What are the guidelines for ordering anticonvulsant (Anti-Epileptic Drugs - AEDs) blood levels?

From the Guidelines

Guidelines for ordering anticonvulsant levels prioritize monitoring trough levels, waiting until steady state is reached, and targeting therapeutic ranges to optimize seizure control while minimizing side effects. When ordering anticonvulsant levels, it is essential to consider the following key recommendations:

• Order trough levels (just before the next dose) for most accurate results.
• Wait until steady state is reached before checking levels:
  • Phenytoin: 5-7 days
  • Carbamazepine: 3-5 days
  • Valproic acid: 2-4 days
  • Phenobarbital: 14-21 days
• Check levels more frequently when starting or adjusting doses, then every 6-12 months once stable.
• Target therapeutic ranges:
  • Phenytoin: 10-20 μg/mL
  • Carbamazepine: 4-12 μg/mL
  • Valproic acid: 50-100 μg/mL
  • Phenobarbital: 15-40 μg/mL
• Consider checking levels if breakthrough seizures occur or side effects develop.
• Interpret results in context of clinical response, as some patients may be well-controlled outside the typical range. According to the most recent and highest quality study 1, anticonvulsant prophylaxis in patients with newly diagnosed brain tumors is not recommended due to lack of efficacy and potential side effects. The choice of anticonvulsant agents has become wider with more drugs available over recent years, and levetiracetam has become the drug of first choice at most neuro-oncology centers in recent years 1. Regular monitoring of anticonvulsant levels allows for dose adjustments as needed, while considering individual patient factors and clinical response, which is crucial for optimizing seizure control while minimizing side effects 1.

From the FDA Drug Label

Monitoring of blood levels has increased the efficacy and safety of anticonvulsants If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the therapeutic range. The clinically effective serum level is usually 10–20 mcg/mL Serum blood level determinations may be necessary for optimal dosage adjustments

• Guidelines for ordering anticonvulsant blood levels:
  • Measure plasma levels if satisfactory clinical response is not achieved
  • Monitor blood levels to increase efficacy and safety of anticonvulsants
  • Optimal dosage adjustments may require serum blood level determinations
  • Therapeutic serum levels for phenytoin are usually 10-20 mcg/mL
  • For carbamazepine, the therapeutic range is not explicitly stated in the provided drug label, therefore no conclusion can be drawn regarding the specific therapeutic range for this medication 2 3

From the Research

Guidelines for Ordering Anticonvulsant Blood Levels

The guidelines for ordering anticonvulsant (Anti-Epileptic Drugs - AEDs) blood levels are as follows:

• Therapeutic drug monitoring is generally only indicated when medications have specific characteristics, such as a narrow therapeutic index, where there is an established therapeutic range, and where the consequences of undertreatment cannot be recognised clinically and can be serious (eg. seizure) 4.
• Commonly used medications where therapeutic drug monitoring is indicated include some antiepileptic drugs (eg. phenytoin, carbamazepine) 4.
• The therapeutic range should be used as a guide to adjust the dose in order to further improve seizure control or reduce toxicity 5.
• Indications for the measurement of serum anticonvulsant concentrations include:
  • Poor seizure control
  • Toxicity
  • Suspected gross noncompliance
  • Status epilepticus
  • The elapse of 2 to 4 weeks after the initiation of therapy
  • Additional drug therapy, pregnancy or illness may alter drug disposition in a well-controlled patient 5.
• The measurement of anticonvulsants in saliva as opposed to serum may be of benefit in some patients 5.
• Therapeutic drug monitoring helps to optimize the dose of antiepileptic drugs and is useful in practice, in tailoring drug dosage in accordance with the needs of individual patients, in distinguishing nonresponders from noncompliants, and in aiding in making critical decisions 6.
• The "reference range" of these antiepileptic drugs was not reliable in predicting the occurrence of breakthrough seizures and clinical symptoms of suspected drug toxicity 6.

Key Considerations

• The plasma concentrations of anticonvulsant drugs tend to be proportionate to the antiepileptic effects of these drugs 7.
• The clinician needs to know the relation between plasma level and biological effect for the various drugs, as well as simple pharmacokinetic principles 7.
• Therapeutic drug monitoring is unlikely to assist management and should not be performed for the majority of medications 4.