What the FDA labels say about taking them together
Acetaminophen/benzhydrocodone and phenytoin
Acetaminophen/benzhydrocodone's FDA label of January 7, 2025 names phenytoin in its drug interactions section; the phenytoin labels PlainMeds reads (2) do not name acetaminophen/benzhydrocodone. The acetaminophen/benzhydrocodone label: “The concomitant use of APADAZ 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 acetaminophen/benzhydrocodone FDA label on DailyMed (effective January 7, 2025, Zevra Therapeutics, Inc.); the phenytoin FDA label on DailyMed (effective October 15, 2024, Mylan Pharmaceuticals Inc.).
What does the acetaminophen/benzhydrocodone label say about phenytoin?
Acetaminophen/benzhydrocodone label, drug interactionsCYP3A4 Inducers Clinical Impact: The concomitant use of APADAZ 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. … patients at frequent intervals for signs of respiratory depression and sedation. Rifampin, carbamazepine, phenytoin etc. Benzodiazepines and Other Central Nervous System (CNS) Depressants
Acetaminophen/benzhydrocodone label, warnings and precautionsSimilarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in APADAZ-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.
Source: FDA drug label (APADAZ), Zevra Therapeutics, Inc., effective January 7, 2025 (SPL set 0590d4e5-7107-4015-a6a8-deac14265aa2), via openFDA; the full label on DailyMed
What does the phenytoin label say about acetaminophen/benzhydrocodone?
Phenytoin's label (effective October 15, 2024) and its 1 other brand-application label do not name acetaminophen/benzhydrocodone 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
| Acetaminophen/benzhydrocodone | Phenytoin | |
|---|---|---|
| Labeled for | Pain | Seizures and epilepsy |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | n/a | $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