Acute Liver Failure Associated with Levetiracetam and Lacosamide Combination Treatment for Unspecified Epileptic Disorder

Background and Aim. Levetiracetam is a second-generation antiepileptic drug. It is approved as an adjunctive treatment of partial onset seizures with or without secondary generalization. It is considered safe with less than 1% of patients with transient elevations of liver enzymes. Methods. We report a case of acute liver failure secondary to Levetiracetam in combination with Lacosamide documented with a liver biopsy. Results. Liver biopsy demonstrated acute liver injury with a predominant submassive necrosis pattern and features of a drug-induced hepatitis. Conclusions. This is the first published case of acute liver failure due to antiepileptic therapy with Levetiracetam in combination with Lacosamide. 1. Introduction Levetiracetam is an established second-generation antiepileptic drug that is approved as a treatment of partial seizures; other indications include adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures associated with generalized epilepsy. In vitro and in vivo studies have shown that levetiracetam does not act as a cytochrome P450 inductor; therefore it does not cause liver function alterations. A previous case report suggested that it can slightly raise gamma glutamyl transpeptidase and transaminases, but the indication of it as first-line treatment for patients with epilepsy and liver damage should not be modified, but liver function tests should be monitorized periodically in patients taking this medication [1]. Levetiracetam lacks cytochrome P450 isoenzyme-inducing potential, and no significant interaction with other drugs, including other antiepileptic drugs, has been described. On the other side, Lacosamide, previously known as Erlosamide, is an adjunctive treatment for epilepsy as well as monotherapy for diabetic neuropathic pain. It appears to have a dual mode of action: selective enhancement of sodium channel inactivation and modulation of collapsin response mediator protein 2. Several trials have demonstrated a reduction in median seizure frequency compared with placebo [2]. Zaccara et al. found, in their study carried out recently, that Lacosamide treatment is associated with symptoms suggestive of vestibulecerebellar dysfunction that worsens with increasing dose without other severe events [3]. Recent data supports this, suggesting that Lacosamide is a safe treatment in critically ill patients, and there is only one report of elevation of liver function tests in a recent retrospective study [4]. Herein we report a case of acute liver failure with