Bupropion and Trospium / Xanomeline: 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
Bupropion
Trospium / Xanomeline
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. Cobenfy contains xanomeline, which your body clears using a liver enzyme called CYP2D6. Bupropion slows that same enzyme down. So when you take them together, the xanomeline can build up a bit more than usual.
In plain terms, that could mean stronger or more frequent side effects from the Cobenfy, like nausea, upset stomach, vomiting, dizziness, or sweating. This is based mostly on how these drugs work on paper, not on lots of real-world reports, so please don't panic. Keep taking both exactly as prescribed and let your care team know how you feel. They can watch you closely and adjust things if needed.
Mechanism: Xanomeline (in Cobenfy) is metabolized in significant part by CYP2D6. Bupropion is a moderate-to-potent CYP2D6 inhibitor, so coadministration may reduce xanomeline clearance and increase its systemic exposure (AUC/Cmax).
Effect: Increased frequency and/or severity of xanomeline-related adverse reactions (cholinergic effects: nausea, vomiting, dyspepsia, diaphoresis, dizziness).
- Direction: Increased xanomeline effect
- Severity: Moderate
- Onset: Unspecified
- Evidence: Theoretical
Management: If used concurrently, monitor for enhanced cholinergic/GI adverse effects. Xanomeline dosing may need to be individualized by the care team.
What happens
Increased xanomeline exposure and an increased risk on severity and frequency of xanomeline-related adverse reactions
Interaction Deep Dive
A substantial portion of xanomeline metabolism is mediated by CYP2D6. When xanomeline is given together with inhibitors of CYP2D6, exposure to xanomeline may rise, potentially heightening both the frequency and the severity of adverse reactions associated with xanomeline. Should the two be administered together, watch patients for any increase in the frequency and/or severity of xanomeline-related adverse reactions1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of xanomeline
How to manage this interaction
The good news: this is manageable. Your care team can keep you on both medicines while watching how you respond.
- Keep taking both bupropion and Cobenfy exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for xanomeline side effects, and your Cobenfy dose may need to be adjusted and individualized.
- Tell your pharmacist or prescriber if you notice more nausea, vomiting, stomach upset, sweating, or dizziness after starting both.
- Ask your pharmacist to review your full medication list for other CYP2D6 inhibitors.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Bupropion and Trospium / Xanomeline together?
Bupropion can slow the breakdown of the xanomeline in Cobenfy, which may make its side effects (nausea, vomiting, sweating, dizziness) stronger or more frequent. Keep taking both as prescribed, watch for those effects, and check with your pharmacist or prescriber. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Bupropion and Trospium / Xanomeline interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Bupropion and Trospium / Xanomeline interaction managed?
The good news: this is manageable. Your care team can keep you on both medicines while watching how you respond. Keep taking both bupropion and Cobenfy exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for xanomeline side effects, and your Cobenfy dose may need to be adjusted and individualized. Tell your pharmacist or prescriber if you notice… 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 Bupropion or Trospium / Xanomeline 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 anything you'd monitor while I'm on both?
References (5)
- Citation #1
- Product Information: APLENZIN(R) oral extended-release tablets, bupropion hydrobromide oral extended-release tablets. Bausch Health US LLC (per FDA), Bridgewater, NJ, 2024. DailyMed
- Product Information: WELLBUTRIN(R) oral tablets, bupropion hydrochloride oral tablets. GlaxoSmithKline (per FDA), Durham, NC, 2024. DailyMed
- Product Information: WELLBUTRIN XL(R) oral extended-release tablets, bupropion hydrochloride oral extended-release tablets. Bausch Health US, LLC (per FDA), Bridgewater, NJ, 2024. DailyMed
- Product Information: WELLBUTRIN(R) SR oral sustained-release tablets, bupropion hydrochloride oral sustained-release tablets. GlaxoSmithKline (per FDA), Durham, NC, 2024. DailyMed
Keep reading about Bupropion
Keep reading about Trospium / Xanomeline
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.
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