Tavaborole

Tavaborole topical solution, 5% is an oxaborole antifungal indicated for the treatment of onychomycosis of the toenails due to Trichophyton rubrum or Trichophyton mentagrophyte. Tavaborole topical solution is an oxaborole antifungal indicated for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum or Trichophyton mentagrophytes . (1)

Tavaborole topical solution, 5% is a clear, colorless alcohol-based solution. Each milliliter of solution contains 43.5 mg (5% w/w) of tavaborole Solution, 5% (3)

None. None. (4)

Common adverse reactions occurring in ≥1% in subjects treated with tavaborole topical solution included application site exfoliation, ingrown toenail, application site erythema, and application site dermatitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 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, 791 subjects were treated with Tavaborole topical solution. The most commonly reported adverse reactions are listed below (Table 1). Table 1 : Adverse Reactions Occurring in ≥1% of Tavaborole topical solution, 5%-Treated Subjects and at a Greater Frequency than Observed with Vehicle Preferred Term Tavaborole topical solution N= 791 n(%) Vehicle N= 395 n(%) Application site exfoliation 21 (2.7%) 1 (0.3%) Ingrown toenail 20 (2.5%) 1 (0.3%) Application site erythema 13 (1.6%) 0 (0%) Application site dermatitis 10 (1.3%) 0 (0%)

6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of Tavaborole topical solution. 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 product exposure: Hypersensitivity; contact allergy

8.1 Pregnancy Risk Summary There are no available data on tavaborole topical solution use in pregnant women to inform a drug associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. In oral animal reproductive studies, administration of tavaborole during the period of organogenesis resulted in embryofetal toxicity and malformations at 570 times the Maximum Recommended Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons in rats and embryofetal toxicity at 155 times the MRHD based on AUC comparisons in rabbits. Embryofetal toxicity was noted following dermal administration in rabbits up to 36 times the MRHD based on AUC comparisons [ see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects in the U.S. general population is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data Oral Administration: In an oral embryofetal development study in rats, oral doses of 30, 100, and 300 mg/kg/day tavaborole were administered during the period of organogenesis (gestational days 6-19) to pregnant female rats. In the presence of maternal toxicity, embryofetal toxicity (increased embryofetal resorption and/or deaths) and drug-related skeletal malformations and variations suggestive of delayed development (i.e., a delay in ossification) were noted in fetuses at 300 mg/kg/day tavaborole [570 times the MRHD based on AUC comparisons]. No developmental toxicity was noted in rats at 100 mg/kg/day tavaborole (26 times the MRHD based on AUC comparisons). In an oral embryofetal development study in rabbits, oral doses of 15, 50, and 150 mg/kg/day tavaborole were administered during the period of organogenesis (gestational days 7-19) to pregnant female rabbits. In the presence of maternal toxicity, excessive embryofetal mortality due to post-implantation loss was noted at 150 mg/kg/day tavaborole. No drug related malformations were noted in rabbits at 150 mg/kg/day tavaborole (155 times the MRHD based on AUC comparisons). No embryofetal mortality was noted in rabbits at 50 mg/kg/day tavaborole (16 times the MRHD based on AUC comparisons). In an oral pre-and post-natal development study in rats, oral doses of 15, 60, and 100 mg/kg/day tavaborole were administered from the beginning of organogenesis (gestation day 6) through the end of lactation (lactation day 20). In the presence of minimal maternal toxicity, no embryofetal toxicity or effects on postnatal development were noted at 100 mg/kg/day (29 times the MRHD based on AUC comparisons). Topical administration: In a dermal embryofetal development study in rabbits, topical doses of 1%, 5%, and 10% tavaborole solution were administered during the period of organogenesis (gestational days 6-28) to pregnant female rabbits. A dose dependent increase in dermal irritation at the treatment site was noted at 5% and 10% tavaborole solution. A decrease in fetal bodyweight was noted at 10% tavaborole solution. No drug related malformations were noted in rabbits at 10% tavaborole solution (36 times the MRHD based on AUC comparisons). No embryofetal toxicity was noted in rabbits at 5% tavaborole solution (26 times the MRHD based on AUC comparisons).

8.2 Lactation Risk Summary There is no information available on the presence of tavaborole in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production after topical application of tavaborole topical solution to women who are breastfeeding. tavaborole topical solution is systemically absorbed. The lack of clinical data during lactation precludes a clear determination of the risk of tavaborole topical solution to a breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tavaborole topical solution and any potential adverse effects on the breastfed child from tavaborole topical solution or from the underlying maternal condition.

8.4 Pediatric Use The safety and efficacy of tavaborole topical solution were established in patients 6 years of age and older. Use of tavaborole topical solution in these age groups is supported by evidence from adequate and well-controlled studies of tavaborole topical solution in adults with additional data from an open-label pharmacokinetics study of tavaborole in subjects 12 years to less than 17 years old [ see Clinical Pharmacology (12.3) ].

8.5 Geriatric Use In clinical trials of 791 subjects who were exposed to tavaborole topical solution, 19% were 65 years of age and over, while 4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Tavaborole topical solution is an oxaborole antifungal [see Clinical Pharmacology (12.4 ) ].