Propafenone and Fluoxetine Interaction
Drug interaction information between Propafenone and Fluoxetine.
Propafenone and Fluoxetine have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Propafenone and Fluoxetine. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Fluoxetine slows down how fast your body processes propafenone. This can lead to higher amounts of the heart medicine in your system than intended.
What To Do
This combination should be used with caution. Your doctor should monitor you closely for side effects or adjust your medication levels.
FDA Label Information
Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs).
Propafenone Also Interacts With
- Nirmatrelvir/Ritonavir major
- Amiodarone moderate
- Nebivolol moderate
- Ketoconazole minor
- Erythromycin minor
Fluoxetine Also Interacts With
- Aspirin major
- Warfarin major
- Olanzapine major
- Pimozide major
- Thioridazine major
Frequently Asked Questions
Can I take Propafenone and Fluoxetine together?
This is a moderate interaction. This combination should be used with caution. Your doctor should monitor you closely for side effects or adjust your medication levels.
How serious is the interaction between Propafenone and Fluoxetine?
This interaction is classified as "moderate" severity by the FDA. Moderate interactions may worsen your condition or change how your medications work.
Why do Propafenone and Fluoxetine interact?
Fluoxetine slows down how fast your body processes propafenone. This can lead to higher amounts of the heart medicine in your system than intended.
Understanding the Propafenone and Fluoxetine Interaction
FDA-approved prescribing information for these two drugs flags their combination as a moderate-severity interaction. Propafenone belongs to the Class IC Antiarrhythmic class and Fluoxetine belongs to the Selective Serotonin Reuptake Inhibitor (SSRI) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Fluoxetine slows down how fast your body processes propafenone. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Propafenone has 26 total documented interactions on file in this dataset, and Fluoxetine has 68. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: This combination should be used with caution. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Propafenone or Fluoxetine based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.