ABSTRACT
Anticonvulsant agents arewell known to cause severe liver injury. Agents such as phenacemide
were removed from clinical use as a consequence of unacceptably high frequencies of liver
toxicity. A clinically significant risk of hepatotoxicity also accompanies the use of phenytoin
(Dilantin
, Parke-Davis, Morris Plains, NJ), carbamazepine (CBZ) (Tegretol
, Novartis Pharma-
ceuticals, Basel, Switzerland) and valproic acid (VPA) (Depakene
, Abbott Laboratories, Abbott
Park, IL), and some of the newer anticonvulsants that have been introduced over the last
decade. Evaluating which drug is causing liver injury in patients with seizure disorders is often
difficult since (1) at least 30% of patients are refractory to treatment and are often on more than
one anticonvulsant; (2) anticonvulsants may have complex interactions with other drugs used
concomitantly in patients; and (3) the whole picture may be complicated by “environmental”
factors such as alcohol misuse, which often accompanies or is a cause of the seizure disorder,
and is also associated with liver injury. As such, it may be difficult to fully evaluate the
hepatotoxic potential of individual agents; in many cases, and particularly for the newer agents,
causality has to be presumed on the basis of case reports in the absence of any mechanistic
laboratory studies. Nevertheless, the purpose of this chapter is to describe the clinical
presentation, histopathology, mechanisms, and determinants of susceptibility of anticonvul-
sant-induced liver injury focusing on established and newer compounds.
