Levetiracetam in critically ill patients with augmented renal clearance: a systematic review

Levetiracetam, a second-generation antiepileptic drug, is predominantly eliminated renally, and its clearance is closely linked to creatinine clearance (CrCl). In critically ill patients with augmented renal clearance (ARC), defined as CrCl > 130 mL/min/1,73 m², levetiracetam elimination is accelerated, potentially resulting in subtherapeutic plasma concentrations when standard doses (500–1500 mg/12 h) are used. This study systematically reviewed the pharmacokinetics of levetiracetam in critically ill patients with ARC to inform alternative dosing strategies. A systematic review of the literature was conducted using PubMed and Embase up to July 2024. The search terms included “levetiracetam,” “pharmacokinetics,” and “pharmacokinetic*,” utilizing both free-text and controlled vocabulary approaches. The PRISMA 2020 methodology guided the study selection and analysis. From 1612 initial records, seven studies comprising 110 patients met the inclusion criteria. The prevalence of ARC within the pooled patient cohort from the included studies was 52.7%, and the CrCl values ranged from 54 to 244 mL/min. The findings suggest that standard levetiracetam doses may be insufficient in critically ill patients with ARC. Simulations indicate that many patients might require higher doses or alternative regimens (e.g., prolonged infusions or doses exceeding 6 g/day) to achieve therapeutic plasma concentrations, although clinical data confirming efficacy at these high doses are limited. This review underscores the potential need for tailored levetiracetam dosing guidelines for patients with ARC. However, given the variability in therapeutic targets and limited data on patients with extreme ARC, further research is essential to validate optimal dosing strategies before standardized protocols can be established. The protocol for this systematic review was registered in PROSPERO (CRD420251246297).