Primidone Dosage and Usage for Seizures and Essential Tremor
For treating seizures and essential tremor, primidone should be initiated at low doses and gradually titrated to minimize side effects, with maintenance dosages of 750-1000 mg/day (250 mg three to four times daily) for seizures in adults and 250 mg/day for essential tremor.
Dosing for Seizures
Adults and Children 8+ Years:
Initial titration schedule:
- Days 1-3: 100-125 mg at bedtime
- Days 4-6: 100-125 mg twice daily
- Days 7-9: 100-125 mg three times daily
- Day 10 to maintenance: 250 mg three times daily 1
Maintenance dosage: 750-1000 mg/day (250 mg three to four times daily)
Maximum dosage: 2000 mg/day (500 mg four times daily) 1
Therapeutic serum level: 5-12 mcg/mL 1
Children Under 8 Years:
Initial titration schedule:
- Days 1-3: 50 mg at bedtime
- Days 4-6: 50 mg twice daily
- Days 7-9: 100 mg twice daily
- Day 10 to maintenance: 125 mg three times daily 1
Maintenance dosage: 10-25 mg/kg/day in divided doses (typically 125-250 mg three times daily) 1
Dosing for Essential Tremor
- Recommended dosage: 250 mg/day 2
- Starting dose: Lower doses (50-62.5 mg) at bedtime with gradual titration
- Important note: Higher doses (750 mg/day) show no additional benefit over 250 mg/day but cause more side effects 2
Special Considerations
Patients Already on Other Anticonvulsants:
- Start primidone at 100-125 mg at bedtime
- Gradually increase primidone while decreasing the other medication
- Complete transition should take at least 2 weeks 1
Managing Acute Intolerance:
- Acute adverse reactions occur in approximately 32% of patients taking primidone for essential tremor 3
- Prevention strategy: Consider pre-treatment with phenobarbital (10 mg/day for 2-3 weeks) before starting primidone, which can reduce acute intolerance from 82% to 17% 4
Side Effect Management
Common Side Effects:
- Somnolence, ataxia/unsteadiness, confusion, dizziness, nausea/vomiting 4
- Behavioral disturbances, irritability, and sleep disturbances (especially in children) 5
Monitoring:
- Regular follow-up every 3-6 months to assess seizure control and medication tolerability 6
- Monitor baseline renal and hepatic function, periodic electrolytes, and drug levels when appropriate 6
Clinical Pearls
For essential tremor: Lower doses (250 mg/day) are equally or more effective than higher doses (750 mg/day) with fewer side effects 2
For seizures in children: Primidone has been shown to reduce recurrence of febrile seizures at doses of 15-20 mg/kg/day, even when derived phenobarbital levels are below therapeutic range 5
Tolerability strategy: Using very low initial doses with graduated titration schedules does not significantly improve primidone tolerability compared to standard titration 7, but phenobarbital pre-treatment does 4
Alternative options: If primidone is not tolerated for essential tremor, propranolol is an alternative first-line treatment, with approximately 50% of patients responding to either medication 8