Antiepileptic drugs and adverse skin reactions: An update

Pharmacol Rep. 2015 Jun;67(3):426-34. doi: 10.1016/j.pharep.2014.11.009. Epub 2014 Nov 27.


This paper summarizes current views on clinical manifestation, pathogenesis, prognosis and management of antiepileptic drug (AED)-induced adverse skin reactions. Cochrane Central Register of Controlled Trials, MEDLINE (PubMed) and ISI Web of Knowledge were searched. The recent classification, among drug-induced skin injuries, points to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis and hypersensitivity syndrome (HSS), which may be also recognized as a drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The use of aromatic AEDs, e.g. phenytoin, carbamazepine, oxcarbazepine, phenobarbital, primidone, zonisamide, and lamotrigine is more frequently associated with cutaneous eruption and other signs or symptoms of drug hypersensitivity. There is a high degree of cross-reactivity (40-80%) in patients with hypersensitivity or allergic reactions to AEDs. Pharmacogenetic variations in drug biotransformation may also play a role in inducing these undesired effects. It is suggested that avoidance of specific AEDs in populations at special risk, cautious dose titration and careful monitoring of clinical response and, if applicable, laboratory parameters can minimize the serious consequences of idiosyncratic reactions.

Keywords: Antiepileptic drugs; Cross-reactivity; Hypersensitivity reactions; Pharmacogenomics; Skin lesions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticonvulsants / adverse effects*
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity Syndrome / diagnosis
  • Drug Hypersensitivity Syndrome / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Humans
  • Skin Diseases / chemically induced*
  • Skin Diseases / diagnosis*
  • Skin Diseases / epidemiology


  • Anticonvulsants