Duloxetine and Fluoxetine Interaction

Drug interaction information between Duloxetine and Fluoxetine.

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

FDA drug labeling documents a minor-severity interaction between Duloxetine 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

Duloxetine

Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Drug B

Fluoxetine

Selective Serotonin Reuptake Inhibitor (SSRI)

How They Interact

Fluoxetine blocks the liver's ability to break down duloxetine, which can lead to a buildup of duloxetine in your system.

FDA Label Information

Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see Warnings and Precautions (5.12) ].

Frequently Asked Questions

What SPL severity band is on file for Duloxetine + 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 Duloxetine's 18. In the minor band specifically: Duloxetine has 17 (also Famotidine, Buspirone, Paroxetine, Lorazepam); Fluoxetine has 43 (also Ketoconazole, Lithium, Moxifloxacin, Erythromycin).

What mechanism field is on file for Duloxetine and Fluoxetine?

Fluoxetine blocks the liver's ability to break down duloxetine, which can lead to a buildup of duloxetine in your system.

Fluoxetine carries more major-labeled pairs than Duloxetine

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

Fluoxetine has 6 major-labeled pairs vs Duloxetine's 0. This page itself is in the minor band, not the major band.

Duloxetine

0 major · 1 moderate · 17 minor · 18 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.