What the FDA labels say about taking them together
Codeine and phenytoin
Codeine's FDA label of December 22, 2025 names phenytoin in its warnings and precautions section; the phenytoin labels PlainMeds reads (2) do not name codeine. The codeine label: “… discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in codeine plasma concentrations with subsequently greater metabolism by cytochrome P450 2D6 …”
Check it at the source: the codeine FDA label on DailyMed (effective December 22, 2025, Hikma Pharmaceuticals USA Inc.); the phenytoin FDA label on DailyMed (effective October 15, 2024, Mylan Pharmaceuticals Inc.).
What does the codeine label say about phenytoin?
Codeine label, warnings and precautionsCytochrome P450 3A4 Interaction: The concomitant use of Codeine Sulfate Tablets with all 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 codeine plasma concentrations with subsequently greater metabolism by cytochrome P450 2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.
Source: FDA drug label (Codeine sulfate), Hikma Pharmaceuticals USA Inc., effective December 22, 2025 (SPL set 010905f9-3bcb-4b50-9fe8-a3ad0010f14c), via openFDA; the full label on DailyMed
What does the phenytoin label say about codeine?
Phenytoin's label (effective October 15, 2024) and its 1 other brand-application label do not name codeine 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
| Codeine | Phenytoin | |
|---|---|---|
| Labeled for | Pain | Seizures and epilepsy |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.726 per tablet 30 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