Use of antiepileptic drugs in hepatic and renal disease

The use of antiepileptic drugs in patients with renal or hepatic disease is common in clinical practice. Since the liver and kidney are the main organs involved in the elimination of most drugs, their dysfunction can have important effects on the disposition of antiepileptic drugs. Renal or hepatic disease can prolong the elimination of the parent drug or an active metabolite leading to accumulation and clinical toxicity. It can also affect the protein binding, distribution, and metabolism of a drug. The protein binding of anionic acidic drugs, such as phenytoin and valproate, can be reduced significantly by renal failure, causing difficulties in the interpretation of total serum concentrations commonly used in clinical practice. Dialysis can further modify the pharmacokinetic parameters or result in significant removal of the antiepileptic drugs. Antiepileptic drugs that are eliminated unchanged by the kidneys or undergo minimal metabolism include gabapentin, pregabalin, vigabatrin, and topiramate when used as monotherapy. Drugs eliminated predominantly by biotransformation include phenytoin, valproate, carbamazepine, tiagabine, and rufinamide. Drugs eliminated by a combination of renal excretion and biotransformation include levetiracetam, lacosamide, zonisamide, primidone, phenobarbital, ezogabine/retigabine, oxcarbazepine, eslicarbazepine, ethosuximide, and felbamate. Drugs in the latter group can be used cautiously in patients with either renal or liver failure. Antiepileptic drugs that are at high risk of being extracted by hemodialysis include ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin and topiramate. The use of antiepileptic drugs in the presence of hepatic or renal disease is complex and requires great familiarity with the pharmacokinetics of these agents. Closer follow-up of the patients and more frequent monitoring of serum concentrations are required to optimize clinical outcomes.