What is Ezetimibe (Ezetimibe)?

From the Guidelines

Ezetimibe is a cholesterol-lowering medication that works by reducing the absorption of cholesterol in the small intestine, and it is recommended as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with primary hyperlipidemia, either alone or in combination with statin therapy, with a standard dose of 10 mg taken once daily, with or without food 1.

Key Points

• Ezetimibe is primarily used to treat high cholesterol levels, particularly in patients who cannot tolerate statins or as an add-on therapy when statins alone are not sufficient to reach target cholesterol levels.
• The medication specifically blocks the Niemann-Pick C1-Like 1 (NPC1L1) protein in the intestinal wall, which is responsible for cholesterol uptake.
• Common side effects may include muscle pain, fatigue, and digestive issues, though it generally causes fewer muscle-related side effects than statins.
• Patients taking ezetimibe should continue following a heart-healthy diet and exercise regimen as the medication works best as part of a comprehensive approach to cholesterol management.

Mechanism of Action and Efficacy

• Ezetimibe reduces cholesterol absorption in the small intestine by inhibiting the activity of the NPC1L1 protein, resulting in reduced intestinal cholesterol absorption.
• The addition of ezetimibe to simvastatin has been shown to further reduce LDL-C levels by approximately 24% compared with simvastatin monotherapy in patients with acute coronary syndrome (ACS) 1.
• The IMPROVE-IT trial demonstrated that the addition of ezetimibe to simvastatin resulted in a significant 2% absolute reduction in the composite of cardiovascular death, major coronary event, or stroke compared with placebo after 7 years 1.

Clinical Use and Recommendations

• Ezetimibe is recommended as a second-line therapy in patients who are statin intolerant or do not achieve desired LDL-C lowering while taking maximally tolerated statin therapy.
• The American College of Cardiology (ACC) and American Heart Association (AHA) guidelines recommend ezetimibe as an add-on therapy to maximally tolerated statin therapy in patients with very high-risk ASCVD, with a class IIa recommendation for adding ezetimibe before considering the addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 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, USP is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols.

Ezetimibe is a lipid-lowering medication that works by selectively inhibiting the intestinal absorption of cholesterol and related phytosterols. It is used to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 2 2.

• Key uses of ezetimibe include:
  • Lowering LDL-C in adults with primary hyperlipidemia
  • Treating heterozygous familial hypercholesterolemia (HeFH)
  • Treating homozygous familial sitosterolemia
• Mechanism of action: Selectively inhibits the intestinal absorption of cholesterol and related phytosterols.

From the Research

Definition and Mechanism of Action

• Ezetimibe is a selective cholesterol absorption inhibitor that blocks the intestinal absorption of both biliary and dietary cholesterol 3, 4, 5.
• It localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes 3.
• Ezetimibe appears to exert its effect by blocking intestinal sterol transporters, specifically Niemann-Pick C1-like 1 proteins 5.

Clinical Uses

• Ezetimibe is indicated for monotherapy or in combination with 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors (statins) in patients with primary hypercholesterolemia 3, 4.
• It is also used in combination with simvastatin or atorvastatin in patients with homozygous familial hypercholesterolemia, and as monotherapy in patients with homozygous familial sitosterolemia 4.
• Ezetimibe may be useful in patients at risk for adverse events from other hypocholesterolemic agents, such as liver toxicity or myopathy 4.

Efficacy and Safety

• Ezetimibe reduces low-density lipoprotein cholesterol (LDL-C) by 15-20% and increases high-density lipoprotein cholesterol by 2.5-5% when given as monotherapy or in combination with statins 3.
• It does not adversely affect triglyceride levels and has a minimal systemic absorption, which results in few drug interactions 3, 4.
• Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins 3, 4.