What is the appropriate next step in managing a 65-year-old male on phenytoin (Dilantin) 100 mg three times daily with a serum phenytoin level of 6.4 µg/mL?

Management of Subtherapeutic Phenytoin Level

Increase the phenytoin dose incrementally by 100 mg daily (to 400 mg/day total) and recheck the level in 7-10 days, as the current level of 6.4 µg/mL is well below the therapeutic range of 10-20 µg/mL. 1, 2

Understanding the Clinical Context

Your patient's phenytoin level of 6.4 µg/mL is significantly subtherapeutic—the standard therapeutic range is 10-20 µg/mL total phenytoin. 1 At 300 mg daily (100 mg three times daily), this patient is receiving a dose within the typical maintenance range of 200-700 mg daily, but clearly insufficient for his individual metabolism. 1

Dose Adjustment Strategy

Increase the total daily dose by 100 mg (to 400 mg/day), which can be given as:

• 100 mg in the morning, 100 mg midday, and 200 mg at bedtime, OR
• 200 mg twice daily 2

Critical timing consideration: Phenytoin requires 7-10 days to reach steady-state blood levels after any dose change due to its saturation kinetics. 2 Do not make further adjustments before this timeframe, as premature changes can lead to unpredictable levels.

Monitoring Plan

• Recheck serum phenytoin level in 7-10 days after the dose increase 2
• If the level remains subtherapeutic, consider an additional 100 mg/day increment (to 500 mg/day total), again waiting 7-10 days before rechecking 1
• The maximum typical adult dose is 1200 mg/day, though most patients are controlled on 300-400 mg/day 1, 2

Important Caveats

Watch for dose-related toxicity as levels rise:

• Nystagmus (often the earliest sign) 3
• Ataxia, tremor, cognitive impairment 1
• Balance disturbances 3

Consider alternative antiepileptic drugs (carbamazepine, oxcarbazepine, valproate, or levetiracetam) if this patient develops cognitive dysfunction or balance problems, as phenytoin can cause insidious encephalopathy, particularly in older adults. 3, 4

Check for drug interactions that may be lowering his phenytoin level—enzyme-inducing medications can accelerate phenytoin metabolism and necessitate higher doses. 3

Special Considerations for This 65-Year-Old Patient

In elderly patients, phenytoin's half-life may be prolonged, but this patient's low level indicates he is a rapid metabolizer or has poor absorption. 4 The principle of therapeutic drug monitoring is to treat the patient's clinical seizure control and measured levels, not arbitrary "standard" doses—some patients require levels at the upper end of the therapeutic range (15-20 µg/mL) for adequate control. 1, 5