Simeprevir 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
Simeprevir
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.
These two medicines can interact. Simeprevir (Olysio) is a hepatitis C medicine, and simvastatin (Zocor, Flolipid) is a cholesterol medicine. Simeprevir slows down how your body clears simvastatin, so the amount of simvastatin in your blood can go up (in studies it rose about 1.5 times).
When there is more simvastatin around, there is a higher chance of side effects, especially muscle aches or weakness. The good news is your care team can manage this easily by using the lowest helpful simvastatin dose and keeping an eye on you. Let them know right away if you notice unexplained muscle pain, tenderness, or dark urine.
Effect: Simeprevir increases simvastatin exposure via inhibition of CYP3A4 and OATP-mediated transport (simvastatin is a substrate of both). This is a pharmacokinetic interaction raising simvastatin levels.
- Magnitude: Simvastatin AUC and Cmax increased ~1.5-fold (simeprevir 150 mg daily x10 days + single simvastatin 40 mg, n=18).
- Direction: Increased simvastatin effect and myopathy/rhabdomyolysis risk.
- Evidence: Established. Onset: unspecified.
- Management: Use caution; titrate simvastatin carefully to the lowest effective dose. Monitor for statin toxicity (myalgia, elevated CK, signs of rhabdomyolysis).
What happens
Increased simvastatin exposure
Interaction Deep Dive
Exercise caution when simeprevir, which inhibits both CYP3A and OATP, is given together with simvastatin, a substrate of CYP3A and OATP, because the combination can raise simvastatin exposure and heighten the likelihood of simvastatin adverse effects. In drug interaction studies conducted in healthy adults (n=18), giving simeprevir 150 mg once daily over 10 days alongside a single 40 mg dose of simvastatin raised simvastatin AUC and Cmax by roughly 1.5-fold. When this combination is clinically required, titrate the simvastatin dose with care, keep the dose as low as possible, and watch patients for signs of simvastatin toxicity1.
Why it happens (mechanism)
Inhibition of CYP3A4- and Organic Anion Transport Protein (OATP)-mediated efflux of simvastatin by simeprevir
How to manage this interaction
This interaction is manageable when your care team is aware of it. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest effective simvastatin dose, adjusted and individualized for you.
- They may monitor you more closely for signs of statin side effects.
- Report any unexplained muscle pain, tenderness, weakness, or dark-colored urine promptly.
Ask your pharmacist or prescriber before making any changes, and confirm the simvastatin dose is right for you while you are on simeprevir.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction studies conducted in healthy adults (n=18), the concurrent administration of simeprevir 150 mg once daily for 10 days together with a single 40 mg dose of simvastatin raised the AUC and Cmax of simvastatin by roughly 1.5-fold (1.51; 90% CI, 1.32 to 1.73 and 1.46; 90% CI, 1.17 to 1.82, respectively) 1.
Common questions
Can I take Simeprevir and Simvastatin together?
Simeprevir raises simvastatin levels (about 1.5-fold), increasing the risk of muscle side effects, so your care team may keep simvastatin at the lowest effective dose and watch for muscle symptoms. Report unexplained muscle pain or dark urine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simeprevir 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 Simeprevir and Simvastatin interaction managed?
This interaction is manageable when your care team is aware of it. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may use the lowest effective simvastatin dose, adjusted and individualized for you. They may monitor you more closely for signs of statin side effects. Report any unexplained muscle pain, tenderness, weakness, or dark-colored urin… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Simeprevir 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 (1)
- Product Information: OLYSIO(TM) oral capsules, simeprevir oral capsules. Janssen Therapeutics (per manufacturer), Titusville, NJ, 2013.
Keep reading about Simeprevir
Keep reading about Simvastatin
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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.
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