ADVERSE REACTIONS SECTION.

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)] 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) To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 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) 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.PsoriasisA total of 439 subjects 14 to 87 years of age were treated with tazarotene gel, 0.05% and 0.1% in two controlled clinical trials. The most frequent adverse events reported with tazarotene 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 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 1 year study. In general, the incidence of adverse events with tazarotene gel 0.05% was to 5% lower than that seen with tazarotene gel 0.1%.. 6.2 Postmarketing Experience. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Tazarotene is 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: RAR, RAR, and RAR, but shows relative selectivity for RAR, and RAR and may modify gene expression. The clinical significance of these findings for the treatment of plaque psoriasis is unknown.. 12.2 Pharmacodynamics. The pharmacodynamics of tazarotene gel in the treatment of plaque psoriasis 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 or psoriatic skin.The human in vivo studies described below were conducted with tazarotene gel applied topically at approximately mg/cm 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 14C-tazarotene gel. Systemic absorption, as determined from radioactivity in the excreta, was less than 1% of the applied dose (without occlusion) in six subjects with psoriasis and approximately 5% of the applied dose (under occlusion) in six healthy subjects. One non-radiolabeled single-dose study comparing the 0.05% gel to the 0.1% gel in healthy subjects indicated that the max and AUC were 40% higher for the 0.1% gel. After 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 max for tazarotenic acid was 0.72 +- 0.58 ng/mL (mean +- SD) occurring 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 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 max for tazarotenic acid was 12.0 +- 7.6 ng/mL occurring 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 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 to 5% of the applied dose was in the stratum corneum (tazarotene: tazarotenic acid 5:1) and to 4% was in the viable epidermis-dermis layer (tazarotene: tazarotenic acid 2:1) 24 hours after topical application of the gel.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. Psoriasis:In two large vehicle-controlled clinical trials, tazarotene 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 tazarotene 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 PsoriasisTazarotene Gel 0.05%Tazarotene Gel 0.1%Vehicle GelTrunk/Arm/Leg Lesions Knee/Elbow Lesions Trunk/Arm/Leg Lesions Knee/Elbow Lesions Trunk/Arm/Leg Lesions Knee/Elbow Lesions N=108N=111N=108N=111N=108N=112N=108N=112N=108N=113N=108N=113Plaque Elevation 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 ScalingB 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 ErythemaB 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 Plaque elevation, scaling, and erythema scored on 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe.B=Mean Baseline Severity: C-12=Mean Change from Baseline at end of 12 weeks of therapy:C-24=Mean Change from Baseline at week 24 (12 weeks after the end of therapy).Global improvement over baseline at the end of 12 weeks of treatment in these two trials is shown in Table 2.Table 2. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for PsoriasisTazarotene Gel 0.05%Tazarotene Gel 0.1%Vehicle GelN=81N=93N=79N=69N=84N=91100% improvement2 (2%)1 (1%)001 (1%)0>=75% improvement23 (28%)17 (18%)30 (38%)17 (25%)10 (12%)9 (10%)>=50% improvement42 (52%)39 (42%)51 (65%)36 (52%)28 (33%)21 (23%)1-49% improvement21 (26%)32 (34%)18 (23%)23 (33%)27 (32%)32 (35%)No change or worse18 (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)].

