How often should Keppra (levetiracetam) levels be checked in patients?

Routine Therapeutic Drug Monitoring of Keppra (Levetiracetam) is Generally Not Necessary

Levetiracetam does not require routine therapeutic drug monitoring in most patients, as it has linear pharmacokinetics, minimal drug interactions, and a broad therapeutic window 1. Unlike traditional antiepileptic drugs, there is no established correlation between serum levels and either efficacy or toxicity 2.

When to Consider Level Monitoring

While routine monitoring is unnecessary, specific clinical scenarios warrant checking levetiracetam levels:

Suspected Non-Adherence

• Check levels when medication non-adherence is suspected to confirm therapeutic dosing 3, 1

Renal Impairment

• Monitor levels every 3-6 months in patients with moderate to severe renal dysfunction 1
• Levetiracetam clearance is directly dependent on creatinine clearance, requiring dosage adjustments as renal function declines 4
• In end-stage renal disease patients on hemodialysis, levels should be checked pre-dialysis, post-dialysis, and after supplemental dosing to ensure adequate recovery 5

Critically Ill Patients

• Consider more frequent monitoring in ICU patients, as levetiracetam clearance may be augmented by 30-40% compared to healthy adults 2, 6
• These patients often require higher doses to maintain therapeutic levels 6

Special Populations with Altered Pharmacokinetics

Pediatric patients:

• Clearance is increased by 30-40% compared to adults, with elimination half-life of 5-7 hours 2, 4
• Consider monitoring when optimizing dosing in this population 2

Elderly patients (>65 years):

• Clearance is decreased by almost 50% with elimination half-life of 10-11 hours 2, 4
• Monitor when initiating therapy or if toxicity is suspected 2

Pregnant patients:

• Levels decline progressively throughout pregnancy due to increased glomerular filtration rate 2
• Monitor each trimester and postpartum to maintain individual therapeutic range 2

Neonates:

• Pharmacokinetics are highly variable in this population 2
• Consider monitoring to establish appropriate dosing 2

Initial Monitoring Recommendation

• Obtain a complete blood count when initiating levetiracetam therapy 3, 1
• This is the only routine laboratory monitoring recommended at initiation

Clinical Context

The reference range of 12-46 μg/mL is not predictive of clinical outcomes, as seizure control and adverse effects occur across all concentration ranges 2. Therefore, establishing an individual therapeutic range based on clinical response is more valuable than targeting a specific laboratory value 2.