Phenytoin Dosing Regimen for Adults
The typical dosing regimen for phenytoin in adults is 300-400 mg/day (100 mg three to four times daily) for maintenance therapy, with an initial loading dose of 15-20 mg/kg IV at a maximum rate of 50 mg/minute when rapid therapeutic levels are needed. 1, 2
Loading Dose Options
Intravenous Loading (for rapid therapeutic levels)
- Dose: 18-20 mg/kg IV 3, 4
- Administration rate: Maximum 50 mg/minute 3
- Expected outcome: Therapeutic serum levels (10-20 mcg/mL) within minutes after infusion 2
- Monitoring: Continuous ECG, blood pressure, and respiratory function 3
- Caution: Risk of hypotension (12% of patients), especially in older patients 3, 5
Oral Loading (when IV administration not preferred)
- Dose: 1 gram divided into three doses (400 mg, 300 mg, 300 mg) 1
- Administration: At 2-hour intervals 1
- Setting: Should be done in a clinical setting where serum levels can be monitored 1
- Contraindication: History of renal or liver disease 1
Maintenance Dosing
Standard Divided Dosing
- Initial dose: 100 mg three times daily 1
- Maintenance dose: 300-400 mg/day (100 mg three to four times daily) 1
- Adjustment: Allow 7-10 days between dose changes to achieve steady-state levels 3, 1
Once-Daily Dosing Option
- Dose: 300 mg once daily 1
- Indication: Only for patients with established seizure control on divided doses 1
- Formulation: Only extended phenytoin sodium capsules are recommended for once-daily dosing 1
- Benefit: Improved compliance 1
Dose Adjustment Guidelines
- When serum levels are below 7 μg/mL: Increase by 100 mg/day 3
- When serum levels are 7-12 μg/mL: Increase by 50 mg/day 3
- When serum levels are above 12 μg/mL: Increase by 30 mg/day 3
- Allow 7-10 days between adjustments to reach stable levels 3, 1
Therapeutic Monitoring
- Target therapeutic range: 10-20 mcg/mL 1, 3
- Time to steady-state: 7-10 days after dose adjustment 1
- Timing of levels: Trough levels (just before next dose) are most reliable 6
- Chronotherapeutic consideration: Administration of most or all daily dose at 8:00 PM may improve efficacy and reduce toxicity 7
Important Considerations
- Formulation differences: The free acid form contains approximately 8% more active ingredient than the sodium salt form, requiring monitoring when switching between formulations 3, 1
- Common adverse effects: Ataxia, nystagmus, tremor, and somnolence 2, 3
- Serious adverse effects: Hypotension, bradycardia, cardiac dysrhythmias (especially with rapid IV administration) 2, 5
- Drug interactions: Numerous significant interactions with other medications affecting phenytoin metabolism 8
Special Populations
- Hepatic impairment: Lower doses and more frequent monitoring required 3
- Renal impairment: Lower total serum levels due to reduced protein binding 3
- Elderly: Higher risk of hypotension with IV administration 5
Phenytoin's narrow therapeutic index and nonlinear pharmacokinetics make careful dosing and monitoring essential for optimal seizure control while minimizing toxicity.