From the Guidelines
Levetiracetam levels should be checked in specific situations such as suspected non-compliance, breakthrough seizures, toxicity, renal impairment, pregnancy, or significant weight changes, and the clinical response should guide treatment decisions rather than absolute numbers. When interpreting levels, there is no well-established therapeutic range, though concentrations between 12-46 mg/L are often cited 1. The correlation between serum levels and efficacy or toxicity is not strong, so clinical response should guide treatment decisions rather than absolute numbers. Blood samples should be drawn at trough levels (just before the next dose) for consistency. Levetiracetam has linear pharmacokinetics, meaning the blood level increases proportionally with dose increases, and it has minimal protein binding (less than 10%), which reduces the risk of interactions with other highly protein-bound medications. This makes levetiracetam a relatively straightforward antiepileptic medication to manage without frequent blood level monitoring in most clinical scenarios. Some studies provide guidance on the management of seizures in specific contexts, such as the use of levetiracetam in paediatric patients receiving chimeric antigen receptor T cell therapy 1, but these do not directly inform the general approach to monitoring levetiracetam levels. In clinical practice, the decision to check levetiracetam levels and how to act on them should prioritize the individual patient's clinical response and specific circumstances, rather than adhering to a one-size-fits-all approach. Key factors to consider include the patient's renal function, as levetiracetam is primarily eliminated by the kidneys, and any significant changes in the patient's condition that could affect drug levels or efficacy. Ultimately, the management of levetiracetam therapy should focus on maximizing efficacy while minimizing toxicity, with level monitoring used judiciously to support these goals.
From the Research
When to Check Levetiracetam Levels
- Levetiracetam levels should be checked in patients with altered pharmacokinetics, such as those with renal failure, liver disease, or those who are critically ill 2, 3, 4.
- Therapeutic drug monitoring (TDM) of levetiracetam may be beneficial in patients who are pregnant, pediatric, or elderly, as their pharmacokinetics may be altered 4.
- TDM may also be useful in patients who are receiving continuous venovenous hemofiltration (CVVH) or have acute liver dysfunction 2, 3.
How to Act on Levetiracetam Levels
- The therapeutic range for levetiracetam is generally considered to be 6-46 mcg/mL, with peak concentrations ranging from 26.5-39.8 μg/mL and trough concentrations ranging from 13.9-18.2 μg/mL 2, 3.
- Dosage adjustments should be made based on therapeutic drug monitoring, with consideration of the patient's individual pharmacokinetics and clinical response 2, 3, 4.
- In patients with renal dysfunction, dosage reductions may be necessary to prevent accumulation, with an initial dose of 1000 mg every 12 hours recommended for patients receiving CVVH 2.
- In patients with acute liver dysfunction, a regimen of 1000 mg twice daily may be considered as an empiric levetiracetam regimen 3.
Special Considerations
- Levetiracetam pharmacokinetics may be altered in patients with chronic liver disease, but the drug appears to be well-tolerated and effective in this population 5.
- In patients who are pregnant, levetiracetam levels may decline as pregnancy progresses, and TDM may be useful to maintain an individual therapeutic range 4, 6.
- Routine TDM of levetiracetam is not recommended for all populations, but may be beneficial in specific clinical situations, such as in patients with altered pharmacokinetics or those who are receiving CVVH 4, 6.