What is the recommended dosage of phenytoin (antiepileptic medication) for adults?

Recommended Phenytoin Dosage for Adults

For adult patients requiring phenytoin therapy, the recommended loading dose is 15-20 mg/kg administered intravenously at a maximum rate of 50 mg/minute, followed by a maintenance dose of 300-400 mg/day (4-6 mg/kg/day) divided into 1-3 doses. 1, 2

Loading Dose Options

Intravenous (IV) Loading:

• 15-20 mg/kg administered at a rate not exceeding 50 mg/minute (approximately 20 minutes for a 70-kg patient) 2
• Target therapeutic serum level: 10-20 mcg/mL (unbound phenytoin concentrations of 1-2 mcg/mL) 2
• Continuous cardiac and blood pressure monitoring is essential during IV administration 2
• Reduce infusion rate to 25 mg/minute in patients over 50 years or with atherosclerotic cardiovascular disease to minimize risk of hypotension and bradycardia 3

Oral Loading:

• 15-20 mg/kg divided into 3 doses (e.g., 400 mg, 300 mg, 300 mg) administered at 2-hour intervals 4
• Should be reserved for patients in clinical settings where serum levels can be closely monitored 4
• Not recommended for patients with history of renal or liver disease 4
• Therapeutic levels typically achieved within 2-4 hours after administration 1

Maintenance Dosing

Intravenous Maintenance:

• 100 mg IV every 6-8 hours (approximately 300-400 mg/day) 2
• Continuous monitoring of serum levels recommended to adjust dosing 2

Oral Maintenance:

• 300-400 mg/day (4-8 mg/kg/day) 4
• Can be administered as:
  • Divided dosing: 100 mg three to four times daily 4
  • Once-daily dosing: 300 mg once daily (only if seizure control is established with divided doses) 4
• Note that only extended phenytoin sodium capsules are recommended for once-daily dosing 4

Monitoring and Dose Adjustments

• Therapeutic serum level range: 10-20 mcg/mL 2, 4
• Trough levels should be obtained just prior to next scheduled dose 2
• Allow 7-10 days to achieve steady-state blood levels before making dosage adjustments 4
• The majority of patients (85.6%) fail to achieve therapeutic concentrations with a standard 300 mg daily dose, highlighting the need for individualized dosing 5
• When adjusting doses, small increments of approximately 25 mg are appropriate once serum levels reach 5-10 μg/mL due to the steep dose-response relationship 6

Important Considerations and Precautions

• Monitor for dose-related adverse effects including ataxia, nystagmus, tremor, and somnolence 1
• IV administration carries risks of hypotension, bradycardia, cardiac arrhythmias, and local tissue reactions 1
• Fosphenytoin (a phenytoin pro-drug) has fewer cardiovascular complications compared to IV phenytoin but similar dose-related adverse effects 7
• For patients with renal or hepatic disease or hypoalbuminemia, monitoring of unbound phenytoin concentrations is more appropriate 2
• When switching between oral and IV formulations, dose adjustments may be necessary as IV phenytoin is 100% bioavailable while oral phenytoin is approximately 90% bioavailable 2
• When changing between sodium salt and free acid forms, dosage adjustments may be needed due to approximately 8% difference in drug content 2, 4

Remember that phenytoin exhibits non-linear pharmacokinetics, meaning small dose changes can result in disproportionate changes in serum concentrations, requiring careful titration and monitoring 6.