Deviations from recommended use of liposomal bupivacaine: a real-world pharmacovigilance study using the FAERS...

Liposomal bupivacaine (L-BUP) is a widely used long-acting local anesthetic, but real-world data on its post-marketing off-label use and medication error risks remain limited. This study aimed to characterize these risks to inform rational clinical use and post-marketing risk management of improved new drug formulations.

L-BUP-related safety reports were extracted from the FAERS database (Q1 2004-Q2 2025). Four disproportionality analysis methods (ROR, PRR, BCPNN, and MGPS) were applied, with a positive signal defined as simultaneously meeting all four predefined criteria. Risk signals were mapped via Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) and Standardized MedDRA Queries (SMQs). Conventional bupivacaine (C-BUP) was used as a comparator in the sensitivity analysis to verify the specificity of risk signals.

Among 19,252,329 included FAERS reports, 4,151 listed L-BUP as the primary suspect drug. Of the top 20 L-BUP positive signals, 35% were associated with deviations from recommended use. Notably, "Labeled drug-drug interaction medication error" exhibited the strongest signal (ROR = 332.7), while "Off-label use" had the highest reporting frequency, with 238 cases. At the SMQ level, medication errors yielded a positive safety signal (ROR = 4.17). Sensitivity analysis confirmed that C-BUP presented a negative signal for medication errors (ROR = 0.88) under identical analytical conditions. The number of concomitant medications was positively correlated with the incidence of serious adverse events, whereas the overall serious adverse event rate was higher for C-BUP than for L-BUP.

L-BUP carries significant off-label use and formulation-specific medication error risks, with a positive correlation between concomitant medication use and serious adverse events. Many of these risks are preventable. These findings support targeted clinical and regulatory risk mitigation strategies for L-BUP, and provide evidence for improved post-marketing surveillance of complex modified-release formulations.