Codeine and Trazodone Interaction
Drug interaction information between Codeine and Trazodone.
Codeine and Trazodone have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Codeine and Trazodone. 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
Both of these drugs affect a chemical in the brain called serotonin. Taking them together can cause serotonin levels to become too high, which can be dangerous.
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
- Tramadol minor
- Cyclobenzaprine minor
- Oxycodone minor
Trazodone Also Interacts With
- Linezolid major
- Aspirin moderate
- Phenelzine moderate
- Tranylcypromine moderate
- Selegiline moderate
Frequently Asked Questions
What SPL severity band is on file for Codeine + Trazodone?
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?
Trazodone has 40 labeled pairs on file vs Codeine's 27. In the minor band specifically: Codeine has 27 (also Bupropion, Fluoxetine, Tramadol, Cyclobenzaprine); Trazodone has 35 (also Tramadol, Buspirone, Clopidogrel, Rivaroxaban).
What mechanism field is on file for Codeine and Trazodone?
Both of these drugs affect a chemical in the brain called serotonin. Taking them together can cause serotonin levels to become too high, which can be dangerous.
Trazodone carries more major-labeled pairs than Codeine
SPL source-record counts only. This page's band is minor · classes on file: Codeine (Opioid Analgesic); Trazodone (Serotonin Antagonist and Reuptake Inhibitor (SARI)).
Trazodone 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
- Tramadol
- Cyclobenzaprine
1 major · 4 moderate · 35 minor · 40 total
- Other minor peers for Trazodone
- Tramadol
- Buspirone
- Clopidogrel
- Rivaroxaban
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.