What the FDA labels say about taking them together
Leucovorin and phenobarbital
Leucovorin's FDA label of March 19, 2025 names phenobarbital in its drug interactions section; the phenobarbital labels PlainMeds reads (2) do not name leucovorin. The leucovorin label: “Folic acid in high doses may reduce the effectiveness of certain antiepileptic drugs and thereby increase the frequency of seizures.”
Check it at the source: the leucovorin FDA label on DailyMed (effective March 19, 2025, Meitheal Pharmaceuticals Inc.); the phenobarbital FDA label on DailyMed (effective August 27, 2026).
What does the leucovorin label say about phenobarbital?
Leucovorin label, drug interactionsDrug Interactions Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible pediatric patients.
Vykoura label (Avyxa Pharma, LLC, March 12, 2026), drug interactionsFolic acid in high doses may reduce the effectiveness of certain antiepileptic drugs (e.g., phenobarbital, phenytoin, and primidone) and thereby increase the frequency of seizures.
Source: FDA drug label (Vykoura, NDA220406), Avyxa Pharma, LLC, effective March 12, 2026 (SPL set d122b875-435e-4e00-b945-7a0546df95c2), via openFDA
Source: FDA drug label (leucovorin calcium), Meitheal Pharmaceuticals Inc., effective March 19, 2025 (SPL set 9df20901-6980-4d4e-89ec-40f3c1f91852), via openFDA; the full label on DailyMed
What does the phenobarbital label say about leucovorin?
Phenobarbital's label (effective August 27, 2026) and its 1 other brand-application label do not name leucovorin in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Phenobarbital), Chartwell RX, LLC, effective August 27, 2026 (SPL set 74428144-fb24-40a5-a670-3b876e2d116c), 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
| Leucovorin | Phenobarbital | |
|---|---|---|
| Labeled for | Colorectal cancer | Seizures and epilepsy |
| Boxed warning | No | No |
| Pharmacy cost (NADAC) | $0.330 per tablet 5 mg tablet | $0.213 per tablet 100 mg tablet |
| Shortage now | No current entry | A presentation being discontinued |
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