Primidone Dosing for Adults
For adults with epilepsy, start primidone at 100-125 mg at bedtime and gradually increase to a maintenance dose of 750-1000 mg/day (250 mg three to four times daily), with a maximum of 2000 mg/day if needed. 1
Initial Titration Schedule for Epilepsy
The FDA-approved initiation regimen for adults and children over 8 years follows a gradual escalation to minimize acute side effects 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
- Standard maintenance: 750-1000 mg/day in divided doses (250 mg three to four times daily) 1
- Maximum dose: 2000 mg/day (500 mg four times daily) if required, though doses should be individualized 1
- Therapeutic serum level: 5-12 mcg/mL (23-46 mmol/L) 1, 2
Essential Tremor Dosing
For essential tremor (off-label use), lower doses of 250 mg/day are equally or more effective than higher doses (750 mg/day) and produce fewer side effects 3:
- Start with 62.5 mg once daily and gradually increase to 250 mg/day in divided doses 4
- Maximum effective dose typically 250 mg/day, though some patients may require up to 750 mg/day 3
- Therapeutic effect often seen within 2 days to 2 weeks 4, 5
Critical Monitoring Considerations
Always monitor both primidone AND phenobarbital levels, as primidone is metabolized to active phenobarbital with highly variable conversion rates between patients 6:
- Primidone therapeutic range: 5-10 mg/L 2
- Phenobarbital therapeutic range: 10-40 mg/L 2
- The conversion rate to phenobarbital varies significantly among individuals 2
Common Pitfalls and Side Effects
Acute adverse reactions occur in approximately 32% of patients starting primidone, typically within the first 48 hours 5, 7:
- Common acute effects include nausea, vomiting, dizziness, and sedation 4
- These acute toxic effects correlate with initial primidone plasma levels rather than metabolite levels 4
- Gradual dose escalation does NOT significantly reduce early side effects 7
- Chronic side effects are rare (0% in one study) compared to alternatives like propranolol (17%) 5
Transitioning from Other Anticonvulsants
When switching from other anticonvulsants 1:
- Start primidone at 100-125 mg at bedtime
- Gradually increase primidone while simultaneously tapering the other medication
- Complete the transition over at least 2 weeks to avoid breakthrough seizures
- Continue until satisfactory combination dosing is achieved or the other medication is fully withdrawn
Tolerance Development
Tolerance to therapeutic effect occurs in approximately 12-13% of patients with chronic use 5, requiring dose adjustment or alternative therapy consideration.