Avacopan 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
Avacopan
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.
Here's what's going on. Avacopan (Tavneos) slows down a liver enzyme called CYP3A4, which is the same enzyme that breaks down your cholesterol medicine, simvastatin. When avacopan is on board, simvastatin builds up in your body. In studies, the amount of simvastatin in the blood went up more than 3 times.
More simvastatin means a higher chance of muscle side effects, like aches, soreness, or weakness. The good news is your care team can manage this easily, often by keeping your simvastatin dose lower while you're on avacopan. Don't change anything on your own, but do check in with your pharmacist or doctor so they can set the right dose for you.
Mechanism: Avacopan inhibits CYP3A4, reducing metabolism of simvastatin (a CYP3A4 substrate). Neither drug is a prodrug here, so inhibition raises active statin exposure.
Magnitude: Avacopan 60 mg daily x7 days increased simvastatin AUC ~3.53-fold and Cmax ~3.20-fold.
Effect: Elevated simvastatin exposure increases risk of myopathy/rhabdomyolysis. Evidence: probable; onset unspecified; severity major.
Management:
- Limit simvastatin to 10 mg daily during avacopan therapy.
- Up to 20 mg daily only if patient previously tolerated simvastatin 80 mg for =1 year without muscle toxicity.
- Monitor for muscle pain, weakness, and consider CK if symptomatic.
What happens
Increased simvastatin exposure
Interaction Deep Dive
Taking avacopan together with simvastatin (a CYP3A4 substrate) can raise simvastatin exposure. When simvastatin was given with avacopan 60 mg once daily for 7 days following food, simvastatin AUC rose 3.53-fold and Cmax rose 3.20-fold. When avacopan is combined with CYP3A4 substrates, a dose reduction of those substrates should be considered. For patients on avacopan, keep simvastatin at no more than 10 mg daily (or up to 20 mg daily in those who have already tolerated simvastatin 80 mg daily for a minimum of one year without any sign of muscle toxicity)1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is well understood and manageable.
Because avacopan raises simvastatin levels, your team will typically keep your simvastatin dose lower while you're on avacopan:
- Simvastatin is usually limited to 10 mg daily during avacopan treatment.
- A 20 mg daily limit may apply only if you've safely tolerated simvastatin 80 mg daily for at least a year without muscle problems.
What to do: Ask your pharmacist or prescriber to confirm your simvastatin dose is right for you, and report any muscle pain, tenderness, or weakness promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Giving simvastatin together with avacopan, at a dose of 60 mg once daily for 7 days taken after food, raised the AUC of simvastatin by 3.53-fold and its Cmax by 3.20-fold 1.
Common questions
Can I take Avacopan and Simvastatin together?
Avacopan raises simvastatin levels about 3-fold by blocking its breakdown, which can increase muscle side effects; your care team will usually cap simvastatin at 10 mg daily (up to 20 mg in select patients) while you're on avacopan. Keep taking both as prescribed and report any muscle aches. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Avacopan 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 Avacopan and Simvastatin interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is well understood and manageable. Because avacopan raises simvastatin levels, your team will typically keep your simvastatin dose lower while you're on avacopan: Simvastatin is usually limited to 10 mg daily during avacopan treatment. A 20 mg daily limit may apply only if you've safely tolerated s… 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 Avacopan 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: TAVNEOS(R) oral capsules, avacopan oral capsules. ChemoCentryx Inc (per FDA), Thousand Oaks, CA, 2024. DailyMed
Keep reading about Avacopan
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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