What is Zetia (ezetimibe) used for?

What is Zetia (Ezetimibe) Used For?

Zetia (ezetimibe) is a cholesterol-lowering medication used to reduce LDL cholesterol by blocking intestinal cholesterol absorption, primarily in patients with high or very high cardiovascular risk who need additional lipid lowering beyond statins alone, or as monotherapy in statin-intolerant patients. 1

Primary Indications

Cardiovascular Risk Reduction

• Ezetimibe reduces myocardial infarctions and stroke in patients with very high and high cardiovascular risk when added to statins or used alone in statin-intolerant patients (moderate to high certainty evidence), but does NOT reduce mortality. 1
• Ezetimibe should NOT be added in patients with low cardiovascular risk, as the burden outweighs benefits. 1

Specific FDA-Approved Uses

Primary Hyperlipidemia (High Cholesterol):

• Used with a cholesterol-lowering diet and statins (or alone when statins cannot be used) to lower elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). 2
• Approved with statins to lower LDL-C in adults and children ≥10 years old with HeFH. 2

Homozygous Familial Hypercholesterolemia (HoFH):

• Used with statins and other cholesterol-lowering treatments in adults and patients ≥10 years old with HoFH (an inherited condition causing extremely high cholesterol). 2

Mixed Hyperlipidemia:

• Used with fenofibrate to lower elevated LDL-C in adults with mixed hyperlipidemia. 2

Homozygous Familial Sitosterolemia:

• Used to lower elevated sitosterol and campesterol levels in adults and children ≥9 years old with this rare inherited condition that prevents elimination of plant cholesterol. 2

Mechanism of Action

• Ezetimibe selectively blocks the Niemann-Pick C1-Like 1 (NPC1L1) protein at the intestinal brush border, preventing cholesterol uptake into enterocytes. 3, 4
• It inhibits absorption of both dietary and biliary cholesterol by approximately 54-58% without affecting fat-soluble vitamins, triglycerides, or bile acids. 4, 5
• This selective mechanism distinguishes it from bile acid sequestrants, which can interfere with absorption of other nutrients and medications. 3

Clinical Positioning Based on Cardiovascular Risk

Very High and High Cardiovascular Risk Patients

When Already on Statins:

• Add ezetimibe when LDL-C remains ≥70 mg/dL (1.8 mmol/L) despite maximally tolerated statin therapy. 1
• Ezetimibe is preferred over PCSK9 inhibitors as the second-line agent due to cost-effectiveness and similar efficacy. 1
• If LDL-C remains ≥100 mg/dL (2.6 mmol/L) on statin plus ezetimibe, consider adding a PCSK9 inhibitor. 1

For Statin-Intolerant Patients:

• Use ezetimibe as monotherapy in patients at very high or high cardiovascular risk who cannot tolerate statins. 1
• Consider adding a PCSK9 inhibitor to ezetimibe if LDL-C goals are not met. 1

Low and Moderate Cardiovascular Risk Patients

• Do NOT add ezetimibe in low cardiovascular risk patients—the burden outweighs any potential benefit. 1
• Evidence does not support use in moderate cardiovascular risk patients. 1

Expected Lipid Effects

• LDL-C reduction: 15-20% as monotherapy; additional 21-25% reduction when added to statins. 6, 4, 5
• HDL-C increase: 2.5-9% (modest benefit). 6, 5
• Triglycerides: No adverse effect (unlike bile acid sequestrants). 6, 5

Important Safety Considerations

Liver Function Monitoring

• Obtain baseline hepatic transaminases before starting ezetimibe. 7
• Monitor liver function tests as clinically indicated, especially when combined with statins. 7
• Discontinue if persistent ALT elevations ≥3 times upper limit of normal occur. 7
• Contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C). 7

Muscle-Related Adverse Effects

• Ezetimibe may cause myopathy and rhabdomyolysis, particularly when combined with statins. 2
• Instruct patients to report unexplained muscle pain, tenderness, or weakness, especially if accompanied by malaise or fever. 2

Drug Interactions

• Cyclosporine: Increases ezetimibe exposure; monitor cyclosporine levels carefully. 8
• Bile acid sequestrants (cholestyramine): Significantly decrease ezetimibe bioavailability; administer ezetimibe at least 2 hours before or 4 hours after bile acid sequestrants. 8
• Fibrates: May increase ezetimibe exposure, but clinical significance is minor. 8
• Minimal interactions with statins, digoxin, warfarin, or oral contraceptives. 8

Dosing and Administration

• Standard dose: 10 mg once daily, with or without food. 2, 8
• Can be taken morning or evening for convenience. 2, 8
• No dosage adjustment needed for age, sex, race, or mild hepatic/renal impairment. 8

Common Pitfalls to Avoid

• Don't use LDL-C targets alone to justify ezetimibe—focus on absolute cardiovascular risk reduction in high and very high-risk patients, not just achieving arbitrary cholesterol numbers. 1
• Don't prescribe in low-risk patients—this represents unnecessary treatment burden without meaningful benefit. 1
• Don't forget liver function monitoring—baseline and periodic monitoring is essential, especially with concomitant statin use. 7
• Don't co-administer with cholestyramine simultaneously—separate administration by several hours to maintain efficacy. 8