CC BY-NC-ND 4.0 · J Knee Surg 2023; 36(09): 925-932
DOI: 10.1055/s-0042-1747945
Original Article

HTX-011 in Combination with Multimodal Analgesic Regimen Minimized Severe Pain and Opioid Use after Total Knee Arthroplasty in an Open-Label Study

Gwo-Chin Lee
1   Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
Richard Berkowitz
2   University Orthopedic and Joint Replacement Center, Tamarac, Florida
Scott Hacker
3   Grossmont Orthopedic Medical Group, La Mesa, California
Jia Hu
4   Heron Therapeutics, Inc., San Diego, California
Alan Rechter
5   Department of Orthopaedic Surgery, Orthopaedic Associates, LLP, Houston, Texas
› Author Affiliations
FundingThis study was funded by Heron Therapeutics. 4242 Campus Point Court Suite 200, San Diego, CA 92121., NCT03974932. Editorial and submission assistance for this article was provided by Katie Luepke, PharmD, BCPS of Heron Therapeutics and Apothecom (funded by Heron Therapeutics)


Total knee arthroplasty (TKA) can be associated with significant postoperative pain despite multimodal analgesic (MMA) protocols, and most patients require the use of opioids postoperatively. HTX-011 is a dual-acting local anesthetic containing bupivacaine and low-dose meloxicam in an extended-release polymer. In a prior randomized controlled trial (RCT), HTX-011 reduced pain and opioid use through 72 hours after TKA compared with bupivacaine hydrochloride. This open-label study (NCT03974932) evaluated the efficacy and safety of HTX-011 combined with an MMA regimen in patients undergoing TKA under spinal anesthesia. All patients received intraoperative HTX-011 (400 mg bupivacaine/12 mg meloxicam) in combination with an MMA regimen consisting of preoperative acetaminophen, celecoxib, and pregabalin and postoperative acetaminophen and celecoxib until discharge. Opioid rescue was allowed upon patient request for additional pain control. Pain scores, opioid consumption, discharge readiness, and adverse events were recorded. Fifty-one patients were treated. Compared with the prior RCT, HTX-011 with this MMA regimen further lowered pain scores and reduced opioid use. Mean patient-reported pain scores remained in the mild range, and 82% of patients or more did not experience severe pain at any individual time point through 72 hours after surgery. Mean total opioid consumption was low over 72 hours: 24.8 morphine milligram equivalents (1–2 tablets of oxycodone 10 mg/day). Approximately 60% of patients were ready for discharge by 12 hours, and 39% were discharged without an opioid prescription and did not call back for pain management. The treatment regimen was well tolerated, and no added risk was observed with the addition of MMA. HTX-011 with an MMA regimen reduced postoperative pain and opioid use following TKA.

Publication History

Received: 30 June 2021

Accepted: 25 February 2022

Article published online:
10 June 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

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