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

Abstract 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.