What are the guidelines for monitoring Phenytoin (Dilantin) levels?

From the Guidelines

Phenytoin monitoring should include regular assessment of serum phenytoin levels, particularly after initiating therapy or adjusting doses, with a target therapeutic range of 10 mg/L or greater, as evidenced by studies such as 1. When monitoring phenytoin levels, it is essential to consider the route of administration, as different methods can achieve therapeutic levels at varying rates.

• Intravenous administration of phenytoin or fosphenytoin can achieve a serum phenytoin level greater than or equal to 10 mg/L within minutes after completion of the infusion, as reported in 1.
• Intra-muscular administration of fosphenytoin generally produces a therapeutic serum phenytoin level within 1 hour of administration, according to 1.
• Oral loading of phenytoin can achieve a therapeutic serum phenytoin level between 3 to 8 hours after the initial ingestion, as stated in 1. Regular monitoring of serum phenytoin levels is crucial to ensure that the patient is within the therapeutic range and to minimize the risk of dose-related adverse effects, such as ataxia, nystagmus, tremor, and somnolence, which are associated with phenytoin and fosphenytoin, as noted in 1. Additionally, clinical monitoring should include assessment for side effects, and periodic checks of complete blood counts, liver function tests, and other relevant parameters may be necessary, particularly in patients with hepatic or renal impairment, pregnancy, hypoalbuminemia, or those on multiple medications due to potential drug interactions. However, the specific details of such monitoring may vary depending on individual patient factors and the clinical context, and should be guided by the most recent and highest-quality evidence available, such as 1.

From the FDA Drug Label

Serum concentrations should be monitored in changing from Dilantin (extended phenytoin sodium capsules, USP to Prompt Phenytoin Sodium Capsules, USP, and from the sodium salt to the free acid form. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum level is usually 10–20 mcg/mL When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out.

Phenytoin monitoring is necessary in certain situations, such as:

• When changing from one dosage form to another (e.g., from sodium salt to free acid form)
• When adjusting dosage to achieve optimal levels
• When switching from one brand to another The clinically effective serum level of phenytoin is usually between 10-20 mcg/mL. 2

From the Research

Phenytoin Monitoring

• Phenytoin toxicity may result from intentional overdose, dosage adjustments, drug interactions, or alterations in physiology 3
• The mainstay of therapy for a patient with phenytoin intoxication is supportive care, including attention to vital functions, management of nausea and vomiting, and prevention of injuries due to confusion and ataxia 3
• Total phenytoin concentration is not a reliable predictor of free drug, which is responsible for the therapeutic effects, especially in severely-ill head trauma patients 4
• Free phenytoin concentration should be measured in all severely ill neurotrauma patients to ensure accurate monitoring of the drug 4

Clinical Manifestations of Phenytoin Toxicity

• Common presenting symptoms of acute phenytoin intoxication include unsteady gait, dizziness/vertigo, nausea/vomiting, general weakness, and drowsiness 5
• Phenytoin-related ataxia is a common adverse effect in patients with epilepsy, with 40% of patients showing clinical evidence of ataxia 6
• Cerebellar ataxia is associated with reduced cerebellar volume, even in patients without clinical evidence of ataxia 6

Therapeutic Drug Monitoring

• Therapeutic drug monitoring of phenytoin is necessary to ensure therapeutic and nontoxic levels, especially in critically ill patients 7
• Free serum concentrations should be measured, or theoretically calculated if measurements are unavailable, to avoid misinterpretation of total serum levels and consequent inappropriate adjustments in the dosage of phenytoin 7
• Protein binding of phenytoin is often altered in critically ill patients, and total serum concentrations may not accurately reflect the pharmacologically active entity 7