Tacrolimus 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
Tacrolimus
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. You may be taking tacrolimus (Prograf, Envarsus, Astagraf), a medicine that quiets your immune system after a transplant or for another condition. Cobenfy contains xanomeline, which can briefly slow down the way your gut breaks down and pushes out tacrolimus.
The result can be a little more tacrolimus in your body than expected. Because tacrolimus works within a narrow range, even small increases can bring on more side effects like kidney strain, tremor, headache, or high blood sugar. This concern is mostly theoretical, and it is very manageable. Your care team can check your tacrolimus blood levels and adjust your dose if needed. Keep taking both exactly as prescribed and let them know how you feel.
Mechanism/direction: Xanomeline (in Cobenfy) transiently inhibits intestinal CYP3A4 and P-gp efflux. Tacrolimus is a sensitive CYP3A4 substrate, a P-gp substrate, and a narrow-therapeutic-index agent, so co-administration may increase oral tacrolimus absorption and systemic exposure (AUC/Cmax), raising the risk and severity of dose-related adverse effects.
- Effect: increased tacrolimus exposure; potential nephrotoxicity, neurotoxicity (tremor, headache), hyperglycemia, hypertension.
- Evidence: theoretical; onset unspecified.
- Management: monitor tacrolimus whole-blood trough levels, renal function, and clinical tolerability; individualize and titrate dose per levels. No fixed adjustment defined.
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
Within the gut, xanomeline produces a transient, localized inhibition of CYP3A4 and P-gp, though this effect does not extend systemically. When xanomeline is taken alongside oral medications that serve as sensitive CYP3A4 substrates, exposure to those oral drugs that are both sensitive CYP3A4 substrates and P-gp substrates with an NTI may rise. As a result, the frequency and/or severity of adverse reactions caused by these substrates may increase. When such combinations are used together, patients should be monitored for a greater frequency and/or severity of adverse reactions associated with 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
The good news: this is manageable. Tacrolimus is already a medicine your team watches closely with blood tests, so this fits into that routine.
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may check your tacrolimus blood level more closely and adjust the dose to keep it in your target range.
- Watch for and report new or worsening side effects such as tremor, headache, nausea, changes in urination, or high blood sugar.
Ask your pharmacist or prescriber before starting or stopping either medicine, and tell them about all your other medications.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Tacrolimus and Trospium / Xanomeline together?
Xanomeline (Cobenfy) may raise tacrolimus levels by briefly blocking gut CYP3A4 and P-gp, which matters because tacrolimus has a narrow safety margin. Your care team can manage this with blood-level checks and dose adjustments, so keep taking both as prescribed and report any new side effects. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tacrolimus 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 Tacrolimus and Trospium / Xanomeline interaction managed?
The good news: this is manageable. Tacrolimus is already a medicine your team watches closely with blood tests, so this fits into that routine. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may check your tacrolimus blood level more closely and adjust the dose to keep it in your target range. Watch for and report new or worsening side effect… 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 Tacrolimus 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 Tacrolimus
Keep reading about Trospium / Xanomeline
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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