Duration of Keppra (Levetiracetam) in the System
In adults with normal kidney function, Keppra is eliminated from the body within approximately 30-40 hours (roughly 5 half-lives), with a half-life of 6-8 hours. 1, 2
Elimination Half-Life
- The elimination half-life of levetiracetam in adults with normal renal function is 6-8 hours 1, 2
- Steady-state blood concentrations are achieved within 24-48 hours of starting the medication 2
- After discontinuation, the drug is essentially cleared from the system after 5 half-lives, which equals approximately 30-40 hours 2
Pharmacokinetic Profile
- Levetiracetam is rapidly absorbed after oral administration, with peak concentrations occurring at approximately 1.3 hours 2
- The bioavailability exceeds 95%, meaning nearly all of the oral dose enters systemic circulation 2
- Approximately 66% of the drug is excreted unchanged in urine, while 34% undergoes metabolism primarily through blood hydrolysis (not hepatic metabolism) 1, 2
Clinical Evidence from Overdose Data
- A case report of levetiracetam overdose demonstrated an elimination half-life of 5.14 hours even at concentrations 10-40 fold higher than therapeutic levels, confirming first-order elimination kinetics 3
- In this overdose case, serum concentrations decreased from 400 mcg/mL at 6 hours to 72 mcg/mL at 18 hours and 60 mcg/mL at 20.5 hours, demonstrating predictable elimination 3
Special Populations Requiring Longer Clearance Times
Elderly Patients
- In elderly patients (age 61-88 years), the half-life increases to 10-11 hours due to decreased renal function 1, 2
- Total body clearance decreases by 38% in elderly patients compared to younger adults 1
Renal Impairment
- Total body clearance is reduced by 40% in mild renal impairment (creatinine clearance 50-80 mL/min), 50% in moderate impairment (30-50 mL/min), and 60% in severe impairment (<30 mL/min) 1
- In anuric patients with end-stage renal disease, total body clearance decreases by 70% compared to normal subjects 1
- Approximately 50% of levetiracetam is removed during a standard 4-hour hemodialysis procedure 1
Pediatric Patients
- In children aged 4-12 years, the half-life is shorter at 5-7 hours due to higher body weight-adjusted clearance (approximately 40% higher than adults) 1, 2
Practical Clinical Implications
- For patients with normal kidney function discontinuing Keppra, the medication will be essentially cleared within 2 days 2
- No hepatic dose adjustment is needed, as levetiracetam metabolism does not occur primarily in the liver 1, 2
- The drug does not accumulate with multiple dosing when renal function is normal 2
- Clearance is directly dependent on creatinine clearance, making renal function the primary determinant of how long the drug stays in the system 1, 2