Objective: Pooled safety data from 10 randomized, double-blind studies of liposome bupivacaine, a novel local analgesic formulation, were examined.
Methods: Eight hundred twenty-three patients received liposome bupivacaine (dose, 66 to 532 mg) given locally at the surgical site in 5 different settings (hemorrhoidectomy, bunionectomy, breast augmentation, total knee arthroplasty, and hernia repair); 446 received bupivacaine HCl (dose, 75 to 200 mg) and 190 received placebo. Adverse events (AEs) were monitored for up to 36 days after administration.
Results: Overall, 48% of patients were men and 21% were 65 years and older. Incidence of AEs was 62% for patients receiving liposome bupivacaine, versus 75% and 43% for patients receiving bupivacaine HCl and placebo, respectively. The most common AEs (incidence >10%) in the liposome bupivacaine arms were nausea, constipation, and vomiting. One death was reported in the liposome bupivacaine group and 1 in the bupivacaine HCl group; both deemed unrelated to study drug. Serious AEs were reported in 2.7% of patients receiving liposome bupivacaine, versus 5.4% and 1.1% of those receiving bupivacaine HCl and placebo, respectively. In both the liposome bupivacaine and bupivacaine HCl groups, 6% of patients experienced a cardiac AE; these were primarily tachycardia (4% vs. 5%, respectively) and bradycardia (2% vs. 1%, respectively). Overall incidence of treatment-related cardiac AEs was <1%; all were associated with liposome bupivacaine. All of these events were assessed by investigators as possibly related to study drug; all were mild or moderate in severity, and none required therapeutic intervention.
Discussion: Liposome bupivacaine exhibited acceptable tolerability across 823 patient exposures.
*Department of Anesthesiology, Thomas Jefferson University, Philadelphia, PA
†Department of Anesthesiology, Yale School of Medicine, New Haven, CT
‡Pacira Pharmaceuticals, Inc., Parsippany, NJ
§Rebecca and John Moores Cancer Center, La Jolla, CA
E.R.V. is a consultant for Pacira Pharmaceuticals, Inc. and E.O. is an employee of Pacira Pharmaceuticals, Inc. The remaining authors declare no conflict of interest. Supported by Pacira Pharmaceuticals, Inc., Parsippany, NJ.
Reprints: Eugene R. Viscusi, MD, Department of Anesthesiology, Thomas Jefferson University, 111 S. 11th Street, Suite G8490, Philadelphia, PA 19107 (e-mail: firstname.lastname@example.org).
Received August 3, 2012
Accepted January 20, 2013