Arazlo

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) ] The most common adverse reactions (occurring in ≥1% of the ARAZLO group and greater than the vehicle group) were application site reactions; pain, dryness, exfoliation, erythema and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 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. In 2 multicenter, randomized, double-blind, vehicle-controlled clinical trials, subjects age 9 years and older applied ARAZLO or vehicle once daily for 12 weeks. The majority of subjects were White (74%) and female (66%). Approximately 22% were Hispanic/Latino and 42% were younger than 18 years of age, fourteen of 779 subjects (1.8%) treated with ARAZLO were between 9 years to less than 12 years of age. Adverse reactions reported by ≥1% of subjects treated with ARAZLO and more frequently than subjects treated with vehicle are summarized in Table 1. Most adverse reactions were mild to moderate in severity. Severe adverse reactions represented 1.3% of the subjects treated. Overall, 2.4% (19/779) of subjects discontinued ARAZLO because of local skin reactions. Table 1:Adverse Reactions Reported by ≥1% of the ARAZLO Group and More Frequently than the Vehicle Group Adverse Reactions N (%) ARAZLO N=779 Vehicle N=791 Application site pain Application site pain defined as application site stinging, burning or pain 41 (5) 2 (<1) Application site dryness 30 (4) 1 (<1) Application site exfoliation 16 (2) 0 (0) Application site erythema 15 (2) 0 (0) Application site pruritus 10 (1) 0 (0) Skin irritation was evaluated by active assessment of erythema, scaling, itching, burning and stinging, with grades for none, mild, moderate, or severe. The maximum severity generally peaked at Week 2 of therapy and decreased thereafter. The percentage of subjects with these signs and symptoms at any post-baseline visit are summarized in Table 2. Table 2: Incidence of Local Cutaneous Irritation at any Post-Baseline Visit ARAZLO Lotion N=774 Mild/Moderate/Severe Vehicle Lotion N=789 Mild/Moderate/Severe Erythema 49% 38% Scaling 51% 23% Itching 29% 14% Burning 30% 6% Stinging 22% 5%

4 CONTRAINDICATIONS ARAZLO is contraindicated in pregnancy. ARAZLO may cause fetal harm when administered to a pregnant patient [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1, 8.3) ] . ARAZLO is contraindicated in pregnancy. ( 4 , 8.1 )

11 DESCRIPTION ARAZLO (tazarotene) is a white to off-white lotion containing 0.045% tazarotene by weight for topical administration. Tazarotene is a member of the acetylenic class of retinoids. The chemical name for tazarotene is 6-[(3,4-Dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-pyridinecarboxylic acid ethyl ester. The structural formula for tazarotene is represented below: Tazarotene: Molecular Formula: C 21 H 21 NO 2 S Molecular Weight: 351.46 Each gram of ARAZLO contains 0.45 mg (0.045%) tazarotene in a white to off-white lotion base consisting of carbomer copolymer type B, carbomer homopolymer type A, diethyl sebacate, edetate disodium dihydrate, light mineral oil, methylparaben, propylparaben, purified water, sodium hydroxide, sorbitan monooleate and sorbitol solution, 70%. chemstructure

2 DOSAGE AND ADMINISTRATION Apply a thin layer of ARAZLO to the affected areas once daily. Avoid the eyes, mouth, paranasal creases, and mucous membranes. If ARAZLO gets in or near eyes, rinse thoroughly with water. ARAZLO is for topical use only. Not for oral, ophthalmic, or intravaginal use. Wash hands thoroughly after applying ARAZLO. Avoid concomitant use with oxidizing agents, such as benzoyl peroxide. If the concomitant use of ARAZLO with oxidizing agents is required, apply each at different times of the day (e.g. one in the morning and the other in the evening) [see Drug Interactions (7) ] . Use effective sunscreens and wear protective clothing while using ARAZLO [see Warnings and Precautions (5.3) ] . Apply a thin layer of ARAZLO to the affected areas once daily. Avoid the eyes, mouth, paranasal creases, and mucous membranes. ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 )

