What are the symptoms of high phenytoin (Dilantin) levels, also known as phenytoin toxicity?

From the Guidelines

High phenytoin levels can cause a range of symptoms, including ataxia, nystagmus, tremor, and somnolence, which typically appear when blood concentrations exceed the therapeutic range. These symptoms are dose-related adverse effects associated with phenytoin and fosphenytoin, as reported in a study published in the Annals of Emergency Medicine 1. The study highlights that irrespective of the route of administration, these adverse effects can occur.

Some of the key symptoms of high phenytoin levels include:

• Ataxia, which is a severe lack of muscle coordination
• Nystagmus, characterized by involuntary eye movements
• Tremor, which can affect various parts of the body
• Somnolence, leading to drowsiness and lethargy

It is essential to monitor serum phenytoin levels, especially in patients with risk factors such as liver disease, hypoalbuminemia, or drug interactions that can increase phenytoin levels 1. Immediate medical attention is necessary if toxicity is suspected, as phenytoin has a narrow therapeutic window and toxicity can progress rapidly.

The symptoms of high phenytoin levels can be managed by adjusting the dosage or switching to a different medication, such as fosphenytoin, which has a better safety profile than intravenously administered phenytoin 1. However, the acquisition costs of fosphenytoin are considerably higher than those of phenytoin preparations.

In clinical practice, it is crucial to balance the benefits and risks of phenytoin therapy and closely monitor patients for signs of toxicity, as reported in the study published in the Annals of Emergency Medicine 1. Prompt recognition and management of high phenytoin levels are critical to preventing severe toxicity and improving patient outcomes.

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 (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

Symptoms of High Phenytoin Level

The symptoms of high phenytoin level can be categorized into several groups, including:

• Central nervous system dysfunction, such as:
  • Nystagmus 3, 4
  • Ataxia 3, 5, 4, 6
  • Confusion 3, 4, 7
  • Decreased coordination 4
  • Hyper-reflexia 4
  • Slurred speech 4
  • Diplopia 4
• Gastrointestinal symptoms, such as:
  • Nausea 3, 5, 7
  • Vomiting 3, 5, 7
• Other symptoms, such as:
  • Dizziness/vertigo 7
  • General weakness 7
  • Drowsiness 7
  • Unsteady gait 7
  • Poor balance 6

Severity of Symptoms

The severity of symptoms can vary depending on the level of phenytoin in the blood. Mild toxicity may manifest as nystagmus, ataxia, and decreased coordination, while more severe cases can lead to confusion, lethargy, and coma 3, 4.

Clinical Presentation

The clinical presentation of high phenytoin level can be similar to other conditions, such as brainstem or cerebellum stroke, which can lead to misdiagnosis 7. A thorough medical history, physical examination, and laboratory tests, including serum phenytoin levels, are essential for accurate diagnosis 3, 5, 4, 7, 6.