Adverse Event Profiles of Coagulopathy-Related Events Caused by Intravenous Cephalosporins Using the Japanese Adverse Drug Event Report (JADER) Database

Introduction: Cephalosporins are widely used antimicrobials; however, their potential to induce coagulopathy-related events, particularly hypoprothrombinemia, raises safety concerns. Methods: This study aimed to comprehensively evaluate the risk of coagulopathy-related events associated with the use of intravenous cephalosporins using the Japanese Adverse Drug Event Report (JADER) database. We analyzed 783,788 cases from the JADER database to identify coagulopathy-related events associated with the use of eleven intravenous cephalosporins between 2004 and 2024. Reporting odds ratios (ROR) with 95% confidence intervals were calculated to detect potential signals. Subsequently, odds ratios were calculated to assess the influence of age and sex on the occurrence of coagulopathy-related events. Results: Cefmetazole (CMZ), cefoperazone/sulbactam (CPZ/SBT), flomoxef (FMOX), and ceftriaxone (CTRX) showed statistically significant signals for coagulopathy-related events (ROR: 10.87, 5.20, 2.67, and 1.38, respectively). Age emerged as a significant factor, with individuals aged >70 years exhibiting higher odds of experiencing coagulopathy-related events associated with CMZ, CPZ/SBT, FMOX, and CTRX use. However, no significant association was observed with sex. Our findings suggest that certain intravenous cephalosporins (CMZ, CPZ/SBT, FMOX, and CTRX) are associated with an increase of coagulopathy-related events, particularly in patients aged >70 years. Conclusions: These findings highlight the need for vigilance and careful consideration of patient-specific factors when prescribing these antibiotics.