Codeine and Fluoxetine Interaction
Drug interaction information between Codeine and Fluoxetine.
Codeine and Fluoxetine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Codeine 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.
How They Interact
Fluoxetine prevents codeine from being converted into its active form, morphine. This can lead to poor pain control or cause you to feel symptoms of opioid withdrawal.
FDA Label Information
The concomitant use of acetaminophen and codeine phosphate tablets and CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, bupropion, quinidine) can increase the plasma concentration of codeine, but can decrease the plasma concentration of active metabolite morphine, which could result in reduced analgesic efficacy or symptoms of opioid withdrawal, particularly when an inhibitor is added after a stable dose of acetaminophen and codeine phosphate tablets is achieved (see CLINICAL PHARMACOLOGY ).
Codeine Also Interacts With
- Bupropion minor
- Trazodone minor
- Tramadol minor
- Cyclobenzaprine minor
- Oxycodone minor
Fluoxetine Also Interacts With
- Aspirin major
- Warfarin major
- Olanzapine major
- Pimozide major
- Thioridazine major
Frequently Asked Questions
What SPL severity band is on file for Codeine + 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 Codeine's 27. In the minor band specifically: Codeine has 27 (also Bupropion, Trazodone, Tramadol, Cyclobenzaprine); Fluoxetine has 43 (also Ketoconazole, Lithium, Moxifloxacin, Erythromycin).
What mechanism field is on file for Codeine and Fluoxetine?
Fluoxetine prevents codeine from being converted into its active form, morphine. This can lead to poor pain control or cause you to feel symptoms of opioid withdrawal.
Fluoxetine carries more major-labeled pairs than Codeine
SPL source-record counts only. This page's band is minor · classes on file: Codeine (Opioid Analgesic); Fluoxetine (Selective Serotonin Reuptake Inhibitor (SSRI)).
Fluoxetine has 6 major-labeled pairs vs Codeine's 0. This page itself is in the minor band, not the major band.
0 major · 0 moderate · 27 minor · 27 total
- Other minor peers for Codeine
- Bupropion
- Trazodone
- Tramadol
- Cyclobenzaprine
6 major · 19 moderate · 43 minor · 68 total
- Other minor peers for Fluoxetine
- Ketoconazole
- Lithium
- Moxifloxacin
- Erythromycin
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.
Read our methodology - how this data is sourced, computed, and verified.