Zetia (ezetimibe) is a prescription medication specifically designed to lower elevated levels of low-density lipoprotein (LDL) cholesterol, often referred to as “bad” cholesterol. It represents a distinct class of lipid-lowering agents that work by selectively inhibiting the absorption of cholesterol at the brush border of the small intestine. Unlike statins, which primarily work by reducing the liver’s production of cholesterol, Zetia offers a complementary mechanism of action, making it a valuable option either as monotherapy or in combination with other lipid-modifying treatments. By addressing cholesterol absorption, it provides clinicians with a targeted tool to help patients achieve their LDL-C goals and supports a comprehensive approach to cardiovascular risk reduction.

Features

• Active Pharmaceutical Ingredient: Ezetimibe
• Standard Tablet Dosage Form: 10 mg
• Mechanism of Action: Selective inhibitor of intestinal cholesterol and related phytosterol absorption
• Administration: Oral, with or without food
• Primary Indication: Adjunct to diet for the reduction of elevated LDL-C
• Available as a single-agent tablet and in fixed-dose combinations with simvastatin

Benefits

• Targeted Action: Works directly in the digestive system to reduce the amount of cholesterol your body absorbs from food, offering a mechanism distinct from statin therapy.
• Effective LDL-C Reduction: Clinically proven to significantly lower LDL (“bad”) cholesterol levels, a key modifiable risk factor for atherosclerotic cardiovascular disease.
• Complementary Therapy: Can be effectively combined with statins (HMG-CoA reductase inhibitors) to provide dual-action, additive LDL-C lowering for patients who require further reduction.
• Generally Well-Tolerated Profile: For many patients, it offers an effective cholesterol-lowering option with a side effect profile that may be suitable for those who cannot tolerate statins.
• A1C Neutral: Does not adversely affect glycemic parameters, such as fasting glucose or hemoglobin A1c, which is a consideration for patients with or at risk for diabetes mellitus.
• Convenient Dosing: Simple once-daily oral regimen supports long-term adherence to therapy.

Common use

Zetia is indicated as an adjunct to diet for the reduction of elevated total cholesterol, LDL cholesterol, and Apo B in patients with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), when diet alone is insufficient. It is also used to reduce elevated sitosterol and campesterol in patients with homozygous sitosterolemia (phytosterolemia). Its most common application in clinical practice is as a second-line agent added to a statin for patients who have not achieved their LDL-C goal on a maximally tolerated statin dose, or as monotherapy for patients who are statin-intolerant. It is a cornerstone of combination lipid-lowering therapy.

Dosage and direction

The recommended dosage of Zetia is 10 mg taken once daily, with or without food. It can be taken at any time of day, but taking it at a consistent time is advised. When used in combination with a statin, Zetia may be administered simultaneously with the statin or at a separate time. For patients also taking a bile acid sequestrant (e.g., cholestyramine), Zetia should be taken at least 2 hours before or at least 4 hours after taking the bile acid sequestrant, as these agents can significantly decrease the absorption of ezetimibe. Dosage adjustments are not necessary for elderly patients or those with mild hepatic impairment. The dosage for the fixed-dose combination product containing ezetimibe and simvastatin is based on the patient’s requirements for each individual component.

Precautions

Before starting Zetia, inform your healthcare provider of your complete medical history, especially if you have active liver disease or unexplained persistent elevations in liver transaminases. Liver function tests are recommended before initiation of therapy and thereafter according to clinical judgement, particularly when combined with a statin. Zetia is not recommended in patients with moderate to severe hepatic impairment. Exercise caution in patients who consume substantial quantities of alcohol. While monotherapy with ezetimibe is not associated with muscle injury (myopathy), the risk increases when it is co-administered with a statin. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise.

Contraindications

Zetia is contraindicated in patients with a known hypersensitivity to ezetimibe or any of the excipients in the formulation. The combination of Zetia with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminase levels. The combination of Zetia with a statin is also contraindicated in pregnant and breastfeeding women. Concomitant administration of Zetia with the fibrate gemfibrozil is contraindicated due to an increased risk of cholelithiasis.

Possible side effect

Zetia is generally well-tolerated. The most commonly reported adverse reactions, occurring at a rate greater than placebo, include:

• Upper respiratory tract infection
• Diarrhea
• Arthralgia (joint pain)
• Sinusitis
• Pain in extremity
• Fatigue Less common but more serious side effects can occur, particularly when Zetia is used with a statin. These include:
• Hepatitis, liver enzyme elevations
• Myopathy and rhabdomyolysis (muscle breakdown)
• Allergic reactions, including angioedema (swelling of the face, lips, tongue, and throat) and rash

Drug interaction

Zetia has a low potential for drug-drug interactions due to its minimal metabolism via the cytochrome P450 system. However, several important interactions exist:

• Bile Acid Sequestrants (e.g., cholestyramine): Co-administration significantly decreases the bioavailability of ezetimibe. Dosing should be separated.
• Fibrates (especially gemfibrozil): Concomitant use increases the risk of cholesterol gallstone formation and is contraindicated. Use with other fibrates (e.g., fenofibrate) increases ezetimibe concentrations; the clinical significance is unknown, and monitoring is advised.
• Cyclosporine: Significantly increases ezetimibe concentrations. Use together should be avoided unless the benefits outweigh the risks, and the patient must be closely monitored.
• Statins: While the interaction is pharmacodynamic (additive lipid-lowering effect) rather than pharmacokinetic, the combination increases the risk of adverse effects associated with statins, particularly elevated liver enzymes and myopathy.

Missed dose

If a dose of Zetia is missed, it should be taken as soon as it is remembered on the same day. If a day has passed, the patient should skip the missed dose and resume the usual dosing schedule the next day. Do not take a double dose to make up for a missed dose.

Overdose

There is limited clinical experience with Zetia overdose. In clinical studies, administration of ezetimibe at doses up to 50 mg/day for two weeks was generally well-tolerated. In the event of a suspected overdose, supportive and symptomatic treatment is recommended. Due to the extensive glucuronidation of ezetimibe and its long half-life, measures to enhance elimination are not expected to be effective. Hemodialysis is not expected to significantly enhance clearance.

Storage

Store Zetia tablets at room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). Keep the medication in its original blister package or bottle to protect it from light and moisture. Keep all medications out of the reach of children and pets. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided may not cover all possible uses, directions, precautions, drug interactions, or adverse effects.

Reviews

• “As a cardiologist, I find Zetia to be an invaluable tool. For my patients who are statin-intolerant or need an extra 15-20% LDL reduction on top of their current statin, it’s highly effective and generally very well-tolerated. It fills a specific and important niche in our lipid-lowering arsenal.” – Dr. A. Reynolds, MD, FACC
• “After struggling with muscle pains on several different statins, my doctor switched me to Zetia. I’ve been on it for over a year now and have had no side effects. My cholesterol numbers are finally in the target range. It’s been a game-changer for me.” – Patient, 58
• “The clinical trial data supporting the use of ezetimibe, particularly when added to a statin, is robust. The IMPROVE-IT trial demonstrated a significant cardiovascular benefit, solidifying its role not just in lowering a number, but in actually improving hard patient outcomes.” – Clinical Pharmacist Specialist
• “I appreciate that it works differently than my other medications. It’s easy to take just one pill a day, and I don’t have to think about timing it with meals. It has seamlessly fit into my routine.” – Patient, 65