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. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Acetaminophen/Oxycodone

Opioid Analgesic Combination

Drug B

Trazodone

Serotonin Antagonist and Reuptake Inhibitor (SARI)

How They Interact

Both drugs increase a brain chemical called serotonin, which can lead to a rare but serious reaction.

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...

Trazodone Also Interacts With

View all Trazodone interactions →

Frequently Asked Questions

What SPL severity band is on file for Acetaminophen/Oxycodone + Trazodone?

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?

Trazodone has 40 labeled pairs on file vs Acetaminophen/Oxycodone's 23. In the minor band specifically: Acetaminophen/Oxycodone has 21 (also Tramadol, Cyclobenzaprine, Oxycodone, Lamotrigine); Trazodone has 35 (also Tramadol, Buspirone, Clopidogrel, Rivaroxaban).

What mechanism field is on file for Acetaminophen/Oxycodone and Trazodone?

Both drugs increase a brain chemical called serotonin, which can lead to a rare but serious reaction.

Trazodone 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); Trazodone (Serotonin Antagonist and Reuptake Inhibitor (SARI)).

Trazodone has 1 major-labeled pair vs Acetaminophen/Oxycodone's 0. This page itself is in the minor band, not the major band.

Acetaminophen/Oxycodone

0 major · 2 moderate · 21 minor · 23 total

Trazodone

1 major · 4 moderate · 35 minor · 40 total

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.