What is the use of Zetia (Ezetimibe)?

From the Guidelines

Zetia (ezetimibe) is a cholesterol-lowering medication that should be used as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia, either alone or in combination with statin therapy, at a dose of 10 mg orally daily, with or without food, as recommended by the 2022 ACC expert consensus decision pathway 1. The primary mechanism of action of ezetimibe is the inhibition of the NPC1L1 protein, which reduces cholesterol absorption in the small intestine.

• The FDA-approved indications for ezetimibe include:
  • Reducing total cholesterol, LDL-C, apolipoprotein B, and non-high-density lipoprotein cholesterol in patients with primary hyperlipidemia, either alone or in combination with statin therapy
  • Reducing total cholesterol, LDL-C, apolipoprotein B, and non-high-density lipoprotein cholesterol in patients with mixed hyperlipidemia in combination with fenofibrate
  • Reducing total cholesterol and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) in combination with atorvastatin or simvastatin
  • Reducing sitosterol and campesterol in patients with homozygous sitosterolemia (phytosterolemia)
• The mean percentage reduction in LDL-C with ezetimibe monotherapy is 18%, and in combination with statin therapy, it is 25% 1.
• Common adverse effects of ezetimibe include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities, and when used in combination with statin therapy, nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, and diarrhea 1.
• Ezetimibe has been shown to reduce the risk of cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) when used in combination with statin therapy, as demonstrated in the IMPROVE-IT and SHARP trials 1.
• The Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult 2021 recommend adding ezetimibe to maximally tolerated statin therapy when LDL cholesterol level remains ≥70 mg/dL (1.8 mmol/L) in patients with very high cardiovascular risk, and adding a PCSK9 inhibitor if the LDL cholesterol level on maximally tolerated statin and ezetimibe therapy remains ≥100 mg/dL (2.6 mmol/L) 1.

From the FDA Drug Label

Ezetimibe tablets is a medicine used with a cholesterol lowering diet: and with other cholesterol medicines called a statin, or alone (when additional cholesterol lowering treatments are not possible), to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia (too many fats in your blood), including heterozygous familial hypercholesterolemia (HeFH). Ezetimibe tablets is also used: with a statin and other cholesterol lowering treatments to lower elevated LDL-C levels in adults and patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH). Ezetimibe tablets may be used to lower elevated sitosterol and campesterol levels in adults and in children 9 years of age and older with homozygous familial sitosterolemia (a rare inherited condition that prevents the body from getting rid of cholesterol from plants)

The use of Zetia (Ezetimibe) is to:

• Lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia
• Treat heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH)
• Lower elevated sitosterol and campesterol levels in adults and children with homozygous familial sitosterolemia 2

From the Research

Use of Zetia (Ezetimibe)

• Zetia (Ezetimibe) is a cholesterol absorption inhibitor used to lower low-density lipoprotein (LDL) cholesterol levels 3, 4, 5, 6.
• It can be used as monotherapy or in combination with statins to achieve significant improvements in LDL-cholesterol levels and other lipid parameters 3, 4, 6.
• The combination of ezetimibe with a statin is more effective than statin monotherapy in lowering LDL-cholesterol and improving other lipid parameters 3, 4, 6.
• Ezetimibe has a favorable pharmacokinetic profile, allowing it to be administered once daily and given in conjunction with statins 3, 6.
• It is used in the management of hypercholesterolemia, particularly in patients who do not reach LDL-cholesterol goals with statins alone 3, 4, 5, 6.
• Ezetimibe has been shown to be effective in reducing major vascular events, including death, cardiovascular death, myocardial infarction, stroke, and coronary revascularization, when used as part of a more-intensive LDL-lowering treatment strategy 7.

Mechanism of Action

• Ezetimibe acts at the brush border of the small intestine, blocking the absorption of dietary and biliary cholesterol and plant sterols, resulting in intracellular cholesterol depletion 6.
• The molecular target of ezetimibe is the Niemann-Pick C1-like transporter 6.

Clinical Use

• Ezetimibe can be used in conjunction with a statin at the beginning of therapy or added if patients do not achieve their LDL-cholesterol goal with statins alone 3, 4, 6.
• It is an attractive adjunct therapy for the treatment of hypercholesterolemia due to its excellent safety and tolerability profile and once-daily dosing 6.