From the FDA Drug Label
Adult Patients With Impaired Renal Function Levetiracetam dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 16. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula: CLcr =[140-age (years)] × weight (kg)(× 0. 85 for female patients) 72 × serum creatinine (mg/dL) Table 16: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance(mL/min) Dosage(mg) Frequency
- Following dialysis, a 250 to 500 mg supplemental dose is recommended Normal >80 500 to 1,500 Every 12 h Mild 50 to 80 500 to 1,000 Every 12 h Moderate 30 to 50 250 to 750 Every 12 h Severe <30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000* Every 24 h
The dosing of Levetiracetam (Keppra) according to creatinine clearance is as follows:
- Normal renal function (>80 mL/min): 500 to 1,500 mg every 12 hours
- Mild renal impairment (50 to 80 mL/min): 500 to 1,000 mg every 12 hours
- Moderate renal impairment (30 to 50 mL/min): 250 to 750 mg every 12 hours
- Severe renal impairment (<30 mL/min): 250 to 500 mg every 12 hours
- ESRD patients using dialysis: 500 to 1,000 mg every 24 hours, with a supplemental dose of 250 to 500 mg after dialysis 1
From the Research
Keppra (levetiracetam) dosing should be adjusted based on creatinine clearance to prevent drug accumulation and potential toxicity, with the most recent study 2 suggesting an initial dosage regimen of 1500 mg twice daily for patients exhibiting augmented renal clearance. For patients with normal renal function (creatinine clearance >80 mL/min), the standard adult dosing is 500-1500 mg twice daily. When creatinine clearance is 50-80 mL/min, no dose adjustment is needed. For creatinine clearance 30-50 mL/min, give 500-1000 mg twice daily. With creatinine clearance <30 mL/min, reduce to 250-750 mg twice daily. For end-stage renal disease patients on dialysis, give 500-1000 mg once daily with a supplemental 250-500 mg dose after dialysis. Levetiracetam is primarily eliminated unchanged through the kidneys, which is why dose adjustment is necessary in renal impairment, as supported by studies 3, 4, 5. Monitor patients with renal impairment closely for side effects such as somnolence, dizziness, and behavioral changes, as reported in studies 5, 6. Dose adjustments should be made gradually to minimize breakthrough seizures while avoiding toxicity. Regular monitoring of renal function is recommended for patients on long-term levetiracetam therapy, especially those with fluctuating renal function. The safety and efficacy of intravenous levetiracetam treatment in patients with renal impairment have been demonstrated in a study 6, but the primary concern remains adjusting the dose according to creatinine clearance to ensure optimal outcomes in terms of morbidity, mortality, and quality of life. Key considerations include:
- Renal function monitoring
- Dose adjustment based on creatinine clearance
- Awareness of potential side effects
- Gradual dose adjustments to avoid toxicity or breakthrough seizures
- The importance of the most recent study 2 in guiding dosing decisions for patients with augmented renal clearance.