicle-controlled trials, a total of 1,485 subjects with moderate-to-severe acne vulgaris were randomized 1:1 to FABIOR Foam or vehicle applied once daily for 12 weeks. Acne severity was evaluated using lesion counts and the 6-point Investigator's Global Assessment (IGA) scale (see Table 2 ). At baseline, 80% of subjects were graded as "moderate" or Grade 3 and 20% were graded as "severe" or Grade 4 on the IGA scale. At baseline, subjects had an average of 79.8 total lesions of which the mean number of inflammatory lesions was 31.9 and the mean number of non-inflammatory lesions was 47.8. Subjects ranged in age from 12 to 45 years, with 860 (58%) subjects aged 12 to 17 years; 428 (29%) subjects aged 18 to 25 years; 143 (10%) subjects aged 26 to 35 years and 54 (4%) subjects aged 36 to 45 years. Subjects enrolled in the trials by race were white (77%), black (15%), Asian (4%), and other (4%). Hispanics comprised 18% of the population. An equal number of males (49%) and females (51%) were enrolled. Treatment success was defined as a score of "clear" (Grade 0) or "almost clear" (Grade 1) and at least 2-grade improvement from the baseline score to Week 12. Table 2. Investigator's Global Assessment Scale Grade Description 0 Clear Clear skin with no inflammatory or non-inflammatory lesions. 1 Almost clear Rare non-inflammatory lesions with no more than rare papules. 2 Mild Greater than Grade 1, some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions). 3 Moderate Greater than Grade 2, up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion. 4 Severe Greater than Grade 3, up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions. 5 Very severe Many non-inflammatory and inflammatory lesions and more than a few nodular lesions. May have cystic lesions. Absolute and percent reductions in lesion counts and the IGA scale after 12 weeks of treatment in these 2 trials are shown in Table 3. Each trial needed to have a statistically significant reduction in 2 out of 3 lesion counts at Week 12. Table 3. Reductions in Lesion Counts and Improvements in Investigator's Global Assessment at Week 12 Trial 1 Trial 2 FABIOR Foam N = 371 Vehicle Foam N = 372 FABIOR Foam N = 373 Vehicle Foam N = 369 Inflammatory Lesions Mean absolute reduction from Baseline 18.0 14.0 18.0 15.0 Mean percent reduction from Baseline 58% 45% 55% 45% Non-inflammatory Lesions Mean absolute reduction from Baseline 28.0 17.0 26.0 18.0 Mean percent reduction from Baseline 55% 33% 57% 41% Total Lesions Mean absolute reduction from Baseline 46.0 31.0 43.0 33.0 Mean percent reduction from Baseline 56% 39% 56% 43% Investigator's Global Assessment (IGA), n (%) Minimum 2-grade improvement and IGA of 0 or 1 107 (29%) 60 (16%) 103 (28%) 49 (13%)

<table ID="T2" width="90%"><caption>Table 2. Investigator&apos;s Global Assessment Scale</caption><col width="10%" align="center" valign="top"/><col width="10%" align="left" valign="top"/><col width="80%" align="left" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Grade</th><th/><th align="center" styleCode="Rrule">Description</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">0</td><td styleCode="Rrule">Clear</td><td styleCode="Rrule">Clear skin with no inflammatory or non-inflammatory lesions.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">1</td><td styleCode="Rrule">Almost clear</td><td styleCode="Rrule">Rare non-inflammatory lesions with no more than rare papules.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">2</td><td styleCode="Rrule">Mild</td><td styleCode="Rrule">Greater than Grade 1, some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions).</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">3</td><td styleCode="Rrule">Moderate</td><td styleCode="Rrule">Greater than Grade 2, up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">4</td><td styleCode="Rrule">Severe</td><td styleCode="Rrule">Greater than Grade 3, up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">5</td><td styleCode="Rrule">Very severe</td><td styleCode="Rrule">Many non-inflammatory and inflammatory lesions and more than a few nodular lesions. May have cystic lesions.</td></tr></tbody></table>