1 INDICATIONS AND USAGE ARAZLO ® (tazarotene) lotion, 0.045% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. ARAZLO is a retinoid indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. ( 1 )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tazarotene is a retinoid prodrug which is converted to its active form, tazarotenic acid, 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 acne vulgaris is unknown. 12.3 Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Tazarotenic acid is highly bound to plasma proteins (greater than 99%). Systemic exposure following topical application of ARAZLO was evaluated in 28 subjects in an open-label, randomized, pharmacokinetic study. Subjects aged 9 years and older with moderate to severe acne applied approximately 4 grams of ARAZLO to the entire face (excluding eyes and lips), neck, upper chest, upper back and shoulders once daily for 14 Days. The majority of collected samples had concentrations below the limit of quantification (LOQ) for tazarotene (0.005 ng/mL). The mean C max and mean AUC (0-t) values for tazarotene from quantifiable samples were 0.007 ng/mL and 0.164 ng•hr/mL on Day 14 to 15, respectively. The mean C max and AUC (0-t) of tazarotene in subjects aged 9 to less than 12 years was approximately 3.7 and 3.6 fold higher, respectively, compared to that observed in subjects 12 years and older. Tazarotenic acid concentrations were measurable in the majority of samples following single and repeated topical administration of ARAZLO (LOQ = 0.005 ng/mL). The mean C max and AUC (0-t) values for tazarotenic acid from quantifiable samples were 0.365 ng/mL and 5.72 ng•hr/mL on Days 14 to 15, respectively. The mean C max and AUC (0-t) of tazarotenic acid in subjects aged 9 to less than 12 years was approximately 2.4 and 2.3 fold higher, respectively, compared to that observed in subjects 12 years and older.

12.1 Mechanism of Action Tazarotene is a retinoid prodrug which is converted to its active form, tazarotenic acid, 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 acne vulgaris is unknown.

12.3 Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Tazarotenic acid is highly bound to plasma proteins (greater than 99%). Systemic exposure following topical application of ARAZLO was evaluated in 28 subjects in an open-label, randomized, pharmacokinetic study. Subjects aged 9 years and older with moderate to severe acne applied approximately 4 grams of ARAZLO to the entire face (excluding eyes and lips), neck, upper chest, upper back and shoulders once daily for 14 Days. The majority of collected samples had concentrations below the limit of quantification (LOQ) for tazarotene (0.005 ng/mL). The mean C max and mean AUC (0-t) values for tazarotene from quantifiable samples were 0.007 ng/mL and 0.164 ng•hr/mL on Day 14 to 15, respectively. The mean C max and AUC (0-t) of tazarotene in subjects aged 9 to less than 12 years was approximately 3.7 and 3.6 fold higher, respectively, compared to that observed in subjects 12 years and older. Tazarotenic acid concentrations were measurable in the majority of samples following single and repeated topical administration of ARAZLO (LOQ = 0.005 ng/mL). The mean C max and AUC (0-t) values for tazarotenic acid from quantifiable samples were 0.365 ng/mL and 5.72 ng•hr/mL on Days 14 to 15, respectively. The mean C max and AUC (0-t) of tazarotenic acid in subjects aged 9 to less than 12 years was approximately 2.4 and 2.3 fold higher, respectively, compared to that observed in subjects 12 years and older.

20230926

5

3 DOSAGE FORMS AND STRENGTHS Lotion, 0.045% Each gram of ARAZLO contains 0.45 mg (0.045%) tazarotene in a white to off-white topical lotion. Lotion, 0.045% ( 3 )

Arazlo tazarotene CARBOMER COPOLYMER TYPE B (ALLYL PENTAERYTHRITOL CROSSLINKED) CARBOMER HOMOPOLYMER TYPE A (ALLYL PENTAERYTHRITOL CROSSLINKED) DIETHYL SEBACATE EDETATE DISODIUM LIGHT MINERAL OIL METHYLPARABEN PROPYLPARABEN WATER SODIUM HYDROXIDE SORBITAN MONOOLEATE SORBITOL TAZAROTENE TAZAROTENE

