Arazlo

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 )

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 )

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 )

5 WARNINGS AND PRECAUTIONS Embryofetal Toxicity : May cause fetal harm when administered during pregnancy. Patients of childbearing potential should have a negative pregnancy test within 2 weeks prior to initiating treatment and use effective contraception during treatment. ( 5.1 ) Skin Irritation : Pain, dryness, exfoliation, erythema, and pruritus may occur with use of ARAZLO. Avoid application to eczematous or sunburned skin. ( 5.2 ) Photosensitivity and Risk for Sunburn : Minimize exposure to sunlight and sunlamps. Use sunscreen and protective clothing when sun exposure cannot be avoided. Administer 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, ARAZLO may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy . Safety in pregnant patients has not been established. The potential risk to the fetus outweighs the potential benefit to the mother; therefore, discontinue ARAZLO as soon as pregnancy is recognized. Tazarotene elicits malformations and developmental effects associated with retinoids after topical and oral administration to pregnant rats and rabbits during organogenesis. However, limited case reports of pregnancy in females enrolled in clinical trials for ARAZLO have not reported a clear association with tazarotene and major birth defects or miscarriage risk [see Contraindications (4) , Use in Specific Populations (8.1) ] . 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 in animals, and it is not known what level of exposure is required for teratogenicity in humans. Advise pregnant patients of the potential risk to a fetus. Obtain a pregnancy test within 2 weeks prior to ARAZLO therapy. Initiate ARAZLO therapy during a menstrual period. Advise patients of childbearing potential to use effective contraception during treatment with ARAZLO [see Dosage and Administration (2) , Use in Specific Populations (8.3) ] . 5.2 Skin Irritation Patients using ARAZLO may experience application site pain, dryness, exfoliation, erythema, and pruritus. Depending upon severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the application of ARAZLO, or discontinue use. Therapy can be resumed, or the frequency of application can be increased, as the patient becomes able to tolerate treatment. Avoid use of concomitant medications and cosmetics that have a strong drying effect. It is recommended to postpone treatment with ARAZLO until the drying effects of these products subside. Avoid application of ARAZLO to eczematous or sunburned skin. 5.3 Photosensitivity and Risk for Sunburn Because of heightened burning susceptibility, minimize unprotected exposure to ultraviolet light including sunlight and sunlamps during the use of ARAZLO. Warn patients who normally experience high levels of sun exposure and those with inherent sensitivity to sun to exercise caution. Use sunscreen products and protective clothing over treated areas when sun exposure cannot be avoided. Patients with sunburn should be advised not to use ARAZLO until fully recovered. ARAZLO should be administered with caution if the patient is taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. Weather extremes, such as wind or cold, may be more irritating to patients using 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%

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).