Levetiracetam Level of 46.8 µg/mL: Interpretation and Management
A serum levetiracetam level of 46.8 µg/mL is at the upper limit of the therapeutic range (12-46 µg/mL) and does not require dose reduction unless the patient is experiencing adverse effects. 1, 2
Clinical Interpretation
The level of 46.8 µg/mL falls just above the established therapeutic range of 12-46 µg/mL, which is the target concentration for seizure control 1, 2
This concentration is not considered toxic or dangerous, as levetiracetam has an excellent safety profile even at supratherapeutic levels 3
Higher levetiracetam concentrations (up to 189 µg/mL) have been documented in clinical studies without serious adverse effects, demonstrating a wide therapeutic window 4
Assessment for Adverse Effects
Evaluate the patient for the following common side effects before making any dose adjustments:
Somnolence, asthenia, and dizziness are the most common adverse effects and typically appear early after initiation 3
Behavioral symptoms (irritability, mood changes) are the most serious adverse effects, particularly in patients with prior behavioral problems 3
Transient symptoms including lightheadedness, tiredness, or imbalance may occur but often resolve without intervention 5
Nausea is reported in approximately 23% of patients but is generally mild 4
Dose Adjustment Algorithm
If the patient is asymptomatic or has only mild, tolerable side effects:
- Continue the current dose without adjustment, as the level is therapeutic and higher concentrations do not correlate with worse outcomes 2
- Monitor clinically for seizure control and adverse effects rather than routinely checking levels 2
If the patient has significant adverse effects (marked somnolence, behavioral disturbances, or intolerable symptoms):
- Reduce the maintenance dose by 25-50% (e.g., from 1000 mg twice daily to 750 mg twice daily or 500 mg twice daily) 1
- Recheck the level in 2-3 days after dose adjustment to ensure it remains above 12 µg/mL for seizure control 1
If the patient is having breakthrough seizures despite this level:
- Do not increase the dose based on the level alone, as exposure does not differ significantly between responders and nonresponders 2
- Consider adding or switching to an alternative antiepileptic medication rather than escalating levetiracetam further 2
Key Clinical Pitfalls
Avoid reflexive dose reduction based solely on the level being slightly above 46 µg/mL, as levetiracetam has minimal concentration-dependent toxicity and the therapeutic range is a guideline rather than a strict cutoff 2, 3
Do not assume higher levels will improve seizure control in non-responders, as pharmacokinetic studies show no correlation between exposure and response 2
Recognize that levetiracetam has a short half-life, making the timing of level measurement critical for interpretation—trough levels are most clinically useful 2