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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Dietary Cholesterol Absorption Inhibitor [EPC]
Ezetimibe is a potent dietary cholesterol absorption inhibitor used to lower LDL cholesterol by targeting the NPC1L1 transporter in the small intestine. It is frequently prescribed as monotherapy or in combination with statins to manage hyperlipidemia.
Name
Ezetimibe
Raw Name
EZETIMIBE
Category
Dietary Cholesterol Absorption Inhibitor [EPC]
Drug Count
5
Variant Count
81
Last Verified
February 17, 2026
RxCUI
476345, 476349, 476350, 476351, 1245420, 1245430, 1245441, 1245449, 349556, 352304, 2283230, 2283236
UNII
EOR26LQQ24, AGG2FN16EV, 1EJ6Z6Q368
About Ezetimibe
Ezetimibe is a potent dietary cholesterol absorption inhibitor used to lower LDL cholesterol by targeting the NPC1L1 transporter in the small intestine. It is frequently prescribed as monotherapy or in combination with statins to manage hyperlipidemia.
Detailed information about Ezetimibe
References used for this content
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Ezetimibe.
Ezetimibe is a lipid-lowering compound that represents a unique class of medications known as dietary cholesterol absorption inhibitors. Unlike statins (HMG-CoA reductase inhibitors), which primarily work by inhibiting the endogenous production of cholesterol in the liver, ezetimibe targets the exogenous pathway—specifically the absorption of cholesterol from the diet and bile within the small intestine. It was first approved by the U.S. Food and Drug Administration (FDA) in October 2002 under the brand name Zetia. Since its introduction, it has become a cornerstone in the management of hypercholesterolemia (high cholesterol), particularly for patients who cannot achieve target Low-Density Lipoprotein (LDL) levels with statins alone or those who are statin-intolerant.
Pharmacologically, ezetimibe belongs to the class of azetidinone derivatives. Its primary role is to reduce the amount of cholesterol available to the liver cells, which in turn leads to an upregulation of LDL receptors on the surface of hepatocytes (liver cells). This upregulation enhances the clearance of LDL cholesterol from the blood, effectively lowering circulating levels of 'bad' cholesterol. Ezetimibe is often utilized as an adjunct to dietary modifications and is frequently co-administered with HMG-CoA reductase inhibitors (statins) or, more recently, with Adenosine Triphosphate-Citrate Lyase (ACL) inhibitors like bempedoic acid to provide a synergistic effect on lipid reduction.
The mechanism of action for ezetimibe is highly localized and specific. The drug targets a transport protein located on the brush border membrane of the enterocytes (intestinal absorptive cells) in the small intestine. This protein is known as Niemann-Pick C1-Like 1 (NPC1L1). By binding to and inhibiting the function of NPC1L1, ezetimibe prevents the uptake of both dietary cholesterol and biliary cholesterol (cholesterol secreted into the bile by the liver) into the intestinal cells.
At the molecular level, this inhibition does not affect the absorption of fat-soluble vitamins (A, D, E, and K), triglycerides, or bile acids, which distinguishes it from older medications like bile acid sequestrants. Once the absorption of cholesterol is reduced, the delivery of intestinal cholesterol to the liver is significantly diminished. This depletion of hepatic cholesterol stores triggers a compensatory mechanism: the liver increases the expression of LDL receptors. These receptors 'pull' LDL particles out of the bloodstream to replenish the liver's cholesterol pool. The net result is a significant reduction in plasma LDL-C levels, typically ranging from 15% to 20% when used as monotherapy. When combined with a statin, the dual inhibition of both synthesis and absorption can lead to much more dramatic reductions in LDL-C, often exceeding 50%.
Understanding the pharmacokinetics of ezetimibe is essential for optimizing its clinical use. The drug follows a complex pathway involving rapid metabolism and extensive enterohepatic recirculation.
Ezetimibe is FDA-approved for several specific indications related to lipid management:
Off-label, healthcare providers may occasionally consider ezetimibe for patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), as some studies suggest it may reduce hepatic fat accumulation, though this is not yet a standard FDA-approved indication.
Ezetimibe is primarily available in the following form:
It is also available in several fixed-dose combination tablets, such as:
> Important: Only your healthcare provider can determine if Ezetimibe is right for your specific condition. The choice between monotherapy and combination therapy depends on your cardiovascular risk profile and baseline lipid levels.
