Trospium / Xanomeline and Everolimus: 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
Everolimus
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. Everolimus (Afinitor, Zortress) is broken down by an enzyme called CYP3A4 and is also handled by a gut protein called P-gp. Cobenfy contains xanomeline, which can briefly slow both of these down inside your gut. That means a little more everolimus may get absorbed into your body.
Since everolimus works within a fairly narrow safe range, even a small increase could raise the chance of side effects like mouth sores, feeling tired, infections, or lab changes. The good news is this is a theoretical concern, and your care team can manage it easily by watching you a bit more closely and adjusting your dose if needed. Please don't change anything on your own, just talk with your doctor or pharmacist.
Mechanism: Xanomeline (in Cobenfy) transiently inhibits intestinal CYP3A4 and P-gp efflux locally in the gut, not systemically. Everolimus is a sensitive CYP3A4 substrate, a P-gp substrate, and has a narrow therapeutic index.
Effect / direction: Increased oral everolimus exposure (AUC/Cmax), raising the risk and severity of everolimus-related adverse effects (stomatitis, myelosuppression, immunosuppression-related infection, metabolic and lab abnormalities).
- Onset: unspecified
- Evidence: theoretical
- Management: If used together, monitor more closely for everolimus toxicity; consider everolimus trough levels and clinical assessment. Dose may be individualized by the care team.
What happens
Increased oral sensitive CYP3A4 substrate that are P-gp substrates with NTI exposure and an increased risk on severity and frequency of sensitive CYP3A4 substrate that are P-gp substrates with NTI-related adverse reactions
Interaction Deep Dive
In the gut, xanomeline produces a temporary, local inhibition of CYP3A4 and P-gp, though this effect does not extend systemically. When xanomeline is taken together with oral medications that act as sensitive CYP3A4 substrates, the exposure of those oral drugs (specifically sensitive CYP3A4 substrates that are also P-gp substrates with a narrow therapeutic index) may rise. Such an increase can raise the frequency and/or severity of adverse reactions associated with these substrates. In cases of concurrent administration, patients should be monitored for any increase in the frequency and/or severity of adverse reactions linked to oral drugs that are sensitive CYP3A4 substrates and P-gp substrates with NTI1.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism by xanomeline; inhibition of P-gp-mediated efflux transport by xanomeline
How to manage this interaction
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This interaction can usually be managed with a little extra attention.
- Your care team may monitor you more closely for everolimus side effects such as mouth sores, fatigue, signs of infection, or changes in blood work.
- Because everolimus works in a narrow range, your dose may be adjusted and individualized by your team if needed.
- Report new or worsening symptoms to your pharmacist or prescriber.
- Let every provider know you take both, especially if either medication is started or stopped.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Trospium / Xanomeline and Everolimus together?
Xanomeline (Cobenfy) may briefly increase how much everolimus your body absorbs, so watch for more everolimus side effects. Keep taking both as prescribed and let your care team monitor and adjust as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Trospium / Xanomeline and Everolimus 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 Trospium / Xanomeline and Everolimus interaction managed?
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This interaction can usually be managed with a little extra attention. Your care team may monitor you more closely for everolimus side effects such as mouth sores, fatigue, signs of infection, or changes in blood work. Because everolimus works in a narrow range, your dose may be adjusted and individualized by yo… 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 Trospium / Xanomeline or Everolimus 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 Everolimus
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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