Journal Article

Original research a real-world study of adverse events of nafamostat mesylate and sodium citrate based on the world health organization-VigiAccess database

Yu, Binbin, Xu, Mengting, Wang, Ziyi

2026

Overview

AimsWhile nafamostat mesylate (NM) and sodium citrate serve as commonly used extracorporeal anticoagulants in clinical practice, the characteristics and potential risks of their adverse events (AEs) need to be systematically evaluated. This study comparatively analyzed the reporting characteristics of the AEs of the above-mentioned two drugs based on the World Health Organization Adverse Drug Reaction Reporting Database (WHO-VigiAccess), to identify their safety signals and provide evidence-based guidance for optimizing their clinical uses.MethodsMining of the global AE reporting data of NM and sodium citrate was conducted using the WHO-VigiAccess database, with the data collected until 29 December 2024. Statistical analysis was performed using the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM). The signal strengths of the AEs of the two drugs at the system organ class and preferred term levels were systematically evaluated in combination with the standardized coding MedDRA.ResultsThis study included 1,572 NM-related reports (59 AEs) and 485 sodium citrate-related reports (102 AEs). NM AEs were mainly concentrated in immune system diseases (23.80%), skin and subcutaneous tissue diseases (16.25%), and gastrointestinal diseases (10.10%), with strong disproportionality signals observed for thrombosis in devices (n = 18, ROR = 264.71), shock (n = 119, ROR = 186.27) and anaphylactoid shock (n = 4, ROR = 143.45). In contrast, sodium citrate-related AEs primarily included systemic diseases with various reactions at the administration site (15.75%) and gastrointestinal disorders (11.63%). The reporting proportion of mortality for sodium citrate (2.83%) was higher than that for NM, although this finding may be influenced by reporting bias and confounding by indication. In addition, this study detected signals not described in the instructions, such as citrate toxicity (ROR = 6,740.61) and spinal muscular atrophy (ROR = 665.94). Both drugs shared several high-incidence AEs, including pruritus, vomiting and dyspnea, but there are significant differences in gender, age and geographical distribution.ConclusionThe use of NM was associated with a strong disproportionality signal for severe immune-related AEs, such as anaphylactic shock, and requires strengthened monitoring. The metabolic complications of sodium citrate and its exposure risks during pregnancy require targeted optimization of medication strategies. Real-world data suggested that both drugs may cause AEs that were not mentioned in the instructions, so risk management needs to be improved through dynamic pharmacological vigilance. This study provided important references for individualized selection and safety management of anticoagulation regimens for patients requiring hemodialysis.

• Publisher: Frontiers Media S.A
• Subject: adverse events / extracorporeal anticoagulation / nafamostat mesylate / pharmacovigilance / sodium citrate