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

Abstract

ObjectiveAntiseizure 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.MethodsUsing 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.ResultsThe 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.SignificanceThis 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.

Incidence of Antiseizure Medication–Induced Severe Cutaneous Adverse Reactions in Malaysia

“…This could be due to the heterogeneity in the source of data for analysis. In Korea, phenytoin and lamotrigine were the 2 most common antiseizure medications leading to severe cutaneous adverse reactions, and the incidence of carbamazepine‐induced severe cutaneous adverse reactions was low 11 . This could be explained by the low prevalence of HLA‐B*15:02 among the Koreans, resulting in lower SCAR incidence compared to our population 27 .…”

“…In Korea, phenytoin and lamotrigine were the 2 most common antiseizure medications leading to severe cutaneous adverse reactions, and the incidence of carbamazepine-induced severe cutaneous adverse reactions was low. 11 This could be explained by the low prevalence of HLA-B*15:02 among the Koreans, resulting in lower SCAR incidence compared to our population. 27 Carbamazepine used to be the most common antiseizure medication leading to severe cutaneous adverse reactions in Hong Kong (2.4 per 1000 person-years).…”

“…These findings are comparable to other countries such as Korea and Hong Kong (Table 4). 11,12 Changes in the Trend of SCAR Incidence: Aromatic Antiseizure Medications…”

“…Taiwan, Hong Kong, and Korea were the only Asian countries with published data on carbamazepine-induced and antiseizure medicationinduced SCAR incidence to date (Table 4). 11,21,22 The comparison among different countries reflected several factors that could affect the SCAR incidence in the country. The genetic and ethnic background of the population determines the HLA allele in the population, which in turn affects the aromatic-based antiseizure medication-induced SCAR incidence.…”

Current Perspectives on Severe Drug Eruption

“…In the European Registry of Serious Adverse Skin Reactions (RegiSCAR), carbamazepine is considered to be the most common reason for DRESS [ 19 ] and the second most common cause of SJS and TEN. Other antiepileptic drugs are also associated with SCARs [ 20 ]. The SCARs risk associated with various drugs depends on a number of variables, including genetic and non-genetic risk factors.…”