Drug Interaction Report

Bretylium and Amitriptyline: Interaction Details

A pharmacist-reviewed analysis of the Bretylium and Amitriptyline 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
+

Bretylium

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 23 documented Bretylium interactions, 23 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 bretylium can add up to prolong the heart's QT interval and raise the risk of a dangerous rhythm, so this pairing is generally not recommended. Talk with your doctor or pharmacist before using both.

Both of these medicines can affect the rhythm of your heart in a similar way. Amitriptyline (a tricyclic antidepressant) and bretylium (a heart rhythm medicine) can each stretch out a part of the heartbeat called the QT interval. When they are taken together, that effect can add up.

In rare cases, a longer QT interval can lead to a dangerous, fast heartbeat. This is why doctors usually try to avoid using these two together. The good news is that your care team knows about this and can watch your heart closely, adjust things, or pick a safer option. Please don't stop either medicine on your own. Just talk with your doctor or pharmacist.

Mechanism: Additive QT prolongation. Amitriptyline (TCA) and bretylium (Class III antiarrhythmic) both prolong ventricular repolarization; combined use raises risk of QTc prolongation, torsades de pointes, and cardiac arrest. This is a pharmacodynamic interaction, not PK; neither agent activation is relevant here.

  • Direction: Additive, increased cardiotoxicity risk
  • Onset: Rapid
  • Evidence: Theoretical (no formal interaction studies)
  • Management: Concurrent use not recommended. If unavoidable, monitor ECG/QTc, correct electrolytes (K+, Mg2+), and consider alternative agents.
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 torsades de pointes have been documented across every Class III antiarrhythmic drug, including acecainide3, amiodarone 4, azimilide 5, bretylium 6, ibutilide 7, sematilide 8, dofetilide 9, and sotalol 10. Although no formal studies of drug interactions have been conducted, giving Class III antiarrhythmics together with other agents recognized to lengthen the QTc interval, such as tricyclic antidepressants, is not advised 211.

Why it happens (mechanism)

Additive QT prolongation

How to manage this interaction

Because both drugs can affect your heart rhythm in the same way, doctors generally prefer not to use them together.

  • Keep taking both exactly as prescribed unless your doctor tells you otherwise, and do not stop either one on your own.
  • Your care team may choose an alternative medicine for one of them, or monitor your heart more closely (such as with an ECG) if both are truly needed.
  • Tell your pharmacist or doctor right away about symptoms like fainting, dizziness, palpitations, or a racing/irregular heartbeat.

Raise this combination with your pharmacist or prescriber so they can decide the safest plan for you.

Management is individual — confirm any change with your pharmacist or prescriber.

Literature reports

2 reports — tap to read

a) Among patients taking therapeutic doses of tricyclic antidepressants, documented electrocardiographic changes include a faster heart rate, a lengthened PR interval, delays in intraventricular conduction, a rise in the corrected QT interval (QTc), and flattening of T waves 1.

b) Using Class III antiarrhythmic agents together with other medications capable of lengthening the QT interval, such as tricyclic antidepressants, is not advised. Dofetilide should be discontinued for a minimum of 2 days before any interacting agent is started. When combined use cannot be prevented, careful dosing along with telemetric monitoring is recommended 2.

Common questions

Can I take Bretylium and Amitriptyline together?

Combining amitriptyline and bretylium can add up to prolong the heart's QT interval and raise the risk of a dangerous rhythm, so this pairing is generally not recommended. Talk with your doctor or pharmacist before using both. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Bretylium 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.

How is the Bretylium and Amitriptyline interaction managed?

Because both drugs can affect your heart rhythm in the same way, doctors generally prefer not to use them together. Keep taking both exactly as prescribed unless your doctor tells you otherwise, and do not stop either one on your own. Your care team may choose an alternative medicine for one of them, or monitor your heart more closely (such as with an ECG) if both are truly needed. Tell your pharm… 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 Bretylium 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 (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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Beyond drug–drug

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:

Amitriptyline + 1,4-butanediol Activated Charcoal American Hellebore Arsenic Beer Cesium Ephedra Gamma-hydroxybutyrate (ghb) + 288 more
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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.