Antiepileptic Drug Removal by Continuous Renal Replacement Therapy: A Review of the Literature

Abstract

Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted. A total of 31 case reports discussing 32 patients were found. AEDs reported were levetiracetam (n = 3), valproic acid (n = 9), carbamazepine (n = 10), phenytoin (n = 3), phenobarbital (n = 4), lacosamide (n = 1), gabapentin (n = 1), and topiramate (n = 1). Two-thirds of the reports were about using CRRT in drug overdose and one-third was about AED removal by CRRT during therapy. Based on the current limited evidence and pharmacokinetic characteristics of AEDs, renally eliminated AEDs and/or AEDs with limited protein binding such as levetiracetam are more likely to be removed by CRRT than AEDs that are mainly metabolized and extensively protein bound such as carbamazepine. In conclusion, there is not enough evidence to provide robust dosing recommendations for AEDs in patients undergoing CRRT. Further studies are needed.

Therapeutic Drug Monitoring of Levetiracetam in Select Populations

“…Another factor contributing to LEV PK variability in patients with renal disease is the extracorporeal removal of levetiracetam in patients undergoing dialysis. LEV's low molecular weight and insignificant protein binding allow it to readily diffuse through dialysis filters and renal replacement devices (60). Thus, hemodialysis and continuous renal replacement therapies (CRRT) are expected to significantly contribute to LEV clearance.…”

Extracorporeal Clearance of Levetiracetam During Continuous Venovenous Hemofiltration in a Critically Ill Patient and New Dosing Recommendation

“…Levetiracetam is a widely used antiepileptic drug; however, robust dosing recommendations for adult patients receiving continuous venovenous hemofiltration (CVVH) are lacking . The present intermittent dosage recommendation of 1000 mg every 12 hours is based on 3 case reports .…”

Successful treatment of seizure disorder by evaluating phenobarbital clearance in a paediatric patient undergoing continuous haemodiafiltration

“…PB is largely metabolized by hepatic cytochromes CYP2C9, CYP2C19 and CYP2E1. [2][3][4][5] However, the appropriate dosage of PB while the patient is receiving continu ous haemodiafiltration (CHDF) has yet to be established. Approximately 25% of the administered dose of PB is excreted unchanged in urine.…”

“…In fact, renal replacement therapy has been used for eliminating PB in cases of poisoning. [2][3][4][5] However, the appropriate dosage of PB while the patient is receiving continu ous haemodiafiltration (CHDF) has yet to be established. Here, we report a case in which the dosage of PB during CHDF was succ essfully calculated based on the evaluation of pharmacokinetic parameters.…”