Association of Stevens‐Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs in pediatric patients: Subgroup analysis based on a Japanese spontaneous database

Abstract

What is known and objective Antiepileptic drugs (AEDs) are known to cause Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are severe cutaneous disorders; however, real‐world data remain limited, especially on pediatric patients. The objective of this study was to investigate the association of AEDs with SJS and TEN in pediatric patients based on the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database. Methods Adverse event reports submitted to the JADER database between 2004 and 2017 were analysed. We performed a retrospective pharmacovigilance disproportionality analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval (CI). Results and Discussion A total of 159 605 adverse events were reported in pediatric patients. Significant SJS signals were detected for ethosuximide, phenytoin, phenobarbital, gabapentin, carbamazepine, zonisamide, clonazepam and lamotrigine. TEN signals were detected for ethosuximide, phenytoin, phenobarbital, gabapentin, carbamazepine and zonisamide, but the signal was strongest for gabapentin (ROR, 24.76; 95% CI, 11.4‐53.9). What is new and conclusion Severe cutaneous disorders were associated with multiple AEDs, but individual AEDs were associated with variable signals. These results may be useful for minimizing the risk of SJS or TEN during treatment of children with AEDs.

Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo

“…Nonetheless, one OIPWE developed TEN induced by phenobarbital. TEN has previously been observed with several AED including phenobarbital [27][28][29]. Our study illustrates the importance of counseling PWE, caretakers, CHW and local health personnel about early identification of adverse events caused by AED to ensure prompt discontinuation of potentially harmful drugs.…”

Single Versus Multiple Dose Ivermectin Regimen in Onchocerciasis-infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo

“…Nonetheless, one OIPWE developed TEN induced by phenobarbital. TEN has previously been observed with several AED including phenobarbital [20][21][22]. Our study illustrates the importance of counseling PWE, caretakers, CHW and local health personnel about early identification of adverse events caused by AED to ensure prompt discontinuation of potentially harmful drugs.…”

Antiepileptic combination therapy with Stevens‐Johnson syndrome and toxic epidermal necrolysis: Analysis of a Japanese pharmacovigilance database

“…This analysis is often used to investigate the association between drugs and SJS or TEN because both conditions are serious diseases, but they rarely occur. [14][15][16][17] However, although there have been several proposals for algorithms to detect the signals of concomitant use of two drugs, 18,19 there are no reports on the association between two-drug combination therapy and SJS or TEN. In this study, we investigated the signals of individual AEDs, AED combination therapies, and SJS/TEN using JADER as a spontaneous reporting system.…”

“…This analysis method is suitable for the early detection of unknown AEs because it is highly sensitive in detecting signals even with a small number of reports. This analysis is often used to investigate the association between drugs and SJS or TEN because both conditions are serious diseases, but they rarely occur 14‐17 …”

“…12,13 Several recent studies investigated AED-induced cases using spontaneous reporting systems. [14][15][16][17] However, despite the need for combination therapy in about 30% of patients with new-onset epilepsy, few studies have investigated the association between AED combination therapy and the occurrence of SJS or TEN.…”