Zevas Mechanism of Action

Lipid Modifying Agents.
Pharmacology: Toxicology: Rosuvastatin: Preclinical data reveal no special hazard to humans based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and carcinogenicity potential.
Reproductive toxicity was evident in rats, with reduced litter sizes, litter weight and pup survival observed at maternally toxic doses, where several times above the therapeutic exposure level.
Pharmacokinetic studies show an approximate 2-fold elevation in median AUC and Cmax in Asian subjects (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with Caucasians. A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics between Caucasian and Black groups.
Ezetimibe: Carcinogenicity: A 104-week dietary carcinogenicity study with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~ 20 x the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). A 104-week dietary carcinogenicity study with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (> 150 x the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). There were no statistically significant increases in tumor incidences in drug-treated rats or mice.
Mutagenicity: No evidence of mutagenicity was observed in vitro in a microbial mutagenicity test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation.
In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test.
Reproductive toxicity: In fertility studies conducted in rats taking ezetimibe orally, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 x the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe).