Aprindine 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
Aprindine
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.
Both of your medicines can affect your heart's rhythm. Amitriptyline (an older antidepressant) and aprindine (a heart rhythm drug) can each stretch out a part of your heartbeat called the QT interval. When you take them together, that effect can add up, which in rare cases could lead to a dangerous irregular heartbeat.
This is a theoretical concern, meaning it is based on how these drugs work rather than on studies of the two together. Please don't stop either one on your own. The good news is your care team can manage this by choosing the safest option for you and keeping a close eye on your heart. Talk with your doctor or pharmacist.
Effect: Additive QTc prolongation, raising the risk of torsades de pointes, cardiac arrest, and other cardiotoxicity.
Mechanism: Pharmacodynamic (PD) additive effect on cardiac repolarization. Aprindine, a Class I antiarrhythmic, prolongs QTc at therapeutic doses; amitriptyline, a TCA, independently prolongs QTc. Neither is a prodrug; this is not a PK interaction.
- Direction: Increased combined cardiotoxic effect.
- Evidence: Theoretical; no formal interaction studies.
- Onset: Unspecified.
- Management: Concurrent use is not recommended. If unavoidable, obtain baseline/serial ECGs, monitor QTc and electrolytes (K+, Mg2+), and individualize therapy.
What happens
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
At the recommended therapeutic dose, Class I antiarrhythmics have demonstrated the ability to lengthen the QTc interval. While no formal studies of drug interactions have been conducted, giving Class I antiarrhythmics together with other agents recognized to prolong the QTc interval, such as tricyclic antidepressants, is advised against345.
Why it happens (mechanism)
Additive effects on QT prolongation
How to manage this interaction
Because both drugs can affect heart rhythm, using them together generally is not recommended. Your care team decides how to handle this safely.
- Keep taking both exactly as prescribed until your doctor or pharmacist advises otherwise. Do not stop on your own.
- Your team may choose an alternative medicine for one of these drugs, since combining them is not recommended.
- If you do stay on both, expect closer heart monitoring, such as ECG checks, and doses may be adjusted and individualized by your care team.
- Tell your prescriber about fainting, dizziness, palpitations, or a very fast or irregular heartbeat right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Electrocardiographic changes documented in patients taking therapeutic doses of tricyclic antidepressants include a faster heart rate, lengthened PR interval, delays in intraventricular conduction, a longer corrected QT interval (QTc), and flattening of the T waves 1.
b) A 68-year-old man with agitated major depression was started on desipramine 125 mg per day, which yielded a subtherapeutic serum concentration of 442 nmol/L (therapeutic range = 500 to 1000 nmol/L). Raising the dose to 175 mg daily achieved an excellent clinical response without any adverse effects. He then developed atrial fibrillation and flutter. Digoxin 0.25 mg daily was added to his regimen, and desipramine was stopped. His arrhythmia was controlled by adding propafenone 150 mg twice daily and 300 mg at bedtime. Desipramine 150 mg daily was restarted, at which time he experienced dry mouth, sedation, and shakiness; the desipramine serum level was measured at 2092 nmol/L. Desipramine was withheld for five days, the adverse effects resolved, and desipramine therapy was reinstated at 75 mg daily. The desipramine serum level was then measured at 1130 nmol/L 2.
Common questions
Can I take Aprindine and Amitriptyline together?
Amitriptyline and aprindine can each prolong the QT interval, and together the heart-rhythm risk adds up, so combining them is generally not recommended. Keep taking both as prescribed and ask your doctor or pharmacist about the safest plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aprindine 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 Aprindine and Amitriptyline interaction managed?
Because both drugs can affect heart rhythm, using them together generally is not recommended. Your care team decides how to handle this safely. Keep taking both exactly as prescribed until your doctor or pharmacist advises otherwise. Do not stop on your own. Your team may choose an alternative medicine for one of these drugs, since combining them is not recommended. If you do stay on both, expect… 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 Aprindine 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 (5)
- Marshall JB & Forker AD: Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J 1982; 103:401-414. PubMed
- Katz MR: Raised serum levels of desipramine with the antiarrhythmic propafenone (letter). J Clin Psychiatry 1991; 52:432-433.
- Product Information: Tambocor(R) flecainide acetate. 3M Pharmaceuticals, Northridge, CA, 1998.
- Larochelle P, Belanger L, Lemire F, et al: Dose-response effect of propafenone in patients with ventricular arrhythmias. Curr Ther Res 1984; 36:959-969. DOI
- Scagliotti D, Strasberg B, Hai HA, et al: Aprindine-induced polymorphous ventricular tachycardia. Am J Cardiol 1982; 49:1297-1300. PubMed
Keep reading about Amitriptyline
Keep reading about Aprindine
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