What the FDA labels say about taking them together
Phenytoin and tramadol
Tramadol's FDA label of March 5, 2026 names phenytoin in its drug interactions section; the phenytoin labels PlainMeds reads (2) do not name tramadol. The tramadol label: “The concomitant use of Tramadol Hydrochloride Extended-Release Capsules and CYP3A4 inducers can decrease the plasma concentration of tramadol, resulting in decreased efficacy or onset of a withdrawal syndrome in …”
Check it at the source: the phenytoin FDA label on DailyMed (effective October 15, 2024, Mylan Pharmaceuticals Inc.); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).
What does the phenytoin label say about tramadol?
Phenytoin's label (effective October 15, 2024) and its 1 other brand-application label do not name tramadol in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Phenytek), Mylan Pharmaceuticals Inc., effective October 15, 2024 (SPL set 0f94c791-8b07-4b41-927e-c9f28bec5f60), via openFDA; the full label on DailyMed
What does the tramadol label say about phenytoin?
Tramadol label, drug interactionsCYP3A4 Inducers Clinical Impact: The concomitant use of tramadol hydrochloride extended-release tablets and CYP3A4 inducers can decrease the plasma concentration of tramadol, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol,. … hydrochloride extended-release tablets and carbamazepine is not recommended. Examples: Rifampin, carbamazepine, phenytoin
Tramadol label, warnings and precautionsCytochrome P450 3A4 Interaction The concomitant use of tramadol hydrochloride extended-release tablets with cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in tramadol plasma concentrations, which could increase or prolong adverse reactions, increase the risk for serious adverse events including seizures and serotonin syndrome, and may cause potentially fatal respiratory depression.
Source: FDA drug label (Tramadol Hydrochloride Extended-Release, NDA022370), Trigen Laboratories, LLC, effective January 23, 2026 (SPL set c0bc7218-3fd0-4646-96f4-25355fc84aa9), via openFDA
Source: FDA drug label (TRAMADOL HYDROCHLORIDE), Lupin Pharmaceuticals, Inc., effective March 5, 2026 (SPL set 46bb9ae6-3ee8-463c-badb-c7a45a89b84b), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Phenytoin | Tramadol | |
|---|---|---|
| Labeled for | Seizures and epilepsy | Pain |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.145 per capsule 100 mg capsule | $0.0248 per tablet 50 mg tablet |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once