Glynn M, Jo W, Minowa K, Sanada H, Nejishima H, Matsuuchi H, Okamura H, Pillai R, Mutter L
Dow Pharmaceutical Sciences, A Division of Valeant Pharmaceuticals North America, LLC, 1330 Redwood Way, Petaluma, CA 94594, USA.
Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka, Japan.
Reprod Toxicol. 2015 Apr;52:18-25. doi: 10.1016/j.reprotox.2014.12.007. Epub 2014 Dec 18.
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=5mg/kg/day) but there were no male reproductive effects even in the presence of paternal toxicity (NOAEL=25mg/kg/day). Rat embryo-fetal and perinatal pup lethality was the most sensitive (NOAEL=5mg/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=10mg/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.
