Postmarketing safety analysis of remimazolam: Identifying unlabelled serious events.

Background: Remimazolam is a new ultra-short-acting benzodiazepine used in anaesthesia, valued for its rapid metabolism and reversibility. Despite its growing clinical use, a comprehensive assessment of its real-world safety profile remains essential.

Objective: To evaluate the postmarketing safety of remimazolam using adverse event (AE) data from the US and Japanese pharmacovigilance databases.

Design: Retrospective analysis of AEs associated with remimazolam using disproportionality analysis techniques.

Setting: FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report database (JADER) from January 2020 to December 2023.

Participants: Patients who experienced remimazolam-related AEs reported in the FAERS and JADER databases.

Main outcome measures: Identification of significant AEs using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network and multiitem gamma Poisson shrinker. Categorisation of AEs using the 'Important Medical Event Terms List' (IME) list (version 26.1).

Results: We identified 199 remimazolam-related reports (69 from FAERS, 130 from JADER) revealing 20 significant AEs. Key findings include previously unlabelled serious AEs such as cardiac, cardio-respiratory, and respiratory arrests; nine events classified as Important Medical Events, including hypotension and anaphylaxis; four AEs not included in current Food and Drug Administration (FDA) labelling; and low-frequency but clinically significant off-label events including arrhythmias and postoperative delirium.

Conclusions: While remimazolam shows a generally acceptable safety profile, our pharmacovigilance analysis identified serious unlabelled reactions requiring clinical vigilance. Practice recommendations include judicious administration with balanced crystalloids and comprehensive cardiorespiratory monitoring. Future research should address prospective surveillance of rare serious events, optimal administration protocols to prevent vascular occlusions and investigation of anaphylactic reactions.

Trial registration: Not applicable.