What the FDA labels say about taking them together
Methadone and phenytoin
Methadone's FDA label of December 8, 2025 names phenytoin in its drug interactions section, and phenytoin's label names methadone too. The methadone label: “The concomitant use of DISKETS Dispersible Tablets and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms in …”
Check it at the source: the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC); the phenytoin FDA label on DailyMed (effective October 15, 2024, Mylan Pharmaceuticals Inc.).
What does the methadone label say about phenytoin?
Methadone label, drug interactionsClinical Impact: The concomitant use of methadone hydrochloride tablets and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent on methadone. … patients at frequent intervals for signs of respiratory depression and sedation. Rifampin, carbamazepine, phenytoin, St. John’s Wort, Phenobarbital Benzodiazepines and other Central Nervous System (CNS) Depressants
Source: FDA drug label (Diskets, NDA017058), Hikma Pharmaceuticals USA Inc., effective December 1, 2025 (SPL set e6af84de-cbfc-4a3b-bd73-6bcf77337168), via openFDA
Source: FDA drug label (Methadose, NDA017116), SpecGx LLC, effective April 27, 2026 (SPL set 808a9d0b-720b-4034-a862-5122ff514608), via openFDA
Source: FDA drug label (Methadone Hydrochloride, NDA021624), Mylan Institutional LLC, effective December 31, 2025 (SPL set 092d78eb-6423-495c-bf0d-e6532bea7138), via openFDA
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), via openFDA; the full label on DailyMed
What does the phenytoin label say about methadone?
Phenytoin label, drug interactionsInteracting Agent: Other; Examples: Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine
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
| Methadone | Phenytoin | |
|---|---|---|
| Labeled for | Pain, Opioid use disorder | Seizures and epilepsy |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.177 per tablet 10 mg tablet | $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