Fentanyl and Tramadol Interaction
Drug interaction information between Fentanyl and Tramadol.
Fentanyl and Tramadol have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Fentanyl 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
Both drugs increase a brain chemical called serotonin, and taking them together can cause serotonin levels to become dangerously high.
FDA Label Information
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Fentanyl Also Interacts With
- Itraconazole moderate
- Tranylcypromine moderate
- Cyclobenzaprine minor
- Ketoconazole minor
- Diazepam 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 Fentanyl + 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 Fentanyl's 28. In the minor band specifically: Fentanyl has 26 (also Cyclobenzaprine, Ketoconazole, Diazepam, Carbamazepine); Tramadol has 34 (also Gabapentin, Bupropion, Fluoxetine, Cyclobenzaprine).
What mechanism field is on file for Fentanyl and Tramadol?
Both drugs increase a brain chemical called serotonin, and taking them together can cause serotonin levels to become dangerously high.
Tramadol carries more major-labeled pairs than Fentanyl
SPL source-record counts only. This page's band is minor · classes on file: Fentanyl (Opioid Analgesic); Tramadol (Opioid Analgesic).
Tramadol has 1 major-labeled pair vs Fentanyl's 0. This page itself is in the minor band, not the major band.
0 major · 2 moderate · 26 minor · 28 total
- Other minor peers for Fentanyl
- Cyclobenzaprine
- Ketoconazole
- Diazepam
- Carbamazepine
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.