LULICONAZOLE

1 INDICATIONS AND USAGE Luliconazole Cream, 1% is indicated for the topical treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum and Epidermophyton floccosum . Luliconazole Cream, 1% is an azole antifungal indicated for the topical treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum and Epidermophyton floccosum. ( 1 )

2 DOSAGE AND ADMINISTRATION For topical use only. Luliconazole Cream, 1% is not for ophthalmic, oral, or intravaginal use. • When treating interdigital tinea pedis, a thin layer of Luliconazole Cream, 1% should be applied to the affected area and approximately 1 inch of the immediate surrounding area(s) once daily for 2 weeks. • When treating tinea cruris or tinea corporis, Luliconazole Cream, 1% should be applied to the affected area and approximately 1 inch of the immediate surrounding area(s) once daily for 1 week. • For topical use only. Not for ophthalmic, oral, or intravaginal use. ( 2 ) • Interdigital Tinea Pedis: Luliconazole Cream, 1% should be applied to the affected and immediate surrounding area(s) once a day for 2 weeks. ( 2 ) • Tinea Cruris and Tinea Corporis: Luliconazole Cream, 1% should be applied to the affected skin and immediate surrounding area(s) once a day for 1 week. ( 2 )

4 CONTRAINDICATIONS None. None. ( 4 )

7 DRUG INTERACTIONS An in vivo study in adult subjects with moderate to severe interdigital tinea pedis and tinea cruris showed that Luliconazole Cream, 1% is mostly a weak inhibitor of CYP2C19. In a separate trial in adolescent subjects with tinea cruris, in vivo blood levels of Luliconazole Cream, 1%, were seen to approach those levels sufficient to show moderate inhibition of CYP2C19 [see Clinical Pharmacology ( 12.3 )] .

8.1 Pregnancy Risk Summary There are no available data with Luliconazole Cream, 1% use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies with pregnant rats and rabbits, there were no adverse developmental effects observed with subcutaneous administration of luliconazole during organogenesis at doses up to 3 and 24 times, respectively, the maximum recommended human dose (MRHD) [see Data] . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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 to 4% and 15 to 20%, respectively. Data Animal Data The animal multiples of human exposure calculations were based on daily dose body surface area (BSA) comparisons (mg/m 2 ) for the reproductive toxicology studies described in this section and in Section 13.1. The maximum recommended human dose (MRHD) was set at 8 g 1% cream per day (1.33 mg/kg/day for a 60 kg individual, which is equivalent to 49.2 mg/m 2 /day). Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 1, 5 and 25 mg/kg/day luliconazole were administered during the period of organogenesis (gestational days 7-17) to pregnant female rats. No treatment-related effects on maternal toxicity or malformations were noted at 25 mg/kg/day (3 times the MRHD based on BSA comparisons). Increased incidences of skeletal variation (14 th rib) were noted at 25 mg/kg/day. No treatment-related effects on skeletal variation were noted at 5 mg/kg/day (0.6 times the MRHD based on BSA comparisons). Subcutaneous doses of 4, 20 and 100 mg/kg/day luliconazole were administered during the period of organogenesis (gestational days 6-18) to pregnant female rabbits. No treatment-related effects on maternal toxicity, embryofetal toxicity or malformations were noted at 100 mg/kg/day (24 times the MRHD based on BSA comparisons). In a pre- and postnatal development study in rats, subcutaneous doses of 1, 5 and 25 mg/kg/day luliconazole were administered from the beginning of organogenesis (gestation day 7) 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 (0.6 times the MRHD based on BSA comparisons). No treatment effects on postnatal development were noted at 25 mg/kg/day (3 times the MRHD based on BSA comparisons).

6 ADVERSE REACTIONS The most common adverse reactions observed in clinical trials were application site reactions, which occurred in less than 1% of subjects. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals 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 three Phase 3 clinical trials, 616 subjects were exposed to Luliconazole Cream, 1%: 305 with interdigital tinea pedis and 311 subjects with tinea cruris. Subjects with interdigital tinea pedis or tinea cruris applied Luliconazole Cream, 1% or vehicle cream once daily for 14 days or 7 days, respectively, to affected and adjacent areas. During clinical trials with Luliconazole Cream, 1%, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Luliconazole and vehicle arms. Most adverse reactions were mild in severity. A post-approval clinical trial was conducted in 75 subjects age 2 to <18 years old with tinea corporis. The adverse reactions in the Luliconazole Cream, 1% treated population were similar to the vehicle treated population. 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of luliconazole cream, 1%: contact dermatitis and cellulitis. 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.