What the FDA labels say about taking them together
Hydrocodone and phenytoin
Hydrocodone's FDA label of May 29, 2026 names phenytoin in its drug interactions section; the phenytoin labels PlainMeds reads (2) do not name hydrocodone. The hydrocodone label: “The concomitant use of HYSINGLA ER and CYP3A4 inducers can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical …”
Check it at the source: the hydrocodone FDA label on DailyMed (effective May 29, 2026); the phenytoin FDA label on DailyMed (effective October 15, 2024, Mylan Pharmaceuticals Inc.).
What does the hydrocodone label say about phenytoin?
Hydrocodone label, drug interactionsCYP3A4 Inducers Clinical Impact: The concomitant use of HYSINGLA ER and CYP3A4 inducers can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone. … frequent intervals for signs of respiratory depression and sedation. Examples: Rifampin, carbamazepine, phenytoin
Hydrocodone label, warnings and precautionsSimilarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in HYSINGLA ER treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.
Source: FDA drug label (Hysingla ER), Knoa Pharma LLC, effective May 29, 2026 (SPL set b7d23ac2-e776-9f62-3290-c64c2d6eb353), via openFDA; the full label on DailyMed
What does the phenytoin label say about hydrocodone?
Phenytoin's label (effective October 15, 2024) and its 1 other brand-application label do not name hydrocodone 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
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
| Hydrocodone | Phenytoin | |
|---|---|---|
| Labeled for | Pain | Seizures and epilepsy |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $7.95 per capsule 15 mg capsule | $0.145 per capsule 100 mg capsule |
| 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