Section 01 · Monograph
Primidone
Reviewed Nov 2026FDA label
MysolineBarbiturate (prodrug)
- Forms
- Tab: 50, 250mg
- Dose
- 750-1500mg/day divided
- MOA
- Metabolized to phenobarbital
Indications
- Management of grand mal, psychomotor (complex partial), and focal epileptic seizures, alone or in combination with other anticonvulsantsFDA-labeled
Off-Label Uses
- Essential tremor, typically at lower doses than those used for epilepsyOff-label
Mechanism of Action
- Prodrug metabolized to two active compounds, phenobarbital and phenylethylmalonamide (PEMA)
- Anticonvulsant and tremor-suppressing effects derive from the parent drug together with phenobarbital's potentiation of GABA-A receptor activity; PEMA potentiates phenobarbital's anticonvulsant effect
Full Dosing
Adult / usual
- Essential tremor (off-label): much lower doses than for epilepsy, often starting at 25–62.5mg at bedtime and titrated slowly as tolerated, with typical maintenance well below anticonvulsant doses
- Abrupt discontinuation should be avoided due to seizure and withdrawal risk (mediated via the phenobarbital metabolite)
Pediatric
- Epilepsy (adults and children ≥8 years, previously untreated): gradual titration to reduce initial sedation — e.g., 100–125mg at bedtime on days 1–3, twice daily on days 4–6, three times daily on days 7–9, then maintenance around 250mg three to four times daily (up to ~2000mg/day divided)
- Children under 8 years: lower weight-based titration schedule
Contraindications
- Hypersensitivity to primidone or phenobarbital
- History of porphyria
Drug Interactions
- Shares phenobarbital's hepatic enzyme–inducing profile — reduces efficacy of hormonal contraceptives, warfarin, corticosteroids, and other drugs metabolized by induced CYP enzymes
- Additive CNS and respiratory depression with alcohol, opioids, benzodiazepines, and other sedatives
- Levels can be affected by interacting AEDs (e.g., phenytoin can increase conversion of primidone to phenobarbital)
Adverse Effects
- Sedation, ataxia, dizziness, and vertigo — most prominent at initiation and with dose increases, often improving with continued treatment at a stable dose
- Nystagmus, diplopia
- Rare: megaloblastic anemia (folate-responsive), granulocytopenia, agranulocytosis, aplastic anemia
- Physical dependence and withdrawal risk with abrupt discontinuation, via the phenobarbital metabolite
- Skin rash
Monitoring Parameters
- Serum primidone and phenobarbital concentrations
- CBC periodically with long-term use
- Sedation and cognitive effects, particularly at treatment initiation
- Tremor severity and functional status when used for essential tremor
Pregnancy & Lactation
- Associated with increased risk of congenital malformations; the active metabolite phenobarbital crosses the placenta
- Substantial quantities are excreted into breast milk — monitor breastfed infants for sedation