Flecainide and Paroxetine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Paroxetine
Flecainide
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 risk of QT interval prolongation, increased flecainide exposure and an increased risk of flecainide toxicity (cardiac arrhythmia)
Interaction Deep Dive
Decrease the dosage of flecainide if needed with concomitant PARoxetine use. Conversely, an increase in dosage of a flecainide may be needed if PARoxetine is discontinued. Use caution with coadministration of PARoxetine (a strong CYP2D6 inhibitor) and flecainide (a CYP2D6 substrate), as increased flecainide exposure may occur1. Delirium was reported when PARoxetine and flecainide was coadministered to a 69-year-old female 2. PARoxetine is also associated with ventricular tachycardia and torsade de pointes. Coadministration of PARoxetine with other QT prolonging drugs may also increase the risk of QT interval prolongation 1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP2D6-mediated flecainide metabolism by PARoxetine
Literature reports
1 report — tap to read
a) In a case report, coadministration of flecainide and PARoxetine caused delirium in a 69-year-old female with symptoms of increasing confusion and paranoia occurring approximately 2 weeks following the initiation of flecainide for atrial fibrillation. Medications upon admission included carvedilol, warfarin, flecainide 100 mg twice daily, folic acid, levothyroxine, pantoprazole, and PARoxetine 40 mg/day (for more than 5 years). Flecainide serum concentration was 1360 mcg/L (reference range 200 mcg/L to 1000 mcg/L) and the dosage was decreased to 50 mg twice daily. PARoxetine was discontinued. Within 3 days, the patient's symptoms completely resolved and within 1 week the patient was discharged with no residual effects 2.
Common questions
Can I take Flecainide and Paroxetine together?
Increased risk of QT interval prolongation, increased flecainide exposure and an increased risk of flecainide toxicity (cardiac arrhythmia) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flecainide and Paroxetine 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Flecainide or Paroxetine 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)
- Product Information: PEXEVA(R) oral tablets, paroxetine mesylate oral tablets. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.
- Tsao YY & Gugger JJ: Delirium in a patient with toxic flecainide plasma concentrations: the role of a pharmacokinetic drug interaction with paroxetine. Ann Pharmacother 2009; 43(7):1366-1369. PubMed
Keep reading about Paroxetine
Keep reading about Flecainide
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