Quinidine and Mexiletine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mexiletine
Quinidine
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.
What happens
Increased mexiletine bioavailability and an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
Mexiletine clearance is decreased and the elimination half-life is increased when given concurrently with quinidine. Cytochrome P450 2D6 hepatic enzymes are partly responsible for the metabolism of mexiletine, and quinidine has been identified as an inhibitor of this enzyme. However, quinidine and mexiletine coadministration has been shown to exhibit greater antiarrhythmic efficacy and to decrease the incidence of side effects1.
Why it happens (mechanism)
Inhibition of cytochrome P450 2D6 hepatic enzymes by quinidine resulting in decreased metabolism of mexiletine; additive cardiac effects
Literature reports
1 report — tap to read
a) Cytochrome P450 2D6 (CYP2D6) enzyme activity has been shown to be genetically determined, with approximately 10% of Caucasians classified as poor metabolizers (PMs) of CYP2D6 because of low enzyme activity. The other 90% of the population are referred to as extensive metabolizers (EMs) of CYP2D6. Quinidine is a selective inhibitor of CYP2D6, thereby causing EMs to exhibit similar metabolizing patterns as PMs. Fourteen volunteers, 10 EMs and 4 PMs, were given a single dose of mexiletine 200 mg on two occasions, separated by one week. Quinidine 50 mg four times daily was coadministered with one of the mexiletine doses, starting two days before and up to two days after the mexiletine dose. Since PMs already have low levels of CYP2D6 activity, the pharmacokinetic parameters of mexiletine were not significantly altered by the administration of quinidine in this population. However, the EMs experienced an increase in the half-life (from 8.9 hours to 10.6 hour) and a decrease in the total clearance from 621 mL/min to 471 mL/min. These results demonstrated that a pharmacokinetic interaction between the two agents may be partly responsible for the greater efficacy and decreased side effects which are seen when quinidine and mexiletine are concomitantly administered 1.
Common questions
Can I take Quinidine and Mexiletine together?
Increased mexiletine bioavailability 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 Quinidine and Mexiletine 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Quinidine or Mexiletine 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 (1)
- Turgeon J, Fiset C, Giguere R, et al: Influence of debrisoquine phenotype and of quinidine on mexiletine disposition in man. J Pharmacol Exp Ther 1991; 259:789-798. DOI
Keep reading about Mexiletine
Keep reading about Quinidine
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist