Tramadol and Phenytoin Interaction
Drug interaction information between Tramadol and Phenytoin.
Tramadol and Phenytoin have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Tramadol and Phenytoin. 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
Phenytoin causes your body to process and remove the pain medicine faster than usual. This means you may not get the full benefit of the pain relief.
FDA Label Information
Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions (5.3) ].
Tramadol Also Interacts With
- Safinamide major
- Carbamazepine moderate
- Rifampin moderate
- Gabapentin minor
- Bupropion minor
Phenytoin Also Interacts With
- Nirmatrelvir/Ritonavir major
- Posaconazole major
- Ranolazine major
- Voriconazole major
- Apixaban moderate
Frequently Asked Questions
What SPL severity band is on file for Tramadol + Phenytoin?
Compiled FDA labeling labels this pair moderate. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Phenytoin has 147 labeled pairs on file vs Tramadol's 38. In the moderate band specifically: Tramadol has 3 (also Carbamazepine, Rifampin); Phenytoin has 23 (also Apixaban, Aprepitant, Canagliflozin, Carbidopa/Levodopa).
What mechanism field is on file for Tramadol and Phenytoin?
Phenytoin causes your body to process and remove the pain medicine faster than usual. This means you may not get the full benefit of the pain relief.
Phenytoin carries more major-labeled pairs than Tramadol
SPL source-record counts only. This page's band is moderate · classes on file: Tramadol (Opioid Analgesic); Phenytoin (Anticonvulsant (Hydantoin)).
Phenytoin has 4 major-labeled pairs vs Tramadol's 1. This page itself is in the moderate band, not the major band.
1 major · 3 moderate · 34 minor · 38 total
- Other moderate peers for Tramadol
- Carbamazepine
- Rifampin
4 major · 23 moderate · 120 minor · 147 total
- Other moderate peers for Phenytoin
- Apixaban
- Aprepitant
- Canagliflozin
- Carbidopa/Levodopa
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.