Hydromorphone and Tramadol Interaction
Drug interaction information between Hydromorphone and Tramadol.
Hydromorphone and Tramadol have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Hydromorphone 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 affect the serotonin system in the brain, 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 affect 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).
Hydromorphone Also Interacts With
- Trazodone minor
- Cyclobenzaprine minor
- Mirtazapine minor
- Linezolid minor
- Phenelzine 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 Hydromorphone + 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 Hydromorphone's 13. In the minor band specifically: Hydromorphone has 13 (also Trazodone, Cyclobenzaprine, Mirtazapine, Linezolid); Tramadol has 34 (also Gabapentin, Bupropion, Fluoxetine, Cyclobenzaprine).
What mechanism field is on file for Hydromorphone and Tramadol?
Both drugs affect the serotonin system in the brain, and taking them together can cause serotonin levels to become dangerously high.
Tramadol carries more major-labeled pairs than Hydromorphone
SPL source-record counts only. This page's band is minor · classes on file: Hydromorphone (Opioid Analgesic); Tramadol (Opioid Analgesic).
Tramadol has 1 major-labeled pair vs Hydromorphone's 0. This page itself is in the minor band, not the major band.
0 major · 0 moderate · 13 minor · 13 total
- Other minor peers for Hydromorphone
- Trazodone
- Cyclobenzaprine
- Mirtazapine
- Linezolid
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.