lammatory lesions, but no more than a few nodular lesions.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">5</td><td styleCode="Rrule">Very severe</td><td styleCode="Rrule">Many non-inflammatory and inflammatory lesions and more than a few nodular lesions. May have cystic lesions.</td></tr></tbody></table> <table width="90%"><caption>Table 3. Reductions in Lesion Counts and Improvements in Investigator&apos;s Global Assessment at Week 12</caption><col width="50%" align="left" valign="top"/><col width="12%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><col width="12%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule"/><th colspan="2" styleCode="Rrule">Trial 1</th><th colspan="2" styleCode="Rrule">Trial 2</th></tr><tr><th styleCode="Lrule Rrule"/><th>FABIOR Foam N = 371 </th><th align="left" styleCode="Rrule">Vehicle Foam N = 372 </th><th>FABIOR Foam N = 373 </th><th align="left" styleCode="Rrule">Vehicle Foam N = 369 </th></tr></thead><tbody><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Inflammatory Lesions</content></td><td/><td styleCode="Rrule"/><td/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Mean absolute reduction from Baseline</td><td>18.0</td><td styleCode="Rrule">14.0</td><td>18.0</td><td styleCode="Rrule">15.0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Mean percent reduction from Baseline</td><td>58%</td><td styleCode="Rrule">45%</td><td>55%</td><td styleCode="Rrule">45%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Non-inflammatory Lesions</content></td><td/><td styleCode="Rrule"/><td/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Mean absolute reduction from Baseline</td><td>28.0</td><td styleCode="Rrule">17.0</td><td>26.0</td><td styleCode="Rrule">18.0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Mean percent reduction from Baseline</td><td>55%</td><td styleCode="Rrule">33%</td><td>57%</td><td styleCode="Rrule">41%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Total Lesions</content></td><td/><td styleCode="Rrule"/><td/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Mean absolute reduction from Baseline</td><td>46.0</td><td styleCode="Rrule">31.0</td><td>43.0</td><td styleCode="Rrule">33.0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Mean percent reduction from Baseline</td><td>56%</td><td styleCode="Rrule">39%</td><td>56%</td><td styleCode="Rrule">43%</td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Investigator&apos;s Global Assessment (IGA),</content>n (%) </td><td/><td styleCode="Rrule"/><td/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Minimum 2-grade improvement <content styleCode="italics">and</content>IGA of 0 or 1 </td><td>107 (29%)</td><td styleCode="Rrule">60 (16%)</td><td>103 (28%)</td><td styleCode="Rrule">49 (13%)</td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied: FABIOR Foam, 0.1% (1 mg/g) is a white to off-white foam, supplied as follows: 100-g aluminum can NDC 51862-295-10 Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP-controlled room temperature. Store upright. Protect from freezing. Flammable. Avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C). Shake can before use. Hold can at an upright angle and press firmly to dispense.

<table width="50%" styleCode="Noautorules"><col width="50%" align="left" valign="top"/><col width="50%" align="left" valign="top"/><tbody><tr><td>100-g aluminum can</td><td>NDC 51862-295-10</td></tr></tbody></table>

Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP-controlled room temperature. Store upright. Protect from freezing. Flammable. Avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C). Shake can before use. Hold can at an upright angle and press firmly to dispense.

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) . Inform the patient of the following: Fetal risk associated with FABIOR Foam for females of childbearing potential. Advise patients to use an effective method of contraception during treatment to avoid pregnancy. Advise the patient to stop medication if she becomes pregnant and call her doctor. If undue irritation (redness, peeling, or discomfort) occurs, reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides. Do not place FABIOR Foam in the freezer. Avoid exposure of the treated areas to either natural or artificial sunlight, including tanning beds and sun lamps. Avoid contact with the eyes. If FABIOR Foam gets in or near their eyes, to rinse thoroughly with water. Wash their hands after applying FABIOR Foam. Avoid fire, flame, or smoking during and immediately following application since FABIOR Foam is flammable. Keep out of the reach of children. Not for ophthalmic, oral, or intravaginal use.

Patient Information FABIOR ® (fab' ee ore) (tazarotene) Foam IMPORTANT: For skin use only. Do not get FABIOR Foam in your eyes, mouth, or vagina. Read the Patient Information that comes with FABIOR Foam before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. What is FABIOR Foam? FABIOR Foam is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older. It is not known if FABIOR Foam is safe and effective in children under 12 years of age. Who should not use FABIOR Foam? Do not use FABIOR Foam if you are pregnant or plan to become pregnant . FABIOR Foam may harm your unborn baby, if used during pregnancy. If you are a female who can become pregnant: Use an effective method of birth control during treatment with FABIOR Foam. Talk with your doctor about birth control methods that are right for you during treatment with FABIOR Foam. Your doctor should do a blood or urine pregnancy test within 2 weeks before you begin to use FABIOR Foam to be sure you are not pregnant. If you have menstrual periods, begin using FABIOR Foam during a normal menstrual period to help assure that you are not pregnant when you begin use. Stop using FABIOR Foam and call your doctor right away if you become pregnant during treatment with FABIOR Foam. What should I tell my doctor before using FABIOR Foam? Before you use FABIOR Foam, tell your doctor if you: or a family member have or had skin cancer. have eczema. have had a reaction to topical products in the past. have any condition that makes you sensitive to light. have any other medical conditions. are pregnant or plan to become pregnant. See " Who should not use FABIOR Foam? " are breastfeeding or plan to breastfeed. It is not known if tazarotene passes into your breast milk. You and your doctor should decide if you will use FABIOR Foam or breastfeed. You should not do both. Talk to your doctor about the best way to feed your baby if you use FABIOR Foam. Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you: use other medicines or products that make your skin dry take other medicines that may increase your sensitivity to sunlight Ask your doctor or pharmacist if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine. How should I use FABIOR Foam? Use FABIOR Foam exactly as your doctor tells you to. Do not use more FABIOR Foam than prescribed and do not use it more often than your doctor tells you to. If you are a female and have menstrual periods, begin using FABIOR Foam during a normal menstrual period to help assure that you are not pregnant when you begin use. See " Who should not use FABIOR Foam? " FABIOR Foam is flammable. Avoid fire, flame, and smoking during and right after you apply FABIOR Foam. Gently clean the affected area (face and/or upper trunk) with a mild cleanser and dry completely before using FABIOR Foam. Apply FABIOR Foam one time each day, before going to bed, to the affected areas (face and/or upper trunk) where you have acne lesions. Use enough foam to cover the entire affected area with a thin film of FABIOR Foam.

