When to check Keppra (Levetiracetam) levels in a patient with a history of seizure who has experienced a recent seizure episode, considering factors such as age, renal function, and medication adherence?

When to Check Keppra (Levetiracetam) Levels in Seizure Patients

Routine levetiracetam level monitoring is generally not indicated in patients presenting with seizures, as the drug has predictable pharmacokinetics, minimal drug interactions, and no established correlation between serum levels and efficacy or toxicity. 1, 2

General Principles

• Levetiracetam does not require therapeutic drug monitoring (TDM) in most clinical scenarios because it exhibits linear, predictable dose-serum concentration relationships and lacks significant drug-drug interactions 1, 2
• Variable levetiracetam levels occur below, within, and above reference ranges (12-46 μg/mL) with respect to adverse effects, seizures, and efficacy, indicating no positive correlation between levels and clinical outcomes 2
• The drug is less than 10% protein-bound, making clinically significant interactions through protein binding unlikely 1

Specific Populations Requiring Level Monitoring

Critical Illness

• Check levels in critically ill patients, as they demonstrate augmented clearance requiring higher doses to maintain therapeutic concentrations 3, 2
• In ICU patients receiving seizure prophylaxis, only 54% achieve target levels with standard dosing, and higher doses (750-1000 mg BID vs 500 mg BID) are needed 3
• Consider monitoring when clinical response is suboptimal despite appropriate dosing 2

Renal Impairment

• Check levels in patients with declining renal function, as clearance decreases by 40% (mild impairment, CrCl 50-80 mL/min), 50% (moderate, CrCl 30-50 mL/min), and 60% (severe, CrCl <30 mL/min) 1
• In end-stage renal disease, total body clearance decreases by 70%, and approximately 50% of levetiracetam is removed during standard 4-hour hemodialysis 1
• Monitor levels to guide dose adjustments and determine need for supplemental post-dialysis dosing 1

Elderly Patients

• Consider checking levels in patients over 65 years, as total body clearance decreases by 38% and half-life increases by 2.5 hours compared to younger adults 1, 2
• This reduction is primarily due to decreased renal function with aging 1

Pediatric Patients

• Check levels in children, as weight-adjusted clearance is approximately 40% higher than adults, requiring higher mg/kg dosing 1, 2
• Clearance increases with body weight in pediatric patients 1
• When co-administered with enzyme-inducing antiepileptic drugs (e.g., carbamazepine), apparent clearance increases by approximately 22% 1

Pregnancy

• Monitor levels throughout pregnancy, as levetiracetam concentrations decline progressively due to increased glomerular filtration rate 2
• Levels remain variable in the postpartum period 2

Neonates

• Check levels in neonates, as pharmacokinetics are highly variable in this population 2

Clinical Scenarios NOT Requiring Routine Levels

• First-time seizure patients who have returned to baseline: Laboratory testing, including drug levels, is of very low yield in otherwise healthy patients 4
• Patients with known seizure disorder on stable levetiracetam: No indication for routine monitoring unless specific concerns arise 2
• Status epilepticus management: Focus is on clinical response rather than serum levels, as studies use levels as surrogate markers rather than primary outcomes 4

Common Pitfalls

• Avoid ordering levels reflexively in all seizure patients, as this does not improve outcomes and increases costs 2
• Do not assume subtherapeutic levels explain breakthrough seizures without considering medication adherence, drug interactions with enzyme-inducing agents, and underlying disease progression 1
• Remember that levetiracetam reaches steady state after only 2 days of twice-daily dosing, so timing of level checks should account for this 1