Primidone

Primidone is an anticonvulsant in the barbiturate class. It is used to treat focal seizures and generalized tonic-clonic seizures, as monotherapy or adjunctive therapy, though it is less commonly used today due to newer agents. It remains in use in certain regimens, particularly in patients who respond well or who have specific metabolic considerations.

Primidone is a prodrug rapidly absorbed from the gut and metabolized in the liver to two active metabolites: phenobarbital and phenylethylmalonamide (PEMA). Phenobarbital accounts for much of the anticonvulsant effect and PEMA contributes as well.

Mechanism of action: The anticonvulsant effects primarily arise from phenobarbital, which enhances GABA-A receptor–mediated inhibition.

Pharmacokinetics: Primidone undergoes hepatic metabolism with active metabolites that have longer half-lives. The phenobarbital metabolite can accumulate with chronic dosing or hepatic impairment. Primidone and its metabolites are excreted in urine.

Adverse effects: Sedation, dizziness, ataxia, and cognitive slowing are common, especially during initiation. Nausea, skin rash, and rarely hematologic or hypersensitivity reactions can occur. It is teratogenic in animal studies and may pose fetal risk in humans; it should be used in pregnancy only if clearly needed.

Interactions: As an inducer of hepatic enzymes, primidone can lower levels of other drugs such as other anticonvulsants, warfarin, and oral contraceptives. It increases CNS depressant effects with alcohol and other sedatives. Dose adjustments and monitoring are advised when co-administered with interacting medications.

History and status: Introduced in the mid-20th century as one of the early broad-spectrum anticonvulsants, primidone has been largely supplanted by newer agents but remains in limited use for select patients.