The standard recommended dose for ezetimibe in adults, regardless of the specific indication (Primary Hyperlipidemia, Homozygous Familial Hypercholesterolemia, or Sitosterolemia), is 10 mg once daily.
Clinical trials have shown that increasing the dose beyond 10 mg does not result in a significant further reduction in LDL cholesterol but may increase the risk of side effects. Therefore, the 10 mg dose is considered the ceiling dose for therapeutic efficacy. When used in combination with a statin, the 10 mg dose of ezetimibe remains constant, while the statin dose is adjusted based on the patient's individual needs and response.
Ezetimibe is approved for use in children and adolescents for specific conditions:
Ezetimibe has not been studied in children under the age of 9 for sitosterolemia or under the age of 10 for hyperlipidemia. Therefore, use in these younger age groups is not recommended unless specifically directed by a pediatric lipid specialist.
No dosage adjustment is necessary for patients with renal impairment (kidney disease). Clinical data suggest that the pharmacokinetics of ezetimibe are not significantly altered in patients with mild, moderate, or severe renal disease, including those on dialysis.
No dosage adjustment is required for geriatric patients. While plasma concentrations of ezetimibe are slightly higher in the elderly (aged 65 and older), the safety and efficacy profiles remain consistent with those observed in younger adults.
If you miss a dose of ezetimibe, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular dosing schedule. Do not take two doses at once to make up for a missed one.
In the event of an overdose, contact your local poison control center or seek emergency medical attention immediately. While ezetimibe has a high safety margin and reports of serious toxicity from overdose are rare, symptoms may include gastrointestinal upset or intensified side effects. Treatment is generally supportive and based on the symptoms presented.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, as this may cause your cholesterol levels to rise rapidly.
Ezetimibe is generally well-tolerated by most patients. However, like all medications, it can cause side effects. When taken as monotherapy (alone), the most commonly reported side effects include:
When ezetimibe is taken with a statin, the profile of common side effects shifts slightly to include:
These effects occur in a smaller percentage of the population but are still documented in clinical literature:
Rare but documented side effects include:
While rare, some side effects are medical emergencies.
> Warning: Stop taking Ezetimibe and call your doctor immediately if you experience any of these:
For most patients, ezetimibe is safe for long-term use. The primary concern with prolonged therapy is the potential for cumulative effects on the liver or muscles, especially when used in combination with other lipid-lowering agents. Long-term data from the IMPROVE-IT trial (2015) involving over 18,000 patients showed that ezetimibe maintained its safety profile over several years of continuous use without an increased risk of cancer or major organ damage.
Unlike some other cardiovascular medications, the FDA has not found it necessary to issue a boxed warning for ezetimibe. However, it is vital to remember that when ezetimibe is used in combination with a statin, the contraindications and warnings associated with that specific statin (such as pregnancy contraindications) must be strictly followed.
Report any unusual symptoms to your healthcare provider. Even mild side effects should be discussed if they interfere with your quality of life or your ability to remain compliant with the medication regimen.
Ezetimibe is a potent medication that requires careful medical supervision. Before starting treatment, patients must provide a full medical history to their healthcare provider. The most critical safety consideration is the health of the liver and muscles, particularly because ezetimibe is often used in conjunction with statins, which are also known to affect these systems. Patients should be aware that while ezetimibe lowers cholesterol, it is not a substitute for a heart-healthy diet and regular exercise. Regular follow-up appointments and blood tests are necessary to ensure the medication is working effectively and safely.
As of the latest clinical updates in 2024, there are no FDA black box warnings for ezetimibe as a monotherapy. It is considered to have a favorable safety profile compared to many other classes of lipid-lowering agents. However, when ezetimibe is prescribed as a fixed-dose combination (e.g., with simvastatin), the black box warnings for the companion drug apply.
When ezetimibe is used alone, the incidence of significant liver enzyme elevations is low (similar to placebo). However, when added to a statin, the risk of liver enzyme elevations (specifically ALT and AST) increases slightly. Healthcare providers typically perform liver function tests (LFTs) before starting therapy and periodically thereafter. If a patient develops persistent elevations in transaminases (greater than 3 times the upper limit of normal), the medication may need to be discontinued.
