JUBLIA

1 INDICATIONS AND USAGE JUBLIA (efinaconazole) topical solution, 10% is an azole antifungal indicated for the topical treatment of onychomycosis of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes . JUBLIA is an azole antifungal indicated for the topical treatment of onychomycosis of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes . (1)

2 DOSAGE AND ADMINISTRATION Apply JUBLIA to affected toenails once daily for 48 weeks, using the integrated flow-through brush applicator. When applying JUBLIA, ensure the toenail, the toenail folds, toenail bed, hyponychium, and the undersurface of the toenail plate, are completely covered. JUBLIA is for topical use only and not for oral, ophthalmic, or intravaginal use. • Apply JUBLIA to affected toenails once daily for 48 weeks using the integrated flow-through brush applicator. (2) • When applying JUBLIA, ensure the toenail, the toenail folds, toenail bed, hyponychium, and the undersurface of the toenail plate, are completely covered. (2) • For topical use only. Not for oral, ophthalmic, or intravaginal use. (2)

4 CONTRAINDICATIONS None. None. (4)

7 DRUG INTERACTIONS In vitro studies have shown that JUBLIA, at therapeutic concentrations, neither inhibits nor induces cytochrome P450 (CYP450) enzymes.

8.1 Pregnancy Risk Summary There are no available human data for the use of JUBLIA during pregnancy to inform any drug associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, efinaconazole did not cause malformations or any harm to the fetus when administered to pregnant rabbits and rats during the period of organogenesis at subcutaneous doses up to 112 and 154 times, respectively, the Maximum Recommended Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons. Embryolethality was observed only in rats in the presence of maternal toxicity at systemic exposures 559 times the MRHD based on AUC comparisons. Subcutaneous efinaconazole administration to pregnant rats from the beginning of organogenesis through the end of lactation did not cause embryofetal toxicity or developmental effects at systemic exposures 17 times the MRHD based on AUC comparisons (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data Animal Data Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 2, 10 and 50 mg/kg/day efinaconazole were administered during the period of organogenesis (gestational days 6-16) to pregnant female rats. In the presence of maternal toxicity, embryofetal toxicity (increased embryofetal deaths, decreased number of live fetuses, and placental effects) was noted at 50 mg/kg/day (559 times the MRHD based on AUC comparisons). No embryofetal toxicity was noted at 10 mg/kg/day (112 times the MRHD based on AUC comparisons). No malformations were observed at 50 mg/kg/day (559 times the MRHD based on AUC comparisons). Subcutaneous doses of 1, 5, and 10 mg/kg/day efinaconazole were administered during the period of organogenesis (gestational days 6-19) to pregnant female rabbits. In the presence of maternal toxicity, there was no embryofetal toxicity or malformations at 10 mg/kg/day (154 times the MRHD based on AUC comparisons). In a pre- and postnatal development study in rats, subcutaneous doses of 1, 5 and 25 mg/kg/day efinaconazole were administered from the beginning of organogenesis (gestation day 6) through the end of lactation (lactation day 20). In the presence of maternal toxicity, embryofetal toxicity (increased prenatal pup mortality, reduced live litter sizes and increased postnatal pup mortality) was noted at 25 mg/kg/day. No embryofetal toxicity was noted at 5 mg/kg/day (17 times the MRHD based on AUC comparisons). No effects on postnatal development were noted at 25 mg/kg/day (89 times the MRHD based on AUC comparisons).

6 ADVERSE REACTIONS The most common adverse reactions (incidence >1%) were ingrown toenails, application site dermatitis, application site vesicles, and application site pain. (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 practice. In two clinical trials, 1227 subjects were treated with JUBLIA, 1161 for at least 24 weeks and 780 for 48 weeks. Adverse reactions reported within 48 weeks of treatment and in at least 1% of subjects treated with JUBLIA and those reported in subjects treated with the vehicle are presented in Table 1 . Table 1: Adverse Reactions Reported by at Least 1% of Subjects Treated for up to 48 Weeks Adverse Event, n (%) JUBLIA (N=1,227) Vehicle (N=413) Ingrown toenail 28 (2.3%) 3 (0.7%) Application site dermatitis 27 (2.2%) 1 (0.2%) Application site vesicles 20 (1.6%) 0 (0.0%) Application site pain 13 (1.1%) 1 (0.2%) 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of JUBLIA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. General Disorders and Administration Site Conditions: Application site erythema and exfoliation Skin and Subcutaneous Tissue Disorders: Onychomadesis, Nail discoloration