title: Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile.
abstract: OBJECTIVE
  Bupivacaine extended-release liposome injection is an investigational local analgesic intended for use in postsurgical pain management. In recognition of the incompletely characterized association of bupivacaine use and cardiac effects, this article reviews the cardiac safety profile of this novel formulation of bupivacaine.
  
  
  METHODS
  Findings from paired electrocardiograms (ECGs), corresponding pharmacokinetic assessments, and cardiovascular adverse events (AEs) in a phase 2, randomized, double-blind, dose-ranging study of bupivacaine extended-release (150, 300, 450, or 600 mg) or bupivacaine HCl 150 mg with epinephrine administered intraoperatively via wound infiltration in patients undergoing total knee arthroplasty (n = 138), were assessed for potential causality. Results from 4 phase 1 bupivacaine extended-release studies that also obtained ECG and/or Holter monitor findings (n = 169) were assessed. In addition, incidences of cardiovascular AEs reported across 10 bupivacaine extended-release wound infiltration studies (n = 1459) were pooled and assessed.
  
  
  RESULTS
  In the phase 2 study, mean change from baseline in QRS duration and QTcF duration across dose levels of bupivacaine extended-release was similar (range, -1 to +4 milliseconds and -7 to -10 milliseconds) compared with bupivacaine HCl (-1 millisecond and -6 milliseconds). Mean change from baseline in heart rate, PR interval, and QRS interval was similar between treatment groups as well. No clinically relevant ECG changes or cardiac AEs with bupivacaine extended-release were observed in the other clinical studies.
  
  
  CONCLUSIONS
  A focused assessment of ECG data from a phase 2 study and cardiac findings/AEs data from other studies in the bupivacaine extended-release development program did not reveal any cardiac safety issues.
authors.affiliation: Department of Anesthesiology, Ohio State University, Columbus, OH 43210, USA. sergio.bergese@osumc.edu
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Bergese
authors.forename: Erol
authors.initials: E
authors.lastname: Onel
authors.forename: Michael
authors.initials: M
authors.lastname: Morren
authors.forename: Joel
authors.initials: J
authors.lastname: Morganroth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002045:Bupivacaine / Q000008:administration & dosage* / Q000009:adverse effects*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D008081:Liposomes; D002045:Bupivacaine