CLINICALLY SIGNIFICANT REMOVAL OF LEVETIRACETAM IN A PATIENT ON CONTINUOUS VENOVENOUS HEMOFILTRATION

Aims: The use of levetiracetam, a second-generation anti-epileptic drug, is increasing due to its favorable side effect profile and lack of drug interactions. Limited data exist to guide dosing during continuous venovenous hemofiltration (CVVH). Therefore, we present a case in which the pharmacokinetic characteristics of levetiracetam were evaluated in a patient with acute kidney injury on CVVH.

Presentation of Case: A 72 year old male in status epilepticus was started on levetiracetam 1000 mg intravenously once followed by 500 mg every 12 hours. Pre-filter-replacement CVVH was performed with a blood flow of 250 ml/min and a fluid replacement rate of 1.5-2 L/hr. Levetiracetam maximum and minimum concentrations were collected in both the serum and CVVH effluent with the first dose and third dose. CVVH clearance (CLCVVH) accounted for 50.8% of total clearance (TC) (0.23-0.3 and 0.59-0.62 ml/min/kg, respectively).

Discussion: This is the first study to measure levetiracetam concentrations in effluent fluid, which allow for a more detailed pharmacokinetic analysis, including the CLCVVH and its contribution to TC. Even though our patient was on pre-filter-replacement CVVH with fluid replacement rates of 1.5-2 L/hr (equivalent to a creatinine clearance (CrCl of approximately 23-29 ml/min)), TC was more consistent with that seen in a patient with mild kidney disease, or a CrCl of 50-80 ml/min.

Conclusion: This case demonstrates that levetiracetam is efficiently removed by CVVH and suggests that patients may require higher doses than what the estimated creatinine clearance based on CVVH flow rate would otherwise predict.