The Impact of Augmented Renal Clearance on the Pharmacokinetics of Levetiracetam in Critically Ill Patients: A Literature Review.

Abstract

Levetiracetam is an antiseizure medication (ASM) that has several advantages over other ASMs, such as dose-proportional pharmacokinetics, high bioavailability, and minimal drug interactions. The drug is primarily eliminated through the kidneys. Therefore, dose adjustments are necessary in patients with renal impairment or patients experiencing augmented renal clearance (ARC) to maintain optimal efficacy and safety. The objective of this review was to explore the existing literature on the influence of ARC on the pharmacokinetics of levetiracetam in critically ill patients. Database searched included MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL. Thirteen articles were included. The prevalence of ARC ranged from 30% to 90%. All studies demonstrated the inadequacy of the levetiracetam starting dose of 500 mg twice daily (BID) in critically ill patients. Studies consistently reported altered pharmacokinetics of levetiracetam in patients with ARC, showing an elevated clearance that can reach up to 6.5L/h (∼3.8 L/h in healthy individuals). Additionally, patients with ARC had a lower area under the concentration-time curve, shorter half-life, and lower trough concentrations than those without ARC. Dosing simulations indicated that the use of at least 1500 mg BID is recommended for ARC patients to achieve similar exposures to those with no ARC on the 1000 mg BID starting dose. In conclusion, ARC significantly enhances the renal elimination of levetiracetam, elevating the risk of sub-therapeutic drug levels and treatment failure. An initial dosage regimen of 1500 mg BID would be recommended for patients exhibiting ARC. Therefore, careful monitoring of creatinine clearance and dosing optimization for patients experiencing ARC is essential.