From the Guidelines
To check for Dilantin (phenytoin) toxicity, order a serum phenytoin level blood test, ideally drawn just before the next scheduled dose (trough level). The therapeutic range for phenytoin is typically 10-20 mcg/mL, with levels above 20 mcg/mL suggesting potential toxicity 1. When ordering the test, specify "total phenytoin level" rather than free phenytoin, unless the patient has conditions affecting protein binding such as hypoalbuminemia, renal failure, or is taking medications that compete for protein binding sites.
Key Considerations
- For accurate interpretation, the blood sample should be collected at steady state, which is reached after approximately 3-7 days of consistent dosing 1.
- Signs of Dilantin toxicity include nystagmus, ataxia, slurred speech, confusion, and in severe cases, seizures or coma.
- If toxicity is suspected clinically, don't wait for lab results before taking action - consider holding the next dose and consulting with a pharmacist or neurologist.
Monitoring and Follow-up
- Monitoring of serum phenytoin levels is important, especially in patients taking phenytoin, as measurements of serum concentrations may be necessary until an appropriate dose is established 1.
- Neuropsychiatric status should be assessed at least at monthly intervals and more frequently if symptoms develop 1.
Important Notes
- Remember that phenytoin follows non-linear kinetics, meaning small dose increases can lead to disproportionately large increases in serum levels, particularly as concentrations approach the therapeutic ceiling.
- Fosphenytoin, a parenteral phenytoin pro-drug, is rapidly converted to phenytoin by blood and tissue phosphatases after intravenous and intramuscular injection, and has a better safety profile than intravenously administered phenytoin 1.
From the FDA Drug Label
When serum level determinations are necessary, they should be obtained at least 5–7 half-lives after treatment initiation, dosage change, or addition or subtraction of another drug to the regimen so that equilibrium or steady-state will have been achieved Trough levels provide information about clinically effective serum level range and confirm patient compliance and are obtained just prior to the patient's next scheduled dose. Peak levels indicate an individual's threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration For Dilantin capsules, peak serum levels occur 4 to 12 hours after administration. Optimum control without clinical signs of toxicity occurs more often with serum levels between 10 and 20 mcg/mL
To check for Dilantin toxicity, serum levels of phenytoin should be obtained.
- Trough levels should be obtained just prior to the patient's next scheduled dose.
- Peak levels should be obtained at the time of expected peak concentration, which for Dilantin capsules is 4 to 12 hours after administration. The target serum level for optimum control without clinical signs of toxicity is between 10 and 20 mcg/mL 2.
From the Research
Checking Dilantin Levels
To check for Dilantin toxicity, it is essential to monitor serum phenytoin concentrations. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L 3. However, some patients may require higher serum concentrations to control seizures, while others may experience toxicity at lower levels.
Signs of Toxicity
Signs of phenytoin toxicity include:
- Ataxia
- Confusion
- Dysarthria
- Nystagmus
- Dystonia
- Dyskinesia
- Giddiness
- Vomiting These symptoms can occur even at therapeutic doses, and it is crucial to individualize drug therapy and monitor patients closely 4, 5.
Monitoring Therapeutic Levels
To monitor therapeutic phenytoin levels, the following steps can be taken:
- Measure total serum phenytoin and serum albumin ratio
- Use an algorithm to provide a quick reference for monitoring therapeutic phenytoin levels 6
- Perform regular serum level monitoring, especially after dose changes or in patients with impaired renal or hepatic function
- Be aware of the potential for cerebellar atrophy, even in patients without clinical signs of intoxication 7
Preventing Toxicity
Preventing phenytoin toxicity requires:
- Awareness of phenytoin pharmacokinetics
- Regular clinic follow-up visits
- Frequent serum level monitoring
- Stepwise dose increase based on serum levels
- Patient education on the importance of monitoring and potential side effects 5