ected area (face and/or upper trunk) with a mild cleanser and dry completely before using FABIOR Foam. Apply FABIOR Foam one time each day, before going to bed, to the affected areas (face and/or upper trunk) where you have acne lesions. Use enough foam to cover the entire affected area with a thin film of FABIOR Foam. Keep FABIOR Foam away from your eyes, mouth, and vagina. If FABIOR Foam comes into contact with your eyes, rinse them well with water. Wash your hands after applying FABIOR Foam. If you use too much FABIOR Foam, you may get redness, peeling, or skin irritation in the treated area. Call your doctor if this happens, or if you accidentally swallow FABIOR Foam. Follow your doctor's directions for other routine skin care and the use of make-up. You may also use a moisturizer as needed. Instructions for applying FABIOR Foam 1. Shake the FABIOR Foam can before use. 2. Remove cap from can. See Figure A . Figure A 3. Hold the FABIOR Foam can upright at a slight angle and press the nozzle. See Figure B . Figure B 4. Dispense a small amount of FABIOR Foam into the palm of your hand. See Figure C . Figure C 5. Use the fingertips of your other hand to apply enough FABIOR Foam to cover the affected area with a thin layer. Gently rub the foam into the affected area until it disappears into the skin. See Figure D . Figure D 6. Wash hands after applying FABIOR Foam. See Figure E . Figure E Avoid getting FABIOR Foam in your eyes, mouth, or vagina. What should I avoid while using FABIOR Foam? Avoid using abrasive soaps or cleansers that might dry or irritate your skin, unless your doctor tells you it is ok. Avoid sunlight. FABIOR Foam can make your skin sensitive to sunlight and the light from sunlamps or tanning beds. You could get a sunburn. Use sunscreen and protective clothing during the day if you must be in sunlight. Avoid using FABIOR Foam if you have a sunburn. If you have a sunburn, wait until it is fully healed before using FABIOR Foam. Talk to your doctor before using FABIOR Foam if you are sensitive to sunlight, take medications that increase your sensitivity to sunlight, or you must spend a lot of time in the sun for your job. Avoid weather extremes, such as wind and cold, because they may irritate your skin more while you are using FABIOR Foam. What are the possible side effects of FABIOR Foam? FABIOR Foam may harm your unborn baby, if used during pregnancy. Do not use FABIOR Foam during pregnancy. See " Who should not use FABIOR Foam? " The most common side effects of FABIOR Foam are: burning or stinging dry skin red skin peeling or flaking skin Sometimes these symptoms can become severe and may be uncomfortable. Tell your doctor if these side effects become uncomfortable for you. Your doctor may tell you to stop using FABIOR Foam until your skin heals and your symptoms improve, or to use FABIOR Foam less often to help you tolerate it better. These are not all the possible side effects of FABIOR Foam. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088. You may also report side effects to Mayne Pharma at 1-844-825-8500. How should I s tore FABIOR Foam? Store FABIOR Foam at room temperature, between 68°F to 77°F (20°C to 25°C). Store FABIOR Foam upright. Do not freeze FABIOR Foam. FABIOR Foam is flammable. Keep the can away from fire and heat. Do not spray FABIOR Foam near fire or direct heat. Do not puncture the can or throw it into a fire, even if the can is empty. Keep FABIOR Foam and all medicines out of the reach of children. General Information about FABIOR Foam Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets.

FABIOR Foam near fire or direct heat. Do not puncture the can or throw it into a fire, even if the can is empty. Keep FABIOR Foam and all medicines out of the reach of children. General Information about FABIOR Foam Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use FABIOR Foam for a condition for which it was not prescribed. Do not give FABIOR Foam to other people even if they have the same symptoms that you have. It may harm them. This Patient Information leaflet summarizes the most important information about FABIOR Foam. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about FABIOR Foam that is written for health professionals. What are the ingredients in FABIOR Foam? Active ingredient: tazarotene Inactive ingredients: butylated hydroxytoluene, ceteareth-12, citric acid anhydrous, diisopropyl adipate, light mineral oil, potassium citrate monohydrate, potassium sorbate, purified water, and sorbic acid. The foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/n-butane/isobutane) propellant. This Patient Information has been approved by the U.S. Food and Drug Administration FABIOR is a registered trademark of Mayne Pharma LLC. ©2016 Mayne Pharma. All rights reserved. Distributed by: Mayne Pharma Raleigh, NC 27609 02/2023 Figure A Figure B Figure C Figure D Figure E

