Ezetimibe and Fenofibrate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fenofibrate
Ezetimibe
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased ezetimibe exposure and an increased risk of cholelithiasis
Interaction Deep Dive
In a pharmacokinetic study in healthy subjects (n=16), concomitant administration of ezetimibe 10 mg once daily with fenofibrate 145 mg once daily for 10 days significantly increased total ezetimibe and ezetimibe glucuronide (active metabolite) AUC and Cmax by 43.4% and 48.8%, and 32.8% and 33.9%, respectively, compared with ezetimibe 10 mg once daily alone5. Fibrates may have an additive effect on cholesterol excretion into the bile resulting in an increased risk for cholelithiasis. If ezetimibe and fenofibrate are coadministered, monitor patients for signs and symptoms of cholelithiasis. If cholelithiasis is suspected, initiate gallbladder studies and consider alternative lipid-lowering therapy 12. Also, coadministration of may increase risk of myopathy and rhabdomyolysis. Consider if the benefit of using fibrates concomitantly with ezetimibe outweighs the increased risk of myopathy and rhabdomyolysis. Monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug 4.
Why it happens (mechanism)
Increase in cholesterol excretion into the bile
Literature reports
3 reports — tap to read
a) In a study of 32 healthy adults with hypercholesterolemia (low-density lipid cholesterol, 130 mg/dL or greater), total ezetimibe Cmax and AUC increased by an approximate mean of 64% and 48%, respectively, following the concomitant administration of ezetimibe 10 mg and fenofibrate 200 mg once daily. The pharmacokinetics of fenofibrate were not significantly altered 1.
b) Concomitant administration of ezetimibe 10 mg daily with fenofibrate 145 mg daily significantly increased total ezetimibe and ezetimibe glucuronide exposure (p less than 0.05) in a phase 1, open-label, 3-regimen, crossover study in healthy subjects (n=16; mean age 43.4 years; range, 27 to 55 years). Subjects were randomized to 1 of 3 regimens: ezetimibe 10 mg, combination ezetimibe 10 mg with fenofibrate 145 mg, or fenofibrate 145 mg, each regimen was administered once daily for 10 days with at least a 14-day washout period before crossover. Following 10 days of concomitant ezetimibe/fenofibrate administration, total ezetimibe AUC and Cmax values were 43.4% (90% confidence interval (CI), 29.3% to 59%) and 32.8% (90% CI, 20.5% to 46.2%) higher, respectively, compared with ezetimibe alone. Total ezetimibe AUC increased from 794.8 +/- 334.8 to 1119.7 +/- 434.8 nanograms (ng) x hour/mL, and Cmax increased from 84.9 +/- 28.6 to 112.5 +/- 32.4 ng/mL. Similarly, on day 10 of ezetimibe/fenofibrate coadministration, ezetimibe glucuronide (active metabolite) AUC and Cmax significantly increased by 48.8% (90% CI, 33.9% to 65.3%) and 33.9% (90% CI, 21.6% to 47.4%), respectively compared with ezetimibe alone. Ezetimibe glucuronide AUC increased from 708.5 +/- 311.6 to 1032.1 +/- 418.9 ng x hour/mL, and Cmax increased from 80.2 +/- 27.1 to 107 +/- 31.1 ng/mL. The Cmin for total ezetimibe and ezetimibe glucuronide also significantly increased with coadministration; however, fenofibrate and free ezetimibe were not significantly affected 5.
c) In a drug interaction study, total ezetimibe AUC and Cmax increased 48% and 64%, respectively, when ezetimibe 10 mg was coadministered with fenofibrate 200 mg twice daily for 14 days 24.
Common questions
Can I take Ezetimibe and Fenofibrate together?
Increased ezetimibe exposure and an increased risk of cholelithiasis Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ezetimibe and Fenofibrate interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Ezetimibe or Fenofibrate need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (5)
- Product Information: ZETIA(R) oral tablets, ezetimibe oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2023. DailyMed
- Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2024. DailyMed
- Product Information: TRICOR(R) oral tablets, fenofibrate oral tablets. Abbott Laboratories, North Chicago, IL, 2007. DailyMed
- Product Information: ROSZET oral tablets, rosuvastatin ezetimibe oral tablets. Althera Pharmaceuticals LLC (per FDA), Wilmington, DE, 2024.
- Gustavson LE, Schweitzer SM, Burt DA, et al: Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: A phase I, open-label, multiple-dose, three-period crossover study in healthy subjects. Clin Ther 2006; 28(3):373-387. PubMed
Keep reading about Fenofibrate
Keep reading about Ezetimibe
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