How should I manage a 61-year-old female patient with epilepsy taking 150 mg of Dilantin (phenytoin) with a serum level of 4.4?

Management of Subtherapeutic Phenytoin Level

Your patient has a critically subtherapeutic phenytoin level of 4.4 mcg/mL (therapeutic range 10-20 mcg/mL) and requires immediate dose adjustment to prevent breakthrough seizures. 1

Immediate Assessment

Before adjusting the dose, evaluate:

• Medication adherence – Subtherapeutic levels most commonly result from noncompliance or missed doses 1
• Recent medication changes – Drug interactions can significantly alter phenytoin metabolism 2
• Hepatic function – Phenytoin is metabolized in the liver, and impairment affects levels 3
• Signs of recent seizure activity – This level provides inadequate seizure protection 1

Dose Adjustment Strategy

Increase the daily dose by 100 mg (from 150 mg to 250 mg daily) and recheck the level in 7-10 days. 1

Here's why this approach is appropriate:

• Phenytoin exhibits saturable kinetics – Small dose increases can produce disproportionate serum level changes, particularly at higher doses, but at this low starting dose (150 mg) and subtherapeutic level (4.4 mcg/mL), a 100 mg increment is safe 1
• Steady-state requires 7-10 days – Phenytoin's half-life averages 22 hours (range 7-42 hours), meaning steady-state is achieved after 5-7 half-lives, or approximately 7-10 days after any dose change 1
• The current dose is inadequate – Most adults require 300-400 mg daily for seizure control, and your patient is receiving only 150 mg 1

Monitoring Plan

Recheck phenytoin level in 7-10 days after the dose increase to ensure steady-state has been achieved 1:

• Target therapeutic range: 10-20 mcg/mL 1
• Timing of blood draw – Obtain trough level just before the next scheduled dose to assess adequacy of dosing 1
• Clinical correlation – Some patients achieve seizure control below 10 mcg/mL, while others require levels at the upper end or above 15 mcg/mL 3

Alternative Dosing Consideration

If more rapid therapeutic levels are needed due to recent seizure activity:

Consider oral loading with 1000 mg divided as 400 mg, 300 mg, 300 mg at 2-hour intervals, followed by maintenance dosing 24 hours later 1:

• This achieves therapeutic levels within 3-8 hours 3
• Reserve this approach for clinic or hospital settings with close monitoring capability 1
• Not appropriate for patients with renal or hepatic disease 1

Ongoing Maintenance

Once therapeutic levels are achieved:

• Typical maintenance range: 200-700 mg daily depending on individual factors 3
• Most adults are maintained on 300 mg daily (either as a single dose or divided as 100 mg three times daily) 1
• Monitor for dose-related toxicity including nystagmus, ataxia, tremor, somnolence, and cognitive impairment 3, 2

Critical Pitfalls to Avoid

Do not make dose adjustments more frequently than every 7-10 days – Phenytoin requires this time to reach steady-state, and premature adjustments risk overshooting therapeutic levels and causing toxicity 1

Watch for saturation kinetics at higher doses – Once levels approach the therapeutic range, small incremental doses (even 10% increases) may produce substantial serum level increases and potential intoxication 1

Consider free phenytoin levels if protein binding is abnormal – In patients with hypoalbuminemia, renal failure, or pregnancy, total phenytoin levels may be misleadingly low while free (active) levels are adequate 1