What is the use of Zetia (Ezetimibe)?

From the Guidelines

Zetia (ezetimibe) is recommended 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. The medication works by inhibiting the NPC1L1 protein, reducing cholesterol absorption in the small intestine 1. According to the 2022 ACC expert consensus decision pathway, ezetimibe is a nonstatin agent that may be used to manage LDL-related atherosclerotic cardiovascular disease (ASCVD) risk 1. The study highlights that ezetimibe can reduce LDL-C by 18% as monotherapy and by 25% when used in combination with statin therapy 1.

Some key considerations when prescribing ezetimibe include:

• Contraindication: history of hypersensitivity to the medication 1
• Warnings/precautions: not recommended in patients with moderate/severe hepatic impairment, and persistent elevations in hepatic transaminases may occur with concomitant statin therapy 1
• Adverse effects: upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 1
• Use during pregnancy/lactation: no safety data in humans, so it is recommended to avoid use 1
• Drug-drug interactions: cyclosporine, fibrates, and bile acid sequestrants 1

The CV outcomes trials, such as IMPROVE-IT and SHARP, have demonstrated the efficacy of ezetimibe in reducing LDL-C and cardiovascular events 1. Ezetimibe is generally well-tolerated, and a generic version is available, making it a viable option for patients who require LDL-C reduction. It is essential to continue monitoring patients' lipid profiles and adjusting treatment as needed to achieve optimal LDL-C levels 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.
• It can be used as monotherapy or in combination with statins, such as simvastatin, atorvastatin, lovastatin, or pravastatin, to achieve greater reductions in LDL cholesterol levels 3, 4.
• The combination of ezetimibe with a statin has been shown to be more effective than statin monotherapy in lowering LDL cholesterol and improving other lipid parameters 3, 4.
• Ezetimibe can also be used in conjunction with other non-statin therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and bempedoic acid, to synergistically lower LDL cholesterol levels and reduce the risk of major adverse cardiovascular events (MACE) 5.

Mechanism of Action

• Ezetimibe works by reducing the intestinal absorption of cholesterol, which helps to lower LDL cholesterol levels 5, 6.
• It has a favorable pharmacokinetic profile, allowing it to be administered once daily and given in conjunction with statins 3.

Clinical Evidence

• Studies have shown that ezetimibe is an effective lipid-lowering agent, with a safety profile comparable to that of placebo when used as monotherapy 3.
• The addition of ezetimibe to ongoing statin therapy has been shown to offer greater reductions in LDL cholesterol levels compared to doubling the initial statin dose 4.
• Ezetimibe has also been shown to be effective in combination with moderate-intensity statins, with considerable efficacy and better safety and adherence compared to statin intensification alone 7.