What is the use of Zetia (ezetimibe)?

From the Guidelines

Zetia (ezetimibe) is recommended as an adjunct to diet and statin therapy to lower LDL-C levels in patients with atherosclerotic cardiovascular disease (ASCVD) risk, with a dose of 10 mg orally daily, as it has been shown to reduce major cardiovascular events by ~7% when started within 10 days of an acute coronary syndrome, as demonstrated in the IMPROVE-IT trial 1.

Key Points

• Zetia works by inhibiting the NPC1L1 protein, reducing cholesterol absorption in the small intestine, and can be used as monotherapy or in combination with statins.
• The medication is generally well-tolerated, with common side effects including diarrhea, joint pain, and fatigue.
• Regular lipid panel monitoring is necessary to assess effectiveness, typically 4-12 weeks after starting treatment.
• Zetia should not replace statins for most patients with cardiovascular disease but serves as an important adjunct therapy for achieving target LDL cholesterol levels.

Important Considerations

• Contraindications include a history of hypersensitivity to the medication, and warnings/precautions include not recommending its use in patients with moderate/severe hepatic impairment and monitoring hepatic transaminases before and during treatment.
• Drug-drug interactions include cyclosporine, fibrates, and bile acid sequestrants (BAS).
• CV outcomes trials, such as IMPROVE-IT and SHARP, have demonstrated the efficacy of ezetimibe in reducing LDL-C levels and major cardiovascular events.

Prescribing Considerations

• Zetia is available in a generic form and is generally well-tolerated, making it a viable option for patients who require adjunct therapy to achieve target LDL cholesterol levels.
• Patients should be advised to take Zetia consistently at the same time each day and continue heart-healthy lifestyle modifications, including diet and exercise.
• Referral to a lipid specialist or a registered dietitian (RD/RDN) may be considered for patients who require additional guidance on managing their LDL-C levels and ASCVD risk.

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).

The safety and effectiveness of ezetimibe tablets has not been established in children: younger than 10 years of age with HeFH or HoFH. younger than 9 years of age with homozygous familial sitosterolemia. with other types of hyperlipemia.

Zetia (Ezetimibe) Uses:

• Lowering elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia
• Treating heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH)
• Lowering elevated sitosterol and campesterol levels in adults and children 9 years of age and older with homozygous familial sitosterolemia

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From the Research

Zetia (Ezetimibe) Overview

• Zetia, also known as ezetimibe, is a selective cholesterol absorption inhibitor used to treat hypercholesterolemia 3, 4.
• It works by inhibiting the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids 3.

Efficacy and Safety

• Ezetimibe has been shown to reduce low-density lipoprotein cholesterol (LDL) by 15-20% while increasing high-density lipoprotein cholesterol by 2.5-5% when given as monotherapy or in combination with statins or fenofibrate 3.
• The safety profile of ezetimibe is similar to that of placebo when given as monotherapy or in combination with statins 3, 4.
• 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 4.

Combination Therapy

• Combination therapy with ezetimibe and a statin has been shown to be more effective than statin monotherapy in lowering LDL-cholesterol and improving other lipid parameters 4, 5.
• The addition of ezetimibe to a statin allows a greater percentage of patients to achieve treatment goals established in National Cholesterol Education Program (NCEP) guidelines 4.
• Ezetimibe can also be used in combination with other lipid-lowering agents, such as bile acid sequestrants, to achieve additional LDL-C reduction 6.

Specific Patient Populations

• Ezetimibe has been evaluated in patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia 3.
• In patients ≥65 years of age with hypercholesterolemia, ezetimibe/simvastatin combination therapy has been shown to be more effective than atorvastatin alone in achieving LDL-cholesterol targets 5.