The Food and Drug Administration (FDA) has approved Zynrelef™ (bupivacaine and meloxicam) extended-release solution 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.
Among patients undergoing unilateral simple bunionectomy (N=412), treatment with Zynrelef was associated with a significant reduction in pain intensity compared with either bupivacaine HCl or saline placebo for up to 72 hours. Additionally, a significant proportion of patients in the Zynrelef arm did not receive opioid analgesia (29% vs 11% for bupivacaine HCl and 2% for saline placebo). Similar results were observed in a study involving 418 patients undergoing unilateral open inguinal herniorrhaphy.
Zynrelef also showed a significant reduction in pain intensity vs saline placebo for the first 48-hour and 72-hour postoperative periods in patient who underwent primary unilateral total knee arthroplasty (N=222). This study also included a group of patients treated with Zynrelef plus ropivacaine, as well as those who received bupivacaine only. Both Zynrelef treatment groups demonstrated a reduction in pain intensity compared with the bupivacaine arm.
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 (incidence 10% or greater) 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 extended-release solution is supplied 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. The product, which is expected to be available July 2021, should only be prepared and administered with the components provided in the kit.
- Heron Therapeutics announces U.S. FDA approval of Zynrelef™ (HTX-011) for the management of postoperative pain for up to 72 hours. [press release]. San Diego, CA: Heron Therapeutics, Inc.; May 13, 2021.
- Zynrelef [package insert]. San Diego, CA: Heron Therapeutics, Inc.; 2021.