There have been rare reports of myopathy (muscle disease) and rhabdomyolysis associated with ezetimibe. The risk is significantly higher when ezetimibe is used with a statin or in patients with pre-existing risks for muscle damage (such as elderly patients, those with hypothyroidism, or those with renal impairment). Patients must be educated to report any unexplained muscle pain, tenderness, or weakness immediately.
Ezetimibe is not recommended for patients with moderate or severe hepatic impairment. In these patients, the 'area under the curve' (AUC)—a measure of drug exposure—can increase by 3 to 4 times the normal level, potentially increasing the risk of toxicity.
While rare, hypersensitivity reactions, including angioedema (swelling under the skin) and skin rashes, have occurred. Patients with a known allergy to any component of the tablet should not take ezetimibe.
To ensure the safety of ezetimibe therapy, the following monitoring is usually recommended:
Ezetimibe is not known to cause significant impairment of motor skills or cognitive function. However, because some patients experience dizziness or fatigue, it is advisable to see how you react to the medication before driving or operating heavy machinery.
There is no direct interaction between ezetimibe and alcohol. However, chronic or excessive alcohol consumption can lead to liver disease and can also raise triglyceride levels, counteracting the benefits of the medication. Patients with a history of heavy alcohol use should discuss this with their doctor, as they may be at a higher risk for liver enzyme elevations when taking ezetimibe with a statin.
Ezetimibe does not require a tapering period. However, if you stop taking the medication, your cholesterol levels will likely return to their previous high levels within a few weeks. Do not stop the medication without consulting your doctor, as this increases your long-term risk of cardiovascular events like heart attack or stroke.
> Important: Discuss all your medical conditions with your healthcare provider before starting Ezetimibe, especially if you have a history of liver disease, kidney disease, or unexplained muscle aches.
While ezetimibe has fewer contraindications than many other drugs, certain combinations are strictly avoided due to the risk of severe side effects:
Cyclosporine is an immunosuppressant used in organ transplants. Co-administration of ezetimibe and cyclosporine can lead to a significant increase in the blood levels of both drugs. In some studies, ezetimibe exposure increased 12-fold in transplant patients taking cyclosporine. If these drugs must be used together, doctors will monitor ezetimibe levels (if possible) and renal function closely.
Fibrates are another class of lipid-lowering drugs. Taking ezetimibe with fibrates (especially gemfibrozil) increases the concentration of ezetimibe in the blood. Furthermore, both fibrates and ezetimibe can increase the amount of cholesterol in the bile, potentially increasing the risk of gallstones (cholelithiasis). The safety and efficacy of ezetimibe with gemfibrozil have not been established, and this combination is generally discouraged.
Bile acid sequestrants work by binding bile acids in the intestine. Unfortunately, they also bind to ezetimibe, reducing its absorption by approximately 50% to 80%. This significantly reduces the efficacy of ezetimibe. To manage this, ezetimibe should be taken at least 2 hours before or 4 hours after the bile acid sequestrant.
There have been rare reports of increased International Normalized Ratio (INR) in patients taking ezetimibe concurrently with warfarin (a blood thinner). If you are taking warfarin, your doctor will likely monitor your INR more frequently when ezetimibe is added to or deleted from your regimen.
Ezetimibe does not typically interfere with standard laboratory tests, other than the intended changes in the lipid profile and potential elevations in liver enzymes or CPK. It does not cause false positives on drug screenings.
Most interactions with ezetimibe occur through one of three mechanisms:
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and vitamins.
There are specific circumstances where ezetimibe must never be used due to the high risk of harm:
These are conditions where the drug should be used with extreme caution and only if the benefits outweigh the risks:
There is no known cross-sensitivity between ezetimibe and other classes of lipid-lowering drugs like statins, fibrates, or PCSK9 inhibitors. However, patients who have experienced severe allergic reactions to other azetidinone-based chemicals (though rare in medicine) should be monitored closely during the first few doses of ezetimibe.
> Important: Your healthcare provider will evaluate your complete medical history, including your liver function and current medications, before prescribing Ezetimibe to ensure it is safe for you.
Ezetimibe is classified by the FDA as Pregnancy Category C for monotherapy. This means that animal reproduction studies have shown an adverse effect on the fetus, but there are no adequate and well-controlled studies in humans. In animal studies, ezetimibe crossed the placenta and was associated with skeletal variations in the fetus at high doses.
