Management of Elevated Phenytoin (Dilantin) Levels
Immediately discontinue phenytoin and provide supportive care focused on preventing injury from ataxia and confusion, managing nausea/vomiting, and monitoring for cardiovascular complications if the drug was administered intravenously. 1, 2
Immediate Assessment and Monitoring
Check the serum phenytoin level and assess for clinical manifestations of toxicity:
- Central nervous system effects are the predominant manifestations: nystagmus, ataxia, confusion, and depressed level of consciousness 2, 3
- Nystagmus is a dose-related adverse effect that commonly occurs with elevated levels 4
- Gastrointestinal symptoms including nausea and vomiting are common 2, 5
- Cardiovascular complications (arrhythmias, hypotension) are rare with oral ingestion but can occur with IV administration 6, 4, 2
- Atypical presentations may include vegetative signs of depression (changes in mood, sleep, and eating patterns) without classic neurologic or GI complaints 5
Supportive Care Measures
The mainstay of treatment is supportive care, as there is no antidote for phenytoin toxicity: 2
- Protect the patient from injury due to confusion and ataxia 2
- Manage nausea and vomiting symptomatically 2
- Monitor vital signs closely, particularly if phenytoin was given intravenously 6, 4
- Ensure adequate hydration and maintain airway protection if consciousness is depressed 2
Decontamination and Enhanced Elimination
Consider activated charcoal only if the patient presents within 1-2 hours of acute ingestion: 2
- Single-dose activated charcoal may be beneficial if given early 2
- Multiple-dose activated charcoal is controversial—experimental studies show increased clearance rates, but this has not translated into proven clinical benefit 2
- Invasive methods (hemodialysis, hemoperfusion, plasmapheresis) have no evidence of benefit and should not be used 2
Understanding Prolonged Toxicity
Be prepared for prolonged hospitalization due to phenytoin's saturable kinetics: 1, 2
- Phenytoin exhibits zero-order (saturable) pharmacokinetics at high plasma levels, meaning small dose increases can produce disproportionately large increases in serum concentration 1
- The half-life is greatly increased in overdose, resulting in prolonged duration of symptoms 2, 3
- Steady-state levels normally take 7-10 days to achieve, and this is further prolonged in toxicity 1
Identifying Contributing Factors
Investigate potential causes of elevated levels:
- Drug interactions that inhibit phenytoin metabolism or displace it from protein binding 6, 3
- Liver disease or congenital enzyme deficiency 1
- Recent dosage adjustments, particularly increases of 10% or more 1
- Medications that increase phenytoin levels include isoniazid (which inhibits metabolism), clarithromycin, and rifabutin 6
Clinical Pitfalls to Avoid
Do not assume all patients with elevated levels will present with classic symptoms:
- Some patients may tolerate supratherapeutic levels (>80 micromol/L or >20 mcg/mL) without toxicity if seizure control requires it, though this is individualized 7
- Depression and vegetative symptoms may be the only manifestation of toxicity in some patients 5
- Phenytoin encephalopathy with cognitive impairment and cerebellar syndrome can develop insidiously, particularly in patients with intellectual disability or pre-existing balance/cognitive issues 3
Long-Term Considerations
Once acute toxicity resolves, reassess the need for phenytoin:
- The therapeutic range is 10-20 mcg/mL (40-80 micromol/L), though some patients achieve control at lower levels 1, 7
- Monitor serum levels at steady state (5-7 half-lives after any dosage change) 1
- Consider switching to alternative antiepileptic drugs (carbamazepine, oxcarbazepine, valproate, levetiracetam) in patients susceptible to balance disturbances, cognitive dysfunction, or those with intellectual disability 6, 3
Prognosis
Deaths are unlikely after phenytoin intoxication alone, and full recovery is expected with supportive care. 2