Summary of a Novel, Non-opioid Local Anesthetic for Post-surgical Pain Relief




Kieltyka, Hunter
Hearn, Elizabeth


0000-0001-5556-1428 (Kieltyka, Hunter)

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Purpose: Introducing Zynrelef (bupivacaine/meloxicam) as a new post-surgical medication to relieve pain provides an alternative to opioid use. In recent years, the opioid epidemic has been the cause of numerous overdoses and addictions. By utilizing non-opioid pain relief, we can help combat the ever-growing opioid crisis. Bupivacaine has been utilized for years as a post-operative local anesthetic, working by competitively inhibiting voltage-gated Na+ channels, causing the muscles nearby to relax. However, the inflammation process that occurs after surgery prevents some absorption of local anesthetics, thereby reducing the efficacy of pain relief. Zynrelef is a novel bupivacaine combination product with the addition of meloxicam, a non-steroidal anti-inflammatory drug (NSAID). Meloxicam inhibits COX enzymes, ultimately reducing the inflammatory response. When combined with bupivacaine, the NSAID action enhances the response of the local anesthetic, producing more efficacious pain relief. Additionally, Zynrelef's irrigation application is a novel technique for local pain relief. By irrigating instead of injecting, the inflammatory response and site pain brought on by the injection will be avoided. Clinical trials have shown reduced pain intensities over a 72-hour period in post-operative patients who were administered combination Zynrelef irrigation compared to bupivacaine HCl injection. While the clinical efficacy of Zynrelef is well-documented, the purpose of this study is to compare the cost-effectiveness of Zynrelef irrigation versus another bupivacaine product, Exparel injection. Methods: A drug formulary monograph of Zynrelef was created by thoroughly researching information about its drug class, indications for use, pharmacology, dosing, pharmacokinetics, drug interactions, and clinical efficacy. Once the basis of the drug was established, the precautions, administration options, adverse effects, availability, and cost were compared with Exparel. Results: In bunionectomy, herniorrhaphy, and total knee arthroplasty procedures, Zynrelef scored the lowest on the pain-intensity scale over a 72-hour period and had the largest percentage of patients who did not request additional opioid therapy compared to bupivacaine HCl and saline placebo. Zynrelef is administered via a needle-free single-dose viscous solution instillation available in both 7- and 14-mL vials, opposed to Exparel's single-dose infiltration injection available in either 10- or 20-mL vials. The average wholesale price of Zynrelef amounts to $267.50 (14-mL) and $135.50 (7-mL), and Exparel equates to $344.20 (20-mL) and $189.37 (10-mL). Conclusion: Zynrelef results in more efficacious pain relief and reduced opioid usage compared to bupivacaine HCl and saline placebo. Additionally, the use of the irrigation administration could curb the site pain and inflammation associated with injections, eliminating additional need for anti-inflammatories and local anesthetics. Lastly, when comparing the cost, Zynrelef shows to be slightly more expensive per dose over a three-day (72-hour) period, but the benefits of adding meloxicam were proven to reduce usage of opioid medications and increase alleviation of pain. A future study that considers potential cost savings from eliminating needles for injection and reducing post-operative opioid prescribing would be beneficial.