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. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
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.
What To Do
Use caution when taking these together and report any symptoms like sweating, muscle stiffness, or agitation to your healthcare provider.
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
Can I take Codeine and Tramadol together?
This is a minor interaction. Use caution when taking these together and report any symptoms like sweating, muscle stiffness, or agitation to your healthcare provider.
How serious is the interaction between Codeine and Tramadol?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Codeine and Tramadol 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.
Understanding the Codeine and Tramadol Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Codeine belongs to the Opioid Analgesic class and Tramadol belongs to the Opioid Analgesic class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: These medications both increase the amount of serotonin in your body. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Codeine has 27 total documented interactions on file in this dataset, and Tramadol has 38. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Use caution when taking these together and report any symptoms like sweating, muscle stiffness, or agitation to your healthcare provider. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Codeine or Tramadol based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.