Primidone Dosing for Essential Tremor
For adults and children over 8 years with essential tremor, start primidone at 100-125 mg at bedtime and gradually titrate over 10 days 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 (Adults and Children ≥8 Years)
The FDA-approved dosing regimen follows a structured 10-day titration 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 Considerations
The optimal maintenance dose is 250 mg/day rather than higher doses, based on high-quality evidence showing equal efficacy with better tolerability 2:
- A double-blind study of 113 patients demonstrated that 250 mg/day was equally or more effective than 750 mg/day over 12 months 2
- Significantly fewer patients discontinued treatment due to side effects with the lower dose (p<0.03) 2
- The standard FDA maintenance range is 750-1000 mg/day (250 mg three to four times daily), but this can be increased to 1250-2000 mg/day if needed 1
Therapeutic Monitoring
- Target serum level: 5-12 mcg/mL 1
- Serum level determinations may be necessary for optimal dosage adjustment in some patients 1
- Maximum daily dose should not exceed 500 mg four times daily (2000 mg/day) 1
Pediatric Dosing (Children <8 Years)
For younger children, use a more gradual 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 (or 10-25 mg/kg/day in divided doses)
Common Pitfalls and Management Strategies
Early side effects are the primary reason for treatment failure, affecting up to one-third of patients 3, 4:
- Side effects in the first 48 hours are common regardless of formulation (suspension vs. tablet) 4
- Very low initial doses (2.5 mg) in suspension form do not improve tolerability compared to 25 mg tablets 4
- The graduated titration schedule outlined above is essential to minimize acute toxicity 1
Combination Therapy
If primidone monotherapy provides inadequate tremor control, combine with propranolol rather than increasing primidone to maximum doses 3:
- Approximately 50% of patients achieve adequate tremor control with either primidone or propranolol alone 3
- Combination therapy is appropriate when monotherapy fails 3
Transitioning from Other Anticonvulsants
When primidone is intended as monotherapy 1:
- Start primidone at 100-125 mg at bedtime while maintaining the other anticonvulsant
- Gradually increase primidone to maintenance level while simultaneously tapering the other medication
- The transition should not be completed in less than 2 weeks 1
Alternative Agents
If primidone is not tolerated or contraindicated 5: