Target Therapeutic Blood Level for Dilantin (Phenytoin)

The target therapeutic blood level for patients taking Dilantin (phenytoin) is between 10 and 20 mcg/mL (or 10-20 mg/L). 1

Understanding Phenytoin Therapeutic Levels

Phenytoin is an antiepileptic medication that works primarily at the motor cortex by promoting sodium efflux from neurons, stabilizing the threshold against hyperexcitability and inhibiting seizure spread 1
Optimum seizure control without clinical signs of toxicity occurs most often with serum levels between 10 and 20 mcg/mL, though some mild cases of tonic-clonic epilepsy may be controlled with lower levels 1
Therapeutic levels are typically achieved after 7-10 days (5-7 half-lives) of therapy at recommended doses of 300 mg/day 1

Trough levels provide information about clinically effective serum ranges and confirm patient compliance - these should be obtained just prior to the patient's next scheduled dose 1
Peak levels indicate an individual's threshold for dose-related side effects and occur 4-12 hours after administration of Dilantin capsules 1
Serum level determinations should be obtained at least 5-7 half-lives after:
- Treatment initiation
- Dosage changes
- Addition or removal of another drug from the regimen 1

Wide interpatient variability exists in phenytoin serum levels with equivalent dosages 1
Unusually low levels may indicate noncompliance or hypermetabolism of phenytoin 1
Unusually high levels may result from liver disease, congenital enzyme deficiency, or drug interactions 1
Patients with large variations in phenytoin plasma levels despite standard doses present a difficult clinical problem, and serum level determinations are particularly helpful in these cases 1

Phenytoin is highly protein-bound, so free phenytoin levels may be altered in patients with different protein binding characteristics 1
The hepatic enzyme system that metabolizes phenytoin is saturable at high plasma levels, meaning small incremental doses may produce substantial increases in serum levels 1
Steady-state levels may disproportionately increase, potentially resulting in toxicity, from even a 10% increase in dosage when levels are already in the upper range 1

For IV administration, phenytoin should be administered at a maximum rate of 50 mg/min to avoid serious adverse effects including hypotension, bradyarrhythmias, and cardiac arrest 2
Fosphenytoin (a prodrug of phenytoin) can be administered more rapidly at 150 PE/min (phenytoin equivalents per minute) with fewer adverse events 2
Intravenous phenytoin is safe when given at recommended infusion rates and doses, but rapid infusion rates (>50 mg/min) have been associated with increased mortality 3
For elderly patients and those with cardiovascular comorbidities, a slower infusion rate is recommended with careful monitoring of heart rhythm and blood pressure 3

While the standard therapeutic range is 10-20 mcg/mL, it's important to recognize that some patients may achieve seizure control with "subtherapeutic" levels (<10 mcg/mL) 4, 5
A randomized prospective study showed no significant difference in seizure occurrence between patients maintained at subtherapeutic levels versus those whose doses were increased to reach therapeutic levels 5
Patients whose doses were increased to reach therapeutic levels experienced more neurotoxic side effects 5