Severe cutaneous adverse reactions in Asians: Trends observed in culprit anti-seizure medicines using VigiBase®

Abstract

Purpose: Diverse ethnic genetic populations display variability in the risk regarding anti-seizure medicine (ASM)-induced severe cutaneous adverse reactions (SCARs). However, clinical and epidemiological data on ASM-induced SCARs in Asians is limited. Methods: We conducted a retrospective, post-market study until April 30, 2020 using VigiBase® for demographic characteristics, causative ASMs, complications and mortality. The study included adverse events as classified by Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries of SCARs, mainly Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and SJS/TEN overlap reported for ASMs. Results: A total of 694,811 adverse events were reported across the world while using ASMs. Of this, skin and subcutaneous tissue adverse events were 122,885 (17.6%). Among ASM-induced skin and subcutaneous tissue adverse events, SJS, TEN, DRESS and SJS/TEN overlap represented 11,181 (9.1%), 3,645 (3.0%), 5,106 (4.1%) and 6 (0.004%) cases, respectively. Female SJS/TEN/DRESS patients were 54.1%, and 75% of them were adults (>18Y). Nearly 64% of the ASM-induced SCARs were serious and culminated in death (3.5%), life-threatening conditions (11.5%), and hospitalization/prolonged hospitalization (43.5%) of patients on ASM therapy. Carbamazepine (31.6%), phenytoin (29.6%), lamotrigine (24.3%), valproic acid (6.4%) and phenobarbital (5.7%) are the most commonly used ASMs linked with SCARs. ASMs associated with significantly higher risk of SCARs in Asians were carbamazepine [n = 3265, ROR 3.55 (95% CI 3.38–3.72, P < 0.0001)], lamotrigine [n = 1253, ROR 3.90 (95% CI 3.63–4.18, P < 0.0001)], gabapentin [n = 85, ROR 3.58 (95% CI 2.79–4.60, P < 0.0001)], pregabalin [n = 68, ROR 3.16 (95% CI 2.40–4.16, P < 0.0001)], clonazepam [n = 53, ROR 3.19 (95% CI 2.31-4.41, P < 0.0001)], lorazepam [n = 31, ROR 3.07 (95% CI 2.06–4.59, P < 0.0001)] and acetazolamide [n = 28, ROR 3.90 (95% CI 2.45-6.21, P < 0.0001)]. Conclusion: Based on our study, carbamazepine, lamotrigine, gabapentin, pregabalin, clonazepam, lorazepam, and acetazolamide are the most common causative ASMs for SCARs in the Asian population.