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATIONTAZAROTENE (taz-AR-oh-teen)Gel, 0.05%Important information: Tazarotene gel is for use on skin only. Do not use tazarotene gel in your eyes, mouth, or vagina. What is the most important information should know about tazarotene gel Tazarotene gel may cause birth defects if used during pregnancy.Females must not be pregnant when they start using tazarotene gel or become pregnant during treatment with tazarotene gel.For females who can become pregnant: Your doctor will order pregnancy test for you within weeks before you begin treatment with tazarotene gel to be sure that you are not pregnant. Your doctor will decide when to do the test.Begin treatment with tazarotene gel during normal menstrual period.Use an effective form of birth control during treatment with tazarotene gel. Talk with your doctor about birth control options that may be used to prevent pregnancy during treatment with tazarotene gel.Stop using tazarotene gel and tell your doctor right away if you become pregnant while using tazarotene gel. What is tazarotene gelTazarotene gel 0.05% is prescription medicine used on the skin (topical) to treat people with stable plaque psoriasis on up to 20% of your body surface.It is not known if tazarotene gel is:safe and effective for use in children under 12 years of age.safe if used over more than 20% of your body for the treatment of psoriasis.Who should not use tazarotene gelDo not use tazarotene gel if you:are pregnant or plan to become pregnant. See What is the most important information should know about tazarotene gel at the beginning of this leaflet.are allergic to tazarotene or any of the ingredients in tazarotene gel. See the end of this leaflet for complete list of ingredients in tazarotene gel.What should tell my doctor before using tazarotene gelBefore you use tazarotene gel, tell your doctor about all of your medical conditions, including if you:have eczema or any other skin problemsare breastfeeding or plan to breastfeed. It is not known if tazarotene gel passes into your breast milk. Talk to your doctor about using tazarotene 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 list of your medicines to show to your doctor and pharmacist when you get new medicine. How should use tazarotene gelUse tazarotene gel exactly as your doctor tells you to use it.Apply tazarotene gel time each day, in the evening.Do not get tazarotene gel in your eyes, on your eyelids, or in your mouth. If tazarotene 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 tazarotene gel.Follow these instructions for applying tazarotene gel:If you have psoriasis: If you shower or bathe before applying tazarotene gel, your skin should be dry before applying the gel.You may use cream or lotion to soften or moisten your skin at least hour before you apply tazarotene gel.Apply thin layer of tazarotene gel to cover only the psoriasis lesions.If you swallow tazarotene gel, call your doctor or go to the nearest hospital emergency room right away.What should avoid while using tazarotene gelAvoid sunlight, including sunlamps, during treatment with tazarotene gel. Tazarotene gel can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get severe sunburn. Use sunscreen and wear hat and clothes that cover your skin if you have to be in sunlight.Talk to your doctor if you get sunburn during treatment with tazarotene gel. If you get sunburn, do not use tazarotene 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 tazarotene gel on unaffected skin or skin with eczema because it may cause severe irritation.What are the possible side effects of tazarotene gelTazarotene gel may cause serious side effects, including:Skin irritation and allergic reactions (hypersensitivity). Tazarotene 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 tazarotene gel. If you develop skin irritation or hives, your doctor may tell you to temporarily stop using tazarotene gel until your skin heals, tell you to use tazarotene gel less often, or change your tazarotene gel dose. Also, wind or cold weather may be more irritating to your skin while you are using tazarotene gel. Sensitivity to sunlight and risk of sunburn. See What should avoid while using tazarotene gel The most common side effects of tazarotene gel in people with plaque psoriasis include itching, burning, redness, worsening of psoriasis, irritation and skin pain. These are not all the possible side effects of tazarotene gel. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store tazarotene gelStore tazarotene gel at 68F to 77F (20C to 25C).Keep tazarotene gel and all medicines out of the reach of children.General information about the safe and effective use of tazarotene gel.