When to Check Dilantin (Phenytoin) Levels
Dilantin (phenytoin) levels should be checked 7-10 days after initiation or dose adjustment, when toxicity is suspected, and periodically during maintenance therapy to ensure therapeutic range of 10-20 mcg/mL. 1
Timing of Phenytoin Level Monitoring
Initial Monitoring
- Check levels 7-10 days after starting therapy or changing dosage
- This timeframe is necessary to achieve steady-state blood levels 1
- Dosage adjustments should not be made at intervals shorter than 7-10 days
Situations Requiring Immediate Level Checks
- When signs of toxicity appear:
- Nystagmus
- Ataxia
- Balance disorders
- Tremors
- Hyperreflexia
- Altered mental status 2
- After loading doses:
- For oral loading doses (1 gram divided into 400mg, 300mg, 300mg at 2-hour intervals)
- Check levels 24 hours after loading dose 1
- When changing formulations:
- Switching between extended phenytoin sodium capsules and prompt phenytoin sodium capsules
- Changing from sodium salt to free acid form (or vice versa)
- Changing brands 1
Routine Monitoring During Maintenance Therapy
- Every 3-6 months during stable therapy
- More frequently in high-risk patients:
- Elderly patients
- Patients with renal or hepatic impairment
- Patients on multiple medications with potential interactions
Therapeutic Range and Interpretation
- Target therapeutic range: 10-20 mcg/mL 1
- Toxicity typically occurs at levels >20 mcg/mL 2
- At concentrations >8-10 mcg/mL, phenytoin's elimination rate diminishes disproportionately, increasing toxicity risk 2
Special Considerations
Drug Interactions
- Monitor levels more frequently when starting or stopping medications that interact with phenytoin
- Particular attention when adding drugs that may:
- Displace phenytoin from protein binding
- Inhibit or induce phenytoin metabolism
- Ethionamide can increase phenytoin (Dilantin) levels 3
Free vs. Total Phenytoin Levels
- Routine free phenytoin level monitoring is generally not necessary in most clinical situations 4
- Consider checking free levels in:
- Patients with hypoalbuminemia
- Renal failure
- Hepatic disease
- Pregnancy
- Patients on multiple medications that may alter protein binding
Monitoring in Special Populations
- Pediatric patients:
- Same therapeutic range applies
- Dosing typically 4-8 mg/kg/day maintenance 1
- Elderly patients:
- May require lower doses
- More susceptible to toxicity at lower serum concentrations
Pitfalls and Caveats
- Avoid checking levels too early after dose initiation or adjustment (before steady state)
- Be aware that toxicity can occur even within the therapeutic range in sensitive individuals
- When administering IV phenytoin, cardiovascular adverse effects are primarily related to rapid infusion rates (>50 mg/min) rather than serum levels 5
- Remember that phenytoin exhibits non-linear (zero-order) pharmacokinetics at therapeutic concentrations, meaning small dose increases can lead to disproportionate increases in serum levels 2
- In cases of toxicity, linear regression calculations may underestimate the time required for levels to return to therapeutic range 2
By following these guidelines for monitoring phenytoin levels, clinicians can optimize seizure control while minimizing the risk of adverse effects.