- Comparative pharmacovigilance analysis of benzodiazepine anticonvulsant therapy and serious skin events
- Physical Description:
- Conference Papers
- Ayad Ali
- ISPOR 19th Annual International Meeting
- Place of Publication:
- New Jersey
- Publication Date:
- May 21, 2014
- OBJECTIVES : In late 2013, the FDA announced to the public that clobazam is linked to serious skin events, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), and consequently approved changes to clobazam label and medication guide. However, no comparative pharmacovigilance analysis was conducted for other anticonvulsant benzodiazepines, including clonazepam, clorazepate, diazepam, and lorazepam. This study aims to detect and clarify signals of serious skin reactions associated with benzodiazepine anticonvulsant therapy in the FDA Adverse Event Reporting System (FAERS). METHODS : Cases reported to FAERS between 1997 and 2012 were retrieved. The MedDRA Preferred Terms were used to define serious skin reactions. Individual anticonvulsant benzodiazepines were identified by generic names. Empirical Bayes Geometric Mean (EBGM) with 95% confidence interval (EB05-EB95) were calculated as disproportionality measures. Drug-event combinations with EB05≥ 2 were considered signals that warrant further review. RESULTS : 4,411 reports of serious skin reactions were submitted for all anticonvulsant agents. 6.3% were for benzodiazepines (279), corresponding to: clobazam (33), clonazepam (54), clorazepate (41), diazepam (82), and lorazepam (69). Signals were detected for clorazepate (EBGM 9.6 EB05-EB95 7.4-12.4) and clobazam (EBGM 8.7 EB05-EB95 6.4-11.5). Disproportional reporting was found for other benzodiazepines, albeit didn’t reach signal threshold: diazepam (EBGM 2.3 EB05-EB95 1.9-2.8), lorazepam (EBGM 2.2 EB05-EB95 1.8-2.7), and clonazepam (EBGM 1.5 EB05-EB95 1.2-1.9). Eighty one (29%) reported serious skin events were fatal, corresponding to: clobazam (7), clonazepam (12), clorazepate (16), diazepam (30), and lorazepam (16). Most of reported events listed patient exposure to ≥ 2 concomitant drugs at event occurrence time. CONCLUSIONS : Anticonvulsant
therapy with benzodiazepines, particularly clobazam and clorazepate, might be
associated with serious skin reactions. In concordance with FDA’s recommendation, patients should seek immediate help when dermal signs and symptoms are appeared and alternative anticonvulsant agent should be considered by prescribers. Signal evaluation activities are required to further characterize this risk.
- Collected for University of Florida's Institutional Repository by the UFIR Self-Submittal tool. Submitted by Ayad Ali.
- Publication Status:
- General Note:
- Suggested Citation: Ali AK. Comparative pharmacovigilance analysis of benzodiazepine anticonvulsant therapy and serious skin events. Value in Health. May 2014; 17(3):A56 Abstract No. PND1.
- Source Institution:
- University of Florida Institutional Repository
- Holding Location:
- University of Florida
- Rights Management:
- All rights reserved by the source institution.
- System ID: