Non-Opioid Pain Management
The first and only dual-acting extended-release local anesthetic — combining bupivacaine with low-dose meloxicam for up to 72 hours of postoperative pain relief.
Applied directly to the surgical site via needle-free applicator. No injection. No reconstitution. One application.
Request Product Information View Clinical EvidenceA synergistic dual-mechanism approach to sustained postoperative pain control
ZYNRELEF combines two complementary mechanisms. Bupivacaine blocks voltage-gated sodium channels to prevent pain signal transmission. Low-dose meloxicam reduces surgical site inflammation and normalizes tissue pH — which keeps more bupivacaine molecules in their active, un-ionized form. The result: potentiated analgesia that outlasts either component alone.
ZYNRELEF uses a proprietary Biochronomer® polymer matrix that provides controlled, sustained diffusion of both active ingredients over 72 hours. Unlike standard bupivacaine (which lasts 4–8 hours), ZYNRELEF maintains therapeutic levels throughout the critical first three postoperative days — the window when patients are most vulnerable to opioid initiation.
ZYNRELEF is instilled directly into the surgical site using a Luer lock cone-shaped applicator — no needle required. The viscous solution coats affected tissue after final irrigation and suction, prior to wound closure. The entire kit (vial, vented vial spike, syringes, and applicators) is included in each single-dose package.
Proven efficacy across multiple Phase 3 trials with 1,627+ patients studied
EPOCH 1 — Phase 3
Randomized, double-blind, controlled trial demonstrating significantly reduced pain intensity and opioid consumption versus bupivacaine HCl. A greater proportion of ZYNRELEF patients remained opioid-free through 72 hours.
EPOCH 2 — Phase 3
23% reduction in mean pain intensity vs. placebo. 21% reduction vs. bupivacaine HCl. 38% reduction in opioid consumption vs. placebo and 25% reduction vs. bupivacaine HCl.
Phase 2b
38% reduction in pain intensity in first 72 hours vs. placebo. 37% of TKA patients experienced no severe pain through 72 hours. 39% received no opioid discharge prescription and had no callbacks through day 11.
Subgroup Analysis
In bunionectomy patients over 65: 58% opioid-free with ZYNRELEF vs. 25% with bupivacaine HCl. In herniorrhaphy patients over 65: 87% opioid-free vs. 64% with bupivacaine HCl. Demonstrates enhanced benefit in populations most vulnerable to opioid side effects.
FDA-approved for a growing range of soft tissue and orthopedic procedures
Primary distal first metatarsal osteotomy
Unilateral herniorrhaphy with mesh placement
Periarticular instillation for TKA pain management
Instillation at the surgical site during C-section
Procedures involving 4 or fewer spinal levels
Periarticular application for shoulder replacement
Breast augmentation surgical pain management
Extended foot and ankle procedure coverage
Available in four vial sizes — each kit includes everything needed for needle-free application
| Vial Volume | Bupivacaine | Meloxicam | Typical Use |
|---|---|---|---|
| 14 mL | 400 mg | 12 mg | TKA, shoulder arthroplasty, larger surgical fields |
| 10.5 mL | 300 mg | 9 mg | Hernia repair, spinal surgery |
| 7 mL | 200 mg | 6 mg | Bunionectomy, foot/ankle procedures |
| 2.3 mL | 60 mg | 1.8 mg | Smaller surgical fields |
Each single-dose ZYNRELEF kit contains: one ready-to-use vial, vented vial spike, Luer lock syringes, and Luer lock cone-shaped applicators. No reconstitution or mixing required. Applied directly to the surgical site after final irrigation and suction, prior to wound closure.
Addressing the critical gap between surgical pain and opioid dependence
Standard bupivacaine provides 4–8 hours of relief. ZYNRELEF extends that to 72 hours through its dual-acting mechanism — covering the full critical postoperative window when opioid initiation risk is highest.
Patients are 3.25× more likely to remain opioid-free at 72 hours vs. placebo, and 2.39× more likely vs. bupivacaine HCl. In elderly hernia patients, 87% remained completely opioid-free. [DOI]
No mixing, no reconstitution, no needles. The ready-to-use vial and included applicators integrate seamlessly into the surgical workflow. Apply after final irrigation, before closing — adding minimal time to the procedure.
From 3 approved procedures in 2021 to 8+ in 2024, ZYNRELEF's expanding label reflects its growing clinical evidence base. As indications expand, more surgical teams can offer patients a non-opioid path to postoperative comfort.
ZYNRELEF is the first and only dual-acting extended-release local anesthetic. It combines bupivacaine with low-dose meloxicam in a proprietary Biochronomer® polymer to provide up to 72 hours of postoperative pain relief, applied directly to the surgical site via a needle-free applicator.
Standard bupivacaine provides 4–8 hours of relief. ZYNRELEF's dual-acting formula delivers sustained analgesia for up to 72 hours. The meloxicam component reduces inflammation and normalizes tissue pH, allowing bupivacaine to work more effectively for longer.
No. ZYNRELEF is instilled directly into the surgical site — it is not a nerve block. However, it can be used in combination with a single nerve block when clinically appropriate.
ZYNRELEF should not be used in patients with known hypersensitivity to amide local anesthetics or NSAIDs, a history of asthma/urticaria with aspirin or NSAIDs, or for obstetrical paracervical block anesthesia or CABG surgery pain. Always refer to the full prescribing information.
Yes. Sunspot Medical Group distributes ZYNRELEF to healthcare providers across Las Cruces, El Paso, Southern New Mexico, and West Texas. Contact our clinical team for product samples, pricing, and ordering information.
Connect with our clinical team to learn how ZYNRELEF can help your patients recover with less pain and fewer opioids.
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