Tramadol and Fluoxetine Interaction
Drug interaction information between Tramadol and Fluoxetine.
Tramadol and Fluoxetine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Tramadol 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 stops your body from breaking down tramadol normally. This can cause the drug to build up to higher levels in your blood.
FDA Label Information
Examples Quinidine, fluoxetine, paroxetine and bupropion Inhibitors of CYP3A4 Clinical Impact: The concomitant use of tramadol hydrochloride extended-release tablets and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1.
Tramadol Also Interacts With
- Safinamide major
- Carbamazepine moderate
- Rifampin moderate
- Phenytoin moderate
- Gabapentin 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 Tramadol + 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 Tramadol's 38. In the minor band specifically: Tramadol has 34 (also Gabapentin, Bupropion, Cyclobenzaprine, Paroxetine); Fluoxetine has 43 (also Ketoconazole, Lithium, Moxifloxacin, Erythromycin).
What mechanism field is on file for Tramadol and Fluoxetine?
Fluoxetine stops your body from breaking down tramadol normally. This can cause the drug to build up to higher levels in your blood.
Fluoxetine carries more major-labeled pairs than Tramadol
SPL source-record counts only. This page's band is minor · classes on file: Tramadol (Opioid Analgesic); Fluoxetine (Selective Serotonin Reuptake Inhibitor (SSRI)).
Fluoxetine has 6 major-labeled pairs vs Tramadol's 1. This page itself is in the minor band, not the major band.
1 major · 3 moderate · 34 minor · 38 total
- Other minor peers for Tramadol
- Gabapentin
- Bupropion
- Cyclobenzaprine
- Paroxetine
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.