Amitriptyline and Mirabegron: 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
Amitriptyline
Mirabegron
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.
You've been prescribed amitriptyline (Elavil) and mirabegron (Myrbetriq) together. Here's the simple version: your body uses a liver enzyme to break down amitriptyline, and mirabegron slows that enzyme down a bit. That means amitriptyline can build up more than usual in your system.
When that happens, you might notice more of amitriptyline's usual side effects, like drowsiness, dry mouth, constipation, blurry vision, or a faster heartbeat. This is based on how these drugs work rather than lots of real-world reports, so it may not be a big deal for you. The good news: your care team can manage this easily by adjusting your dose if needed and keeping an eye on how you feel.
Effect: Increased amitriptyline exposure via mirabegron inhibition of CYP2D6, the enzyme responsible for amitriptyline metabolism. Amitriptyline is an active drug (not a prodrug), so reduced clearance raises plasma levels and PD effects.
- Direction: Higher amitriptyline AUC/Cmax, greater anticholinergic, sedative, and cardiac (QT/conduction) risk.
- Evidence: Theoretical; mirabegron is a moderate CYP2D6 inhibitor.
- Onset: Unspecified.
- Management: Consider a lower TCA (or mirabegron) dose; monitor amitriptyline response, anticholinergic/CNS effects, and consider plasma levels and ECG where clinically indicated. Doses should be individualized by the care team.
What happens
Increased amitriptyline exposure
Interaction Deep Dive
When mirabegron, which acts as a moderate inhibitor of CYP2D62, is given alongside amitriptyline, a substrate of CYP2D61, the exposure to amitriptyline may rise, along with the potential for adverse events. Using tricyclic antidepressants together with CYP2D6 inhibitors may call for dose reductions of either the tricyclic antidepressant or the CYP2D6 inhibitor, and monitoring of the tricyclic antidepressant is advised1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated amitriptyline metabolism by mirabegron
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. This interaction is usually manageable.
- Your care team may adjust and individualize the dose of amitriptyline (or mirabegron) to account for the higher levels.
- They may monitor you more closely for how you respond and for side effects.
- Tell your pharmacist or doctor if you notice more drowsiness, dry mouth, constipation, blurred vision, dizziness, or a racing or irregular heartbeat.
Bring an up-to-date list of all your medicines to appointments so your team can watch for this.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Mirabegron together?
Mirabegron can raise amitriptyline levels and increase its side effects, but your care team can manage this by adjusting the dose and monitoring you; report any new drowsiness, dry mouth, or heart-rhythm changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Mirabegron 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 Amitriptyline and Mirabegron interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. This interaction is usually manageable. Your care team may adjust and individualize the dose of amitriptyline (or mirabegron) to account for the higher levels. They may monitor you more closely for how you respond and for side effects. Tell your pharmacist or doctor if you notice more drowsiness, dry mouth… 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 Amitriptyline or Mirabegron 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 (2)
- Product Information: amitriptyline HCl oral tablet, amitriptyline HCl oral tablet. RemedyRepack Inc. (per DailyMed), Indiana, PA, 2010. DailyMed
- Product Information: MYRBETRIQ(TM) oral extended-release tablets, mirabegron oral extended-release tablets. Astellas Pharma US, Inc. (per FDA), Northbrook, IL, 2012. DailyMed
Keep reading about Amitriptyline
Keep reading about Mirabegron
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