Management of Phenytoin Level 32.2 µg/mL
Immediately discontinue phenytoin and initiate an alternative anticonvulsant such as levetiracetam while the phenytoin level declines, as this concentration is significantly above the therapeutic range of 10-20 µg/mL and places the patient at high risk for serious toxicity. 1
Immediate Actions
Hold all phenytoin doses immediately. A level of 32.2 µg/mL is 60% above the upper therapeutic limit and carries substantial risk for neurological toxicity and potentially irreversible cerebellar dysfunction. 2
Clinical Assessment for Toxicity
Monitor closely for dose-related adverse effects that occur at supratherapeutic levels: 1, 3
- Nystagmus (often the earliest sign)
- Ataxia and gait disturbance
- Tremor
- Somnolence and altered mental status
- Cognitive impairment
- Confusional states, delirium, or encephalopathy 2
At the first sign of acute toxicity, dose reduction or termination is indicated; if symptoms persist despite holding the drug, termination is recommended. 2
Bridging Anticonvulsant Therapy
Start an alternative anticonvulsant immediately to maintain seizure control while phenytoin levels decline. 1 Levetiracetam is an excellent choice because:
- It can be loaded rapidly (1,500 mg orally or IV) 4
- It has minimal drug interactions
- No seizures occurred within 24 hours of loading in clinical studies 4
- Adverse effects are generally mild (fatigue, dizziness) 4
Alternatively, consider valproate 30 mg/kg IV at a maximum rate of 10 mg/kg/min, which is safe and well-tolerated. 4
Monitoring Strategy
Recheck phenytoin level in 24-48 hours to document declining concentrations, as phenytoin exhibits zero-order (saturable) kinetics at toxic levels, meaning elimination may be prolonged. 5
Continuous cardiac monitoring is mandatory if the patient received IV phenytoin recently, as toxic levels increase risk for bradyarrhythmias and heart block. 3
Obtain baseline liver function tests (AST, ALT, bilirubin) if not recently checked, particularly in high-risk patients, as phenytoin toxicity can precipitate hepatotoxicity. 3
Critical Pitfalls to Avoid
Do not simply reduce the phenytoin dose and continue therapy at this toxic level. The FDA labeling explicitly states that dose reduction is indicated for excessive plasma levels, but if symptoms persist, termination is recommended. 2
Do not assume the patient will tolerate this level even if asymptomatic. While rare case reports describe patients requiring supratherapeutic levels for seizure control 6, a level of 32.2 µg/mL represents a 60% elevation above the therapeutic range and the risk-benefit ratio strongly favors discontinuation.
In critically ill or hypoalbuminemic patients, recognize that total phenytoin may not correlate well with free (active) drug. 7, 8 If the patient has albumin <2.5 g/dL, the free phenytoin concentration may be disproportionately elevated, increasing toxicity risk even further.
Long-Term Management Considerations
Once phenytoin levels normalize and the patient is stable on alternative therapy:
Reassess the need to restart phenytoin versus continuing the alternative agent. Valproate provides superior seizure control for primary generalized tonic-clonic seizures compared to phenytoin (66% vs 42% control; NNT = 4.3). 1
If phenytoin is restarted, reduce the maintenance dose substantially (typically by 100-200 mg/day) and monitor levels weekly until stable in the 10-15 µg/mL range. 1, 9
Educate the patient on strict adherence to prescribed dosing, as phenytoin's nonlinear kinetics mean small dose changes can produce large concentration changes. 2