Remimazolam: Five Years of Clinical Experience Since Its First-in-World Approval in Japan

Background: Remimazolam besylate, an ultra-short-acting benzodiazepine anesthetic, received its first-in-world approval in Japan in January 2020, marking a significant milestone in anesthetic drug development. Five years of clinical experience have provided substantial evidence on its clinical utility and safety profile, offering unprecedented insights into the practical application of this novel agent across diverse patient populations and clinical scenarios. Methods: This narrative review synthesized published literature from PubMed-indexed sources, focusing on Japanese clinical trials, international studies, and post-marketing surveillance data to evaluate remimazolam’s clinical performance over the five years since its approval. The analysis encompassed randomized controlled trials, observational studies, case reports, and pharmacovigilance data, to provide a comprehensive assessment of clinical outcomes, safety profiles, and practical considerations for its clinical use. Results: Clinical trials demonstrated remimazolam’s non-inferiority to propofol for general anesthesia, with superior cardiovascular stability and reduced injection site pain. Japanese researchers led pivotal Phase III trials showing drug efficacy in both standard and high-risk (ASA III) patients, establishing a robust evidence base for its clinical implementation. Post-marketing surveillance revealed rare but serious adverse events, including anaphylaxis and circulatory collapse, particularly in elderly patients, while simultaneously demonstrating excellent overall tolerability. Notably, remimazolam showed no increased risk of postoperative delirium in cardiovascular surgery patients, distinguishing it from other benzodiazepines, and suggesting potential cognitive advantages. Conclusions: Five years of clinical experience confirm that remimazolam is a valuable addition to the anesthetic armamentarium, with particular advantages in terms of hemodynamic stability and reversibility. While the overall safety profile remains favorable, vigilance for rare, albeit serious allergic reactions is warranted, especially in older patients. The accumulated evidence supports judicious use of remimazolam in selected clinical scenarios where traditional agents may be suboptimal.