Acetaminophen/Oxycodone and Tramadol Interaction
Drug interaction information between Acetaminophen/Oxycodone and Tramadol.
Acetaminophen/Oxycodone and Tramadol have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Acetaminophen/Oxycodone and Tramadol. 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
Using these two drugs together can cause too much serotonin to build up in your body.
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
- Trazodone minor
- Cyclobenzaprine minor
- Oxycodone minor
Tramadol Also Interacts With
- Safinamide major
- Carbamazepine moderate
- Rifampin moderate
- Phenytoin moderate
- Gabapentin minor
Frequently Asked Questions
What SPL severity band is on file for Acetaminophen/Oxycodone + Tramadol?
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?
Tramadol has 38 labeled pairs on file vs Acetaminophen/Oxycodone's 23. In the minor band specifically: Acetaminophen/Oxycodone has 21 (also Trazodone, Cyclobenzaprine, Oxycodone, Lamotrigine); Tramadol has 34 (also Gabapentin, Bupropion, Fluoxetine, Cyclobenzaprine).
What mechanism field is on file for Acetaminophen/Oxycodone and Tramadol?
Using these two drugs together can cause too much serotonin to build up in your body.
Tramadol carries more major-labeled pairs than Acetaminophen/Oxycodone
SPL source-record counts only. This page's band is minor · classes on file: Acetaminophen/Oxycodone (Opioid Analgesic Combination); Tramadol (Opioid Analgesic).
Tramadol has 1 major-labeled pair vs Acetaminophen/Oxycodone's 0. This page itself is in the minor band, not the major band.
0 major · 2 moderate · 21 minor · 23 total
- Other minor peers for Acetaminophen/Oxycodone
- Trazodone
- Cyclobenzaprine
- Oxycodone
- Lamotrigine
1 major · 3 moderate · 34 minor · 38 total
- Other minor peers for Tramadol
- Gabapentin
- Bupropion
- Fluoxetine
- Cyclobenzaprine
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.