A comparison of the incidence and breadth of adverse events between levobupivacaine and racemic bupivacaine in the UK

Background and Goal of Study: We attempted to examine whether the assumed preclinical advantages of levobupivacaine translate into clinical practice. Materials and Methods: We conducted a retrospective analysis of adverse events (AE's) reported to the Medicines and Healthcare products Regulatory Agency (MHRA) via the Yellow Card Reporting Scheme between 2001 and 2007. This was correlated with total drug use during the same period provided by the International Medicines Statistics database, thus capturing 96% of hospital pharmacy sales. Statistical analysis (Yates chi-square test) was performed using AE's per 100kg of drug dispensed. Usage of the 0.5% concentration of each drug was almost equivalent (0.1% difference). Results and Discussion: When considering the amount of drug dispensed (977.2 kg bupivacaine v 344.6kg levobupivacaine) and the number of procedures performed, the overall incidence of adverse events is low, thus illustrating the good safety profile of both drugs. Over the study period there were more adverse events reported with bupivacaine (232) than levobupivacaine (44) as to be expected by the greater amount of drug dispensed. When 100kg equivalents of drug were compared, levobupivacaine had 46% fewer AE's (12.8 v 23.8, p< 0.01). AE's were reported in all 20 adverse event headings for bupivacaine compared to only 11 for levobupivacaine. The AE's for bupivacaine exceeded those for levobupivacaine in 17 of these categories, including those most commonly reported-cardiac and nervous system disorders. 4 deaths in total were associated with bupivacaine whereas none were associated with levobupivacaine. Conclusion(s): Given the tendency for a potential bias towards reporting adverse events with a new drug, the decreased incidence of adverse events and lack of fatalities with levobuopivacaine suggests that some of the putative advantages suggested by its preclinical data are real.