How should I manage a 70-year-old female nursing‑home resident with a sub‑therapeutic phenytoin (Dilantin) serum concentration of 7.1 µg/mL?

Management of Subtherapeutic Phenytoin Level (7.1 µg/mL) in a 70-Year-Old Nursing Home Resident

Administer an intravenous loading dose of 18–20 mg/kg phenytoin (or fosphenytoin 18–20 PE/kg) at a maximum rate of 50 mg/min to rapidly achieve therapeutic concentrations, then increase the maintenance dose by 100–200 mg/day. 1, 2

Immediate Assessment and Loading Strategy

Confirm the Subtherapeutic State

• A phenytoin level of 7.1 µg/mL is clearly below the therapeutic range of 10–20 µg/mL, indicating inadequate seizure prophylaxis. 1
• In elderly patients, phenytoin clearance progressively declines with age—decreasing by approximately one-third between ages 65 and 85—which may contribute to dosing challenges but does not explain a subtherapeutic level. 3

Loading Dose Administration

• For rapid correction, administer 18–20 mg/kg IV phenytoin at a maximum rate of 50 mg/min with continuous cardiac monitoring for bradycardia, arrhythmias, heart block, and hypotension throughout the infusion. 1, 2
• Alternatively, fosphenytoin 18–20 PE/kg can be infused at 150 PE/min (three times faster than phenytoin) with fewer adverse events, and is now available generically. 4, 2
• If the patient is awake and cooperative without active seizures, oral loading with 20 mg/kg divided into maximum doses of 400 mg every 2 hours is safer and cheaper than IV, though it takes more than 5 hours to reach therapeutic levels. 2

Post-Loading Monitoring

• Recheck the phenytoin level 2–4 hours after IV loading to confirm therapeutic range achievement, as approximately 50% of patients exhibit subtherapeutic concentrations at 12 hours post-loading. 1, 5
• A critical second monitoring point is at 12 hours, when half of patients may have dropped below therapeutic levels despite adequate loading. 5

Maintenance Dose Adjustment

Dose Escalation Protocol

• Increase the maintenance dose by 100–200 mg/day at weekly intervals, monitoring for both efficacy and toxicity, with a typical adult maximum of 1200 mg/day. 1, 5
• Standard maintenance dosing is 300–400 mg/day (4–6 mg/kg/day), which can be administered as a single daily dose or divided into 1–3 doses. 2, 6
• Because phenytoin exhibits zero-order (saturable) pharmacokinetics, small dose increases can produce disproportionately large increases in serum concentration; therefore, dose adjustments should not be made at intervals shorter than 7–10 days. 6

Special Considerations in the Elderly

• Elderly patients typically receive lower dosages (mean 4.4 mg/kg/day versus 5.3 mg/kg/day in younger adults) due to age-related decline in drug metabolizing capacity. 3
• In this 70-year-old patient, start conservatively with the lower end of dose increases (100 mg/day increments) and monitor closely, as interindividual variability in clearance is considerable in the elderly. 3

Alternative Management if Breakthrough Seizures Occur

When to Add a Second Agent

• If the patient experiences breakthrough seizures despite achieving therapeutic phenytoin levels (10–20 µg/mL), add a second antiepileptic agent rather than pushing phenytoin into toxic ranges. 1
• Some patients require concentrations above 15 µg/mL for optimal seizure control, but this must be balanced against dose-related adverse effects such as ataxia, nystagmus, tremor, somnolence, and cognitive impairment. 1, 5

Second-Line Agent Selection

• Valproate provides superior seizure control for primary generalized tonic-clonic seizures compared with phenytoin (66% vs 42% control; number needed to treat = 4.3). 1
• Levetiracetam can be administered as a loading dose of approximately 1500 mg orally or intravenously with generally mild adverse effects (fatigue and dizziness), and no seizures were observed within the first 24 hours after loading in clinical studies. 1

Common Pitfalls to Avoid

Formulation-Specific Issues

• Only extended-release phenytoin capsules (Dilantin) are recommended for once-daily dosing; inherent differences in dissolution characteristics of different formulations preclude this recommendation for other phenytoin products. 6
• In nursing home patients receiving phenytoin via nasogastric tube, extended-release capsules produce significantly lower steady-state concentrations than immediate-release tablets at the same dose (mean 3.80 µg/mL vs 6.03 µg/mL), which may explain subtherapeutic levels. 7

Monitoring Frequency

• Do not wait the full 7–10 days to recheck levels after loading; the 2–4 hour and 12-hour timepoints are critical to ensure sustained therapeutic concentrations. 1, 5
• Once maintenance dosing is adjusted, allow 7–10 days to achieve new steady-state levels before making further changes. 6

Toxicity Recognition

• Watch for classic signs of phenytoin toxicity: nystagmus, ataxia, dizziness, somnolence, and cognitive changes—particularly important in elderly nursing home residents where falls and confusion carry significant morbidity. 1, 8
• Some patients may tolerate supratherapeutic levels (even twice the normal range) with minimal toxicity beyond nystagmus, emphasizing the need to treat the patient's clinical condition rather than "numbers." 9