Amitriptyline and Quinidine: 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
Quinidine
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.
Taking amitriptyline (Elavil) with quinidine needs a little extra care. Quinidine slows down the liver enzyme that breaks amitriptyline down. That means more amitriptyline can build up in your body, which can lead to stronger side effects like drowsiness, dry mouth, dizziness, or a fast heartbeat.
On top of that, both medicines can affect your heart's rhythm in similar ways, so together they may put more strain on your heart. This concern is based mostly on how the drugs work rather than lots of patient reports, but it's worth taking seriously. Please don't change anything on your own. Your care team can manage this by adjusting your dose and keeping a closer eye on you.
Effect: Quinidine inhibits CYP2D6, reducing amitriptyline metabolism and increasing amitriptyline exposure (higher plasma concentrations, greater risk of anticholinergic and CNS adverse effects).
Additive PD risk: Amitriptyline (TCA) plus quinidine (class IA antiarrhythmic) may prolong PR, QRS, and QTc, raising cardiotoxicity risk.
- Direction: Increased amitriptyline effect (not a prodrug).
- Onset: Unspecified. Evidence: Theoretical. Severity: Major.
- Management: Consider an alternative. If combined, consider amitriptyline dose reduction, monitor for TCA toxicity and ECG changes. If quinidine is stopped, amitriptyline dose may need to be increased.
What happens
Increased amitriptyline plasma concentrations; an increased risk of cardiotoxicity
Interaction Deep Dive
Taking amitriptyline, which is metabolized by CYP2D6, together with quinidine, a CYP2D6 inhibitor, can raise amitriptyline exposure and heighten the likelihood of amitriptyline adverse effects because the metabolism of amitriptyline is inhibited16. Furthermore, combining tricyclic antidepressants with class IA antiarrhythmics may raise the incidence of cardiotoxicity, given that these agents produce comparable cardiac effects 23. For this reason, an alternative therapy may be appropriate. Should amitriptyline and quinidine be used together, consideration should be given to adjusting the amitriptyline dose 6. It is also advisable to watch for amitriptyline adverse effects while the two are used concurrently. An increase in the amitriptyline dose may be required if quinidine is stopped 1. Monitoring the patient for signs and symptoms of cardiac toxicity may likewise be needed.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated amitriptyline metabolism by quinidine; additive cardiac effects
How to manage this interaction
Here is how a care team typically handles this combination:
- Choosing an alternative: Your prescriber may consider a different medication for one of these roles.
- Dose tailoring: If both are used together, your amitriptyline dose may be reduced and individualized by your care team. If quinidine is later stopped, that dose may need to be raised again.
- Closer monitoring: Your team may watch for amitriptyline side effects and check your heart rhythm (ECG) for changes.
What you should do: Keep taking both exactly as prescribed, and tell your pharmacist or doctor about any drowsiness, palpitations, dizziness, or fainting.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A higher rate of sudden death was noted in 6 of 53 patients with cardiac disease who were given amitriptyline, versus 0 of 53 in the control group. The recommendation was that amitriptyline should not be used in patients with underlying cardiac disease, unless the depression was debilitating and no other medications provided benefit 5. Further studies were performed that gave additional confirmation that amitriptyline was linked to a greater incidence of sudden death in patients with existing cardiac disease 45.
Common questions
Can I take Amitriptyline and Quinidine together?
Quinidine can raise amitriptyline levels and both can affect heart rhythm, so your care team may pick an alternative, lower the amitriptyline dose, and monitor your heart. Keep taking both as prescribed and report any palpitations, dizziness, or fainting. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Quinidine 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 Amitriptyline and Quinidine interaction managed?
Here is how a care team typically handles this combination: Choosing an alternative: Your prescriber may consider a different medication for one of these roles. Dose tailoring: If both are used together, your amitriptyline dose may be reduced and individualized by your care team. If quinidine is later stopped, that dose may need to be raised again. Closer monitoring: Your team may watch for amitri… 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 Quinidine 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 (6)
- Product Information: amitriptyline hcl oral tablets, amitriptyline hcl oral tablets. Vintage Pharmaceuticals,LLC, Huntsville, AL, 2006. DailyMed
- Kantor SJ, Glassman AH, Bigger JT Jr. et al: The cardiac effects of therapeutic plasma concentrations of imipramine. Am J Psychiatry 1978; 135:534-538. PubMed
- Bigger JT, Giardina EG, Perel JM, et al: Cardiac antiarrhythmic effect of imipramine hydrochloride. N Engl J Med 1977; 296:206-208. PubMed
- Moir DC, Crooks J, Cornwell WB, et al: Cardiotoxicity of amitriptyline. Lancet 1972; 2:561-564. PubMed
- Coull DC, Crooks J, Dingwall-Fordyce I, et al: Amitriptyline and cardiac disease. Lancet 1970; 1:590-591. DOI
- Product Information: NUEDEXTA(TM) oral capsules, dextromethorphan hydrobromide and quinidine sulfate oral capsules. Avanir Pharmaceuticals, Inc, Aliso Viejo, CA, 2010. DailyMed
Keep reading about Amitriptyline
Keep reading about Quinidine
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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