Comparison of Levetiracetam Dosing Regimens in End-Stage Renal Disease Patients Undergoing Intermittent Hemodialysis

Abstract

Background: Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels. Objective: To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD. Methods: Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses. Results: We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing (P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily (P = 0.045). No seizures were reported during hospital admission in either group. Conclusions: Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.