Colchicine and 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
Colchicine
Xanomeline
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.
Let me explain this one simply. Colchicine (used for gout and pericarditis) is carried out of your gut by a natural "pump" called P-gp. Xanomeline can briefly slow that pump down in the gut. When the pump is slowed, a little more colchicine can get absorbed into your body than usual.
Because colchicine is a drug where even small increases matter, that extra amount could make side effects like nausea, diarrhea, stomach cramps, or muscle aches more likely. The good news is this is a theoretical concern, and your care team can manage it easily by watching how you feel and adjusting your dose if needed. Just don't change anything on your own.
Mechanism: Xanomeline transiently inhibits intestinal P-glycoprotein (P-gp) locally in the gut (not systemically). Colchicine is a narrow-therapeutic-index oral P-gp substrate; reduced efflux may increase its enteric absorption and systemic exposure.
Direction/effect: Increased colchicine exposure, raising frequency/severity of dose-related adverse effects (GI toxicity, myopathy, myelosuppression). Neither agent is relevant as a prodrug here.
- Severity: Moderate
- Onset: Unspecified
- Evidence: Theoretical
Management: Monitor for colchicine adverse reactions if co-administered. Colchicine dose may need individualization by the care team; exercise caution in hepatic/renal impairment where toxicity risk is greatest.
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 occur systemically. When xanomeline is taken together with oral medications that act as P-gp substrates with NTI, the exposure to those oral substrates may rise. Such an increase can lead to a greater frequency and/or intensity of adverse reactions caused by these substrates. Should the two be used together, patients should be watched for a heightened frequency and/or severity of adverse reactions tied to oral drugs that are P-gp substrates with NTI1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport by xanomeline
How to manage this interaction
Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Because colchicine is a sensitive drug, your care team will simply keep an eye on how you're tolerating it.
- Watch for and report increased side effects such as diarrhea, nausea, vomiting, stomach pain, unusual muscle pain or weakness, or tiredness.
- Your colchicine dose may need to be adjusted and individualized by your care team.
- Let your pharmacist or doctor know about all your medications, and mention any kidney or liver problems, since those raise colchicine risk.
This is a manageable situation with a little extra monitoring.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Colchicine and Xanomeline together?
Xanomeline can briefly increase how much colchicine your body absorbs, so watch for more colchicine 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 Colchicine and 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 Colchicine and Xanomeline interaction managed?
Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Because colchicine is a sensitive drug, your care team will simply keep an eye on how you're tolerating it. Watch for and report increased side effects such as diarrhea, nausea, vomiting, stomach pain, unusual muscle pain or weakness, or tiredness. Your colchicine dose may need to be adjusted and individ… 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 Colchicine or 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)
- Product Information: COBENFY(TM) oral capsules, xanomeline, trospium chloride oral capsules. Bristol-Myers Squibb Company (Per FDA), Princeton, NJ, 2024. DailyMed
Keep reading about Colchicine
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