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use tazarotene gel for condition for which it was not prescribed. Do not give tazarotene 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 tazarotene gel that is written for health professionals. What are the ingredients in tazarotene gelActive 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:Cosette Pharmaceuticals, Inc.South Plainfield, NJ 07080This Patient Information has been approved by the U.S. Food and Drug Administration Revised: October/2021. Females must not be pregnant when they start using tazarotene gel or become pregnant during treatment with tazarotene gel.. For females who can become pregnant: Your doctor will order pregnancy test for you within weeks before you begin treatment with tazarotene gel to be sure that you are not pregnant. Your doctor will decide when to do the test.Begin treatment with tazarotene gel during normal menstrual period.Use an effective form of birth control during treatment with tazarotene gel. Talk with your doctor about birth control options that may be used to prevent pregnancy during treatment with tazarotene gel.Stop using tazarotene gel and tell your doctor right away if you become pregnant while using tazarotene gel. Your doctor will order pregnancy test for you within weeks before you begin treatment with tazarotene gel to be sure that you are not pregnant. Your doctor will decide when to do the test.. Begin treatment with tazarotene gel during normal menstrual period.. Use an effective form of birth control during treatment with tazarotene gel. Talk with your doctor about birth control options that may be used to prevent pregnancy during treatment with tazarotene gel.. Stop using tazarotene gel and tell your doctor right away if you become pregnant while using tazarotene gel.. Tazarotene gel 0.05% is prescription medicine used on the skin (topical) to treat people with stable plaque psoriasis on up to 20% of your body surface.. safe and effective for use in children under 12 years of age.. safe if used over more than 20% of your body for the treatment of psoriasis.. are pregnant or plan to become pregnant. See What is the most important information should know about tazarotene gel at the beginning of this leaflet.. are allergic to tazarotene or any of the ingredients in tazarotene gel. See the end of this leaflet for complete list of ingredients in tazarotene gel.. have eczema or any other skin problems. are breastfeeding or plan to breastfeed. It is not known if tazarotene gel passes into your breast milk. Talk to your doctor about using tazarotene gel while breastfeeding.. Use tazarotene gel exactly as your doctor tells you to use it.. Apply tazarotene gel time each day, in the evening.. Do not get tazarotene gel in your eyes, on your eyelids, or in your mouth. If tazarotene 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 tazarotene gel.. If you have psoriasis: If you shower or bathe before applying tazarotene gel, your skin should be dry before applying the gel.You may use cream or lotion to soften or moisten your skin at least hour before you apply tazarotene gel.Apply thin layer of tazarotene gel to cover only the psoriasis lesions.. If you shower or bathe before applying tazarotene gel, your skin should be dry before applying the gel.. You may use cream or lotion to soften or moisten your skin at least hour before you apply tazarotene gel.. Apply thin layer of tazarotene gel to cover only the psoriasis lesions.. If you swallow tazarotene gel, call your doctor or go to the nearest hospital emergency room right away.. Avoid sunlight, including sunlamps, during treatment with tazarotene gel. Tazarotene gel can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get severe sunburn. Use sunscreen and wear hat and clothes that cover your skin if you have to be in sunlight.. Talk to your doctor if you get sunburn during treatment with tazarotene gel. If you get sunburn, do not use tazarotene 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 tazarotene gel on unaffected skin or skin with eczema because it may cause severe irritation.. Skin irritation and allergic reactions (hypersensitivity). Tazarotene 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 tazarotene gel. If you develop skin irritation or hives, your doctor may tell you to temporarily stop using tazarotene gel until your skin heals, tell you to use tazarotene gel less often, or change your tazarotene gel dose. Also, wind or cold weather may be more irritating to your skin while you are using tazarotene gel. Sensitivity to sunlight and risk of sunburn. See What should avoid while using tazarotene gel Store tazarotene gel at 68F to 77F (20C to 25C).. Keep tazarotene gel and all medicines out of the reach of children.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryBased on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, tazarotene gel may cause fetal harm when administered to 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 tazarotene gel during pregnancy; therefore, tazarotene 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 tazarotene gel have not established 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 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 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.DataAnimal DataIn rats, tazarotene gel, 0.05% formulation dosed topically during gestation days 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., mg/cm over 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 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, during gestation days 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 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, which represented 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. low incidence of retinoid-related malformations was observed at that dose.In 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 SummaryThere is no information regarding the presence of tazarotene in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of 14C-tazarotene gel to the skin of lactating rats, radioactivity was detected in rat milk. The lack of clinical data during lactation precludes clear determination of the risk of tazarotene gel to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for tazarotene gel and any potential adverse effects on the breastfed child from tazarotene gel or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential. Pregnancy TestingPregnancy testing is recommended for females of reproductive potential within weeks prior to initiating tazarotene gel therapy which should begin during menstrual period.ContraceptionFemalesBased on animal studies, tazarotene gel may cause fetal harm when administered to pregnant woman [see Use in Specific Populations 8.1)] Advise females of reproductive potential to use effective contraception during treatment with tazarotene gel. 8.4 Pediatric Use. The safety and efficacy of tazarotene gel have not been established in pediatric patients with psoriasis under the age of 12 years.. 