Antiepileptic Drugs and Liver Disease

Acute, symptomatic seizures or epilepsy may complicate the course of hepatic disease. Choosing the most appropriate antiepileptic drug in this setting represents a difficult challenge, as most medications are metabolized by the liver. This article focuses on the acute and chronic treatment of seizures in patients with advanced liver disease and reviews the hepatotoxic potential of specific antiepileptic drugs. Newer antiepileptic drugs without, or with minimal, hepatic metabolism, such as levetiracetam, lacosamide, topiramate, gabapentin, and pregabalin should be used as first-line therapy. Medications undergoing extensive hepatic metabolism, such as valproic acid, phenytoin, and felbamate should be used as drugs of last resort. In special circumstances, as in patients affected by acute intermittent porphyria, exposure to most antiepileptic drugs could precipitate attacks. In this clinical scenario, bromides, levetiracetam, gabapentin, and vigabatrin constitute safe choices. For the treatment of status epilepticus, levetiracetam and lacosamide, available in intravenous preparations, are good second-line therapies after benzodiazepines fail to control seizures. Hepatotoxicity is also a rare and unexpected side effect of some antiepileptic drugs. Drugs such as valproic acid, phenytoin, and felbamate, have a well-recognized association with liver toxicity. Other antiepileptic drugs, including phenobarbital, benzodiazepines, ethosuximide, and the newer generations of antiepileptic drugs, have only rarely been linked to hepatotoxicity. Thus physicians should be mindful of the pharmacokinetic profile and the hepatotoxic potential of the different antiepileptic drugs available to treat patients affected by liver disease.