1 INDICATIONS AND USAGE TAZORAC ® Gel, 0.05% and 0.1% is a retinoid indicated for the topical treatment of plaque psoriasis of up to 20% body surface area involvement. ( 1.1 ) TAZORAC Gel, 0.1% is indicated for the topical treatment of mild to moderate facial acne vulgaris. ( 1.2 ) Limitations of Use The safety of TAZORAC Gel use on more than 20% body surface area has not been established. ( 1.3 ) 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. Apply a thin layer of TAZORAC Gel only to the affected area once daily in the evening. ( 2.1 , 2.2 ) Not for ophthalmic, oral, or intravaginal use. ( 2.2 ) If contact with eyes occurs, rinse thoroughly with water. ( 2.2 ) 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/cm 2 ) 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/cm 2 ) 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. Gel, 0.05% and 0.1% ( 3 )

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 )]. Pregnancy ( 4 , 8.1 ) Hypersensitivity ( 4 )

5 WARNINGS AND PRECAUTIONS Embryofetal Toxicity: TAZORAC Gel contains tazarotene, which is a teratogen. TAZORAC Gel is contraindicated in pregnancy. Females of child-bearing 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 ) 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 consider reducing dosing frequency or in the case of psoriasis, consider switching to the lower concentration. TAZORAC Gel should not be used on eczematous skin, as it may cause severe irritation. ( 5.2 ) Photosensitivity and Risk for Sunburn: Avoid exposure to sunlight, sunlamps, and 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 ) 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.

e 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 )] Plaque Psoriasis: Most common adverse reactions occurring in 10 to 30% of patients are pruritus, burning/stinging, erythema, worsening of psoriasis, irritation, and skin pain. ( 6.1 ) Acne Vulgaris: Most common adverse reactions occurring in 10 to 30% of patients are desquamation, burning/stinging, dry skin, erythema and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Allergan, Inc. at 1-800-678-1605 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. 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 C max and AUC 0-24 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/cm 2 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.

opically 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 14 C-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.

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/cm 2 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.

opically 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%.

8.5 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: 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. The structural formula for 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.

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: RARα, 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/cm 2 and left on the skin for 10 to 12 hours. Both the peak plasma concentration (C max ) and area under the plasma concentration time curve (AUC) refer to the active metabolite only. Two single, topical dose studies were conducted using 14 C-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 C max 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 C max for tazarotenic acid was 0.72 ± 0.58 ng/mL (mean ± SD) occurring 9 hours after the last dose, and the AUC 0-24hr 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 C max for tazarotenic acid was 12.0 ± 7.6 ng/mL occurring 6 hours after the final dose, and the AUC 0-24hr 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 C max of 18.9 ± 10.6 ng/mL and AUC 0-24hr 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.

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: RARα, 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.

12.3 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/cm 2 and left on the skin for 10 to 12 hours. Both the peak plasma concentration (C max ) and area under the plasma concentration time curve (AUC) refer to the active metabolite only. Two single, topical dose studies were conducted using 14 C-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 C max 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 C max for tazarotenic acid was 0.72 ± 0.58 ng/mL (mean ± SD) occurring 9 hours after the last dose, and the AUC 0-24hr 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 C max for tazarotenic acid was 12.0 ± 7.6 ng/mL occurring 6 hours after the final dose, and the AUC 0-24hr 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 C max of 18.9 ± 10.6 ng/mL and AUC 0-24hr 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 )] .

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 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). TAZORAC ® 0.05% Gel TAZORAC ® 0.1% Gel Vehicle Gel Trunk/Arm/Leg Lesions Knee/Elbow Lesions Trunk/Arm/Leg Lesions Knee/Elbow Lesions Trunk/Arm/Leg Lesions Knee/Elbow 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 Elevation B* C-12* C-24* 2.5 -1.4 -1.2 2.6 -1.3 2.6 -1.3 -1.1 2.6 -1.1 2.5 -1.4 -1.1 2.6 -1.4 2.6 -1.5 -1.0 2.6 -1.3 2.4 -0.8 -0.9 2.6 -0.7 2.6 -0.7 -0.7 2.6 -0.6 Scaling B* C-12* C-24* 2.4 -1.1 -0.9 2.5 -1.1 2.5 -1.1 -0.8 2.6 -0.9 2.4 -1.3 -1.0 2.6 -1.3 2.5 -1.2 -0.8 2.7 -1.2 2.4 -0.7 -0.8 2.6 -0.7 2.5 -0.6 -0.7 2.7 -0.6 Erythema B* C-12* C-24* 2.4 -1.0 -1.1 2.7 -0.8 2.2 -0.9 -0.7 2.5 -0.8 2.4 -1.0 -0.9 2.8 -1.1 2.3 -1.0 -0.8 2.5 -0.8 2.3 -0.6 -0.7 2.7 -0.5 2.2 -0.5 -0.6 2.5 -0.5 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.

wo 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%)