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 equivalent to the MRHD (based on AUC comparison). A long-term study with topical application of up to 0.1% of tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Tazarotenic acid systemic exposures at the highest dose was 7 times the MRHD (based on AUC comparison). Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in human lymphocytes. Tazarotene was non-mutagenic in CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in an 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 a tazarotene gel formulation 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 equivalent to the MRHD (based on AUC comparison). No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of tazarotene up to 1 mg/kg/day which produced a systemic exposure 4 times the MRHD (based on AUC comparison). 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 a systemic exposure 6 times the MRHD (based on AUC comparison).

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 equivalent to the MRHD (based on AUC comparison). A long-term study with topical application of up to 0.1% of tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Tazarotenic acid systemic exposures at the highest dose was 7 times the MRHD (based on AUC comparison). Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in human lymphocytes. Tazarotene was non-mutagenic in CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in an 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 a tazarotene gel formulation 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 equivalent to the MRHD (based on AUC comparison). No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of tazarotene up to 1 mg/kg/day which produced a systemic exposure 4 times the MRHD (based on AUC comparison). 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 a systemic exposure 6 times the MRHD (based on AUC comparison).

NDA211882

Arazlo

tazarotene

0187-2098

HUMAN PRESCRIPTION DRUG

TOPICAL

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 45 gram Carton NDC 0187-2098-45 For Topical Use Only Not For Eye Use Rx only ARAZLO ® (tazarotene) Lotion, 0.045% Net Wt. 45 g Ortho Dermatologics carton

7 DRUG INTERACTIONS No formal drug-drug interaction studies were conducted with ARAZLO. Concomitant use with oxidizing agents, as benzoyl peroxide, may cause degradation of tazarotene and may reduce the clinical efficacy of tazarotene. 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, the 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.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryofetal Toxicity Inform patients of childbearing potential of the potential risk to a fetus. To avoid pregnancy, advise these patients to use effective contraception during treatment with ARAZLO. Advise patients to discontinue the medication if pregnant and to inform their healthcare provider of a known or suspected pregnancy [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1), (8.3) ] . Lactation Advise patients to use ARAZLO for the shortest duration possible while breastfeeding. Advise breastfeeding patients not to apply ARAZLO directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.2) ] . Skin Irritation Advise patients to avoid applying ARAZLO to eczematous or sunburned skin. If undue irritation occurs, reduce frequency of application, temporarily interrupt treatment, or discontinue use. Treatment may be resumed once irritation subsides [see Warnings and Precautions (5.2) ] . Photosensitivity and Risk of Sunburn Advise patients to minimize exposure to sunlight and sunlamps; recommend the use of sunscreen products and protective apparel (e.g., wide-brimmed hat) when sun exposure cannot be avoided. Advise patients to avoid using ARAZLO if also taking other medicines that may increase sensitivity to sunlight [see Warnings and Precautions (5.3) ] . Distributed by: Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Companies Inc. Laval, Quebec H7L 4A8, Canada Patented. See https://patents.ortho-dermatologics.com for US patent information. ARAZLO is a trademark of Bausch Health Companies Inc. or its affiliates. © 2023 Bausch Health Companies Inc. or its affiliates 9701202

