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What the FDA labels say about taking them together

Levoleucovorin and phenobarbital

Levoleucovorin's FDA label of August 29, 2023 names phenobarbital in its drug interactions section; the phenobarbital labels PlainMeds reads (2) do not name levoleucovorin. The levoleucovorin label: “DRUG INTERACTIONS 7.1 Effects of Leucovorin Products on Other Drugs Antiepileptic Drugs Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the …”

Check it at the source: the levoleucovorin FDA label on DailyMed (effective August 29, 2023, Slate Run Pharmaceuticals); the phenobarbital FDA label on DailyMed (effective August 27, 2026).

What does the levoleucovorin label say about phenobarbital?

Levoleucovorin label, drug interactions

DRUG INTERACTIONS 7.1 Effects of Leucovorin Products on Other Drugs Antiepileptic Drugs Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the frequency of seizures in susceptible children.

Source: FDA drug label (LEVOLEUCOVORIN CALCIUM), Slate Run Pharmaceuticals, effective August 29, 2023 (SPL set 124bc214-62f8-40f9-a227-a35e2d1ff2a0), via openFDA; the full label on DailyMed

What does the phenobarbital label say about levoleucovorin?

Phenobarbital's label (effective August 27, 2026) and its 1 other brand-application label do not name levoleucovorin 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

8Levoleucovorin generic labelers
0Phenobarbital generic labelers
LevoleucovorinPhenobarbital
Labeled forColorectal cancerSeizures and epilepsy
Boxed warningNoNo
Pharmacy cost (NADAC)n/a$0.213 per tablet 100 mg tablet
Shortage nowNo current entryA 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?