Crucial Note: If ezetimibe is used in combination with a statin, the combination is Category X (Contraindicated). Statins are known to be teratogenic (cause birth defects) and are essential for fetal development of cholesterol-dependent structures. Ezetimibe should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, which is rarely the case for cholesterol management during the nine months of gestation.
It is unknown whether ezetimibe is excreted in human breast milk. However, animal studies have shown that ezetimibe is present in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Most clinicians recommend avoiding ezetimibe while breastfeeding.
Ezetimibe is approved for use in children aged 10 and older for the treatment of Heterozygous Familial Hypercholesterolemia (HeFH) and Homozygous Familial Hypercholesterolemia (HoFH). For Sitosterolemia, it is approved for children aged 9 and older.
In clinical trials, approximately 25% of patients were 65 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. However, elderly patients are more likely to have decreased renal function and are more susceptible to muscle-related side effects when ezetimibe is used with a statin. Healthcare providers should be mindful of polypharmacy (taking multiple medications) in the elderly, as the risk of drug interactions increases.
For patients with renal disease, ezetimibe is generally considered safe. No dosage adjustment is required for any degree of renal impairment. In the SHARP (Study of Heart and Renal Protection) trial, the combination of ezetimibe and simvastatin was shown to safely reduce major atherosclerotic events in patients with advanced chronic kidney disease.
As discussed, hepatic impairment significantly affects ezetimibe levels. While mild impairment requires no adjustment, the drug is not recommended for moderate or severe impairment. Patients with liver disease should have their liver enzymes monitored more frequently if a physician decides to proceed with therapy.
> Important: Special populations, particularly pregnant women and those with liver disease, require individualized medical assessment and frequent monitoring when taking Ezetimibe.
Ezetimibe's molecular target is the Niemann-Pick C1-Like 1 (NPC1L1) protein. This protein is a sterol transporter located on the apical membrane of enterocytes in the small intestine. Ezetimibe binds to the extracellular loop of the NPC1L1 protein, which induces a conformational change that inhibits the internalisation of the protein-cholesterol complex.
By blocking this pathway, ezetimibe reduces the transport of dietary and biliary cholesterol from the intestinal lumen into the enterocyte. This leads to a decrease in the cholesterol content of chylomicrons (particles that transport fat). Consequently, fewer cholesterol remnants are delivered to the liver. The liver responds to this 'cholesterol hunger' by increasing the expression of LDL receptors, which clear LDL-C from the blood. Ezetimibe does not inhibit cholesterol synthesis in the liver, nor does it increase bile acid excretion.
| Parameter | Value |
|---|---|
| Bioavailability | Variable (Insoluble); Peak levels in 1-2 hours |
| Protein Binding | >90% (Ezetimibe and Glucuronide) |
| Half-life | ~22 hours (Terminal) |
| Tmax | 4 to 12 hours (Parent drug); 1-2 hours (Metabolite) |
| Metabolism | Intestinal and Hepatic Glucuronidation (UGT1A1, 1A3, 2B7) |
| Excretion | Fecal 78%, Renal 11% |
Ezetimibe is the first and primary member of the Dietary Cholesterol Absorption Inhibitor class. It is therapeutically distinct from statins, fibrates, niacin, and bile acid sequestrants. In 2024, it remains the only drug in this specific class, though it is often used as a component of combination therapies with newer classes like ACL inhibitors.
Medications containing this ingredient
Common questions about Ezetimibe
Ezetimibe is primarily used to lower high levels of cholesterol in the blood, specifically Low-Density Lipoprotein (LDL) or 'bad' cholesterol. It is prescribed for patients with primary hyperlipidemia, either as a standalone treatment or in combination with statins when diet and exercise alone are not enough. Additionally, it is used for rare genetic conditions such as Homozygous Familial Hypercholesterolemia and Homozygous Sitosterolemia. By reducing the amount of cholesterol the body absorbs from food and bile, it helps prevent the buildup of plaque in the arteries. This reduction in plaque is crucial for lowering the long-term risk of heart disease and stroke.
