Simvastatin and Teriflunomide: 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
Teriflunomide
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.
What's going on: Teriflunomide (Aubagio) can block a liver transporter that helps move simvastatin (Zocor) out of your blood. Because of this, your body may hold onto more simvastatin than usual, so its levels can climb higher.
Higher statin levels can raise the chance of side effects like muscle aches, weakness, or (rarely) more serious muscle problems. The good news is your care team can manage this easily by adjusting your simvastatin dose and keeping an eye on how you feel. Keep taking both medicines as prescribed, and let your pharmacist or doctor know if you notice new muscle pain or tenderness.
Mechanism: Teriflunomide inhibits OATP1B1/1B3, the hepatic uptake transporters for HMG-CoA reductase inhibitors. Simvastatin is an OATP substrate (not a prodrug requiring this transporter for activation), so reduced hepatic uptake increases systemic exposure.
- Direction: increased simvastatin exposure (higher Cmax/AUC).
- Magnitude: extrapolated from rosuvastatin data (approx 2.65-fold Cmax, 2.51-fold AUC).
- Evidence: theoretical for simvastatin specifically.
- Onset: unspecified.
Management: Consider reducing the statin dose and monitor for myopathy/rhabdomyolysis (muscle pain, weakness, CK elevation). Dose should be individualized by the care team.
What happens
Increased exposure of OATP1B1/1B3 substrate
Interaction Deep Dive
By blocking Organic Anion Transporting Polypeptide B1 and B3 (OATP1B1/1B3), teriflunomide alters the disposition of substrate drugs. Pharmacokinetic studies showed that repeated dosing of teriflunomide raised the mean Cmax and AUC of rosuvastatin by 2.65-fold and 2.51-fold, respectively, so rosuvastatin must be given at a lower dose when the two are used together. When teriflunomide is combined with OATP family substrates, particularly HMG-CoA reductase inhibitors, a dose reduction of the substrate drug should be considered along with close monitoring of patients for signs and symptoms of heightened exposure1.
Why it happens (mechanism)
Inhibition of OATP1B1/1B3 transport by teriflunomide
How to manage this interaction
How your care team may handle this:
- They may lower your simvastatin dose, since teriflunomide can raise its blood levels.
- They may monitor you more closely for signs of increased statin exposure, especially muscle-related symptoms.
What you can do:
- Keep taking both medications exactly as prescribed unless told otherwise.
- Tell your pharmacist or prescriber promptly about new muscle pain, tenderness, weakness, or dark urine.
- Ask your team whether your simvastatin dose should be adjusted and individualized for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Simvastatin and Teriflunomide together?
Teriflunomide can raise simvastatin levels and increase the risk of muscle side effects, so your care team may lower the statin dose and watch you more closely. Keep taking both as prescribed and report any muscle pain. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Teriflunomide 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 Simvastatin and Teriflunomide interaction managed?
How your care team may handle this: They may lower your simvastatin dose, since teriflunomide can raise its blood levels. They may monitor you more closely for signs of increased statin exposure, especially muscle-related symptoms. What you can do: Keep taking both medications exactly as prescribed unless told otherwise. Tell your pharmacist or prescriber promptly about new muscle pain, tenderness… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Simvastatin or Teriflunomide 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 (1)
- Product Information: AUBAGIO(R) oral tablets, teriflunomide oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2019. DailyMed
Keep reading about Teriflunomide
Keep reading about Simvastatin
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