Ezetimibe with Clofibrate Interaction Details

Brand Names Associated with Ezetimibe

  • Ezetimibe
  • Liptruzet® (as a combination product containing Atorvastatin, Ezetimibe)
  • Nexlizet® (as a combination product containing Bempedoic Acid, Ezetimibe)
  • Vytorin® (as a combination product containing Ezetimibe, Simvastatin)
  • Zetia®

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Last updated Feb 28, 2024

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Interaction Effect

Increased ezetimibe exposure and an increased risk of cholelithiasis

Interaction Summary

Coadministration of ezetimibe and a fibrate may cause increased cholesterol excretion into the bile, thereby increasing the risk of cholelithiasis. In a study, total ezetimibe AUC and Cmax increased 64% and 91%, respectively, when ezetimibe was coadministered with gemfibrozil (a fibrate). With the exception of fenofibrate, coadministration of ezetimibe and a fibrate is not recommended[1][2].

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Coadministration of ezetimibe and a fibrate may cause increased cholesterol excretion into the bile, thereby increasing the risk of cholelithiasis. With the exception of fenofibrate, coadministration of ezetimibe and a fibrate is not recommended[1][2].

Mechanism Of Interaction

Additive increase of cholesterol excretion into the bile

Literature Reports

A) In a study, total ezetimibe AUC and Cmax increased 64% and 91%, respectively, when ezetimibe 10 mg was coadministered with gemfibrozil 600 mg twice daily for 7 days [1][2].

References

    1 ) Product Information: Ezetimibe oral tablets, ezetimibe oral tablets. Aurobindo Pharma USA Inc (per DailyMed), East Windsor, NJ, 2020.

    2 ) Product Information: ZETIA(R) oral tablets, ezetimibe oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2023.

Ezetimibe Overview

  • Ezetimibe is used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of cholesterol (a fat-like substance) and other fatty substances in the blood. It may be used alone or in combination with an HMG-CoA reductase inhibitor (statin). Ezetimibe is in a class of medications called cholesterol-lowering medications. It works by preventing the absorption of cholesterol in the intestine.

  • Buildup of cholesterol and fats along the walls of the blood vessels (a process known as atherosclerosis) decreases blood flow, which decreases the oxygen supply to the heart, brain, and other parts of the body. Lowering blood levels of cholesterol and fats may help reduce this buildup and may decrease your chances of developing heart conditions such as angina (chest pain), strokes, and heart attacks. Results of a clinical study that compared people who took ezetimibe and simvastatin with people who took simvastatin alone found that although the group of people taking ezetimibe and simvastatin had lower amounts of cholesterol in the blood, there was no difference between the two groups in the amount of cholesterol and fat buildup on the insides of the blood vessels in the neck. It is not currently understood why the additional lowering of cholesterol levels in the blood did not lead to a greater decrease in cholesterol and fat buildup along the walls of the blood vessels in people taking ezetimibe and simvastatin. Further studies are underway to compare treatment with ezetimibe and simvastatin to treatment with simvastatin alone to see if there is a difference in the risk of developing heart disease. Talk to your doctor if you have questions about the risks and benefits of treating increased amounts of cholesterol in your blood with ezetimibe and other medications.

  • In addition to taking a cholesterol-lowering medication, making certain changes in your daily habits can also lower your blood cholesterol levels. You should eat a diet that is low in saturated fat and cholesterol (see SPECIAL DIETARY); exercise 30 minutes on most, if not all, days; and lose weight if you are overweight.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.


Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.


Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.


Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.