Fenofibrate and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fenofibrate
Simvastatin
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.
Both of these drugs lower cholesterol, but taken together they can be harder on your muscles. Simvastatin (Zocor) and fenofibrate can each cause muscle aches, and using them at the same time adds up that risk. In rare cases this can lead to a serious muscle problem called rhabdomyolysis, where muscle tissue breaks down and can affect the kidneys.
The good news is that this is very manageable. Doctors do prescribe these together on purpose sometimes when the cholesterol benefit is worth it. Keep taking both exactly as prescribed, and let your pharmacist or doctor know right away if you get unusual muscle pain, tenderness, weakness, or dark-colored urine.
Interaction: Additive myotoxicity when fenofibrate is combined with simvastatin, increasing risk of myopathy and rhabdomyolysis.
- Mechanism: Pharmacodynamic (additive muscle toxicity), not primarily a CYP-mediated PK interaction. Neither agent is a prodrug relevant here.
- Direction/magnitude: Observational data show elevated rhabdomyolysis risk with fibrate plus statin combinations. Fenofibrate carries lower risk than gemfibrozil.
- Evidence: Probable. Severity: Major.
- Management: Avoid unless lipid benefit outweighs risk. If coadministered, monitor for myopathy signs (myalgia, weakness, elevated CK), especially at initiation and titration. Discontinue if myopathy suspected.
What happens
An increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
The combined use of fenofibrate with HMG-CoA reductase inhibitors such as simvastatin should be avoided because it can raise the likelihood of myopathy or rhabdomyolysis2, except in cases where the expected benefit of additional lipid level control is greater than the added risk 345. When the two must be given together, watch the patient for signs and symptoms of myopathy or rhabdomyolysis, especially when treatment is being started and when doses are being increased. Treatment should be stopped if myopathy is diagnosed or suspected 1. Observational study data show that coadministering fibrates with a statin heightens the risk of rhabdomyolysis 2.
Why it happens (mechanism)
Additive risk of myopathy
How to manage this interaction
Care teams do sometimes use these two together when the added cholesterol benefit is worth it, so this is manageable.
- Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- Your team may watch you more closely, especially when you first start or when a dose is increased, and may check a blood test (CK) for muscle breakdown.
- Report new or unexplained muscle pain, tenderness, weakness, or dark/cola-colored urine promptly.
- Ask your pharmacist or doctor whether this combination is right for you, or if a different lipid strategy might be considered.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Findings from observational studies show that the likelihood of rhabdomyolysis rises when fibrates are given together with a statin. Giving atorvastatin at 20 mg once daily for 10 days alongside fenofibrate at 160 mg once daily for 10 days decreased fenofibrate's AUC and Cmax by 2% and 4%, respectively. In comparison, giving pravastatin as a single 40 mg dose together with fenofibrate as a single dose of three times 67 mg(2) decreased fenofibrate's AUC and Cmax by 1% and 2%, respectively. Additionally, giving fluvastatin as a single 40 mg dose with fenofibrate as a single 160 mg once dose decreased fenofibrate's AUC and Cmax by 2% and 10%, respectively 2.
b) Findings from observational studies indicate that the likelihood of rhabdomyolysis is increased when fibrates, particularly gemfibrozil, are given together with an HMG-CoA reductase inhibitor (statin) 5.
Common questions
Can I take Fenofibrate and Simvastatin together?
Taking fenofibrate and simvastatin together adds up the risk of muscle injury, so watch for muscle pain, weakness, or dark urine and report it right away. Don't stop either drug on your own; talk with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fenofibrate and Simvastatin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Fenofibrate and Simvastatin interaction managed?
Care teams do sometimes use these two together when the added cholesterol benefit is worth it, so this is manageable. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Your team may watch you more closely, especially when you first start or when a dose is increased, and may check a blood test (CK) for muscle breakdown. Report new or unexplained muscle p… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Fenofibrate or Simvastatin 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: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2023. DailyMed
- Product Information: TRIGLIDE(R) oral tablets, fenofibrate oral tablets. Casper Pharma LLC (per FDA), East Brunswick, NJ, 2024. DailyMed
- Product Information: ANTARA(R) oral capsules, fenofibrate micronized oral capsules. Lupin Pharmaceuticals Inc (per FDA), Naples, FL, 2024. DailyMed
- Product Information: TRICOR oral tablets, fenofibrate oral tablets. AbbVie Inc (per FDA), North Chicago, IL, 2021. DailyMed
- Product Information: FIBRICOR(R) oral tablets, fenofibric acid oral tablets. Athena Bioscience LLC (per FDA), Athens, GA, 2021. DailyMed
Keep reading about Fenofibrate
Keep reading about Simvastatin
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist