Alprazolam and Fluoxetine Interaction

Drug interaction information between Alprazolam and Fluoxetine.

Alprazolam and Fluoxetine have a documented moderate interaction in FDA labeling.

FDA drug labeling documents a moderate-severity interaction between Alprazolam 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

Alprazolam

Benzodiazepine

Drug B

Fluoxetine

Selective Serotonin Reuptake Inhibitor (SSRI)

How They Interact

Fluoxetine raises the amount of alprazolam in your blood. This can make you feel more sluggish and affect your ability to move or think clearly.

FDA Label Information

Monoamine Oxidase Inhibitors (MAOIs): ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( 7.7 ) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued ( 5.2 , 7.7 ) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs ( 7.2 ) Benzodiazepines: Diazepam – increased t½, alprazolam - further psychomotor performance decrement due to increased levels ( 7.7 ) Antipsychotics: Potential for elevation...

Alprazolam Also Interacts With

View all Alprazolam interactions →

Frequently Asked Questions

What SPL severity band is on file for Alprazolam + 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 Alprazolam's 27. In the moderate band specifically: Alprazolam has 7 (also Ketoconazole, Clarithromycin, Itraconazole, Digoxin); Fluoxetine has 19 (also Diazepam, Carbamazepine, Haloperidol, Clozapine).

What mechanism field is on file for Alprazolam and Fluoxetine?

Fluoxetine raises the amount of alprazolam in your blood. This can make you feel more sluggish and affect your ability to move or think clearly.

Fluoxetine carries more major-labeled pairs than Alprazolam

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

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

Alprazolam

0 major · 7 moderate · 20 minor · 27 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.