<table ID="table1" width="775" styleCode="Noautorules"><caption>Table 1. Plaque Elevation, Scaling, and Erythema in Two Controlled Clinical Trials for Psoriasis</caption><col width="8%"/><col width="5.8%"/><col width="6.2%"/><col width="6.2%"/><col width="6.2%"/><col width="6%"/><col width="6.2%"/><col width="6.2%"/><col width="6.2%"/><col width="6%"/><col width="6.2%"/><col width="6.2%"/><col width="6.2%"/><col width="6%"/><tfoot><tr valign="top"><td colspan="14" align="left"><paragraph styleCode="footnote">Plaque elevation, scaling, and erythema scored on a 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe.</paragraph><paragraph styleCode="footnote">B*=Mean Baseline Severity: C-12*=Mean Change from Baseline at end of 12 weeks of therapy:</paragraph><paragraph styleCode="footnote">C-24*=Mean Change from Baseline at week 24 (12 weeks after the end of therapy).</paragraph></td></tr></tfoot><tbody><tr valign="top"><td styleCode="Toprule Lrule Rrule " colspan="2"/><td styleCode="Toprule Lrule Rrule " colspan="4" align="center"><content styleCode="bold">TAZORAC</content><content styleCode="bold">^&#xAE;</content><content styleCode="bold"> 0.05% Gel</content></td><td styleCode="Toprule Lrule Rrule " colspan="4" align="center"><content styleCode="bold">TAZORAC</content><content styleCode="bold">^&#xAE;</content><content styleCode="bold"> 0.1% Gel</content></td><td styleCode="Toprule Lrule Rrule " colspan="4" align="center"><content styleCode="bold">Vehicle Gel</content></td></tr><tr valign="top"><td styleCode="Lrule Rrule " colspan="2"/><td styleCode="Toprule Lrule Rrule " colspan="2" align="center">Trunk/Arm/Leg Lesions</td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center">Knee/Elbow Lesions</td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center">Trunk/Arm/Leg Lesions</td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center">Knee/Elbow Lesions</td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center">Trunk/Arm/Leg Lesions</td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center">Knee/Elbow Lesions</td></tr><tr valign="top"><td styleCode="Lrule Rrule " colspan="2"/><td styleCode="Toprule Lrule Rrule " align="center">N=108</td><td styleCode="Toprule Lrule Rrule " align="center">N=111</td><td styleCode="Toprule Lrule Rrule " align="center">N=108</td><td styleCode="Toprule Lrule Rrule " align="center">N=111</td><td styleCode="Toprule Lrule Rrule " align="center">N=108</td><td styleCode="Toprule Lrule Rrule " align="center">N=112</td><td styleCode="Toprule Lrule Rrule " align="center">N=108</td><td styleCode="Toprule Lrule Rrule " align="center">N=112</td><td styleCode="Toprule Lrule Rrule " align="center">N=108</td><td styleCode="Toprule Lrule Rrule " align="center">N=113</td><td styleCode="Toprule Lrule Rrule " align="center">N=108</td><td styleCode="Toprule Lrule Rrule " align="center">N=113</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center" valign="middle">Plaque Elevation</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">B*</content> C-12* C-24*</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -1.4 -1.2</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.3</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.3 -1.1</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6

t> -1.4 -1.2</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.3</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.3 -1.1</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6 </content> -1.1</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -1.4 -1.1</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.4</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.5 -1.0</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.3</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.4</content> -0.8 -0.9</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -0.7</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -0.7 -0.7</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -0.6</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center" valign="middle">Scaling</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">B*</content> C-12* C-24*</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.4</content> -1.1 -0.9</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -1.1</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -1.1 -0.8</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -0.9</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.4</content> -1.3 -1.0</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -1.3</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -1.2 -0.8</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.7</content> -1.2</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.4</content> -0.7 -0.8</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.6</content> -0.7</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -0.6 -0.7</td><td styleCode="Toprule Lrule Rrule " align="center"><content styleCode="underline">2.7</content> -0.6</td></tr><tr valign="top"><td styleCode="Toprule Botrule Lrule Rrule " align="center" valign="middle">Erythema</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">B*</content> C-12* C-24*</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.4</content> -1.0 -1.1</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.7</content> -0.8</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.2</content> -0.9 -0.7</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -0.8</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.4</content> -1.0 -0.9</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.8</content> -1.1</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.3</content> -1.0 -0.8</td><td styleCode="Toprule Botrule Lrule Rrule " al

"underline">2.4</content> -1.0 -0.9</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.8</content> -1.1</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.3</content> -1.0 -0.8</td><td styleCode="Toprule Botrule Lrule Rrule " al ign="center"><content styleCode="underline">2.5</content> -0.8</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.3</content> -0.6 -0.7</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.7</content> -0.5</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.2</content> -0.5 -0.6</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -0.5</td></tr></tbody></table> <table ID="table2" width="775" styleCode="Noautorules"><caption>Table 2.

