{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:24:28Z","timestamp":1780485868814,"version":"3.54.1"},"reference-count":28,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To review data for bupivacaine\/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>Literature search of PubMed (1946 to August 2021) and ProQuest (1946 to August 2021) was performed using the terms: Zynrelef, HTX-011, and \u201cbupivacaine AND meloxicam.\u201d Additional information sources include ClinicalTrials.gov, prescribing information, Heron Therapeutics\u2019 Clinical and Economic Evidence Dossier, meeting abstracts, and references of identified articles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection and Data Extraction<\/jats:title>\n                    <jats:p>Clinical trials and articles evaluating bupivacaine\/meloxicam ER for postoperative pain management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis<\/jats:title>\n                    <jats:p>Bupivacaine is a short-acting local anesthetic. Its efficacy is negatively impacted by the acidic environment of surgical sites. Meloxicam, a nonsteroidal antiinflammatory, reduces inflammation at the surgical site and increases pH propagating bupivacaine movement into the neurons. In Phase 2 and Phase 3 clinical trials, bupivacaine\/meloxicam ER was compared with bupivacaine HCl, bupivacaine ER, and meloxicam ER with and without scheduled nonopioid multimodal analgesia (MMA) in bunionectomies, herniorrhaphies, total knee arthroplasty and abdominoplasty. Postoperative pain was well controlled for 72 hours and consistently superior to placebo, with minimal or no opioid use. Wound healing was not impacted and adverse effects were similar to placebo (most commonly nausea, dizziness, constipation, and headaches).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance to Patient Care and Clinical Practice<\/jats:title>\n                    <jats:p>Bupivacaine\/meloxicam ER is a viable, safe, nonopioid local anesthetic for sustained 72-hour postoperative pain management mitigating opioid consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bupivacaine\/meloxicam ER is the only dual-acting, extended-release local anesthetic available. It provides effective analgesia in the postoperative setting and successfully reduces or eliminates postoperative opioid consumption.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280221086639","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T10:04:25Z","timestamp":1652177065000},"page":"71-85","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Bupivacaine\/meloxicam ER: A New Dual-acting Extended-Release Local Anesthetic for Opioid-Sparing Postoperative Pain Management"],"prefix":"10.1177","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4043-5063","authenticated-orcid":false,"given":"Taylor","family":"Bourn","sequence":"first","affiliation":[{"name":"Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2993-9081","authenticated-orcid":false,"given":"Sister Michaela","family":"Serpa","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"bibr1-10600280221086639","doi-asserted-by":"publisher","DOI":"10.17226\/13172"},{"key":"bibr2-10600280221086639","unstructured":"Clinical Economic Evidence Dossier for ZYNRELEF TM, (bupivacaine meloxicam) extended-release solution. San Diego, CA: Heron Therapeutics, Inc; 2021."},{"key":"bibr3-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1002\/jso.24814"},{"key":"bibr4-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1016\/j.anclin.2017.01.018"},{"key":"bibr5-10600280221086639","unstructured":"ZYNRELEF [package insert] . Heron Therapeutics, Inc, San Diego, CA. 2021."