Phenobarbital and Primidone interaction

Phenobarbital and Primidone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Phenobarbital (SEZABY) label · effective 2025-12-23

Major

SEZABY is contraindicated in patients with: acute porphyrias [see Warnings and Precautions (5.8)], or a history of hypersensitivity reaction to phenobarbital or other barbiturates [see Warnings and Precautions (5.7)] Acute porphyrias (4)

Contraindicationsby drug classView label on DailyMed
Major

Hypersensitivity to phenobarbital or other barbiturates (4)

Contraindicationsby drug classView label on DailyMed
Major

SEZABY is contraindicated in patients who have experienced hypersensitivity to phenobarbital or other barbiturates.

Warnings and precautionsby drug classView label on DailyMed

From the Primidone (Mysoline) label · effective 2020-07-06

Major

CONTRAINDICATIONS Primidone is contraindicated in: 1) patients with porphyria and 2) patients who are hypersensitive to phenobarbital (see ACTIONS ).

Contraindicationsnames PhenobarbitalView label on DailyMed
Minor

Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.

Warningsnames PhenobarbitalView label on DailyMed
Minor

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants.

Warningsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.