Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia

Abstract

Sergio D Bergese1, Sonia Ramamoorthy2, Gary Patou3, Kenneth Bramlett4, Stephen R Gorfine5, Keith A Candiotti61Department of Anesthesiology and Neurological Surgery, Ohio State University, Columbus, OH, USA; 2Department of Surgery, University of California at San Diego, La Jolla, CA, USA; 3Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA; 4Private Practice, Alabama Orthopaedic Institute, Birmingham, AL, USA; 5Department of Surgery, The Mount Sinai Medical Center, New York, NY, USA; 6Department of Anesthesiology, University of Miami, Miami, FL, USABackground: Liposome bupivacaine is a novel formulation of the local anesthetic bupivacaine, designed to provide prolonged postsurgical analgesia. This analysis examined pooled efficacy data as reflected in cumulative pain scores from 10 randomized, double-blind liposome bupivacaine clinical studies in which the study drug was administered via local wound infiltration.Methods: A total of 823 patients were exposed to liposome bupivacaine in 10 local wound infiltration studies at doses ranging from 66 mg to 532 mg in five surgical settings; 446 patients received bupivacaine HCl (dose: 75–200 mg) and 190 received placebo. Efficacy measures were assessed through 72 hours after surgery.Results: Overall, 45% of patients were male and 19% were ≥65 years of age. In the analysis of cumulative pain intensity scores through 72 hours, liposome bupivacaine was associated with lower pain scores than the comparator in 16 of 19 treatment arms assessed, achieving statistically significant differences compared with bupivacaine HCl (P < 0.05) in five of 17 treatment arms. These results were supported by results of other efficacy measures, including time to first use of opioid rescue medication, proportion of patients avoiding opioid rescue medication, total postsurgical consumption of opioid rescue medication, and patient/care provider satisfaction with postoperative analgesia. Local infiltration of liposome bupivacaine resulted in significant systemic plasma levels of bupivacaine, which could persist for 96 hours; systemic plasma levels of bupivacaine following administration of liposome bupivacaine were not correlated with local efficacy. Liposome bupivacaine and bupivacaine HCl were generally well tolerated.Conclusion: Based on this integrated analysis of multiple efficacy measures, liposome bupivacaine appears to be a potentially useful therapeutic option for prolonged reduction of postsurgical pain in soft tissue and orthopedic surgeries.Keywords: pain, postsurgical; wound infiltration; local anesthetic; analgesic