What are the symptoms of high phenytoin (Dilantin) levels?

From the Guidelines

High phenytoin levels can cause several concerning symptoms, including nystagmus, ataxia, tremor, and somnolence, as reported in a study published in the Annals of Emergency Medicine 1. These symptoms are dose-related adverse effects associated with phenytoin and fosphenytoin, and can occur irrespective of the route of administration.

• Common symptoms of high phenytoin levels include:
  • Nystagmus (involuntary eye movements)
  • Ataxia (poor coordination)
  • Tremor
  • Somnolence (drowsiness)
• Other possible symptoms include:
  • Slurred speech
  • Confusion
  • Impaired thinking
  • Double vision
  • Dizziness
  • Headache
  • Unsteady gait
  • Nausea
  • Vomiting
  • Lethargy
  • Seizures or coma in severe cases It is essential to monitor serum phenytoin levels and adjust the medication dose accordingly to prevent toxicity, as phenytoin has a narrow therapeutic window and follows non-linear kinetics, meaning small dose increases can cause disproportionately large increases in blood levels 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 symptoms of high phenytoin levels are:

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

From the Research

Symptoms of High Phenytoin Levels

• Nausea and vomiting 3, 4, 5, 6
• Central nervous system dysfunction, including:
  • Confusion 3, 4, 6
  • Nystagmus 3, 4, 5, 7
  • Ataxia 3, 4, 5, 6, 7
  • Dizziness/vertigo 6
  • Dysarthria 7
  • Double vision 7
  • Slurred speech 4
  • Diplopia 4
  • Hyper-reflexia 4
  • Decreased coordination 4
  • Lethargy 4
  • Coma 3, 4
• Cardiac complications, such as arrhythmias and hypotension, are rare but may occur in cases of parenteral administration of phenytoin or fosphenytoin 3
• Cerebellar atrophy may occur in some cases, even with relatively mild and short intoxication 7

Clinical Presentation

• The clinical course of phenytoin intoxication can be prolonged due to the drug's zero-order pharmacokinetics, resulting in a greatly increased half-life in overdose situations 3, 4
• The primary toxicity is on the central nervous system 4
• Unsteady gait and dizziness/vertigo are common presenting symptoms 6
• Misdiagnosis can occur, with brainstem or cerebellum stroke being a common initial misdiagnosis 6

Treatment and Management

• Supportive care is the mainstay of therapy for patients with phenytoin intoxication 3, 4, 6
• Treatment includes attention to vital functions, management of nausea and vomiting, and prevention of injuries due to confusion and ataxia 3
• Activated charcoal may be considered if the patient presents early, but its role is controversial 3, 4
• There is no antidote, and no evidence that any method of gastrointestinal decontamination or enhanced elimination improves outcome 3, 4