ABSTRACT
Although the signs and symptoms of antiepileptic drug (AED)-induced idiosyncratic organ toxicities (also called idiosyncratic drug reactions, or IDRs) are well documented, clinical and genetic susceptibility factors are poorly understood. By understanding the mechanisms underlying the interaction between specific AEDs and an individual patient’s clinical and genetic characteristics, treatment approaches can be developed to reduce the risk of developing these severe life-threatening reactions. The goal of this chapter is to narrow this knowledge gap and to help improve clinical care. The chapter is divided into four interrelated sections. The first section will describe the general characteristics of idiosyncratic drug reactions, while the second section will address the mechanisms through which they occur. In the third section, the clinical characteristics, patient-related clinical risk factors and-if known-potential mechanisms of lifethreatening IDRs associated with specific AEDs (e.g., phenobarbital, phenytoin, carbamazepine, oxcarbazepine, valproic acid, felbamate, lamotrigine, ethosuximide, and zonisamide) will be discussed. Gabapentin, levetiracetam, tiagabine, and topiramate will not be discussed since they have not been associated with life-threatening IDRs. Lastly, the future role of pharmacogenetics in the identification of patients at high risk for IDRs will be briefly addressed.