ign="center"><content styleCode="underline">2.5</content> -0.8</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.3</content> -0.6 -0.7</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.7</content> -0.5</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.2</content> -0.5 -0.6</td><td styleCode="Toprule Botrule Lrule Rrule " align="center"><content styleCode="underline">2.5</content> -0.5</td></tr></tbody></table> <table ID="table2" width="775" styleCode="Noautorules"><caption>Table 2. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Psoriasis</caption><col width="22%"/><col width="13%"/><col width="13%"/><col width="13%"/><col width="13%"/><col width="13%"/><col width="13%"/><tbody><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center"/><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">TAZORAC&#xAE; 0.05% Gel</content></td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">TAZORAC&#xAE; 0.1% Gel</content></td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">Vehicle Gel</content></td></tr><tr valign="top"><td styleCode="Lrule Rrule " align="center"/><td styleCode="Toprule Lrule Rrule " align="center">N=81</td><td styleCode="Toprule Lrule Rrule " align="center">N=93</td><td styleCode="Toprule Lrule Rrule " align="center">N=79</td><td styleCode="Toprule Lrule Rrule " align="center">N=69</td><td styleCode="Toprule Lrule Rrule " align="center">N=84</td><td styleCode="Toprule Lrule Rrule " align="center">N=91</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center">100% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">2 (2%)</td><td styleCode="Toprule Lrule Rrule " align="center">1 (1%)</td><td styleCode="Toprule Lrule Rrule " align="center">0</td><td styleCode="Toprule Lrule Rrule " align="center">0</td><td styleCode="Toprule Lrule Rrule " align="center">1 (1%)</td><td styleCode="Toprule Lrule Rrule " align="center">0</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center">75% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">23 (28%)</td><td styleCode="Toprule Lrule Rrule " align="center">17 (18%)</td><td styleCode="Toprule Lrule Rrule " align="center">30 (38%)</td><td styleCode="Toprule Lrule Rrule " align="center">17 (25%)</td><td styleCode="Toprule Lrule Rrule " align="center">10 (12%)</td><td styleCode="Toprule Lrule Rrule " align="center">9 (10%)</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center">50% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">42 (52%)</td><td styleCode="Toprule Lrule Rrule " align="center">39 (42%)</td><td styleCode="Toprule Lrule Rrule " align="center">51 (65%)</td><td styleCode="Toprule Lrule Rrule " align="center">36 (52%)</td><td styleCode="Toprule Lrule Rrule " align="center">28 (33%)</td><td styleCode="Toprule Lrule Rrule " align="center">21 (23%)</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule " align="center">1-49% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">21 (26%)</td><td styleCode="Toprule Lrule Rrule " align="center">32 (34%)</td><td styleCode="Toprule Lrule Rrule " align="center">18 (23%)</td><td styleCode="Toprule Lrule Rrule " align="center">23 (33%)</td><td styleCode="Toprule Lrule Rrule " align="center">27 (32%)</td><td styleCode="Toprule Lrule Rrule " align="center">32 (35%)</td></tr><tr valign="top"><td styleCode="Toprule Botrule Lrule Rrule " align="center">No change or worse</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">18 (22%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">22 (24%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">10 (13%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">10 (14%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">29

e Rrule " align="center">18 (22%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">22 (24%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">10 (13%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">10 (14%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">29 (35%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">38 (42%)</td></tr></tbody></table>

e Rrule " align="center">18 (22%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">22 (24%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">10 (13%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">10 (14%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">29 (35%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">38 (42%)</td></tr></tbody></table> <table ID="table3" width="600" styleCode="Noautorules"><caption>Table 3. Reduction in Lesion Counts after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne</caption><col width="28%"/><col width="18%"/><col width="18%"/><col width="18%"/><col width="18%"/><tbody><tr valign="top"><td styleCode="Toprule Lrule Rrule "/><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">TAZORAC</content><content styleCode="bold">^&#xAE;</content><content styleCode="bold"> 0.1% Gel</content></td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">Vehicle Gel</content></td></tr><tr valign="top"><td styleCode="Lrule Rrule "/><td styleCode="Toprule Lrule Rrule " align="center">N=150</td><td styleCode="Toprule Lrule Rrule " align="center">N=149</td><td styleCode="Toprule Lrule Rrule " align="center">N=148</td><td styleCode="Toprule Lrule Rrule " align="center">N=149</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule ">Noninflammatory lesions</td><td styleCode="Toprule Lrule Rrule " align="center">55%</td><td styleCode="Toprule Lrule Rrule " align="center">43%</td><td styleCode="Toprule Lrule Rrule " align="center">35%</td><td styleCode="Toprule Lrule Rrule " align="center">27%</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule ">Inflammatory lesions</td><td styleCode="Toprule Lrule Rrule " align="center">42%</td><td styleCode="Toprule Lrule Rrule " align="center">47%</td><td styleCode="Toprule Lrule Rrule " align="center">30%</td><td styleCode="Toprule Lrule Rrule " align="center">28%</td></tr><tr valign="top"><td styleCode="Toprule Botrule Lrule Rrule ">Total lesions</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">52%</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">45%</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">33%</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">27%</td></tr></tbody></table>

