Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting

Abstract

Objective:

Assess comparative efficacy of liposome bupivacaine administered at doses ≤266 mg and bupivacaine HCl administered at doses ≤200 mg for postsurgical analgesia.

Research design and methods:

Analysis of pooled efficacy and safety data from nine double-blind, placebo or active (bupivacaine HCl) controlled multimodal analgesia studies using a single dose of liposome bupivacaine or comparator, given via administration into the surgical site before end of surgery (i.e., inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Data from study arms that received liposome bupivacaine doses ≤266 mg were included.

Clinical trial registration:

Pooled data analysis includes nine studies: Study 1 – NCT01203644; Study 2 – NCT00485433; Study 3 – NCT00485693; Study 4 – NCT00529126; Study 5 – NCT00745290; Study 6 – NCT00744848; Study 7 – NCT00813111; Study 8 – NCT00890721; Study 9 – NCT00890682.

Main outcome measures:

Outcome measures included area under the curve (AUC) of pain intensity scores assessed by numeric rating scale (NRS) through 72 h postsurgery, time to first use of rescue opioid medications, total amount (mg) of opioid medications used, and occurrence of opioid-related adverse events (ORAEs). Incidence of overall AEs was also assessed.

Results:

Mean cumulative pain score (AUC of NRS through 72 h) was significantly lower with liposome bupivacaine (283) compared with bupivacaine HCl (329, p = 0.039). Median time from administration of study drug to first use of opioid rescue medication was significantly longer for liposome bupivacaine (10 h vs 3 h, p < 0.0001). Liposome bupivacaine was associated with a significant reduction in opioid use (12 mg vs 19 mg; p < 0.0001) and incidence of ORAEs (20% vs 36%; p < 0.0001), compared with bupivacaine HCl.

Conclusions:

In this pooled analysis from nine studies representing five different surgical procedures, liposome bupivacaine administered at doses ≤266 mg in a multimodal setting was associated with statistically significant and clinically meaningful lower cumulative pain score at 72 h, delayed and less consumption of opioids, and fewer ORAEs than bupivacaine HCl.

Keywords::

• Analgesic
• Infiltration
• Liposome bupivacaine
• Opioid-related adverse event
• Opioid sparing
• Postsurgical analgesia
• Postsurgical pain

Transparency

Declaration of funding

This manuscript was funded by Pacira Pharmaceuticals, Inc.

Declaration of financial/other relationships

J.D. is a Consultant for Pacira Pharmaceuticals, AceIRX Pharmaceuticals, Hospira, and Cadence Pharmaceuticals, and is a member of the speakers bureaus for Cadence Pharmaceuticals and Pacira Pharmaceuticals. G.P. is Chief Medical Officer of Pacira Pharmaceuticals and is a stock option holder. S.R. is a Consultant for Pacira Pharmaceuticals. R.S. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Editorial assistance was provided by Peloton Advantage, LLC, supported by Pacira Pharmaceuticals, Inc.

Previous presentations: this manuscript incorporates preliminary data that have been presented at three recent congress meetings:

Dasta J, Ramamoorthy S, Patou G, Sinatra R. Bupivacaine extended-release liposome injection (DepoFoam® bupivacaine) vs. bupivacaine HCl: a meta-analysis of multimodal trials of doses up to and including 300 mg. Presented at the Annual Meeting of the American College of Clinical Pharmacy, 16–19 October 2011, Pittsburgh, PA, USA.

Ramamoorthy S, Dasta J, Sinatra R. Comparison of immediate-release bupivacaine vs. EXPAREL™ (bupivacaine extended-release liposome injection) on opioid requirements and related adverse events from phase 2 and 3 studies utilizing multimodal analgesia across multiple surgical models. Presented at the 97th Annual American College of Surgeons Clinical Congress, 23–27 October 2011, San Francisco, CA, USA.

Sinatra R, Ramamoorthy S, Dasta J. Comparison of immediate-release bupivacaine vs EXPAREL™ (bupivacaine extended-release liposome injection) on opioid requirements and related adverse events from phase 2 and 3 studies utilizing multimodal analgesia across multiple surgical models. Presented at the American Society of Anesthesiologists 2011 Annual Meeting, 15–19 October 2011, Chicago, IL, USA.

Notes

*Exparel is a registered trade name of Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA.

*Marcain is a registered trade name of AstraZeneca UK Limited, Bedfordshire, UK.

†Marcaine is a registered trade name of Hospira, Inc., Lake Forest, IL, USA.