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. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Propafenone

Class IC Antiarrhythmic

Drug B

Fluoxetine

Selective Serotonin Reuptake Inhibitor (SSRI)

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.

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).

Frequently Asked Questions

What SPL severity band is on file for Propafenone + Fluoxetine?

Compiled FDA labeling labels this pair moderate. That is a source-record field, not an individual medication-combination decision.

Which drug in this pair has the larger labeled-interaction portfolio?

Fluoxetine has 68 labeled pairs on file vs Propafenone's 26. In the moderate band specifically: Propafenone has 3 (also Amiodarone, Nebivolol); Fluoxetine has 19 (also Alprazolam, Diazepam, Carbamazepine, Haloperidol).

What mechanism field is on file for Propafenone and Fluoxetine?

Fluoxetine slows down how fast your body processes propafenone. This can lead to higher amounts of the heart medicine in your system than intended.

Fluoxetine carries more major-labeled pairs than Propafenone

SPL source-record counts only. This page's band is moderate · classes on file: Propafenone (Class IC Antiarrhythmic); Fluoxetine (Selective Serotonin Reuptake Inhibitor (SSRI)).

Fluoxetine has 6 major-labeled pairs vs Propafenone's 1. This page itself is in the moderate band, not the major band.

Propafenone

1 major · 3 moderate · 22 minor · 26 total

Fluoxetine

6 major · 19 moderate · 43 minor · 68 total

Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.