Drug Interaction Report

Flecainide and Bupropion: Interaction Details

A pharmacist-reviewed analysis of the Flecainide and Bupropion 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

Flecainide

Tambocor®
+

Bupropion

Aplenzin Aplenzin® Budeprion® SR Budeprion® XL Buproban® Forfivo Forfivo® XL Wellbutrin
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 300 documented Flecainide interactions, 270 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
probable
Severity
Major

What happens

Increased exposure of CYP2D6 substrates

Interaction Deep Dive

Use caution with concurrent administration of buPROPion (a CYP2D6 inhibitor) and a CYP2D6 substrate as this may increase the exposure of the CYP2D6 substrate. Coadministration of buPROPion and a single dose of desipramine (a CYP2D6 substrate) resulted in a 2-fold, 5-fold, and 2-fold increase in desipramine Cmax, AUC, and t(1/2), respectively. The CYP2D6 substrate should be initiated at the lower end of the dose range when given with buPROPion. If buPROPion is added to an existing regimen with a CYP2D6 substrate, consider reducing the CYP2D6 substrate dose, especially if it has a narrow therapeutic index12345.

Why it happens (mechanism)

Inhibition of CYP2D6-mediated metabolism by buPROPion and its hydroxybuPROPion metabolite

Literature reports

1 report — tap to read

a) Coadministration of buPROPion (a CYP2D6 inhibitor) 150 mg twice daily and a single dose of desipramine 50 mg (a CYP2D6 substrate) in healthy volunteers who were extensive CYP2D6 metabolizers (n=15) resulted in a 2-fold, 5-fold, and 2-fold increase in desipramine Cmax, AUC, and t(1/2), respectively. The effect persisted for 7 days following the last dose of buPROPion 2345.

Common questions

Can I take Flecainide and Bupropion together?

Increased exposure of CYP2D6 substrates Always confirm with your pharmacist or prescriber before making any change.

How serious is the Flecainide and Bupropion 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 "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Flecainide or Bupropion 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 (5)

  1. Product Information: CONTRAVE(R) oral extended-release tablets, naltrexone HCl bupropion HCl oral extended-release tablets. Currax Pharmaceuticals LLC (per FDA), Brentwood, TN, 2024. DailyMed
  2. Product Information: WELLBUTRIN XL(R) oral extended-release tablets, bupropion hydrochloride oral extended-release tablets. Bausch Health US, LLC (per FDA), Bridgewater, NJ, 2024. DailyMed
  3. Product Information: WELLBUTRIN(R) SR oral sustained-release tablets, bupropion hydrochloride oral sustained-release tablets. GlaxoSmithKline (per FDA), Durham, NC, 2024. DailyMed
  4. Product Information: WELLBUTRIN(R) oral tablets, bupropion hydrochloride oral tablets. GlaxoSmithKline (per FDA), Durham, NC, 2024. DailyMed
  5. Product Information: FORFIVO XL(R) oral extended-release tablets, bupropion hydrochloride oral extended-release tablets. TWi Pharmaceuticals USA, Inc (per FDA), Paramus, NJ, 2024. DailyMed
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Flecainide

Keep reading about Flecainide

All Flecainide interactions (300) Flecainide drug information
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Bupropion

Keep reading about Bupropion

All Bupropion interactions (117) Bupropion drug information
Also serious with: Linezolid Injection Desonide Nebivolol Penicillin V Potassium
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:

Flecainide + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Sida Cordifolia 1,3-dmaa + 78 more
Bupropion + Activated Charcoal Adrafinil African Wild Potato Artichoke Astaxanthin Beer Biofeedback Cannabidiol (cbd) + 38 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.