Qelbree: which tox species, and why?

“There are substantial species differences in the metabolism of viloxazine between the nonclinical species (rats and dogs) and humans.”

“It should be noted that despite the differences in the metabolic profiles, the exposure level to both the parent drug and its major human metabolite (glucuronidated-5-hydroxy-viloxazine) are adequately represented and characterized in rat”

“Viloxazine did not increase the incidence of tumors in rats treated for 2 years at oral doses of 30/22, 87/65/43, and 217/130/87 mg/kg/day.”

“In all three species (rat, mouse, and dog), repeat administration of viloxazine caused dose-dependent hepatocellular hypertrophy and/or vacuolation in the liver.”

“oral administration of viloxazine during the period of organogenesis caused fetal toxicities and delayed fetal development in the rat and maternal toxicities in the rabbit at doses approximately equal to the maximum recommended human dose (MRHD) of 600 mg in adults, based on mg/m 2 .Oral administration of viloxazine to pregnant rats and mice during pregnancy and lactation caused maternal toxicities and deaths and fetal toxicities”

“One Two Year Oral Gavage Carcinogenicity Study in Wistar Rats and One Six-Month Oral Gavage Carcinogenicity Study in rasH2 Transgenic Mice.”

“Viloxazine did not increase the incidence of tumors in rats treated for 2 years at oral doses of 30/22, 87/65/43, and 217/130/87 mg/kg/day.”