From the Guidelines
Levetiracetam is the most renal safe antiepileptic medication due to its minimal hepatic metabolism and primary excretion unchanged in the urine, allowing for straightforward dose adjustments based on creatinine clearance. When considering antiepileptic medications for patients with renal disease, it's crucial to prioritize those with minimal renal toxicity and straightforward dosing adjustments.
- Key characteristics of renal safe antiepileptics include minimal hepatic metabolism, primary excretion unchanged in the urine, and limited drug interactions.
- Levetiracetam, gabapentin, and pregabalin are preferred options because they can be dose-adjusted based on creatinine clearance, although gabapentin and pregabalin require more significant dose reductions in renal impairment 1.
- Other alternatives like lacosamide offer predictable pharmacokinetics, making them safer than traditional antiepileptics with complex metabolism and potential nephrotoxicity.
- Regular monitoring of renal function and dose adjustments according to creatinine clearance values are essential when prescribing these medications for patients with kidney disease.
- The choice of antiepileptic medication should be based on the individual patient's renal function and medical history, with a focus on minimizing potential renal toxicity and drug interactions.
From the FDA Drug Label
The disposition of levetiracetam was studied in adult subjects with varying degrees of renal function Total body clearance of levetiracetam is reduced in patients with impaired renal function by 40% in the mild group (CLcr = 50 to 80 mL/min), 50% in the moderate group (CLcr = 30 to 50 mL/min) and 60% in the severe renal impairment group (CLcr <30 mL/min). Apparent oral clearance (CL/F) of gabapentin decreased as age increased, from about 225 mL/min in those under 30 years of age to about 125 mL/min in those over 70 years of age. Renal clearance (CLr) and CLr adjusted for body surface area also declined with age; however, the decline in the renal clearance of gabapentin with age can largely be explained by the decline in renal function.
Most Renal Safe Antiepileptics:
- Levetiracetam and gabapentin are both primarily renally excreted.
- Levetiracetam has a more predictable pharmacokinetic profile in patients with renal impairment, with a decrease in total body clearance of 40% in mild, 50% in moderate, and 60% in severe renal impairment.
- Gabapentin has a more variable pharmacokinetic profile in patients with renal impairment, with a decrease in apparent oral clearance and renal clearance that can be largely explained by the decline in renal function.
- However, gabapentin has a more significant effect on renal elimination in anuric subjects, with a reduction in apparent elimination half-life from about 132 hours to 3.8 hours during dialysis.
- Based on the available data, levetiracetam may be considered a more renal safe option compared to gabapentin, due to its more predictable pharmacokinetic profile in patients with renal impairment 2.
From the Research
Renal Safe Antiepileptics
The following antiepileptics are considered to be renal safe:
- Gabapentin
- Pregabalin
- Vigabatrin
- Topiramate (when used as monotherapy)
- Levetiracetam, lacosamide, zonisamide, primidone, phenobarbital, ezogabine/retigabine, oxcarbazepine, eslicarbazepine, ethosuximide, and felbamate can be used cautiously in patients with either renal or liver failure 3
Levetiracetam Dosing
For levetiracetam, the recommended dosing regimen is:
- 750-1000 mg every 12 hours for adult patients receiving continuous renal replacement therapy (CRRT) 4, 5, 6
- A loading dose of 60 mg/kg (up to a maximum of 4.5 g) can be considered to reduce the time to achievement of therapeutic drug concentrations 4
- For Child-Pugh class C cirrhotic patients undergoing CRRT, a lower dosing regimen of 500-750 mg every 12 hours may be required 6
Pharmacokinetics of Levetiracetam
The pharmacokinetics of levetiracetam in patients undergoing renal replacement therapy are: