Ezetimibe is the first agent of a novel class of selective
cholesterol absorption inhibitors recently approved by the Food and Drug Administration for treatment in the United States.
Ezetimibe inhibits the absorption of biliary and
dietary cholesterol from the small intestine without affecting the absorption of fat-soluble
vitamins,
triglycerides, or
bile acids.
Ezetimibe localizes at the brush border of the small intestine and decreases
cholesterol uptake into the enterocytes. Preclinical studies demonstrated
lipid-lowering properties of
ezetimibe as monotherapy and showed a synergistic effect in combination with 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors (
statins). The efficacy and safety of
ezetimibe 10 mg/day have been established in phase III clinical trials. In these trials,
ezetimibe was investigated as monotherapy, as an add-on to ongoing
statin therapy, and as combination
therapy with
statins in patients with primary
hypercholesterolemia. In addition,
ezetimibe has been evaluated in patients with homozygous and heterozygous
familial hypercholesterolemia and in those with
sitosterolemia. When given as monotherapy or in combination with
statins or
fenofibrate,
ezetimibe reduces
low-density lipoprotein cholesterol (
LDL) by 15-20% while increasing
high-density lipoprotein cholesterol by 2.5-5%. Unlike other intestinally acting
lipid-lowering agents,
ezetimibe does not adversely affect
triglyceride levels and, due to its minimal systemic absorption, drug interactions are few.
Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with
statins. In clinical practice,
ezetimibe has a role as monotherapy for patients who require modest
LDL reductions or cannot tolerate other
lipid-lowering agents. In combination
therapy with a
statin,
ezetimibe is used in patients who cannot tolerate high
statin doses or in those who need additional
LDL reductions despite maximum
statin doses.