Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center

Lamotrigine and levetiracetam are widely used second-generation anti-epileptic drugs. Existing literature indicates that overdose of either drug is typically benign, but neurologic and cardiac toxicity can occur in some cases. In this retrospective study, we analyzed a large dataset of serum/plasma drug levels for lamotrigine and levetiracetam. The data covered 1,930 unique patients (5,046 levels) for lamotrigine and 2,451 patients (4,359 levels) for levetiracetam. We performed detailed chart review on all patients with one or more lamotrigine levels greater than 14.0 mg/L (293 unique patients) and all patients with one or more levetiracetam levels of 80 mg/L or higher (106 unique patients). No deaths directly attributable to lamotrigine or levetiracetam toxicity were reported. For cases with lamotrigine levels greater than 14.0 mg/L, the majority of patients were asymptomatic (55.3 %, n = 162). The most common presenting symptoms were ataxia (14.3 %, n = 42), seizures (14.0 %, n = 41), dizziness (11.9 %, n = 35), and altered mental status (11.6 %, n = 34). There were 12 overdoses (11 intentional) involving lamotrigine, all of which presented with either altered mental status (n = 8) or seizures (n = 4). The highest estimated dose reportedly ingested was 20 g. Cardiac toxicity was observed in two cases involving intentional overdose of lamotrigine. For patients with levetiracetam serum/plasma levels of 80 mg/L or higher, 48 patients (45.3 %) were asymptomatic. Symptomatic patients most commonly presented with seizures (31.1 %, n = 33) and altered mental status (15.1 %, n = 16), and none showed cardiac symptoms. There were only two cases involving intentional levetiracetam overdose, one of which presented with altered mental status after ingestion of 45 g and the other asymptomatic after ingestion of 6 g. Overall, our data is consistent with previous investigations that lamotrigine and levetiracetam toxicity most typically presents with neurologic symptoms and rarely cardiac arrhythmias. Approximately half of the patients with elevated lamotrigine or levetiracetam drug levels are asymptomatic.