Drug Interaction Report

Fluoxetine and Flecainide: Interaction Details

A pharmacist-reviewed analysis of the Fluoxetine and Flecainide 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

Fluoxetine

RECONCILE
+

Flecainide

Tambocor®
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 142 documented Fluoxetine interactions, 130 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

Increased flecainide exposure and an increased risk of QT interval prolongation

Interaction Deep Dive

Avoid coadministration of flecainide, a CYP2D6 substrate1, and FLUoxetine, a CYP2D6 inhibitor, as this may increase flecainide exposure and increase the risk for QT interval prolongation 2. Both flecainide 1 and FLUoxetine, as single agents, prolong the QT interval. Additionally, flecainide has a narrow therapeutic index. If concomitant use is required, obtain a baseline ECG and periodically monitor ECG during therapy. Consider discontinuation of FLUoxetine if signs or symptoms of ventricular arrhythmia occur and obtain a cardiac evaluation. Agents that have a narrow therapeutic index should be initiated at the low end of the dosing range if the patient is already taking FLUoxetine or has used FLUoxetine in the previous 5 weeks. If FLUoxetine is initiated, consider dose reduction of the CYP2D6 substrate (eg, flecainide) 2.

Why it happens (mechanism)

Inhibition of CYP2D6-mediated flecainide metabolism by FLUoxetine; additive QT interval prolongation

Common questions

Can I take Fluoxetine and Flecainide together?

Increased flecainide exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.

How serious is the Fluoxetine and Flecainide 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 Fluoxetine or Flecainide 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. Product Information: FLECAINIDE ACETATE oral tablets, flecanide acetate oral tablets. Roxane Laboratories (per DailyMed), Columbus, OH, 2012. DailyMed
  2. Product Information: PROZAC(R) oral capsules, fluoxetine oral capsules. Lilly USA LLC (per FDA), Indianapolis, IN, 2023. DailyMed
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Fluoxetine

Keep reading about Fluoxetine

All Fluoxetine interactions (142)
Also serious with: Linezolid Injection Anagrelide Palonosetron Injection Dolasetron Injection
Flecainide

Keep reading about Flecainide

All Flecainide interactions (300) Flecainide drug information
Also serious with: Nirmatrelvir Mesoridazine Pimozide Mavorixafor
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:

Fluoxetine + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Lithium Sida Cordifolia + 155 more
Flecainide + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Sida Cordifolia 1,3-dmaa + 78 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.