Opioid-Free Recovery from Bunionectomy with HTX-011, a Dual-Acting Local Anesthetic Combining Bupivacaine and Meloxicam, as the Foundation of Non-Opioid Multimodal Analgesia

Abstract

Background: There is a need for postoperative pain control that minimizes/eliminates opioid use during the first 72 hours following surgery, when pain is most severe. HTX-011 is an extended-release, dual-acting local anesthetic that demonstrated superior 72-hour analgesia over standard of care bupivacaine hydrochloride (HCl) and saline placebo in a phase 3 bunionectomy study (EPOCH-1). Having shown HTX-011 monotherapy is superior to bupivacaine HCl in reducing postoperative pain intensity and opioid use, this follow-on study evaluated the safety and efficacy of HTX-011 as the foundation of a multimodal analgesia (MMA) regimen using over-the-counter medications recommended by practice guidelines for pain management. Methods: Following regional anesthesia administered as a lidocaine block, patients underwent unilateral bunionectomy with osteotomy and internal fixation. Prior to closure, HTX-011 (up to 60 mg bupivacaine/1.8 mg meloxicam) was applied without a needle. Patients received scheduled postoperative MMA alternating ibuprofen (600 mg) and acetaminophen (1 g) every 3 hours for 72 hours. Efficacy was assessed based on pain intensity (numeric rating scale [NRS; 0-10]) and consumption of opioid rescue medication (intravenous morphine milligram equivalents [MME]). Adverse event and vital sign monitoring, plus laboratory and wound healing assessments, were used to determine safety. Results: Over the 72-hour assessment period following bunionectomy, mean pain scores were mild in severity (NRS <4) and 22/31 patients (71%) experienced no severe pain (NRS {greater than or equal to}7) with HTX-011 as the foundation of scheduled, non-opioid MMA. Patients consumed an average of 1.61 MME total, with 24/31 (77%) requiring no opioid rescue medication (opioid-free). HTX-011 was well-tolerated and demonstrated no safety concerns with the inclusion of postoperative MMA. Conclusions: HTX-011 as the foundation of an MMA regimen including scheduled ibuprofen and acetaminophen maintained mean postoperative pain scores in the mild range and enabled opioid-free recovery for 77% of bunionectomy patients through the 28-day recovery period.

HTX-011 Effectively Reduces Postoperative Pain Intensity and Opioid use in the Elderly

“…At this dose the daily exposure to meloxicam would be lower than the lowest recommended adult oral dose of 7.5 mg, as confirmed by in vitro data demonstrating that approximately 5 mg of meloxicam in HTX-011 is released in the first 24 h [20,27]. HTX-011 has also been studied in open-label trials where ibuprofen or celecoxib had been given as part of a scheduled multimodal analgesia regimen without any evidence of cardiovascular, gastrointestinal or renal toxicity [28,29].…”

Opioid-Free Recovery After Hernia Repair with HTX-011 as the Foundation of a Non-Opioid, Multimodal Analgesia Regimen in a Real-World Setting: A Randomized, Open-Label Study

“…Though decreasing opioid use can decrease opioid-related AEs, the scheduled use of acetaminophen and NSAIDs, especially long-term use, is also not without risk. In single-arm follow-on studies involving HTX-011 as the foundation of non-opioid MMA, coadministration of HTX-011 with scheduled NSAIDs and acetaminophen for a minimum of 3 days did not impact safety; there was no evidence of NSAID- or acetaminophen-related toxicity based on treatment-emergent AEs or clinical laboratory test results [ 11 , 15 ]. The current study confirmed these findings for a 5-day MMA regimen.…”

“…This study, Helping Opioid Prescription Elimination Hernia-1 (HOPE Hernia-1), is part of the HOPE project, which is designed to provide surgeons with practical real-world solutions to effectively manage postoperative pain and eliminate the need for opioid prescriptions using an HTX-011-based non-opioid MMA regimen. Oral ibuprofen and acetaminophen are commonly used after surgery [11][12][13][14][15]; however, there are limited data regarding the optimal schedule for their concomitant use. This study was designed to identify which of two postoperative MMA regimens-concurrent or alternating ibuprofen/acetaminophen-following intraoperative administration of HTX-011 in patients undergoing open inguinal herniorrhaphy, with prospective verification of an opioid prescribing algorithm, would result in a higher proportion of patients not requiring a prescription for postoperative opioids in a realworld setting.…”

Bupivacaine/meloxicam ER: A New Dual-acting Extended-Release Local Anesthetic for Opioid-Sparing Postoperative Pain Management

“…15,16 No clinically meaningful safety differences were noted in either follow-on study, with the addition of ibuprofen and acetaminophen to bupivacaine/meloxicam ER. 15,16…”

“…Phase 2 follow-on studies further evaluated bupivacaine/ meloxicam ER as a foundation for a scheduled, nonopioid multimodal analgesia (MMA) postoperative regimen. 15,16 Study 218 (EPOCH 1 follow-on) by Pollak et al evaluated patients undergoing bunionectomy (n = 31) dosed with 60 mg/1.8 mg bupivacaine/meloxicam and Study 215 (EPOCH 2 follow-on) by Singla et al included patients undergoing herniorrhaphy (n = 63) dosed with 300 mg/9 mg bupivacaine/meloxicam using needle-free application into the surgical sites. Both studies utilized the same MMA regimen of postsurgical patients receiving oral ibuprofen 600 mg every 6 hours alternating with oral acetaminophen 1 g every 6 hours providing an oral analgesic every 3 hours throughout the 72-hour postop period.…”