Codeine and Cyclobenzaprine Interaction
Drug interaction information between Codeine and Cyclobenzaprine.
Codeine and Cyclobenzaprine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Codeine and Cyclobenzaprine. 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
Taking these two drugs together can raise serotonin levels in your brain to an unsafe level. This increases the risk of a serious reaction called serotonin syndrome.
What To Do
Your healthcare provider should monitor you closely for any signs of a serotonin reaction while you are taking both medications.
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
- Tramadol minor
- Oxycodone minor
Cyclobenzaprine Also Interacts With
- Clozapine moderate
- Tapentadol moderate
- Tranylcypromine moderate
- Acetaminophen/Oxycodone minor
- Buprenorphine minor
Frequently Asked Questions
Can I take Codeine and Cyclobenzaprine together?
This is a minor interaction. Your healthcare provider should monitor you closely for any signs of a serotonin reaction while you are taking both medications.
How serious is the interaction between Codeine and Cyclobenzaprine?
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 Cyclobenzaprine interact?
Taking these two drugs together can raise serotonin levels in your brain to an unsafe level. This increases the risk of a serious reaction called serotonin syndrome.
Understanding the Codeine and Cyclobenzaprine 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 Cyclobenzaprine belongs to the Muscle Relaxant class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Taking these two drugs together can raise serotonin levels in your brain to an unsafe level. 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 Cyclobenzaprine has 17. 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: Your healthcare provider should monitor you closely for any signs of a serotonin reaction while you are taking both medications. 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 Cyclobenzaprine 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.