Metaxalone and Trazodone Interaction
Drug interaction information between Metaxalone and Trazodone.
Metaxalone and Trazodone have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Metaxalone 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
Taking these two drugs together can cause a build-up of serotonin in your body, which can be life-threatening if levels become too high.
What To Do
Tell your doctor immediately if you experience shivering, sweating, or a very high fever while taking these medications.
FDA Label Information
Examples of serotonergic drugs include: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Metaxalone Also Interacts With
- Tapentadol moderate
- Mirtazapine minor
- Linezolid minor
- Norepinephrine minor
- Acetaminophen/Oxycodone minor
Trazodone Also Interacts With
- Linezolid major
- Aspirin moderate
- Phenelzine moderate
- Tranylcypromine moderate
- Selegiline moderate
Frequently Asked Questions
Can I take Metaxalone and Trazodone together?
This is a minor interaction. Tell your doctor immediately if you experience shivering, sweating, or a very high fever while taking these medications.
How serious is the interaction between Metaxalone 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 Metaxalone and Trazodone interact?
Taking these two drugs together can cause a build-up of serotonin in your body, which can be life-threatening if levels become too high.
Understanding the Metaxalone and Trazodone Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Metaxalone belongs to the Muscle Relaxant 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: Taking these two drugs together can cause a build-up of serotonin in your body, which can be life-threatening if levels become too high. 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. Metaxalone has 18 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 immediately if you experience shivering, sweating, or a very high fever while taking these 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 Metaxalone 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.