Primidone Dosing for Essential Tremor
For essential tremor in adults and children over 8 years, start primidone at 100-125 mg at bedtime and gradually titrate up to a maintenance dose of 250 mg three times daily (750 mg/day), though lower maintenance doses of 250 mg/day are equally effective with fewer side effects. 1, 2
Initial Titration Schedule
The FDA-approved initiation regimen for patients 8 years and older follows this gradual escalation 1:
- 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 onward: 250 mg three times daily (maintenance)
Maintenance Dosing
The optimal maintenance dose is 250 mg three times daily (750 mg/day total), though evidence strongly supports that 250 mg once daily is equally effective with significantly better tolerability. 1, 2
- Standard maintenance: 250 mg three to four times daily (750-1000 mg/day) 1
- Lower-dose alternative: 250 mg/day total is equally effective with fewer adverse effects 2
- Maximum dose: 500 mg four times daily (2000 mg/day), though rarely needed 1
- Therapeutic serum level: 5-12 mcg/mL 1
Pediatric Dosing (Under 8 Years)
For children under 8 years, use a more conservative approach 1:
- Days 1-3: 50 mg at bedtime
- Days 4-6: 50 mg twice daily
- Days 7-9: 100 mg twice daily
- Day 10 onward: 125-250 mg three times daily
- Alternative dosing: 10-25 mg/kg/day in divided doses 1
Critical Pitfalls and Management Strategies
Acute intolerance occurs in 32% of patients within the first 48 hours, manifesting as severe somnolence, ataxia, confusion, dizziness, and nausea. 3, 4, 5
Preventing Acute Intolerance
Pre-treatment with phenobarbital 10 mg/day for 2-3 weeks before starting primidone reduces acute intolerance from 82% to 17% through functional cross-tolerance. 5
- Without phenobarbital pre-treatment: 82% experience acute neurotoxic symptoms 5
- With phenobarbital pre-treatment: Only 17% experience symptoms 5
- This strategy should be offered to all patients starting primidone 5
Long-Term Tolerability Issues
- Chronic side effects are minimal (0%) with primidone compared to 17% with propranolol 4
- Tolerance to therapeutic effect develops in 13% of patients over time 4
- Higher doses (750 mg/day) cause significantly more treatment discontinuation than lower doses (250 mg/day) 2
- 30-32% of patients show no therapeutic benefit regardless of dose 4
When Transitioning from Other Anticonvulsants
Start primidone at 100-125 mg at bedtime while gradually tapering the other medication; complete the transition over at least 2 weeks. 1
Efficacy Considerations
Primidone demonstrates sustained efficacy for essential tremor over 12 months at both low (250 mg/day) and high (750 mg/day) doses, with no significant difference in tremor control between dosing regimens. 2