Sunday, September 24, 2017

Antiepileptic drugs and liver disease

Jorge Vidaurre, Satya Gedela , Shannon Yarosz. Antiepileptic Drugs and Liver Disease.  Pediatric Neurology.  In press.


Acute, symptomatic seizures or epilepsy may complicate the course of hepatic disease.

Choosing the most appropriate antiepileptic drug (AED) 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 AEDs.

Newer AEDs with no, or 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, such as patients affected by acute intermittent porphyria; exposure to most AEDs 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 IV preparations, are good second line therapies after benzodiazepines fail to control seizures.

Hepatotoxicity is also a rare and unexpected side effect of AED therapy. Some drugs, such as valproic acid, phenytoin and felbamate have a well-recognized association with liver toxicity. Other AEDs, including phenobarbital, benzodiazepines, ethosuximide and the newer generations of AEDs, have only rarely been linked to hepatotoxicity.

It is therefore necessary for physicians to be mindful of the pharmacokinetic profile and hepatotoxic potential of the different AEDs available to treat patients affected by liver disease. 

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