Drug Interaction Report

Amitriptyline and Azimilide: Interaction Details

A pharmacist-reviewed analysis of the Amitriptyline and Azimilide interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

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

Elavil
+

Azimilide

No brand names on record
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Jul 2, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 525 documented Amitriptyline interactions, 421 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Theoretical Effects may be stronger
The Bottom Line
Combining amitriptyline and azimilide can add up to prolong the QT interval and raise the risk of a dangerous heart rhythm, so this pairing is generally not recommended. Do not change anything on your own; check with your pharmacist or doctor.

Both of your medicines can affect the electrical timing of your heartbeat, something doctors call the QT interval. Amitriptyline (a medicine often used for mood or nerve pain) and azimilide (a heart rhythm medicine) can each stretch out that timing a little. Taken together, that effect can add up and, in rare cases, lead to a dangerous fast or irregular heartbeat.

This concern is based on how these drugs work rather than on direct studies, but because the heart is involved, doctors take it seriously. The good news is that your care team can manage this by choosing the safest combination for you and watching your heart closely. Please talk with your pharmacist or doctor before making any changes.

Effect: Additive QTc prolongation with increased risk of torsades de pointes and cardiac arrest when a tricyclic antidepressant (amitriptyline) is combined with a Class III antiarrhythmic (azimilide).

Mechanism: Pharmacodynamic additivity; both agents delay cardiac repolarization (K+ channel effects). Not a prodrug or PK interaction.

  • Onset: rapid
  • Evidence: theoretical; no formal interaction studies, but Class III agents are established QT prolongers
  • Severity: major

Management: Coadministration is not recommended. If unavoidable, obtain baseline and follow-up ECG, monitor QTc, correct hypokalemia/hypomagnesemia, and consider an alternative antidepressant.

Onset
rapid
Evidence
theoretical
Severity
Major

What happens

An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)

Interaction Deep Dive

QTc prolongation and/or torsades de pointes have been documented with every Class III antiarrhythmic agent, such as acecainide 3, amiodarone 4, azimilide 5, bretylium 6, ibutilide 7, sematilide 8, dofetilide 9, and sotalol 10. Although formal studies of drug interactions have not been conducted, it is advised against giving Class III antiarrhythmics together with other agents recognized to prolong the QTc interval, including tricyclic antidepressants 211.

Why it happens (mechanism)

Additive QT prolongation

How to manage this interaction

Doctors generally do not recommend taking a Class III heart rhythm drug like azimilide together with a tricyclic antidepressant like amitriptyline because their heart-timing effects can add up.

  • Keep taking both as prescribed unless your doctor tells you otherwise, do not stop on your own.
  • Your care team may check your heart tracing (ECG) and blood minerals like potassium and magnesium.
  • They may consider switching one medicine to a safer alternative.

Ask your pharmacist or prescriber if these two were meant to be used together, and report any fainting, dizziness, or a pounding 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, an increased corrected QT interval (QTc), and flattening of the T waves 1.

b) Simultaneous administration of Class III antiarrhythmic drugs, along with other agents capable of prolonging the QT interval, such as tricyclic antidepressants, is not advised. Dofetilide should be discontinued for a minimum of 2 days prior to starting any interacting medication. When concurrent use cannot be avoided, careful dosing together with telemetric monitoring is recommended 2.

Common questions

Can I take Amitriptyline and Azimilide together?

Combining amitriptyline and azimilide can add up to prolong the QT interval and raise the risk of a dangerous heart rhythm, so this pairing is generally not recommended. Do not change anything on your own; check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Amitriptyline and Azimilide interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.

How is the Amitriptyline and Azimilide interaction managed?

Doctors generally do not recommend taking a Class III heart rhythm drug like azimilide together with a tricyclic antidepressant like amitriptyline because their heart-timing effects can add up. Keep taking both as prescribed unless your doctor tells you otherwise, do not stop on your own. Your care team may check your heart tracing (ECG) and blood minerals like potassium and magnesium. They may co… 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 Azimilide 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 (11)

  1. 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
  2. Yamreudeewong W, DeBisschop M, Martin LG, et al: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Safety 2003; 26(6):421-438. PubMed
  3. Chow MJ, Piergies AA, Bowsher DJ, et al: Torsade de pointes induced by N-acetylprocainamide. J Am Coll Cardiol 1984; 4:621-624. PubMed
  4. Faggiano P, Gardini A, D'Aloia A, et al: Torsade de pointes occurring early during oral amiodarone treatment. Int J Cardiol 1996; 55(2):205-208. DOI
  5. Corey AE, Agnew JR, Valentine SN, et al: Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation. J Clin Pharmacol 1999; 39(12):1272-1276. PubMed
  6. Gilman AG, Goodman LS, Rall TW, et alGilman AG, Goodman LS, Rall TW, et al (Eds): The Pharmacological Basis of Therapeutics, 7th. Macmillan Publishing Co, New York, NY, 1985.
  7. Rodriguez I, Kilborn MJ, Liu XK, et al: Drug-induced QT prolongation in women during the menstrual cycle. JAMA 2001; 285(10):1322-1326. PubMed
  8. Singh BN: The coming of age of the class III antiarrhythmic principle: retrospective and future trends. Am J Cardiol 1996; 78(suppl):17-27. PubMed
  9. Allen MJ, Oliver SD, Newgreen MW, et al: Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT interval. Br J Clin Pharmacol 2002; 53:59-65.
  10. Marill KA & Runge T: Meta-analysis of the risk of torsades de pointes in patients treated with intravenous racemic sotalol. Acad Emerg Med 2001; 8(2):117-124. PubMed
  11. Product Information: Corvert(R), ibutilide fumarate injection. Pharmacia & Upjohn Company, Kalamazoo, MI, 2000. DailyMed
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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.