Methadone and Tramadol Interaction
Drug interaction information between Methadone and Tramadol.
Methadone and Tramadol have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Methadone 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 serotonin levels in the brain, which can lead to a dangerous reaction called serotonin syndrome.
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).
Methadone Also Interacts With
- Itraconazole major
- Safinamide major
- Phenobarbital moderate
- Tranylcypromine moderate
- Gabapentin 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 Methadone + 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?
Methadone has 41 labeled pairs on file vs Tramadol's 38. In the minor band specifically: Methadone has 37 (also Gabapentin, Sertraline, Trazodone, Cyclobenzaprine); Tramadol has 34 (also Gabapentin, Bupropion, Fluoxetine, Cyclobenzaprine).
What mechanism field is on file for Methadone and Tramadol?
Both drugs increase serotonin levels in the brain, which can lead to a dangerous reaction called serotonin syndrome.
Methadone carries more major-labeled pairs than Tramadol
SPL source-record counts only. This page's band is minor · classes on file: Methadone (Opioid Agonist); Tramadol (Opioid Analgesic).
Methadone has 2 major-labeled pairs vs Tramadol's 1. This page itself is in the minor band, not the major band.
2 major · 2 moderate · 37 minor · 41 total
- Other minor peers for Methadone
- Gabapentin
- Sertraline
- Trazodone
- Cyclobenzaprine
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.