When should serum phenytoin (antiepileptic medication) levels be checked?

From the Guidelines

Phenytoin levels should be checked 3 to 7 days after initiation of oral therapy without a loading dose, or within minutes to 1 hour after intravenous or intramuscular administration of fosphenytoin, and then monitored on an outpatient basis. When initiating therapy, the timing of phenytoin level checks depends on the route of administration, with intravenous administration of fosphenytoin achieving therapeutic levels within minutes, and oral loading achieving therapeutic levels between 3 to 8 hours after the initial ingestion 1. For patients on chronic oral phenytoin therapy without a loading dose, serum phenytoin levels greater than or equal to 10 mg/L can be achieved in 3 to 7 days, and some patients may require an increased daily maintenance dose to reach therapeutic levels 1. Key factors to consider when monitoring phenytoin levels include:

• The route of administration and its impact on the time to reach therapeutic levels
• The potential for dose-related adverse effects, such as ataxia, nystagmus, tremor, and somnolence
• The importance of follow-up and monitoring of serum phenytoin levels on an outpatient basis to ensure therapeutic levels are maintained and to minimize the risk of toxicity. In clinical practice, monitoring phenytoin levels is crucial to ensure efficacy and minimize toxicity, and the timing of these checks should be individualized based on the patient's specific clinical situation and response to therapy.

From the FDA Drug Label

Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected Phenytoin serum level determinations may be necessary to achieve optimal dosage adjustments. When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out. 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 With recommended dosage, a period of seven to ten days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days

Phenytoin levels should be checked:

• When changing the dosage form or brand of phenytoin
• When possible drug interactions are suspected
• To achieve optimal dosage adjustments
• In some cases, to determine the clinically effective serum level (usually 10-20 mcg/mL)
• After a period of 7-10 days to achieve steady-state blood levels 2 2

From the Research

Phenytoin Level Monitoring

• Phenytoin levels should be checked to optimize clinical efficacy while avoiding adverse effects 3
• Total phenytoin levels can be misleading in patients with low plasma albumin, and direct measurement of free phenytoin concentrations or calculation of adjusted phenytoin levels can provide more accurate information 3, 4
• In critically ill patients, free serum concentrations should be measured or theoretically calculated to avoid misinterpretation of total serum levels and consequent inappropriate adjustments in the dosage of phenytoin 4

Timing of Phenytoin Level Checks

• Phenytoin levels should be checked within 2-24 hours after a loading dose to ensure adequate serum levels 5
• Close laboratory surveillance and phenytoin dose adjustments are recommended to ensure adequate and sustained serum levels early in treatment 5
• Albumin plasma concentrations up to 7 days prior to total phenytoin measurements can be used for adjusted phenytoin concentrations 3

Special Considerations

• In patients with hypoalbuminemia, renal failure, or interactions with other highly protein-bound drugs, free serum concentrations or adjusted phenytoin levels should be used to guide phenytoin dosing 3, 4
• In oral phenytoin overdoses, serum phenytoin levels should be checked, especially in patients with hypoalbuminemia 6