14 CLINICAL STUDIES The safety and efficacy of once daily use of ARAZLO for the treatment of acne vulgaris were assessed in two multicenter, randomized, double-blind clinical trials in subjects 9 years and older with facial acne vulgaris. Enrolled subjects had a score of moderate (3) or severe (4) on the Evaluator’s Global Severity Score (EGSS), 20 to 50 inflammatory lesions (papules, pustules, and nodules), 25 to 100 non-inflammatory lesions (open and closed comedones) and two or fewer facial nodules. The majority of subjects were White (74%) and female (66%). Approximately 22% were Hispanic/Latino and 42% were younger than 18 years of age. The efficacy endpoints of success on the EGSS, absolute change in noninflammatory lesion count, and absolute change in inflammatory lesion count were assessed at Week 12. Success on the EGSS was defined as at least a 2-grade improvement from Baseline and an EGSS score of clear (0) or almost clear (1). Table 3 lists the efficacy results for trials 1 (NCT03168321) and 2 (NCT03168334). Table 3: Efficacy Results at Week 12 Trial 1 ARAZLO Lotion N=402 Vehicle N=411 Treatment Difference (95% Confidence Interval) EGSS Clear or Almost Clear and 25.5% 13% 12.5% (7.1%, 17.9%) 2-Grade Reduction from Baseline Non-Inflammatory Facial Lesions Mean Absolute Reduction 21.0 16.4 4.5 (2.6, 6.4) Mean Percent Reduction 51.4% 41.5% Inflammatory Facial Lesions Mean Absolute Reduction 15.6 12.4 3.3 (1.9, 4.7) Mean Percent Reduction 55.5% 45.7% Trial 2 ARAZLO Lotion N=397 Vehicle N=404 EGSS Clear or Almost Clear and 2-Grade Reduction from Baseline 29.6% 17.3% 12.3% (6.5%, 18.1%) Non-Inflammatory Facial Lesions Mean Absolute Reduction 24.6 16.6 8.1 (5.9, 10.2) Mean Percent Reduction 60% 41.6% Inflammatory Facial Lesions Mean Absolute Reduction 16.7 13.4 3.2 (1.9, 4.5) Mean Percent Reduction 59.5% 49%

8.5 Geriatric Use Clinical trials of ARAZLO did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.

8.4 Pediatric Use Safety and effectiveness of ARAZLO for the topical treatment of acne vulgaris have been established in pediatric patients age 9 years and older based on evidence from two multicenter, randomized, double-blind, parallel-group, vehicle-controlled, 12-week clinical trials and an open-label pharmacokinetic study. A total of 300 pediatric subjects aged 9 to less than 17 years received ARAZLO in the clinical studies [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . The safety and effectiveness of ARAZLO in pediatric patients below the age of 9 years have not been established.

8.1 Pregnancy Risk Summary ARAZLO is contraindicated in pregnancy. There are no available data on ARAZLO use in pregnant patients to inform a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Based on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, ARAZLO may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The potential risk to the fetus outweighs the potential benefit to the mother; therefore, ARAZLO should be discontinued as soon as pregnancy is recognized. In animal reproduction studies with pregnant rats, reduced fetal body weights and reduced skeletal ossification were observed after topical administration of a tazarotene gel formulation during the period of organogenesis at a dose equivalent to the maximum recommended human dose (MRHD) (based on AUC comparison). In animal reproduction studies with pregnant rabbits, single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies were observed after topical administration of a tazarotene gel formulation at 15 times the MRHD (based on AUC comparison) (see Data) . In animal reproduction studies with pregnant rats and rabbits, malformations, fetal toxicity, developmental delays, and/or behavioral delays were observed after oral administration of tazarotene during the period of organogenesis at doses 1 and 30 times, respectively, the MRHD (based on AUC comparison). In pregnant rats, decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations were observed after oral administration of tazarotene prior to mating through early gestation at doses 6 times the MRHD (based on AUC comparison) (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. 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 an embryofetal development study in rats, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) was topically administered to pregnant rats during gestation days 6 through 17. Reduced fetal body weights and reduced skeletal ossification occurred at this dose (equivalent to the MRHD based on AUC comparison). In an embryofetal development study in rabbits, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) was topically administered to pregnant rabbits during gestation days 6 through 18. Single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies were noted at this dose (15 times the MRHD based on AUC comparison). When tazarotene was given orally to animals, developmental delays were seen in rats; malformations and post- implantation loss were observed in rats and rabbits at doses producing 1 and 30 times, respectively, the MRHD (based on AUC comparison). In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, classic developmental effects of retinoids including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights were observed at this dose (6 times the MRHD based on AUC comparison). A low incidence of retinoid-related malformations was observed at this dose. In a pre- and postnatal development toxicity study, topical administration of a tazarotene gel formulation (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 systemic drug exposure in the rat at this dose would be equivalent to the MRHD (based on AUC comparison).