},{"key":"bibr6-10600280221086639","author":"ZYNRELEF Assessment Report","year":"2020","journal-title":"European Medicines Agency;"},{"key":"bibr7-10600280221086639","unstructured":"Onel E, Chu A, Patel S, Ottoboni T, Wilker C, Quart B. Synergistic effect of bupivacaine and meloxicam in HTX-011 across multiple doses and surgeries [poster 256]. ACCP Annual Meeting. October, 2017. https:\/\/www.herontx.com\/wp-content\/uploads\/2020\/11\/150103492_ACCP_2017_Poster.pdf. Accessed January 6, 2022"},{"key":"bibr8-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2019-100714"},{"key":"bibr9-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2020-101488"},{"key":"bibr10-10600280221086639","unstructured":"MELOXICAM [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2021."},{"key":"bibr11-10600280221086639","unstructured":"BUPIVACAINE [package insert]. Lake Forest, IL: Hospira, Inc; 2021."},{"key":"bibr12-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpa.2019.07.012"},{"key":"bibr13-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2019-100531"},{"key":"bibr14-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1007\/s10029-019-02023-6"},{"key":"bibr15-10600280221086639","doi-asserted-by":"publisher","DOI":"10.7547\/20-204"},{"key":"bibr16-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2020.06.036"},{"key":"bibr17-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2020.05.044"},{"key":"bibr18-10600280221086639","unstructured":"Hacker S. Postoperative Pain Management of Total Knee Arthroplasty Using HTX-011 With Multimodal Analgesia: Results from a Phase 3b Open-Label Study [poster 306]. Orthopedics Today 2020 CME Meeting; January 12-16, 2020; Kauai, HI, USA. https:\/\/www.herontx.com\/wp-content\/uploads\/2020\/11\/150106975_Ortho_Today_306_TKA_FINAL.pdf. Accessed January 6, 2022"},{"key":"bibr19-10600280221086639","doi-asserted-by":"publisher","DOI":"10.1007\/s40122-021-00289-2"},{"key":"bibr20-10600280221086639","unstructured":"Leiman D, Minkowitz H, Patel S, Boccia G, Chu A, Heiner L, et al. HTX-011, a proprietary, unique, long-acting local anesthetic, reduces acute postoperative pain intensity and opioid consumption following abdominoplasty [poster]. Conference of American College of Surg, October 2017. https:\/\/www.herontx.com\/wp-content\/uploads\/2020\/11\/ACS_2017_Abdominoplasty_ePoster_D3.pdf. Accessed January 6, 2022"},{"key":"bibr21-10600280221086639","unstructured":"ClinicalTrialsgov. [Internet]. National Library of Medicine (US). Identifier NCT04911062. HTX-011 in spinal surgery; 2021 June 2. Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04911062?term=htx-011&draw=2&rank=2. Accessed December 13, 2021"},{"key":"bibr22-10600280221086639","doi-asserted-by":"publisher","DOI":"10.2217\/pmt-2021-0043"},{"key":"bibr23-10600280221086639","unstructured":"Heron Therapeutics data on file personal communication February 7, 2022."},{"key":"bibr24-10600280221086639","unstructured":"Heron Therapeutics data on file personal communication February 15, 2022."},{"key":"bibr25-10600280221086639","unstructured":"ClinicalTrialsgov. [Internet]. National Library of Medicine (US). Identifier NCT04911062. HTX-011 in spinal surgery; 2021 June 2. Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04911062?term=htx-011&draw=2&rank=2. Accessed December 13, 2021"},{"key":"bibr26-10600280221086639","unstructured":"Yamamoto A, Ottoboni T, Quart B. Pharmacokinetics and safety of different bupivacaine formulations and administration techniques in augmentation mammoplasty [poster]. ASHP Summer Meeting and Exhibition. 2019. https:\/\/www.herontx.com\/wp-content\/uploads\/2020\/11\/ASHP_2019_Poster.pdf. Accessed January 10, 2022"},{"key":"bibr27-10600280221086639","unstructured":"Viscusi E, Minkowitz H, Hu J. HTX-011: no evidence of local anesthetic systemic toxicity [poster A4279]. American Society of Anesthesiology (ASA) Annual Meeting. October. 2020. https:\/\/www.herontx.com\/wp-content\/uploads\/2020\/11\/150102654_ASRA_2017_Abdominoplasty_Poster_L2d_FINAL.pdf. Accessed January 6, 2022"},{"key":"bibr28-10600280221086639","unstructured":"Fast Track Breakthrough Therapy Accelerated Approval Priority Review . US Food and Drug Administration website. https:\/\/www.fda.gov\/ForPatients\/Approvals\/Fast\/default.htm. Updated February 23, 2018. 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