A case of levetiracetam (Keppra®) poisoning with clinical and toxicokinetic data

Background: Levetiracetam (Keppra(R)) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations. Case report: A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 mug/mL at 6 hours, 72 mug/mL at 18 hours, and 60 mug/mL at 20.5 hours (therapeutic serum concentration is 10-37 mug/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae. Conclusion: In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.