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary ARAZLO is contraindicated in pregnancy. There are no available data on ARAZLO use in pregnant patients to inform a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Based on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, ARAZLO may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The potential risk to the fetus outweighs the potential benefit to the mother; therefore, ARAZLO should be discontinued as soon as pregnancy is recognized. In animal reproduction studies with pregnant rats, reduced fetal body weights and reduced skeletal ossification were observed after topical administration of a tazarotene gel formulation during the period of organogenesis at a dose equivalent to the maximum recommended human dose (MRHD) (based on AUC comparison). In animal reproduction studies with pregnant rabbits, single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies were observed after topical administration of a tazarotene gel formulation at 15 times the MRHD (based on AUC comparison) (see Data) . In animal reproduction studies with pregnant rats and rabbits, malformations, fetal toxicity, developmental delays, and/or behavioral delays were observed after oral administration of tazarotene during the period of organogenesis at doses 1 and 30 times, respectively, the MRHD (based on AUC comparison). In pregnant rats, decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations were observed after oral administration of tazarotene prior to mating through early gestation at doses 6 times the MRHD (based on AUC comparison) (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. 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 an embryofetal development study in rats, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) was topically administered to pregnant rats during gestation days 6 through 17. Reduced fetal body weights and reduced skeletal ossification occurred at this dose (equivalent to the MRHD based on AUC comparison). In an embryofetal development study in rabbits, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) was topically administered to pregnant rabbits during gestation days 6 through 18. Single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies were noted at this dose (15 times the MRHD based on AUC comparison). When tazarotene was given orally to animals, developmental delays were seen in rats; malformations and post- implantation loss were observed in rats and rabbits at doses producing 1 and 30 times, respectively, the MRHD (based on AUC comparison). In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, classic developmental effects of retinoids including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights were observed at this dose (6 times the MRHD based on AUC comparison). A low incidence of retinoid-related malformations was observed at this dose. In a pre- and postnatal development toxicity study, topical administration of a tazarotene gel formulation (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 systemic drug exposure in the rat at this dose would be equivalent to the MRHD (based on AUC comparison). 8.2 Lactation Risk Summary There are no data on the presence of tazarotene or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of a 14 C-tazarotene gel formulation to the skin of lactating rats, radioactivity was detected in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ARAZLO and any potential adverse effects on the breastfed child from ARAZLO. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use ARAZLO for the shortest duration possible while breastfeeding. Advise breastfeeding patients not to apply ARAZLO directly to the nipple and areola to prevent direct infant exposure. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Pregnancy testing is recommended for patients of childbearing potential within 2 weeks prior to initiating ARAZLO therapy which should begin during a menstrual period. Contraception Advise patients of childbearing potential to use effective contraception during treatment with ARAZLO. 8.4 Pediatric Use Safety and effectiveness of ARAZLO for the topical treatment of acne vulgaris have been established in pediatric patients age 9 years and older based on evidence from two multicenter, randomized, double-blind, parallel-group, vehicle-controlled, 12-week clinical trials and an open-label pharmacokinetic study. A total of 300 pediatric subjects aged 9 to less than 17 years received ARAZLO in the clinical studies [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . The safety and effectiveness of ARAZLO in pediatric patients below the age of 9 years have not been established. 8.5 Geriatric Use Clinical trials of ARAZLO did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.

16 HOW SUPPLIED/STORAGE AND HANDLING ARAZLO (tazarotene) Lotion, 0.045% is a white to off-white lotion supplied in a white aluminum tube as follows: 45 g (NDC 0187-2098-45) Storage and Handling Conditions Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.