In a 70-year-old woman taking phenytoin (Dilantin) 300 mg daily with a serum phenytoin concentration of 8.3 µg/mL, what is the recommended next step in management?

Management of Subtherapeutic Phenytoin Level

Increase the phenytoin dose incrementally, as a level of 8.3 µg/mL is subtherapeutic and requires dose adjustment to achieve the target therapeutic range of 10-20 µg/mL. 1, 2

Understanding the Current Clinical Situation

• The patient's phenytoin level of 8.3 µg/mL falls below the therapeutic range of 10-20 µg/mL, which is where optimum seizure control without clinical toxicity typically occurs 2
• At 300 mg daily, approximately 85.6% of patients fail to achieve therapeutic concentrations between 10-20 µg/mL, indicating this is a common dosing issue 3
• The majority of patients require individualized dose adjustments beyond the standard 300 mg daily starting dose 3

Recommended Dose Adjustment Strategy

Increase phenytoin by 100 mg increments (to 400 mg daily initially), monitoring levels weekly until therapeutic range is achieved 1

Critical Dosing Considerations Due to Nonlinear Kinetics

• Phenytoin exhibits saturable (Michaelis-Menten) kinetics, meaning small dose increases can produce disproportionately large increases in serum levels once approaching the upper therapeutic range 2, 4
• When levels reach 5-10 µg/mL (as in this patient at 8.3 µg/mL), dose adjustments should be made in smaller increments of approximately 25-50 mg to avoid overshooting into toxic range 4
• At steady state, a 10% dose increase can produce substantial, disproportionate increases in serum levels when concentrations are in the upper therapeutic range 2

Practical Dosing Algorithm for This Patient

1. Increase from 300 mg to 350-400 mg daily (given current level of 8.3 µg/mL allows for a moderate increase) 1, 4
2. Recheck phenytoin level in 7-10 days (5-7 half-lives required to reach new steady state) 2
3. If level reaches 10-15 µg/mL, make subsequent adjustments in 25-50 mg increments only 4
4. If level remains <10 µg/mL after reaching 400 mg, increase by another 50-100 mg 1

Monitoring Parameters During Dose Adjustment

• Watch for dose-related adverse effects including ataxia, nystagmus, tremor, somnolence, and cognitive impairment 1, 5
• Obtain trough levels (just prior to next scheduled dose) to assess therapeutic adequacy and confirm compliance 2
• Peak levels (4-12 hours post-dose for capsules) can identify threshold for dose-related toxicity if symptoms develop 2

Special Considerations for This 70-Year-Old Patient

• Age positively correlates with serum phenytoin concentration, meaning elderly patients may achieve higher levels at equivalent doses 6
• Body weight and height negatively correlate with phenytoin levels, though these factors contribute less to interindividual variation than genetic differences and saturation kinetics 6
• Hepatic or renal impairment requires more frequent monitoring in elderly patients 1

Common Pitfall to Avoid

Do not increase the dose by more than 100 mg at a time when the level is already approaching 10 µg/mL, as the nonlinear kinetics can cause rapid progression to toxicity 2, 4. The steep dose-concentration relationship means careful titration is essential once therapeutic range is approached.