The most common side effects of ezetimibe include diarrhea, joint pain (arthralgia), and symptoms of upper respiratory tract infections like a sore throat or runny nose. Some patients also report feeling tired or experiencing muscle aches, especially when the drug is taken alongside a statin. These side effects are generally mild and often diminish as the body adjusts to the medication. However, if you experience severe muscle pain or signs of liver trouble like yellowing of the eyes, you should contact your doctor immediately. Most people find the drug very easy to tolerate compared to other cholesterol medications.
There is no known direct interaction between ezetimibe and alcohol that would make moderate drinking strictly prohibited. However, because ezetimibe is often taken with statins, which can affect liver function, excessive alcohol consumption can increase the risk of liver damage. Alcohol can also raise your triglyceride levels, which may counteract the benefits of your cholesterol-lowering therapy. It is generally recommended to limit alcohol intake to moderate levels—one drink per day for women and two for men. Always discuss your alcohol consumption habits with your healthcare provider to ensure it is safe for your specific liver health profile.
Ezetimibe is not generally recommended during pregnancy unless the benefits clearly outweigh the potential risks to the fetus. It is classified as Pregnancy Category C, meaning animal studies have shown potential for harm, but human data is lacking. Most importantly, if ezetimibe is taken with a statin, the combination is strictly forbidden during pregnancy because statins can cause serious birth defects. If you are planning to become pregnant or find out you are pregnant while taking ezetimibe, you should consult your doctor immediately. They will likely advise you to stop the medication for the duration of your pregnancy.
Ezetimibe begins to lower cholesterol levels relatively quickly after you start taking the daily 10 mg dose. You can expect to see a measurable reduction in your LDL cholesterol levels within 1 to 2 weeks of starting the treatment. However, the full therapeutic effect is typically reached after about 4 weeks of consistent use. Your healthcare provider will usually schedule a follow-up blood test (lipid panel) about 4 to 12 weeks after you start the medication to assess how well it is working. It is important to continue taking the medication even if you feel fine, as high cholesterol does not have obvious symptoms.
You can physically stop taking ezetimibe without experiencing withdrawal symptoms, but you should never do so without consulting your doctor first. Stopping the medication will cause your cholesterol levels to rise back to their baseline within a few weeks, which increases your risk of cardiovascular complications. Cholesterol management is typically a lifelong commitment to prevent heart attacks and strokes. If you are concerned about side effects or the cost of the medication, talk to your healthcare provider about alternatives rather than stopping abruptly. They can help you transition to a different treatment plan safely.
If you miss a dose of ezetimibe, you should take it as soon as you remember that day. However, if you do not remember until the following day, simply skip the missed dose and take your next regularly scheduled dose at the usual time. You should never take two doses at once to 'catch up' for the one you missed, as this can increase the risk of side effects without providing extra benefit. To help prevent missing doses, try taking your medication at the same time every day, such as with breakfast or right before bed. Using a pillbox or a phone reminder can also be very helpful.
Weight gain is not a recognized or common side effect of ezetimibe based on extensive clinical trials and post-marketing surveillance. The medication works specifically in the digestive tract to block cholesterol absorption and does not typically interfere with metabolic processes that lead to fat storage or increased appetite. If you notice significant or rapid weight gain while taking ezetimibe, it is likely due to other factors such as changes in diet, physical activity, or other medications you may be taking. You should discuss any unexpected weight changes with your doctor to identify the underlying cause. Maintaining a healthy weight is an important part of your overall cholesterol management strategy.
Ezetimibe can be taken with many other medications, but there are some important exceptions you must be aware of. It is frequently and safely prescribed with statins like atorvastatin or rosuvastatin to provide an additive cholesterol-lowering effect. However, it can interact with cyclosporine, fibrates, and bile acid sequestrants like cholestyramine. Bile acid sequestrants can prevent ezetimibe from being absorbed, so they must be taken several hours apart. Always provide your doctor with a complete list of all prescription drugs, over-the-counter medicines, and herbal supplements you are using to avoid potentially dangerous interactions.
Yes, ezetimibe is widely available as a generic medication, which is typically much more affordable than the brand-name version, Zetia. The generic version contains the same active ingredient and meets the same FDA standards for safety, strength, and quality as the brand-name drug. Most insurance plans cover the generic version of ezetimibe, making it a cost-effective option for long-term cholesterol management. You can ask your pharmacist for the generic version to save on your prescription costs. The efficacy in lowering LDL cholesterol is identical between the generic and brand-name tablets.