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What the FDA labels say about taking them together

Leucovorin and primidone

Leucovorin's FDA label of March 19, 2025 names primidone in its drug interactions section; the primidone label PlainMeds reads does 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 primidone FDA label on DailyMed (effective September 10, 2026, Bausch Health US, LLC).

What does the leucovorin label say about primidone?

Leucovorin label, drug interactions

Drug 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 interactions

Folic 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 primidone label say about leucovorin?

Primidone's label (effective September 10, 2026) does 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 (Mysoline), NDA009170 (Valeant), as published by Bausch Health US, LLC, effective September 10, 2026 (SPL set af593171-dabb-4ea3-b44c-89ed457b2c46), 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

16Leucovorin generic labelers
21Primidone generic labelers
LeucovorinPrimidone
Labeled forColorectal cancerSeizures and epilepsy
Boxed warningNoNo
Pharmacy cost (NADAC)$0.330 per tablet 5 mg tablet$0.0914 per tablet 50 mg tablet
Shortage nowNo current entryNo 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?