Acetaminophen/Oxycodone and Trazodone Interaction
Drug interaction information between Acetaminophen/Oxycodone and Trazodone.
Acetaminophen/Oxycodone and Trazodone have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Acetaminophen/Oxycodone and Trazodone. 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
Both drugs increase a brain chemical called serotonin, which can lead to a rare but serious reaction.
What To Do
Tell your doctor right away if you feel confused, shaky, or have a very fast heartbeat.
FDA Label Information
Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tryptans, 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 (those intended to treat psychiatric disorders and also others, such as linezolid and...
Acetaminophen/Oxycodone Also Interacts With
- Gabapentin moderate
- Pregabalin moderate
- Tramadol minor
- Cyclobenzaprine minor
- Oxycodone minor
Trazodone Also Interacts With
- Linezolid major
- Aspirin moderate
- Phenelzine moderate
- Tranylcypromine moderate
- Selegiline moderate
Frequently Asked Questions
Can I take Acetaminophen/Oxycodone and Trazodone together?
This is a minor interaction. Tell your doctor right away if you feel confused, shaky, or have a very fast heartbeat.
How serious is the interaction between Acetaminophen/Oxycodone and Trazodone?
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 Acetaminophen/Oxycodone and Trazodone interact?
Both drugs increase a brain chemical called serotonin, which can lead to a rare but serious reaction.
Understanding the Acetaminophen/Oxycodone and Trazodone Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Acetaminophen/Oxycodone belongs to the Opioid Analgesic Combination class and Trazodone belongs to the Serotonin Antagonist and Reuptake Inhibitor (SARI) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Both drugs increase a brain chemical called serotonin, which can lead to a rare but serious reaction. 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. Acetaminophen/Oxycodone has 23 total documented interactions on file in this dataset, and Trazodone has 40. 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: Tell your doctor right away if you feel confused, shaky, or have a very fast heartbeat. 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 Acetaminophen/Oxycodone or Trazodone 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.