Sertraline and Avacopan: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Avacopan
Sertraline
No brand names on record
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: Avacopan (Tavneos) can slow down one of the liver's clean-up enzymes (called CYP3A4). Sertraline is partly cleared by that same enzyme, so when you take both, a little more sertraline may build up in your body than usual. That could mean stronger sertraline effects or more side effects, like nausea, trouble sleeping, or feeling jittery.
The good news: this concern is based mostly on lab-style predictions, not on lots of real-world cases with these two specific drugs. Keep taking both exactly as prescribed, and let your pharmacist or doctor know so they can watch how you feel and adjust the sertraline dose if needed. This is very manageable.
Mechanism: Avacopan inhibits CYP3A4, reducing metabolism of CYP3A4 substrates and increasing their systemic exposure. Sertraline is partially metabolized via CYP3A4 (among other pathways), so coadministration may raise sertraline AUC/Cmax.
- Direction: increased sertraline exposure (neither drug is a prodrug here).
- Magnitude: unquantified for sertraline; probe substrates showed simvastatin AUC up ~3.5-fold and midazolam AUC up ~1.55-fold with avacopan.
- Evidence: theoretical/extrapolated. Onset: unspecified.
- Management: monitor for serotonergic and dose-related adverse effects; the sertraline dose may be individualized and reduced if warranted.
What happens
Increased CYP3A4 substrate exposure
Interaction Deep Dive
Taking avacopan together with a CYP3A4 substrate can raise exposure to that substrate. When simvastatin (a CYP3A4 substrate) was given alongside avacopan at 60 mg once daily for 7 days following food, the simvastatin AUC rose 3.53-fold and the Cmax rose 3.20-fold. Similarly, when midazolam (a CYP3A4 substrate) was combined with avacopan at 30 mg once daily for 11 days on an empty stomach, the AUC and Cmax of simvastatin increased 1.55-fold and 1.81-fold respectively. Reducing the dose of CYP3A4 substrates should be considered when they are administered together with avacopan1.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism by avacopan
How to manage this interaction
Keep taking both medications as prescribed unless your care team tells you otherwise. Because avacopan can raise sertraline levels, your team may take simple steps to keep you safe:
- Watch more closely for sertraline-related effects such as nausea, restlessness, tremor, or sleep changes.
- Individualize and, if needed, adjust (lower) the sertraline dose based on how you respond.
What to do: tell your pharmacist and prescriber you are on both, and report any new or worsening side effects. Do not start, stop, or change a dose on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) When simvastatin (a CYP3A4 substrate) was given together with avacopan at 60 mg daily for 7 days following food, the AUC and Cmax of simvastatin rose by 3.53-fold and 3.20-fold, respectively 1.
b) When midazolam (a CYP3A4 substrate) was given together with avacopan at 30 mg daily for 11 days on an empty stomach, the AUC and Cmax of simvastatin rose by 1.55-fold and 1.81-fold, respectively 1.
Common questions
Can I take Sertraline and Avacopan together?
Avacopan can raise sertraline levels by slowing its breakdown, so watch for more sertraline side effects and let your care team monitor you and adjust the dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Avacopan 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 Sertraline and Avacopan interaction managed?
Keep taking both medications as prescribed unless your care team tells you otherwise. Because avacopan can raise sertraline levels, your team may take simple steps to keep you safe: Watch more closely for sertraline-related effects such as nausea, restlessness, tremor, or sleep changes. Individualize and, if needed, adjust (lower) the sertraline dose based on how you respond. What to do: tell your… 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 Sertraline or Avacopan 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 Sertraline
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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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