Terbinafine 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
Terbinafine
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 CYP2D6 to break down amitriptyline (Elavil). Terbinafine (Lamisil), the antifungal, slows that enzyme down. So while you're taking both, your amitriptyline may not clear as quickly and its levels can climb higher than usual.
That could mean more of the usual amitriptyline side effects, like drowsiness, dry mouth, constipation, dizziness, or a faster heartbeat. This is based mostly on how the drugs work rather than lots of real-world reports, so please don't panic. Keep taking both as prescribed, and let your pharmacist or doctor know you're on the pair so they can watch you closely and adjust if needed.
Mechanism: Terbinafine is a potent CYP2D6 inhibitor; amitriptyline is a CYP2D6 substrate (not a prodrug). Inhibition reduces amitriptyline clearance, increasing its exposure (AUC/Cmax) and potentially those of its active metabolite nortriptyline.
Direction: Increased amitriptyline effect and toxicity risk (anticholinergic effects, sedation, orthostasis, QT/conduction effects).
- Evidence: theoretical; onset: unspecified. Terbinafine's CYP2D6 inhibition is prolonged given its long half-life.
- At-risk: CYP2D6 poor metabolizers.
- Management: use caution, monitor clinically and via ECG as indicated, obtain amitriptyline plasma levels, and reduce dose if warranted. Anticipate a dose increase requirement if terbinafine is stopped.
What happens
Increased exposure of amitriptyline
Interaction Deep Dive
When amitriptyline, which is metabolized by CYP2D6, is taken together with an agent that inhibits CYP2D6, amitriptyline exposure may rise. This risk is particularly pronounced in poor metabolizers. Should the combination be necessary, exercise caution and keep the patient under close observation. It is also advisable to check amitriptyline plasma concentrations and modify the dose as required. Discontinuation of the CYP2D6 inhibitor may make it necessary to raise the amitriptyline dose1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of amitriptyline
How to manage this interaction
The good news: your care team can manage this by tailoring your dose and keeping a closer eye on you.
- Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for amitriptyline side effects (drowsiness, dry mouth, constipation, dizziness, fast or irregular heartbeat).
- They may check amitriptyline blood levels and adjust the dose to individualize it for you.
- If the terbinafine is later stopped, your amitriptyline dose may need to be increased again.
Let your pharmacist or doctor know you are taking these two together, and report any new or worsening symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Terbinafine and Amitriptyline together?
Terbinafine can raise amitriptyline levels by blocking the CYP2D6 enzyme that clears it, so watch for increased amitriptyline side effects. Keep taking both as prescribed and let your care team monitor and adjust your dose as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Terbinafine and Amitriptyline 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 Terbinafine and Amitriptyline interaction managed?
The good news: your care team can manage this by tailoring your dose and keeping a closer eye on you. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for amitriptyline side effects (drowsiness, dry mouth, constipation, dizziness, fast or irregular heartbeat). They may check amitriptyline blood levels and adjust t… 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 Terbinafine 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: amitriptyline HCl oral tablet, amitriptyline HCl oral tablet. RemedyRepack Inc. (per DailyMed), Indiana, PA, 2010. DailyMed
Keep reading about Amitriptyline
Keep reading about Terbinafine
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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