Codeine and Tramadol Interaction
Drug interaction information between Codeine and Tramadol.
Codeine and Tramadol have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Codeine and Tramadol. 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
These medications both increase the amount of serotonin in your body. Having too much serotonin can lead to a serious condition called serotonin syndrome.
FDA Label Information
Examples of these drugs include, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (used to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see PRECAUTIONS; Information for Patients/Caregivers ).
Codeine Also Interacts With
- Bupropion minor
- Fluoxetine minor
- Trazodone minor
- Cyclobenzaprine minor
- Oxycodone minor
Tramadol Also Interacts With
- Safinamide major
- Carbamazepine moderate
- Rifampin moderate
- Phenytoin moderate
- Gabapentin minor
Frequently Asked Questions
What SPL severity band is on file for Codeine + Tramadol?
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?
Tramadol has 38 labeled pairs on file vs Codeine's 27. In the minor band specifically: Codeine has 27 (also Bupropion, Fluoxetine, Trazodone, Cyclobenzaprine); Tramadol has 34 (also Gabapentin, Bupropion, Fluoxetine, Cyclobenzaprine).
What mechanism field is on file for Codeine and Tramadol?
These medications both increase the amount of serotonin in your body. Having too much serotonin can lead to a serious condition called serotonin syndrome.
Tramadol carries more major-labeled pairs than Codeine
SPL source-record counts only. This page's band is minor · classes on file: Codeine (Opioid Analgesic); Tramadol (Opioid Analgesic).
Tramadol has 1 major-labeled pair 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
- Fluoxetine
- Trazodone
- Cyclobenzaprine
1 major · 3 moderate · 34 minor · 38 total
- Other minor peers for Tramadol
- Gabapentin
- Bupropion
- Fluoxetine
- Cyclobenzaprine
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.