Rrule ">Total lesions</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">52%</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">45%</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">33%</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">27%</td></tr></tbody></table> <table ID="table4" width="600" styleCode="Noautorules"><caption>Table 4. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne</caption><col width="28%"/><col width="18%"/><col width="18%"/><col width="18%"/><col width="18%"/><tbody><tr valign="top"><td styleCode="Toprule Lrule Rrule "/><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">TAZORAC</content><content styleCode="bold">^&#xAE;</content><content styleCode="bold"> 0.1% Gel</content></td><td styleCode="Toprule Lrule Rrule " colspan="2" align="center"><content styleCode="bold">Vehicle Gel</content></td></tr><tr valign="top"><td styleCode="Lrule Rrule "/><td styleCode="Toprule Lrule Rrule " align="center">N=105</td><td styleCode="Toprule Lrule Rrule " align="center">N=117</td><td styleCode="Toprule Lrule Rrule " align="center">N=117</td><td styleCode="Toprule Lrule Rrule " align="center">N=110</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule ">100% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">1 (1%)</td><td styleCode="Toprule Lrule Rrule " align="center">0</td><td styleCode="Toprule Lrule Rrule " align="center">0</td><td styleCode="Toprule Lrule Rrule " align="center">0</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule ">75% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">40 (38%)</td><td styleCode="Toprule Lrule Rrule " align="center">21 (18%)</td><td styleCode="Toprule Lrule Rrule " align="center">23 (20%)</td><td styleCode="Toprule Lrule Rrule " align="center">11 (10%)</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule ">50% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">71 (68%)</td><td styleCode="Toprule Lrule Rrule " align="center">56 (48%)</td><td styleCode="Toprule Lrule Rrule " align="center">47 (40%)</td><td styleCode="Toprule Lrule Rrule " align="center">32 (29%)</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule ">1-49% improvement</td><td styleCode="Toprule Lrule Rrule " align="center">23 (22%)</td><td styleCode="Toprule Lrule Rrule " align="center">49 (42%)</td><td styleCode="Toprule Lrule Rrule " align="center">48 (41%)</td><td styleCode="Toprule Lrule Rrule " align="center">46 (42%)</td></tr><tr valign="top"><td styleCode="Toprule Botrule Lrule Rrule ">No change or worse</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">11 (10%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">12 (10%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">22 (19%)</td><td styleCode="Toprule Botrule Lrule Rrule " align="center">32 (29%)</td></tr></tbody></table>

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: For the patient with psoriasis, apply TAZORAC Gel only to psoriasis skin lesions, avoiding uninvolved skin. 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 Adminstration ( 2.1 )] . Moisturizers may be used as frequently as desired. Patients with psoriasis may use a cream or lotion to soften or moisten skin at least 1 hour before applying TAZORAC Gel. Avoid contact with the eyes. If TAZORAC Gel gets in or near eyes, rinse thoroughly with water. Seek medical attention if eye irritation continues. TAZORAC Gel is for topical use only. Do not apply to eyes, mouth, or other mucous membrane. Not for ophthalmic, oral, or intravaginal use. 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. 71722AM11 Pharmacist: Please cut or tear at dotted line and provide this patient package insert to your customer.

This Patient Information has been approved by the U.S. Food and Drug Administration Revised: April/2018 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: 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. Begin treatment with TAZORAC Gel during a normal menstrual period. 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. 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.

ly 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 : ○ If you shower or bathe before applying TAZORAC Gel, your skin should be dry before applying the gel. ○ You may use a cream or lotion to soften or moisten your skin at least 1 hour before you apply TAZORAC Gel. ○ Apply a thin layer of TAZORAC Gel to cover only the psoriasis lesions. If you have acne : ○ Gently wash and dry your face before applying TAZORAC Gel. ○ 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 plaque 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?

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 © 2018 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 71722US17

<table width="100%" styleCode="Noautorules"><col width="72%"/><col width="28%"/><tfoot><tr valign="top"><td align="left"><paragraph styleCode="footnote">This Patient Information has been approved by the U.S. Food and Drug Administration</paragraph></td><td align="right"><paragraph styleCode="footnote">Revised: April/2018</paragraph></td></tr></tfoot><tbody><tr><td colspan="2" styleCode="Toprule Lrule Rrule " align="center"><content styleCode="bold">PATIENT INFORMATION</content> <content styleCode="bold">TAZORAC</content>^&#xAE;<content styleCode="bold">(TAZ-or-ac)</content> <content styleCode="bold">(tazarotene) </content> <content styleCode="bold">Gel, 0.05% and 0.1%</content></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">Important information</content>: TAZORAC Gel is for use on skin only. Do not use TAZORAC Gel in your eyes, mouth, or vagina.</td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">What is the most important information I should know about TAZORAC Gel?</content> <content styleCode="bold">TAZORAC Gel may cause birth defects if used during pregnancy.</content><list listType="unordered" styleCode="Disc"><item><content styleCode="bold">Females must not be pregnant when they start using TAZORAC Gel or become pregnant during treatment with TAZORAC Gel.</content> </item><item>For females who can become pregnant: <list listType="unordered" styleCode="Circle"><item>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.</item><item>Begin treatment with TAZORAC Gel during a normal menstrual period.</item><item>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.</item><item><content styleCode="bold">Stop using TAZORAC Gel and tell your doctor right away if you become pregnant while using TAZORAC Gel.</content></item></list></item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">What is TAZORAC Gel?</content> <list listType="unordered" styleCode="Disc"><item>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. </item><item>TAZORAC Gel 0.1% is also used on the skin to treat people with mild to moderate facial acne vulgaris.</item></list>It is not known if TAZORAC Gel is:<list listType="unordered" styleCode="Disc"><item>safe and effective for use in children under 12 years of age. </item><item>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. </item><item>safe if used over more than 20% of your body for the treatment of psoriasis or acne.</item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">Who should not use TAZORAC Gel?</content> <content styleCode="bold">Do not use TAZORAC Gel if you:</content><list listType="unordered" styleCode="Disc"><item>are pregnant or plan to become pregnant. See &#x201C;What is the most important information I should know about TAZORAC Gel?&#x201D; at the beginning of this leaflet.

