title: Cardiovascular toxicity with levetiracetam overdose.
abstract: OBJECTIVE
  To describe the cardiovascular toxicity and pharmacokinetics of levetiracetam in overdose.
  
  
  METHODS
  A 43-year-old female presented 8 h post ingestion of 60-80 g of levetiracetam with mild central nervous system depression, bradycardia, hypotension and oliguria. Her cardiovascular toxicity transiently responded to atropine and intravenous fluids. A bedside echocardiogram demonstrated normal left and right ventricular contractility. Despite her cardiovascular toxicity and oliguria, she had normal serial venous lactates and renal function; and made a complete recovery over 48 h. Her levetiracetam concentration was 463 mcg/ml 8 h post ingestion (therapeutic range 10-40 mcg/ml) and her concentration-time data best fitted a one-compartment model with first-order input and an elimination half-life of 10.4 h.
  
  
  CONCLUSIONS
  Levetiracetam in large ingestions appears to cause bradycardia and hypotension that is potentially responsive to atropine and intravenous fluids. Based on a normal echocardiogram, the mechanism for this effect may be levetiracetam acting at muscarinic receptors at high concentration. The pharmacokinetics of levetiracetam in overdose appeared to be similar to therapeutic levetiracetam dosing.
authors.affiliation: a Clinical Toxicology Research Group , University of Newcastle , Newcastle , Australia ;|b School of Medicine , University of Queensland , Brisbane , Australia ;|c Emergency Department , Princess Alexandra Hospital , Brisbane , Australia ;
authors.forename: Colin B
authors.initials: CB
authors.lastname: Page
authors.affiliation: d Therapeutics Research Centre , Translational Research Institute, University of Queensland , Brisbane , Australia ;|e Pharmaceutical Chemistry Department , Helwan University , Helwan , Egypt ;
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mostafa
authors.affiliation: a Clinical Toxicology Research Group , University of Newcastle , Newcastle , Australia ;
authors.forename: Ana
authors.initials: A
authors.lastname: Saiao
authors.affiliation: d Therapeutics Research Centre , Translational Research Institute, University of Queensland , Brisbane , Australia ;
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Grice
authors.affiliation: d Therapeutics Research Centre , Translational Research Institute, University of Queensland , Brisbane , Australia ;|f School of Pharmacy and Medical Sciences , University of South Australia , Adelaide , Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: a Clinical Toxicology Research Group , University of Newcastle , Newcastle , Australia ;
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D000328:Adult; D001285:Atropine / Q000494:pharmacology; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000473:pathology; D062787:Drug Overdose / Q000188:drug therapy; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D000077287:Levetiracetam; D009846:Oliguria / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000506:poisoning
chemical_list: D000077287:Levetiracetam; D001285:Atropine; D010889:Piracetam
keywords: Anticonvulsant; CNS/psychological; heart