Incidence rates of severe cutaneous adverse reactions due to antiseizure medication: A nationwide study using health claims data in Korea

Epilepsia. 2021 Jan;62(1):250-257. doi: 10.1111/epi.16751. Epub 2020 Nov 13.


Objective: Antiseizure medications (ASMs) can rarely result in severe, sometimes fatal, cutaneous adverse reactions. To date, few studies have reported on the incidence rates (IRs) of severe cutaneous adverse reactions (SCARs) due to ASM use. This study aimed to determine the IRs of SCAR resulting from the use of seven commonly prescribed ASMs, carbamazepine (CBZ), phenytoin (PHT), oxcarbazepine (OXC), lamotrigine (LMT), zonisamide (ZNS), levetiracetam (LVT), and topiramate (TPM), and to compare the associated risks among the drugs.

Methods: Using a nationwide health claims database, we selected all the patients prescribed with one of the target ASMs. We defined a SCAR case as the first hospitalization with one of three specific codes provided by the International Classification of Diseases, 10th revision (L511, L512, and L27). We then calculated the IR of SCARs according to each target ASM.

Results: The IR of SCARs for each ASM was as follows: 870/1 000 000 person-years (PYs) for CBZ, 5750/1 000 000 PYs for PHT, 1490/1 000 000 PYs for OXC, 3860/1 000 000 PYs for LMT, 1540/1 000 000 PYs for ZNS, 830/1 000 000 PYs for LVT, and 400/1 000 000 PYs for TPM. Concomitant use of antibiotics and nonsteroidal anti-inflammatory drugs significantly increased the risk of SCARs with OXC, LVT, or TPM use. Comorbid skin disease was associated with a significantly higher IR of SCARs from CBZ, PHT, OXC, LMT, or LVT use.

Significance: This is the first study in Asia to determine the IRs of SCARs for various ASMs and compare the rates across drugs using a large dataset. The results from this study should help clinicians select safer ASMs in practice.

Keywords: Stevens-Johnson syndrome; antiseizure medications; drug hypersensitivity; incidence; insurance claim reporting; risk factor; toxic epidermal necrolysis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / adverse effects*
  • Carbamazepine / adverse effects
  • Child
  • Drug Hypersensitivity Syndrome / epidemiology*
  • Drug Hypersensitivity Syndrome / etiology
  • Female
  • Humans
  • Incidence
  • Lamotrigine / adverse effects
  • Levetiracetam / adverse effects
  • Male
  • Middle Aged
  • Oxcarbazepine / adverse effects
  • Phenytoin / adverse effects
  • Republic of Korea / epidemiology
  • Severity of Illness Index
  • Stevens-Johnson Syndrome / epidemiology*
  • Stevens-Johnson Syndrome / etiology
  • Topiramate / adverse effects
  • Young Adult
  • Zonisamide / adverse effects


  • Anticonvulsants
  • Topiramate
  • Carbamazepine
  • Levetiracetam
  • Zonisamide
  • Phenytoin
  • Lamotrigine
  • Oxcarbazepine