should not use TAZORAC Gel?</content> <content styleCode="bold">Do not use TAZORAC Gel if you:</content><list listType="unordered" styleCode="Disc"><item>are pregnant or plan to become pregnant. See &#x201C;What is the most important information I should know about TAZORAC Gel?&#x201D; at the beginning of this leaflet. </item><item>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. </item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">What should I tell my doctor before using TAZORAC Gel?</content> <content styleCode="bold">Before you use TAZORAC Gel, tell your doctor about all of your medical conditions, including if you:</content> <list listType="unordered" styleCode="Disc"><item>have eczema or any other skin problems </item><item>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. </item></list>Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. <content styleCode="bold">Certain medicines, vitamins, or supplements may make your skin more sensitive to sunlight</content>. 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.</td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">How should I use TAZORAC Gel?</content> <list listType="unordered" styleCode="Disc"><item>Use TAZORAC Gel exactly as your doctor tells you to use it. </item><item>Apply TAZORAC Gel 1 time each day, in the evening. </item><item><content styleCode="bold">Do not</content> 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. </item><item>Wash your hands after applying TAZORAC Gel.</item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">Follow these instructions for applying TAZORAC Gel:</content><list listType="unordered" styleCode="Disc"><item><content styleCode="bold">If you have psoriasis</content>: &#x25CB; If you shower or bathe before applying TAZORAC Gel, your skin should be dry before applying the gel. &#x25CB; You may use a cream or lotion to soften or moisten your skin at least 1 hour before you apply TAZORAC Gel. &#x25CB; Apply a thin layer of TAZORAC Gel to cover only the psoriasis lesions. </item><item><content styleCode="bold">If you have acne</content>: &#x25CB; Gently wash and dry your face before applying TAZORAC Gel. &#x25CB; Apply a thin layer of TAZORAC Gel to cover only the acne lesions. </item><item>If you swallow TAZORAC Gel, call your doctor or go to the nearest hospital emergency room right away.</item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">What should I avoid while using TAZORAC Gel?</content><list listType="unordered" styleCode="Disc"><item>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. </item><item>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.

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. </item><item>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. </item><item>Avoid using cosmetics or topical medicines that may make your skin more sensitive to sunlight or make your skin dry. </item><item>Avoid using TAZORAC Gel on unaffected skin or skin with eczema because it may cause severe irritation.</item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">What are the possible side effects of TAZORAC Gel?</content> <content styleCode="bold">TAZORAC Gel may cause serious side effects, including:</content> <list listType="unordered" styleCode="Disc"><item><content styleCode="bold">Skin irritation and allergic reactions (hypersensitivity). </content>TAZORAC Gel<content styleCode="bold"> </content>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. </item><item><content styleCode="bold">Sensitivity to sunlight and risk of sunburn. </content>See &#x201C;What should I avoid while using TAZORAC Gel?&#x201D;</item></list><content styleCode="bold">The most common side effects of TAZORAC Gel in people with plaque psoriasis include </content>itching, burning, redness, worsening of psoriasis, irritation and skin pain. <content styleCode="bold">The most common side effects of TAZORAC Gel in people with acne include </content>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.</td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">How should I store TAZORAC Gel?</content><list listType="unordered" styleCode="Disc"><item>Store TAZORAC Gel at 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C). </item><item>Keep TAZORAC Gel and all medicines out of the reach of children.</item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule "><content styleCode="bold">General information about the safe and effective use of TAZORAC Gel.</content> 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.</td></tr><tr><td colspan="2" styleCode="Toprule Botrule Lrule Rrule "><content styleCode="bold">What are the ingredients in TAZORAC Gel?

ople, 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.</td></tr><tr><td colspan="2" styleCode="Toprule Botrule Lrule Rrule "><content styleCode="bold">What are the ingredients in TAZORAC Gel? </content> <content styleCode="bold">Active ingredient:</content> tazarotene <content styleCode="bold">Inactive ingredients:</content> 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 <paragraph styleCode="footnote">Distributed by: Almirall, LLC</paragraph><paragraph styleCode="footnote">Exton, PA 19341</paragraph><paragraph styleCode="footnote">&#xA9; 2018 Almirall. All rights reserved.</paragraph><paragraph styleCode="footnote">All trademarks are the property of their respective owners.</paragraph><paragraph styleCode="footnote">For more information, call 1-800-678-1605 or go to <linkHtml href="https://www.tazorac.com">www.tazorac.com</linkHtml></paragraph></td></tr></tbody></table>