Drug Interaction Report

Disopyramide and Protriptyline: Interaction Details

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

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Protriptyline

No brand names on record
+

Disopyramide

Norpace Norpace® Norpace® CR
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 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 284 documented Disopyramide interactions, 247 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.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

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

Interaction Deep Dive

Concomitant use of tricyclic antidepressants, including protriptyline, and class IA antiarrhythmics, including disopyramide, may increase the risk of cardiotoxicity due to similar cardiac effects of these drugs12. Therefore, monitoring the patient for signs and symptoms of cardiac toxicity during coadministration of disopyramide and protriptyline may be warranted.

Why it happens (mechanism)

Additive cardiac effects

Common questions

Can I take Disopyramide and Protriptyline together?

An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Disopyramide and Protriptyline 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 strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Disopyramide or Protriptyline 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 (2)

  1. 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
  2. Bigger JT, Giardina EG, Perel JM, et al: Cardiac antiarrhythmic effect of imipramine hydrochloride. N Engl J Med 1977; 296:206-208. DOI
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Protriptyline

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Disopyramide

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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:

Protriptyline + Activated Charcoal Henbane Lithium Scopolia 5-htp Acetyl-l-carnitine Alfalfa Angel's Trumpet + 85 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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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.