Treatment with lacosamide or levetiracetam in patients with renal replacement therapy. What is really known?

No reports were found about the influence of PD on the pharmacokinetics of LCM. Two papers on the use of LCM in patients undergoing IHD were identified. In a phase 1 study (Cawello et al., 2013), eight patients with end-stage renal disease, receiving haemodialysis were administered 100 mg of LCM. They received 100 mg of LCM 2.5 hours before a 4-hour session. It was observed that haemodialysis removed 50.9 ± 6.3 g LCM which represented more than 50% of circulating LCM reaching a mean concentration of 0.89 mg/l compared with 2.19 mg/l when haemodialysis free. An anuric patient with acute kidney injury received a daily dose of 100 mg of LCM and an additional dose of 150 mg post-haemodialysis. The concentration values were between 8.6 mg/l and 8.8 mg/l on dialysis days and also on non-dialysis days alike (Nei et al., 2019).

Two patients receiving LCM while undergoing CVVH have been published. One patient received 200 mg LCM twice/day intravenously (Franquiz et al., 2018) resulting in a peak concentration at steady state of 7.7 mg/l and a trough concentration of 5.9 mg/l. With the same dose of LCM in another patient a peak concentration of 7.4 mg/l and a trough concentration of 3.7 mg/l (Wieruszewski et al., 2018b) were measured. The lower trough concentration in the second case may be due to the higher replacement rate of 30 ml/kg/hr (Wieruszewski et al., 2018b) in contrast to 20 ml/kg/hr (Franquiz et al., 2018).

Two papers have reported on the effect of PD on LEV pharmacokinetics. In one patient 1000 mg LEV daily and 10-hour PD peak concentrations ranged from 42 mg/l to 56 mg/l and trough concentrations from 27 mg/l to 49 mg/l (Ratté et al., 2018). There was only a small amount of LEV removal by PD. This observation is supported by the case of a 73-year-old man (160 cm, 93 kg), who had been undergoing PD for two years. Eight weeks after being put on LEV 500 mg twice/day he presented to an emergency department with a Glasgow Coma Scale of 10. Unfortunately, no LEV concentrations were measured at this point. But even 24 hours after discontinuation of LEV. a concentration of 29.8 mg/l was recorded (Bathe et al., 2014).

We found two case reports on LEV treatment and IHD. A 43-year-old lean woman (158 cm, 48.1 kg) (Wieruszewski et al., 2018a) received a loading dose of 2000 mg, continuing with 500 mg of LEV daily and a supplemental dose of 750 mg post-dialysis. On off-dialysis days a peak concentration at steady state of 20.2 mg/l and a trough concentration of 12.2 mg/l were documented. About 85% of LEV was cleared within a 3-hour-dialysis session. A peak concentration of 31.2 mg/l and a trough concentration of just 4.47 mg/l were measured. A second 25-year-old lean women (40 kg) developed seizures during IHD when given 500 mg LEV daily and a 250 mg supplementary dose after HD (Company-Albir et al., 2017) were given. After increasing the supplementary dose to 500 mg, peak concentrations ranging from 20 mg/l to 35 mg/l and trough concentrations ranging from 3.7 mg/l to 9.4 mg/l were measured. To achieve seizure freedom valproate was added.

Additionally, a case series of 14 patients receiving doses ranging from 250 mg to 1000 mg LEV twice/day and 8 patients receiving 500 mg to 1500 mg daily with a supplementary dose after haemodialysis was published (Shive et al., 2017). LEV twice/day resulted in higher peak and trough concentrations than LEV daily. Since patients with LEV twice/day received a mean daily dose of 1367 mg and patients with LEV daily 1219 mg on days with dialysis and 812.5 mg on dialysis-off days, this difference may be explained by the differences in dosage. No recommendation for a specific LEV dose can be derived from this study.

Five case reports on patients receiving LEV while on CCVH have been published. In one 51-year-old woman who was administered a dose of 1000 mg LEV intravenously every 12 hours, trough concentrations of 19 mg/l were obtained (Louie et al., 2015). In a strongly built (175 cm, 116.9 kg) 67-year old man after a loading dose of 2000 mg LEV and maintenance doses of 1000 mg LEV every 12 hours were administered (Nei et al., 2015). Peak concentrations ranged from 26.5 mg/l after the loading dose to 39.8 mg/l at steady state. Trough concentrations ranged from 13.9 mg/l to 18.2 mg/l at steady state. In a 59-year-old tall man (187 cm, 83.4 kg) administered 1000 mg LEV every 12 hours, a peak concentration of 32.2 mg/l and a trough concentration of 16.1 mg/l (New et al., 2016) were measured. In a 78-year-old (93.2 kg) man treated with the same LEV dosage, a peak concentration of 30.7 mg/l and a trough concentration of 16.1 mg/l (Van Matre et al., 2017) were measured. In a 79-year-old man (175 cm, 90 kg) treated with a dose of LEV 1000 mg twice/day, a median concentration of 12.4 mg/l was measured (le Noble et al., 2017).

Unfortunately, the authors do not state the levels of peak concentrations and trough concentrations separately. But to avoid the large differences between peak concentrations and trough concentrations they recommended continuous LEV infusion of 2000 mg/24 h.