Tacrolimus and Amitriptyline: 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
Tacrolimus
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.
Both amitriptyline and tacrolimus can affect the electrical rhythm of your heart. Doctors call this QT prolongation. When two medicines that both do this are taken together, the effect can add up and, rarely, lead to a dangerous heartbeat.
I want to be clear that this concern is based on how these drugs work rather than a lot of real-world reports, so please don't panic. Keep taking both exactly as prescribed. The good news is that your care team can manage this easily by checking your heart tracing (an EKG) and your blood minerals like potassium and magnesium now and then. Just let your doctor or pharmacist know you take both.
Effect: Additive QT-interval prolongation with concurrent amitriptyline (a TCA with known QT effects) and tacrolimus, raising theoretical risk of serious cardiac toxicity including torsade de pointes.
Mechanism: Pharmacodynamic (additive), not PK; neither agent's metabolism drives this interaction.
- Direction/magnitude: Additive QTc effect; magnitude undefined.
- Onset: Unspecified.
- Evidence: Theoretical.
- Management: Obtain baseline and periodic ECGs; monitor and correct magnesium, potassium, and calcium. Assess other QT-prolonging drugs and bradycardia. Individualize therapy; consider alternatives if QTc rises.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
Taking tacrolimus together with an agent that produces additive QT-prolonging effects can heighten the likelihood of severe cardiac toxicity, such as torsade de pointes. Should these drugs be given together, periodic electrocardiograms and monitoring of electrolytes (calcium, potassium, magnesium) throughout the course of treatment should be considered12.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is usually managed with simple monitoring.
- Your team may order an EKG before and periodically during treatment to watch your heart rhythm.
- They may check electrolytes (magnesium, potassium, calcium) and correct any that are low.
- Tell your pharmacist about all other medicines, since several can add to this effect.
Seek care promptly if you feel fainting, dizziness, palpitations, or an irregular heartbeat. Ask your pharmacist or prescriber before starting or stopping anything.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Tacrolimus and Amitriptyline together?
Taking amitriptyline and tacrolimus together can add up their effects on your heart rhythm, so your care team may check EKGs and blood minerals; keep taking both as prescribed and report any fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tacrolimus and Amitriptyline interaction?
It is rated major. Potentially serious — often needs a change or close 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 Amitriptyline interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is usually managed with simple monitoring. Your team may order an EKG before and periodically during treatment to watch your heart rhythm. They may check electrolytes (magnesium, potassium, calcium) and correct any that are low. Tell your pharmacist about all other medicines, since several can add… 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 Tacrolimus or Amitriptyline 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 a safer alternative to one of these medications for me?
References (2)
- Product Information: PROGRAF(R) oral capsules, oral granules for suspension, intravenous injection, tacrolimus oral capsules, oral granules for suspension, intravenous injection. Astellas Pharma US Inc (per FDA), Northbrook, IL, 2023. DailyMed
- Product Information: ENVARSUS XR(R) oral extended-release tablets, tacrolimus oral extended-release tablets. Veloxis Pharmaceuticals Inc (per FDA), Cary, NC, 2023. DailyMed
Keep reading about Amitriptyline
Keep reading about Tacrolimus
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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