ZYNRELEF® (HTX-011): A Comprehensive Pharmacological and Clinical Review of a Novel Dual-Acting, Extended-Release Local Anesthetic for Postoperative Pain Management

Executive Summary

ZYNRELEF® (bupivacaine and meloxicam extended-release solution), formerly known as HTX-011, represents a first-in-class, non-opioid, dual-acting local anesthetic (DALA) developed by Heron Therapeutics.[1] It is engineered to provide sustained postsurgical analgesia for up to 72 hours, directly addressing a critical period of acute postoperative pain.[1] The formulation's innovation lies in its synergistic mechanism, which combines the potent local anesthetic bupivacaine with a low dose of the nonsteroidal anti-inflammatory drug (NSAID) meloxicam.[4] This combination is encapsulated within a proprietary Biochronomer® polymer technology, a tri(ethylene glycol) poly(orthoester)-based system that facilitates a controlled, extended release of both active ingredients directly at the surgical site.[4] The inclusion of meloxicam is not merely additive but mechanistically essential; it counteracts surgery-induced local inflammation and subsequent tissue acidosis, a physiological state that otherwise limits the efficacy of bupivacaine. By normalizing the local pH, meloxicam potentiates the penetration of bupivacaine into nerve cells, thereby maintaining its analgesic effect for the full 72-hour duration.[6]