A missed opportunity – consequences of unknown levetiracepam pharmacokinetics in a peritoneal dialysis patient

Abstract

BackgroundLevetiracetam is a frequently used drug in the therapy of partial onset, myoclonic and generalized tonic-clonic seizures. The main route of elimination is via the kidneys, which eliminate 66% of the unchanged drug as well as 24% as inactive metabolite that stems from enzymatic hydrolysis. Therefore dose adjustments are needed in patients with chronic kidney disease stage 5 D, i.e. patients undergoing dialysis treatment. In this patient population a dose reduction by 50% is recommended, so that patients receive 250–750 mg every 12 hours. However “dialysis” can be performed in using different modalities and treatment intensities. For most of the drugs pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis are not available. This is the first report on levetiracetam pharmacokinetics in a peritoneal dialysis patient.Case presentationA 73-y-old Caucasian male (height: 160 cm, weight 93 kg, BMI 36.3 kg/m2) was admitted with a Glasgow Coma Scale of 10. Due to diabetic and hypertensive nephropathy he was undergoing peritoneal dialysis for two years. Eight weeks prior he was put on levetiracetam 500 mg twice daily for suspected partial seizures with secondary generalization. According to the patient’s wife, levetiracetam lead to fatigue and somnolence leading to trauma with fracture of the metatarsal bone. Indeed, even 24 hours after discontinuation of levetiracetam blood level was still 29.8 mg/l (therapeutic range: 12 – 46 mg/l). Fatigue and stupor had disappeared five days after discontinuation of the levetiracepam. A single dose pharamockinetic after re-exposure showed an increased half life of 18.4 hours (normal half life 7 hours) and levetiracetam content in the peritoneal dialysate. Both half-life and dialysate content might help to guide dosing in this patient population.ConclusionIf levetiracetam is used in peritoneal dialysis patients it should be regularly monitored to avoid supratherapeutic levels that could lead to severe sequelae.

Use of Antiepileptic Drugs in Patients with Chronic Kidney Disease and End Stage Renal Disease

“…Dosing in peritoneal dialysis has not been studied. A case of sedating side effects related to levetiracetam use in a peritoneal dialysis patient has been reported . More recently, hypokalemia and hypomagnesemia were also reported as a suspected adverse reaction to levetiracetam .…”

Levetiracetam Use in Peritoneal Dialysis

“…To our knowledge, the only literature regarding levetiracetam pharmacokinetics described a patient receiving levetiracetam while on PD who experienced fatigue and somnolence as a result of prolonged levetiracetam half-life. 1 Limited data are available to guide dose adjustments; suggested doses range from 500 to 1000 mg every 24 hours in PD or hemodialysis with or without a 250- to 500-mg supplemental dose following hemodialysis. 2 Therapeutic drug monitoring for levetiracetam has not yet been established because the evidence for reference ranges with antiepileptic drugs have purely statistical meaning and may not be applicable to all patients.…”