Primidone is a classic antiepileptic metabolised to phenobarbital and phenylethylmalonamide.
Also known as: mysoline
DailyMed/FDA — Mysoline; EMC-UK — Primidone
DailyMed/FDA — Mysoline; EMC-UK
Barbiturate + prodrug: primidone is converted to phenobarbital. Additive CNS depressant effect.
Primidone is metabolised to phenobarbital (50-60%, half-life 80-120 h) and phenylethylmalonamide (25-30%). Co-administration with phenobarbital results in additive phenobarbital levels, multiplying the risk of respiratory depression, profound sedation, and coma. This combination is clinically redundant — both act via GABA-A potentiation. If primidone is essential (rare), reduce phenobarbital by 50% and monitor phenobarbital levels (target: 15-40 μg/mL). Alternative: switch primidone directly to phenobarbital.
Primidone = phenobarbital prodrug (50-60%). Dangerous additive CNS depressant effect.
Primidone is metabolised to phenobarbital (50-60%) and phenylethylmalonamide (25-30%). Co-administration with phenobarbital results in additive phenobarbital levels, significantly increasing CNS depression.
Phenobarbital levels, sedation, respiratory function.
Severe respiratory depression, coma.
Avoid combination. If primidone is essential, reduce phenobarbital by 50% and monitor levels.
DailyMed/FDA; EMC-UK
Two CYP inducers: additive effect on metabolism of other drugs. Risk of toxicity.
Both are potent inducers of CYP3A4, CYP2C9, CYP2C19, and UGT. The combination may reduce levels of warfarin, oral contraceptives, anticoagulants, and other drugs by >50%. This combination is clinically redundant (both treat epilepsy) and dangerous. Avoid. If necessary, adjust all concomitant medications and monitor levels.
Two potent CYP/UGT inducers: drastically reduce levels of other drugs.
Both are potent inducers of CYP3A4, CYP2C9, CYP2C19, and UGT. The combination may drastically reduce levels of other drugs (anticoagulants, contraceptives).
Levels of all concomitant drugs.
Therapeutic failure of other drugs.
Avoid combination if possible. If necessary, adjust doses of all concomitant drugs.
DailyMed/FDA; EMC-UK
No documented food or drink interactions.
No documented disease interactions.
Risk of neural tube defects and fetal barbiturate syndrome. Historical data.
Increased risk in 1st trimester. Supplement folic acid.
Excreted in breast milk. Risk of neonatal sedation.
Reliable contraception. Supplement folic acid.
DailyMed/FDA — Mysoline; EMC-UK
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Barbiturate antiepileptic activity. Active prodrug.
Metabolised to phenobarbital (active, 50-60%) and phenylethylmalonamide (active, 25-30%). Both contribute to antiepileptic effect. Phenobarbital potentiates GABA-A. Phenylethylmalonamide blocks Na⁺ channels.
Complete oral absorption. Bioavailability: 100%. Peak: 2-4 h.
Metabolised by CYP3A4, CYP2C9, CYP2C19 and glucuronidation. Induces CYP3A4, CYP2C9, CYP2C19, UGT (same profile as phenobarbital).
Primidone: 5-15 h. Phenobarbital (metabolite): 80-120 h.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
