Efinaconazole: Developmental and reproductive toxicity potential of a novel antifungal azole

•The reproductive toxicity of SC efinaconazole was characterized.•Efinaconzole did not impair rat fertility.•Efinaconazole reduced F1 viability and survival in rats but not rabbits.•Efinaconazole, unlike other triazole antifungals, was not teratogenic.•Efinaconazole is safe for topical nail treatment of onychomycosis.

Efinaconazole is a new triazole antifungal for topical treatment of onychomycosis. The reproductive and developmental toxicity of efinaconazole was characterized in fertility and early embryonic development (rat), embryo-fetal development (rat and rabbit), and peri/post-natal development (rat) studies in accordance with current ICH guidances. In the fertility study, maternal reproductive toxicity was noted as estrous cycle prolongation (NOAEL = 5 mg/kg/day) but there were no male reproductive effects even in the presence of paternal toxicity (NOAEL = 25 mg/kg/day). Rat embryo-fetal and perinatal pup lethality was the most sensitive (NOAEL = 5 mg/kg/day) efinaconazole developmental toxicity and was noted at maternally toxic doses. Efinaconazole did not affect rabbit embryo-fetal development at maternally toxic doses (NOAEL = 10 mg/kg/day). No malformations were induced by efinaconazole in rats or rabbits. When compared with systemic exposures observed in onychomycosis patients, embryo-fetal toxicity in rats was noted at high (>100-fold) multiples of systemic exposure.