Dong Xu Chen,1,2,* Xuan Ming Chen,3,* Shou Ming Chen,1,2 Yi Da Wang3 

1Department of Anesthesiology, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China; 3Key Laboratory of Bioresource and Eco-Environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Da Wang, Key Laboratory of Bioresource and Eco-Environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, People’s Republic of China, Email scu_wyd@foxmail.com Shou Ming Chen, Department of Anesthesiology, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China, Email 761858401@qq.com

Purpose: Liposomal bupivacaine, a novel formulation of bupivacaine, is increasingly employed for the long-lasting pain relief. The primary goal of this study was to conduct a thorough safety evaluation of liposomal bupivacaine and bupivacaine.
Patients and Methods: This study analyzed adverse events (AEs) associated with liposomal bupivacaine and bupivacaine using the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q2 2024. Reports were screened for signal detection, focusing on the onset time and disproportionality analysis to identify positive safety signals. We evaluated the AEs associated with liposomal bupivacaine and bupivacaine. Then, we further categorized them according to the Important Medical Event Terms List (IME list).
Results: The analysis revealed 8,023 AE reports in total. Liposomal bupivacaine had 58 positive safety signals, 24 of which were off-label and listed in the IME list. These signals were primarily associated with cardiac (eg, cardiogenic shock), gastrointestinal (eg, paralytic ileus), and neurological disorders. Bupivacaine generated 107 safety signals, with 49 being off-label but also on the IME list. These signals mainly affected the fetus (eg, fetal bradycardia), respiratory system (eg, respiratory depression), and nervous system (eg, neurotoxicity).
Conclusion: This study identified unexpected AEs associated with liposomal bupivacaine and bupivacaine. Physicians must exercise particular caution when administering liposomal bupivacaine due to its associated risks. Monitoring for delayed analgesia-related AEs may enhance the safe use of this medication for pain management.

Keywords: FAERS database, liposomal bupivacaine, bupivacaine, postoperative pain, adverse reactions