Digoxin 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
Digoxin
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.
What's going on: Cobenfy (which contains xanomeline) can briefly slow down a 'pump' in your gut called P-gp. That pump normally helps push some of your digoxin back out before it's absorbed. When the pump is slowed, a little more digoxin may get into your body.
Digoxin is a medicine where the right amount matters a lot, so even a small rise can bring on side effects like nausea, loss of appetite, tiredness, dizziness, or changes in your heartbeat. The good news is this is a theoretical concern, and your care team can manage it easily by keeping an eye on you and adjusting your dose if needed. Don't stop either medicine on your own, just check in with your pharmacist or doctor.
Mechanism: Xanomeline (in Cobenfy) transiently inhibits intestinal P-glycoprotein locally in the gut, not systemically. Digoxin is a narrow-therapeutic-index P-gp substrate, so reduced enterocyte efflux may increase digoxin absorption and exposure.
- Direction: increased digoxin exposure, increased risk/severity of digoxin-related adverse effects.
- Evidence: theoretical; magnitude not quantified.
- Onset: unspecified.
- Management: monitor for signs of digoxin toxicity (GI, visual, CNS, arrhythmias); consider serum digoxin levels and ECG per clinical judgment; individualize dosing.
No prodrug considerations apply; both are active drugs.
What happens
Increased oral P-gp substrate with NTI exposure and an increased risk on severity and frequency of oral P-gp substrate with NTI-related adverse reactions
Interaction Deep Dive
Within the gut, xanomeline produces a temporary local inhibition of P-gp involving NTI, though this effect does not extend systemically. When xanomeline is taken together with oral medications that act as substrates of P-gp with NTI, the exposure to those oral substrates may rise. As a result, the frequency and/or severity of adverse reactions associated with such substrates may increase. During concurrent administration, patients should be observed for any increase in the frequency and/or severity of adverse reactions linked to oral drugs that are substrates of P-gp with NTI1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport by xanomeline
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is theoretical, and it is manageable.
Your care team may:
- Watch you more closely for signs of too much digoxin, such as nausea, poor appetite, tiredness, dizziness, blurry or yellow-tinged vision, or an irregular or slow heartbeat.
- Adjust your digoxin dose if needed, individualized to you, based on how you're doing and possibly digoxin blood levels.
What to do: Tell your pharmacist and prescriber you take both, and report any new symptoms promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Digoxin and Trospium / Xanomeline together?
Cobenfy (xanomeline) may modestly raise digoxin levels by slowing a gut transporter, so watch for signs of digoxin side effects and let your care team monitor and adjust your dose as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin 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 Digoxin and Trospium / Xanomeline interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is theoretical, and it is manageable. Your care team may: Watch you more closely for signs of too much digoxin, such as nausea, poor appetite, tiredness, dizziness, blurry or yellow-tinged vision, or an irregular or slow heartbeat. Adjust your digoxin dose if needed, individualized to you, based on… 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.
Questions for your pharmacist
- Does my dose of Digoxin 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 (1)
- Citation #1
Keep reading about Digoxin
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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