What is the use of Zetia (ezetimibe)?

From the Guidelines

Zetia (ezetimibe) should be considered as an adjunct to diet and statin therapy to lower LDL-C levels in patients with atherosclerotic cardiovascular disease (ASCVD) risk, with a recommended dose of 10 mg orally daily, as evidenced by the 2022 ACC expert consensus decision pathway 1. The medication works by inhibiting the NPC1L1 protein, reducing cholesterol absorption in the small intestine.

Key Points to Consider

• Ezetimibe is FDA-approved for use as an adjunct to diet to reduce TC, LDL-C, ApoB, and non-HDL-C in patients with primary hyperlipidemia, either alone or in combination with statin therapy 1.
• The mean percentage reduction in LDL-C with ezetimibe monotherapy is 18%, and 25% when used in combination with statin therapy 1.
• Common adverse effects of ezetimibe include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 1.
• Ezetimibe has been shown to reduce the primary composite endpoint of CV death, nonfatal MI, UA requiring rehospitalization, coronary revascularization, or nonfatal stroke in patients with recent ACS when added to moderate-intensity statin therapy, as demonstrated in the IMPROVE-IT trial 1.
• It is essential to monitor hepatic transaminases before and during treatment with ezetimibe, especially when used in combination with statin therapy 1.

Clinical Considerations

• Patients with ASCVD and baseline LDL-C ≥190 mg/dL who do not achieve ≥50% reduction in LDL-C and LDL-C <70 mg/dL on maximally tolerated statin therapy in combination with nonstatin therapy may benefit from referral to a lipid specialist 1.
• Ezetimibe is generally well-tolerated, and a generic version is available 1.
• The medication should be avoided during pregnancy and lactation due to lack of safety data in humans 1.
• Drug-drug interactions with cyclosporine, fibrates, and bile acid sequestrants should be considered when prescribing ezetimibe 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).

The safety and effectiveness of ezetimibe tablets has not been established in children: younger than 10 years of age with HeFH or HoFH.

Do not take ezetimibe tablets: if you are allergic to ezetimibe or any of the ingredients in ezetimibe tablets

Zetia (Ezetimibe) Uses:

• Lowering elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia
• Used with a statin to lower LDL-C in adults and children 10 years of age and older with heterozygous familial hypercholesterolemia (HeFH)
• 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)
• Lowering elevated sitosterol and campesterol levels in adults and in children 9 years of age and older with homozygous familial sitosterolemia

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From the Research

Zetia Overview

• Zetia, also known as ezetimibe, is a cholesterol absorption inhibitor used to lower low-density lipoprotein (LDL) cholesterol levels 3.
• It is often used in combination with statins to achieve greater LDL cholesterol reduction and improve other lipid parameters 3, 4.

Mechanism of Action

• Ezetimibe works by blocking the intestinal absorption of cholesterol, phytosterols, and certain oxysterols by inhibiting intestinal sterol transporters, specifically Niemann-Pick C1-like 1 proteins 5.
• This mechanism of action allows ezetimibe to decrease LDL cholesterol levels by 10-18% and apolipoprotein B by 11-16% when used as monotherapy 4.

Clinical Efficacy

• Ezetimibe has been shown to be effective in lowering LDL cholesterol levels and reducing the risk of atherosclerotic cardiovascular disease (ASCVD) when used alone or in combination with statins 3, 4, 6.
• The addition of ezetimibe to statin therapy has been found to provide additional LDL cholesterol reduction and ASCVD risk reduction without significant safety concerns 4, 6.
• In patients who are statin intolerant or not receiving statins, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been found to lower LDL cholesterol levels more significantly than ezetimibe 7.

Safety and Side Effects

• Ezetimibe has a favorable safety profile, with a low risk of side effects when used as monotherapy or in combination with statins 3, 4.
• The combination of ezetimibe and statins is generally well-tolerated, with a safety profile comparable to that of statin monotherapy 3, 4.
• However, PCSK9i have been found to have a higher cost and a risk of adverse events such as injection site reactions 6.