Patrick M Wieruszewski1, Kianoush B Kashani2,3, Alejandro A Rabinstein4, Erin Frazee5. 1. Department of Pharmacy, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA. 2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. 3. Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA. 4. Department of Neurology, Mayo Clinic, Rochester, MN, USA. 5. Department of Pharmacy, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA. Barreto.Erin@mayo.edu.
Abstract
BACKGROUND: In patients requiring hemodialysis, the extracorporeal circuit is expected to remove the majority of serum levetiracetam. The preferred levetiracetam dosing regimen in critically ill patients exhibiting complex pharmacokinetic profiles undergoing hemodialysis is unknown. The objective of this case is to describe levetiracetam pharmacokinetics in a critically ill anephric patient receiving intermittent hemodialysis. METHODS: This is a case report of a single patient. RESULTS: A 43-year-old anephric female was admitted to the intensive care unit for concerns of new onset seizure activity. She was loaded with 2000 mg levetiracetam followed by a 750 mg daily maintenance dose. The levetiracetam volume of distribution was 0.48 L/kg, and the interdialytic elimination half-life was 31 h. Hemodialysis removed nearly 85% of serum levetiracetam, and the patient exhibited slightly higher than expected non-renal elimination. Pharmacokinetic simulations identified 500 mg daily with 750 mg post-dialysis supplements as the regimen most likely to reduce variability in serum levetiracetam concentrations and achieve levels in the therapeutic range. CONCLUSION: Substantial elimination of levetiracetam by hemodialysis occurred in this case, and non-renal clearance was slightly higher than in previous reports. Insufficient intradialytic or post-dialysis levetiracetam concentrations may place patients at risk of breakthrough seizures. This case indicates that dialysis patients on levetiracetam may require higher post-dialysis supplemental doses than currently recommended and tailored therapy supported by therapeutic drug monitoring.
BACKGROUND: In patients requiring hemodialysis, the extracorporeal circuit is expected to remove the majority of serum levetiracetam. The preferred levetiracetam dosing regimen in critically illpatients exhibiting complex pharmacokinetic profiles undergoing hemodialysis is unknown. The objective of this case is to describe levetiracetam pharmacokinetics in a critically ill anephricpatient receiving intermittent hemodialysis. METHODS: This is a case report of a single patient. RESULTS: A 43-year-old anephric female was admitted to the intensive care unit for concerns of new onset seizure activity. She was loaded with 2000 mg levetiracetam followed by a 750 mg daily maintenance dose. The levetiracetam volume of distribution was 0.48 L/kg, and the interdialytic elimination half-life was 31 h. Hemodialysis removed nearly 85% of serum levetiracetam, and the patient exhibited slightly higher than expected non-renal elimination. Pharmacokinetic simulations identified 500 mg daily with 750 mg post-dialysis supplements as the regimen most likely to reduce variability in serum levetiracetam concentrations and achieve levels in the therapeutic range. CONCLUSION: Substantial elimination of levetiracetam by hemodialysis occurred in this case, and non-renal clearance was slightly higher than in previous reports. Insufficient intradialytic or post-dialysis levetiracetam concentrations may place patients at risk of breakthrough seizures. This case indicates that dialysis patients on levetiracetam may require higher post-dialysis supplemental doses than currently recommended and tailored therapy supported by therapeutic drug monitoring.
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