Recommended Dosage of Oral Phenytoin

For adult patients requiring phenytoin therapy, the recommended maintenance dosage is 300-400 mg/day (4-6 mg/kg/day) divided into 1-3 doses. 1

Loading Dose Considerations

For patients who require rapid achievement of therapeutic levels, an oral loading dose of 1 gram can be administered, divided into three doses (400 mg, 300 mg, 300 mg) given at two-hour intervals 2
Loading doses should only be administered in clinical settings where phenytoin serum levels can be closely monitored 2
Patients with renal or liver disease should not receive oral loading regimens 2
Therapeutic serum levels (10-20 μg/ml) are typically achieved within 2-4 hours after oral administration 1, 3

For most adults, a satisfactory maintenance dosage is one 100-mg capsule three to four times a day (300-400 mg/day) 2
If needed, dosage may be increased up to two capsules three times a day (600 mg/day) 2
Once-daily dosing with 300 mg may be considered if seizure control is established with divided doses totaling 300 mg daily 2
Only extended phenytoin sodium capsules are recommended for once-a-day dosing 2

Serum concentrations should be monitored when changing between different phenytoin formulations (extended capsules, prompt capsules, or suspension) 2
The clinically effective serum level is usually 10–20 mcg/mL 2
A period of seven to ten days may be required to achieve steady-state blood levels, so dosage adjustments should not be made at intervals shorter than 7-10 days 2
When serum concentrations reach 5-10 μg/ml, subsequent dose adjustments should be made in small increments of about 25 mg to avoid toxicity 4

Monitor for dose-related adverse effects including ataxia, nystagmus, tremor, and somnolence 1
Studies show that the majority of patients (85.6%) fail to achieve therapeutic concentrations between 10-20 μg/ml when receiving the standard 300 mg daily dose, highlighting the importance of individualized dosing based on serum level monitoring 5
Phenytoin follows Michaelis-Menten pharmacokinetics, meaning small dose increases can lead to disproportionately large increases in serum concentration once the elimination pathway begins to saturate 4, 5

Initial pediatric dosage is 5 mg/kg/day divided into two or three equal doses 2
Recommended daily maintenance dosage for children is usually 4-8 mg/kg 2
Children over 6 years and adolescents may require the minimum adult dose (300 mg/day) 2
Infants in the first three months of life may require higher doses (10-20 mg/kg/day) to achieve therapeutic levels 6

Changing phenytoin brands or formulations without monitoring serum levels can lead to therapeutic failure or toxicity 2
Failing to account for genetic polymorphisms affecting metabolism (CYP2C9 and CYP2C19) may result in unexpected serum concentrations 7
Using standard adult dosing in all patients without consideration of individual pharmacokinetics often results in subtherapeutic levels 5
Making dosage adjustments too frequently (less than 7-10 days apart) can lead to unpredictable serum levels due to phenytoin's long half-life 2