Bupropion and Fluoxetine Interaction

Drug interaction information between Bupropion and Fluoxetine.

Bupropion and Fluoxetine have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Bupropion 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

Bupropion

Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)

Drug B

Fluoxetine

Selective Serotonin Reuptake Inhibitor (SSRI)

How They Interact

Bupropion blocks a liver protein that normally breaks down fluoxetine, which can cause fluoxetine to build up in your body.

FDA Label Information

( 7.1 ) Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers...

Frequently Asked Questions

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

Compiled FDA labeling labels this pair minor. 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 Bupropion's 35. In the minor band specifically: Bupropion has 32 (also Metoprolol, Sertraline, Clopidogrel, Venlafaxine); Fluoxetine has 43 (also Ketoconazole, Lithium, Moxifloxacin, Erythromycin).

What mechanism field is on file for Bupropion and Fluoxetine?

Bupropion blocks a liver protein that normally breaks down fluoxetine, which can cause fluoxetine to build up in your body.

Fluoxetine carries more major-labeled pairs than Bupropion

SPL source-record counts only. This page's band is minor · classes on file: Bupropion (Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)); Fluoxetine (Selective Serotonin Reuptake Inhibitor (SSRI)).

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

Bupropion

1 major · 2 moderate · 32 minor · 35 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.