Drug Interaction Report

Mexiletine and Disopyramide: Interaction Details

A pharmacist-reviewed analysis of the Mexiletine and Disopyramide 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

Mexiletine

Mexitil®
+

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 82 documented Mexiletine interactions, 64 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
delayed
Evidence
theoretical
Severity
Major

What happens

Disopyramide toxicity (cardiac arrhythmias, hypotension, syncope) and an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)

Interaction Deep Dive

Class Ia antiarrhythmics have been shown to prolong the QTc interval at the recommended therapeutic dose. Even though no formal drug interactions studies have been done, the coadministration of Class Ia antiarrhythmics, and other drugs known to prolong the QTc interval, including mexilitine, is not recommended3.

Why it happens (mechanism)

Additive cardiac effects

Literature reports

2 reports — tap to read

a) One study reported increased effectiveness with the combination of mexiletine and disopyramide in patients with refractory ventricular tachyarrhythmia 2.

b) Torsade de pointes (variant of ventricular tachycardia) in a 59-year-old male following mexiletine 100 mg orally every 6 hours has been reported 1. The ventricular tachycardia did not recur upon discontinuation of the drug.

Common questions

Can I take Mexiletine and Disopyramide together?

Disopyramide toxicity (cardiac arrhythmias, hypotension, syncope) and 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 Mexiletine and Disopyramide interaction?

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

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

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 Mexiletine or Disopyramide 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 (3)

  1. Cocco G, Strozzi C, Chu D, et al: Torsades de pointes as a manifestation of mexiletine toxicity. Am Heart J 1980; 100:878-880. DOI
  2. Kim SG, Felder SD, Waspe Le, et al: Electrophysiologic effects and clinical efficacy of mexiletine used alone or in comvination with Class Ia agents for refractory recurrent ventricular tachycardis or ventricular fibrillation. Am J Cardiol 1986; 58:485-490.
  3. Kim SG, Felder SD, Waspe Le, et al: Electrophysiologic effects and clinicil efficacy of mexilitine used alone or in combination with class Ia agents for refractory recurrent ventricular tachycardias or ventricular fibrillation. Am J Cardiol 1986; 58:485-490.
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Mexiletine

Keep reading about Mexiletine

All Mexiletine interactions (82) Mexiletine drug information
Also serious with: Mavorixafor Fezolinetant Levomethadyl Vernakalant
Disopyramide

Keep reading about Disopyramide

All Disopyramide interactions (284) Disopyramide drug information
Also serious with: Levomethadyl Mesoridazine Levoketoconazole Itraconazole
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:

Mexiletine + Activated Charcoal 1,3-dmaa Acacia Rigidula Active Hexose Correlated Compound (ahcc) Adrafinil African Wild Potato Ashitaba Ayahuasca + 144 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.