Xanomeline and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Simvastatin
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.
Here's what's going on. Your body uses an enzyme called CYP3A4 to break down simvastatin. Xanomeline can briefly slow that enzyme down in your gut, which means more simvastatin may get into your system than usual. When there's more statin around, you may be a bit more likely to notice statin side effects, like muscle aches or soreness.
I want to be honest with you: this is based on how the drugs work in theory, not on strong real-world reports, so it's not something to panic about. Please keep taking both exactly as prescribed. Just let your pharmacist or doctor know you're on both, and mention any new muscle pain or weakness so your team can keep an eye on things.
Mechanism: Xanomeline transiently inhibits intestinal CYP3A4 (not systemic), reducing first-pass metabolism of oral sensitive CYP3A4 substrates. Simvastatin is a sensitive CYP3A4 substrate, so co-administration may increase simvastatin exposure (AUC/Cmax) and the frequency/severity of dose-related adverse effects, notably myalgia and, rarely, myopathy/rhabdomyolysis.
- Direction: increased simvastatin effect/exposure
- Magnitude: not quantified
- Onset: unspecified
- Evidence: theoretical
Management: Monitor for statin toxicity (muscle pain, weakness, elevated CK). Dose may be individualized by the care team; consider closer follow-up if symptoms arise.
What happens
Increased oral sensitive CYP3A4 substrate exposure and an increased risk on severity and frequency of sensitive CYP3A4 substrate-related adverse reactions
Interaction Deep Dive
In the gut, xanomeline produces a transient, local inhibition of CYP3A4, though this effect does not extend systemically. When xanomeline is taken alongside oral medications that are sensitive substrates of CYP3A4, the exposure to those oral CYP3A4 sensitive substrates may rise. As a result, adverse reactions attributable to these substrates could become more frequent and/or more severe. In cases of concurrent administration, patients should be watched for any increase in the frequency and/or severity of adverse reactions tied to oral drugs that are sensitive substrates of CYP3A41.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism by xanomeline
How to manage this interaction
The good news is this is manageable. Keep taking both simvastatin and xanomeline exactly as prescribed unless your care team tells you otherwise.
- Watch for and report any new or worsening muscle pain, tenderness, or weakness, especially if it comes with dark urine or feeling unwell.
- Your care team may monitor you more closely and can adjust and individualize your simvastatin dose if needed.
- Make sure both prescribers and your pharmacist know you take both drugs.
Because this concern is theoretical, the aim is simply awareness and follow-up, not alarm.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Xanomeline and Simvastatin together?
Xanomeline may raise simvastatin levels by slowing its breakdown in the gut, so watch for muscle aches and keep your care team informed; this is a theoretical, manageable concern, not a reason to stop either drug. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Xanomeline and Simvastatin 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 Xanomeline and Simvastatin interaction managed?
The good news is this is manageable. Keep taking both simvastatin and xanomeline exactly as prescribed unless your care team tells you otherwise. Watch for and report any new or worsening muscle pain, tenderness, or weakness, especially if it comes with dark urine or feeling unwell. Your care team may monitor you more closely and can adjust and individualize your simvastatin dose if needed. Make s… 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 Xanomeline or Simvastatin 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 Simvastatin
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist