selecting an appropriate antiepileptic drug ( aed ) for patients affected by liver dysfunction and new - onset epileptic seizures can be challenging since first - line aeds may contribute to worsen encephalopathy and result in hepatotoxicity . efficacy , tolerability , and toxicity represent the main factors influencing the choice of an aed , mainly when specific comorbidity may affect epilepsy . since the liver and kidney represent the main organs involved in the elimination of most drugs , their dysfunction may highly influence the pharmacokinetics of aeds . in the past two decades , the introduction of newer aeds with a better pharmacokinetic profile than traditional aeds has improved the management of these patients . lacosamide ( lcm ) , ( r)-2-acetamido - n - benzyl-3-methoxyproprionamide , is a new aed with selective enhancement of sodium channel inactivation . lacosamide is well absorbed after oral administration ( 100% ) , food does not affect the rate or the extent of the absorption , and the binding to plasma protein is minimal ( less than 15% ) . after oral or intravenous intake , 95% of lcm is recovered in the urine and <  0.5% in the feces . the major compounds found in the urine include unchanged drug ( 40% ) , about 30% as the inactive o - desmethyl metabolite , and a structurally unknown polar fraction ( about 20% ) . metabolism is through the cyp450 2c19 without any significant drug interaction . in the presence of mild to moderate ( child a and b ) liver disease , no dose adjustment is usually recommended . elimination and toxicity in the presence of severe hepatic failure ( child c ) have not been studied . therefore , lcm may represent a valid alternative aed when previous treatment failed , and the remaining aeds should be cautiously utilized in patients with hepatic impairment . a 64-year - old man affected by moderate alcoholic liver cirrhosis ( meld score : 14 ; child pugh class b ) experienced focal seizures with secondary generalization characterized by ascending paraesthesias followed by hypoesthesia and jerks of the right limbs . after the neurosurgery procedure , seizures recurred and were initially managed with levetiracetam ( lev ) ( up to 3000  mg / day ) . because of seizure reappearance , pregabalin was firstly added ( up to 150  mg bid ) , but pregabalin was quickly withdrawn for lack of tolerability ( excessive daytime somnolence ) . after one month , the patient experienced focal seizures with secondary generalization while on stable treatment with levetiracetam ( 3000  mg / day ) ; therefore , he was evaluated in the emergency ward and received phenobarbital ( 50  mg / day ) as add - on treatment . after 24  h , metabolic encephalopathy was confirmed by eeg showing generalized polymorphic slowing , diffuse triphasic sharp waves , and left temporal blood ammonia level was 168  mol / l ( normal range : 3085 ) , phenobarbital level was 9  g / ml ( normal range : 1540 ) , and aspartate aminotransferase and alanine aminotransferase were slightly altered but substantially unchanged when compared with previous values . phenobarbital was immediately stopped , and a single oral loading dose of lcm ( 200  mg ) , followed approximately 12  h later by 100  mg twice daily up to 200  mg twice a day maintenance dose , was started . by the third day of lcm therapy , the patient became more responsive , and blood ammonia level was in the reference range . after six months , the patient was still seizure - free at follow - up . after this follow - up , the hepatic failure progressively worsened ( meld score : 20 ; child pugh class c ) ; therefore , we slowly reduced lacosamide to 200  mg daily in order to avoid possible hepatic toxicity due to the probable increase of the area under the curve . transjugular intrahepatic portosystemic shunt ( tips ) was performed to treat portal hypertension and previous esophageal bleeding . the patient remained seizure - free , but he was also added to the liver transplant waiting list . the use of aeds in the presence of hepatic failure is complex and requires great familiarity with the pharmacokinetics of these agents . this report showed the common difficulties encountered when hepatically metabolized standard antiseizure medications such as phenobarbital are prescribed for patients affected by alcoholic liver cirrhosis . the pharmacokinetics of elimination of many classical aeds becomes unpredictable , and the threshold for developing or detecting central nervous system side effects diminishes . lev is considered as a valid treatment for patients affected by liver dysfunction and epilepsy , though a dose reduction may be needed in patients with severe liver cirrhosis . we found only a previous case report describing an acute liver failure in a young patient affected by an unspecified epileptic disorder . this subject was previously treated with lev and lcm , and the liver dysfunction appeared after the increase of lev dose during a convulsive status epilepticus ( cse ) . although liver biopsy confirmed a toxic origin of hepatic failure , specific clinical details are lacking ( other treatments , cse outcome , eeg and mri findings , lev and/or lcm withdrawal ) ; therefore even if possible , this report does not allow the conclusion to be made that lev treatment induced the acute liver failure . pgb was also considered in our patient because it is not metabolized by the liver and is excreted renally . it has negligible binding to plasma proteins and does not have any significant drug  drug interactions . the pharmacokinetic properties of pgb are favorable , but it provoked a significant sleepiness in our patient when added to lev , leading to pgb discontinuation . a low dose of phenobarbital induced an unpredictable hepatic encephalopathy as demonstrated by mental status fluctuations associated with eeg slowing and triphasic sharp waves . phenobarbital withdrawal and lcm addition induced a prompt recovery of hepatic encephalopathy and seizure freedom . lacosamide was chosen as an alternative to other aeds because of its favorable pharmacokinetic properties . lacosamide may offer some advantages in the treatment of epilepsy in patients with liver failure . its bioavailability is not affected by food , and its pharmacokinetics are linear and time - invariant . it has a 13-hour half - life , and a steady state is achieved after 2  days of twice - daily dosing . in addition , lcm has properties that make it unlikely to produce clinically significant drug  drug interactions in patients with liver cirrhosis . the major metabolic pathway is enzymatic hydrolysis , producing an inactive o - desmethyl metabolite , but more than 40% of the dose is excreted unchanged in the urine , . in addition , the 12  months of seizure freedom obtained after lcm addition represented a significant improvement of quality of life in a patient affected by alcoholic cirrhosis with a poor prognosis . although a single case report does not allow any generalization , we can state that lcm may represent a valid alternative when lev and pgb are ineffective or not tolerated in patients with moderate to severe liver dysfunction . however , further prospective evaluation of its effectiveness and safety in this clinical setting is needed .
the occurrence of epileptic seizures in the presence of hepatic disease is not uncommon in clinical practice . selecting an appropriate aed for patients affected by liver failure who have new - onset epileptic seizures 
 can be challenging . 
 we describe a 64-year - old man affected by liver cirrhosis . 
 the patient developed partial epilepsy with secondary generalization because of an intracerebral hemorrhage in the left parieto - occipital regions . 
 after the neurosurgery procedure , seizures reappeared and were initially managed with levetiracetam . 
 after one month , the patient experienced clusters of seizures while on stable treatment with levetiracetam . 
 pregabalin as add - on was not tolerated ; therefore , he received a low dose of phenobarbital as add - on treatment . 
 the patient developed hepatic encephalopathy . 
 phenobarbital was immediately stopped , and oral lacosamide was added . 
 a rapid recovery of encephalopathy with a 6-month seizure freedom was obtained . 
 the patient died 6  months later because of progressive impairment of liver function . 
 lacosamide may represent an alternative to other aeds in patients with liver failure ; however , further prospective evaluation of its efficacy and safety in this clinical setting is needed .