What are the key clinical indicators to assess for Phenytoin (Dilantin) toxicity in a patient?

From the Guidelines

To check for phenytoin toxicity, it is crucial to monitor for dose-related adverse effects such as ataxia, nystagmus, tremor, and somnolence, as these are common signs of toxicity 1. When assessing a patient for phenytoin toxicity, several key points should be checked:

• Neurological signs:
  • Nystagmus (involuntary eye movements) is an early sign of toxicity, typically appearing at levels above 20 mcg/mL.
  • Ataxia, slurred speech, decreased coordination, and confusion usually emerge at levels exceeding 30 mcg/mL.
  • Severe toxicity (>40 mcg/mL) may present with lethargy, seizures, or coma.
• Dermatological reactions:
  • Gingival hyperplasia
  • Hirsutism
  • Rash
• Laboratory assessment:
  • Serum phenytoin levels (therapeutic range: 10-20 mcg/mL) 1
  • Complete blood count to detect blood dyscrasias
  • Liver function tests
  • Albumin levels, as low albumin increases free phenytoin It is essential to understand that phenytoin follows zero-order kinetics at therapeutic doses, meaning small dose increases can cause disproportionate rises in serum levels 1. Risk factors for toxicity include renal or hepatic impairment, hypoalbuminemia, drug interactions (especially with medications competing for protein binding or affecting CYP450 enzymes), and genetic variations in metabolism 1. Regular therapeutic drug monitoring is essential, particularly after dose adjustments or when adding interacting medications, to prevent and manage phenytoin toxicity 1.

From the FDA Drug Label

The initial symptoms are nystagmus, ataxia, and dysarthria. Other signs are tremor, hyperreflexia, lethargy, slurred speech, nausea, vomiting. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL; dysarthria and lethargy appear when the plasma concentration is over 40 mcg/mL

The points to be checked in a patient for phenytoin toxicity are:

• Nystagmus (usually appears at 20 mcg/mL)
• Ataxia (usually appears at 30 mcg/mL)
• Dysarthria (appears when the plasma concentration is over 40 mcg/mL)
• Lethargy (appears when the plasma concentration is over 40 mcg/mL)
• Tremor
• Hyperreflexia
• Slurred speech
• Nausea
• Vomiting 2

From the Research

Points to Check in a Patient for Phenytoin Toxicity

The following points should be checked in a patient for phenytoin toxicity:

• Nausea and vomiting 3, 4, 5
• Central nervous system dysfunction, including:
  • Confusion 3, 4, 6
  • Nystagmus 3, 4, 6
  • Ataxia 3, 4, 5, 6, 7
  • Dizziness/vertigo 4
  • Dysarthria 6
  • Gait disturbances 4, 7
• Depressed conscious state, coma, and seizures in more severe cases 3
• Cardiac complications, such as arrhythmias and hypotension, particularly with parenteral administration of phenytoin or fosphenytoin 3
• Serum phenytoin levels to confirm toxicity 3, 4, 5, 6
• Magnetic resonance imaging (MRI) findings to rule out other causes of symptoms and to assess cerebellar involvement 5, 7

Clinical Presentation and Diagnosis

Phenytoin toxicity can present with a range of symptoms, from mild to severe. The clinical presentation may include:

• Unsteady gait and dizziness/vertigo 4
• Nausea and vomiting 3, 4, 5
• General weakness and drowsiness 4
• Confusion, nystagmus, and ataxia 3, 4, 6
• Dysarthria and gait disturbances 6, 7

Risk Factors and Prevention

The risk factors for phenytoin toxicity include:

• Unawareness of phenytoin pharmacokinetics 6
• Lack of clinic follow-up visits 6
• Infrequent serum level monitoring following drug dosage change 6
• Using wrong doses 6
• Long-term exposure to phenytoin 7

Prevention of phenytoin toxicity can be achieved through:

• Better patient education 6
• Stepwise dose increase based on serum level 6
• Regular drug level monitoring 2-4 weeks after dose change 6
• Therapeutic drug monitoring (TDM) 5