Bupivacaine and Meloxicam Now Available for Postsurgical Analgesia for Up to 72 Hours

Zynrelef is a dual-acting local anesthetic that delivers a fixed-dose combination of bupivacaine, an amide local anesthetic, and meloxicam, an NSAID.

Zynrelef™ (bupivacaine and meloxicam) extended-release solution is now available for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours in adults after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty.

Zynrelef is a dual-acting local anesthetic that delivers a fixed-dose combination of bupivacaine, an amide local anesthetic, and meloxicam, a nonsteroidal anti-inflammatory drug (NSAID). The needle-free product is intended for single-dose administration only.

The approval was based on data from multiple double-blind, placebo- and active-controlled phase 3 (ClinicalTrials.gov: NCT03295721, NCT03237481) and phase 2 (ClinicalTrials.gov: NCT03015532) studies involving over 1000 patients. Findings from the studies showed that Zynrelef was associated with a significant reduction in pain intensity compared with either bupivacaine HCl or saline placebo.

Zynrelef is contraindicated for use in patients undergoing obstetrical paracervical block anesthesia or coronary artery bypass graft (CABG) surgery, as well as among patients with a history of asthma, urticaria, other allergic-type reactions after taking aspirin or other NSAIDs or in those with hypersensitivity to any local anesthetic agent of the amide-type. The product carries a Boxed Warning regarding the risk of serious cardiovascular and gastrointestinal events.

The most common adverse reactions reported with Zynrelef included constipation, vomiting, and headache. The safety and efficacy of Zynrelef have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. 

“Zynrelef is the only local anesthetic for postoperative pain designated by the FDA to be extended-release for up to 72 hours after surgery, which may help patients and healthcare providers reduce overreliance on opioids but also mitigate exposure to their unwanted side effects and the potential for long-term safety risks like opioid misuse, abuse, or addiction,” said Barry Quart, PharmD, Chairman and CEO of Heron.

Zynrelef extended-release solution is available in 4 dosage strengths as single-dose vials: 400mg bupivacaine/12mg meloxicam, 300mg bupivacaine/9mg meloxicam, 200mg bupivacaine/6mg meloxicam, and 60mg bupivacaine/1.8mg meloxicam. 


  1. Heron Therapeutics announces U.S. commercial launch and availability of Zynrelef™ for the management of postoperative pain for up to 72 hours. [press release]. San Diego, CA: Heron Therapeutics, Inc.; July 1, 2021. 
  2. Zynrelef [package insert]. San Diego, CA: Heron Therapeutics, Inc.; 2021.

This article originally appeared on MPR