8.5 Geriatric Use. Of the total number of subjects in clinical trials of tazarotene 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 tazarotene 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Embryofetal Toxicity: Tazarotene gel contains tazarotene, which is teratogen. Tazarotene gel is contraindicated in pregnancy. Females of child-bearing potential should have negative pregnancy test within 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. Tazarotene 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. Tazarotene gel should be administered with caution if the patient is also taking drugs known to be photosensitizers. 5.3) Embryofetal Toxicity: Tazarotene gel contains tazarotene, which is teratogen. Tazarotene gel is contraindicated in pregnancy. Females of child-bearing potential should have negative pregnancy test within 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. Tazarotene 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. Tazarotene 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, tazarotene gel may cause fetal harm when administered to 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.Tazarotene is 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 PotentialFemales of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when tazarotene gel is used. The possibility that 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 weeks prior to tazarotene gel therapy. Tazarotene gel therapy should begin during normal menstrual period [see Use in Specific Populations 8.1)]. 5.2 Local Irritation and Hypersensitivity Reactions. Application of tazarotene 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 strong drying effect should be avoided. It is also advisable to rest patients skin until the effects of such preparations subside before treatment with tazarotene gel is initiated.Tazarotene 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 tazarotene 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 tazarotene gel. Patients must be warned to use sunscreens and protective clothing when using tazarotene gel. Patients with sunburn should be advised not to use tazarotene 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 tazarotene gel.Tazarotene 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.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information).Embryofetal ToxicityInform females of reproductive potential of the potential risk to fetus. Advise these patients to use effective contraception during treatment with tazarotene gel. Advise patients to inform their healthcare provider of known or suspected pregnancy [see Warnings and Precautions 5.1) and Use in Specific Populations 8.1, 8.3)] Photosensitivity and Risk of SunburnAdvise patients to avoid excessive sun exposure and to use of sunscreens and protective measures (hat, visor). Advise patients to avoid using tazarotene gel if also taking other medicines may increase sensitivity to sunlight.Important Administration InstructionsAdvise the patient of the following:For the patient with psoriasis, apply tazarotene 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 cream or lotion to soften or moisten skin at least hour before applying tazarotene gel.Avoid contact with the eyes. If tazarotene gel gets in or near eyes, rinse thoroughly with water. Seek medical attention if eye irritation continues.Tazarotene 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 tazarotene gel.Distributed by:Cosette Pharmaceuticals, Inc.South Plainfield, NJ 070808-0805CPLNC1Revised: 10/2021 VC7598Pharmacist: Please cut or tear at dotted line and provide this patient package insert to your customer.. For the patient with psoriasis, apply tazarotene 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 cream or lotion to soften or moisten skin at least hour before applying tazarotene gel.. Avoid contact with the eyes. If tazarotene gel gets in or near eyes, rinse thoroughly with water. Seek medical attention if eye irritation continues.. Tazarotene 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 tazarotene gel.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. 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 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 gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 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 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 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 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 with oral doses of tazarotene up to mg/kg/day. However, there was significant decrease in the number of estrous stages and an increase in developmental effects at that dose, which produced systemic exposure times that observed in subjects treated with the MRHD of tazarotene gel, 0.1% [see Use in Specific Populations 8.1)].