Do serum levetiracetam (Keppra) levels require monitoring?

From the Guidelines

Levetiracetam levels do not need to be routinely tested for most patients. Unlike other antiepileptic drugs such as phenytoin or carbamazepine, levetiracetam has a wide therapeutic window, predictable pharmacokinetics, minimal drug interactions, and good correlation between dose and serum concentration 1. However, level testing may be beneficial in specific situations:

• when assessing medication adherence
• evaluating potential toxicity
• managing pregnancy (when levels may decrease)
• adjusting doses in patients with significant kidney dysfunction
• or investigating breakthrough seizures despite appropriate dosing 1. When testing is performed, the typical therapeutic range is considered to be 12-46 μg/mL, though clinical response rather than specific levels should guide treatment decisions. Levetiracetam is typically started at 500-1000 mg twice daily for adults and titrated based on clinical response and tolerability, with most patients requiring 1000-3000 mg daily in divided doses. The medication is primarily eliminated by the kidneys, so dose adjustments are needed in patients with renal impairment. Some key points to consider when using levetiracetam include:
• The medication has a favorable safety profile, with minimal risk of adverse drug interactions 1
• Dose adjustments may be necessary in patients with renal dysfunction 1
• Levetiracetam can be used as an adjunctive therapy for partial seizures, and its efficacy has been demonstrated in several studies 1
• The choice of administration route (oral versus parenteral) is at the discretion of the emergency physician, as there is a lack of evidence to support one route over the other in terms of preventing early recurrent seizure 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Levetiracetam Levels Testing

• Levetiracetam is a broad spectrum antiepileptic drug with a favorable side effect profile and linear pharmacokinetics, making therapeutic drug monitoring (TDM) generally unnecessary 2.
• However, TDM may be beneficial in certain populations, such as critically ill patients, pregnant women, pediatrics, and elderly patients, where levetiracetam pharmacokinetics may be altered 2, 3.
• Studies have shown that levetiracetam levels do not correlate with efficacy or toxicity, and variable levels are reported in the literature with respect to adverse effects, seizures, and efficacy 2, 4.
• Age is a major contributor to altered pharmacokinetics of levetiracetam, with decreased clearance in elderly patients and increased clearance in pediatric patients 2.
• Renal function also affects levetiracetam pharmacokinetics, with decreased clearance in patients with renal failure or those requiring renal replacement therapy 2, 3.
• The use of high-performance liquid chromatography (HPLC) and immunoassay for measuring levetiracetam levels has been evaluated, with the immunoassay method being fully acceptable for routine use 3.
• Monitoring levetiracetam levels may be important for detecting potential adverse effects and optimizing treatment, particularly in patients with altered pharmacokinetics 4.