ADVERTISEMENT
ZYNRELEF
ZYNRELEF (bupivacaine and meloxicam) extended-release solution, for soft tissue or periarticular instillation use, contains bupivacaine, an amide local anesthetic, and meloxicam, a nonsteroidal anti-inflammatory drug (NSAID).
Heron Therapeutics
Heron Therapeutics
Our mission is to improve the lives of patients by developing novel, best-in-class treatments to address some of the most important unmet patient needs. We aim to develop patient-focused solutions by applying our innovative science and technologies with well-known pharmacology.
ZYNRELEF® (bupivacaine and meloxicam) extended-release solution is a clear, pale-yellow to yellow viscous liquid available in 4 presentations. Each single-dose glass vial is filled with a solution of 29.25 mg/mL bupivacaine and 0.88 mg/mL meloxicam. * Each ZYNRELEF vial contains overfill to compensate for residual amounts that remain in the vial, vented vial spike, Luer lock applicator, and syringe(s) during drug withdrawal and administration.
The following replacement components are individually supplied separate from the kit:
- Carton containing 5 vented vial spikes
- Carton containing 10 Luer lock applicators
- Carton containing 10 sterile 3 mL Luer lock syringes
- Carton containing 8 sterile 12 mL Luer lock syringes
With a novel mechanism of action and a single, needle-free application into the surgical site, ZYNRELEF provides patients with up to 72 hours of postoperative pain relief and has been proven to reduce, possibly even eliminate, the need for opioids after surgery. As the first and only extended-release dual-acting local anesthetic (DALA), ZYNRELEF combines bupivacaine with a low dose of meloxicam for a synergistic analgesic effect.1-3,5 It is the only local anesthetic considered by FDA to be extended-release, based on superiority to bupivacaine through 72 hours.3
References
1. Viscusi E, Gimbel JS, Pollack RA, Hu J, Lee G-C. HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study. Reg Anesth Pain Med. 2019;44(7):700-706. doi:10.1136/rapm-2019-100531.
2. Viscusi E, Minkowitz H, Winkle P, Ramamoorthy S, Hu J, Singla N. HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the Phase 3 EPOCH 2 study. Hernia. 2019;23(6):1071-1080. doi:10.1007/s10029-019-02023-6.
3. ZYNRELEF [package insert]. San Diego, CA: Heron Therapeutics, Inc; 2021.
4. Lachiewicz PF, Lee G-C, Pollak R, Leiman D, Hu J, Sah A. HTX-011 reduced pain and opioid use after primary total knee arthroplasty: results of a randomized Phase 2b trial. J Arthroplasty. 2020;35(10):2843-2851. doi:10.1016/j.arth.2020.05.044.
5. Ottoboni T, Quart B, Pawasauskas J, Dasta JF, Pollak RA, Viscusi ER. Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain. Reg Anesth Pain Med. 2020;45(2):117-123. doi:10.1136/rapm-2019-100714.
6. Minkowitz H, Soto R, Fanikos J, et al. Opioid-free recovery after hernia repair with HTX-011 as the foundation of a non-opioid, multimodal analgesia regimen in a real-world setting: a randomized, open-label study. Pain Ther. 2021;10(2):1295-1308. doi:10.1007/s40122-021-00289-2.
7. Berde CB, Strichartz GR. Local anesthetics. In: Miller RD, Cohen NH, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL, eds. Miller’s Anesthesia. Vol 1. 8th ed. Philadelphia, PA: Saunders; 2015:1028-1054.e4.
8. Ali A, Sundberg M, Hansson U, Malmvik J, Flivik G. Doubtful effect of continuous intraarticular analgesia after total knee arthroplasty: a randomized, double-blind study of 200 patients. Acta Orthop. 2015;86(3):373-377. doi:10.3109/17453674.2014.991629.
9. Kim J, Burke SM, Kryzanski JT, et al. The role of liposomal bupivacaine in reduction of postoperative pain after transforaminal lumbar interbody fusion: a clinical study. World Neurosurg. 2016;91:460-467. doi:10.1016/j.wneu.2016.04.058.
10. Data on file. DRG physician survey. San Diego, CA: Heron Therapeutics Inc; 2017.
11. Exparel [package insert]. San Diego, CA: Pacira Pharmaceuticals Inc; 2021.
12. Becker DE, Reed KL. Essentials of local anesthetic pharmacology. Anesth Prog. 2006;53(3):98-109. doi:10.2344/0003-3006(2006)53[98:EOLAP]2.0.CO;2.
13. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. US Food and Drug Administration website. https://www.fda.gov/ForPatients/Approvals/Fast/default.htm. Updated February 23, 2018. Accessed April 8, 2021.
ZYNRELEF is indicated in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures.
Limitations of Use: Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures.
ZYNRELEF is contraindicated for:
- Patients with a known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to any local anesthetic agent of the amide-type, NSAIDs, or to any of the other components of ZYNRELEF
- Patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients
- Patients undergoing obstetrical paracervical block anesthesia
- Patients undergoing coronary artery bypass graft (CABG) surgery
Dose-Related Toxicity: Monitor cardiovascular and respiratory vital signs and patient’s state of consciousness after application of ZYNRELEF. When using ZYNRELEF with other local anesthetics, overall local anesthetic exposure must be considered through 72 hours. Hepatotoxicity: If abnormal liver tests persist or worsen, perform a clinical evaluation of the patient. Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. Heart Failure and Edema: Avoid use of ZYNRELEF in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure. Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of ZYNRELEF in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs. Chondrolysis: Limit exposure to articular cartilage due to the potential risk of chondrolysis. Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetic use. Serious Skin Reactions: NSAIDs, including meloxicam, can cause serious skin adverse reactions. If symptoms present, evaluate clinically. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): If symptoms are present, evaluate clinically. Fetal Toxicity: Limit use of NSAIDs, including ZYNRELEF, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/ fetal renal dysfunction and premature closure of the ductus arteriosus. Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.
Most common adverse reactions (incidence ≥10%) are constipation, vomiting, and headache.
Drug interactions:
Drugs that Interfere with Hemostasis (e.g., warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking ZYNRELEF with drugs that interfere with hemostasis.
ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), or Beta-Blockers: Concomitant use with ZYNRELEF may diminish the antihypertensive effect of these drugs. Monitor blood pressure.
ACE Inhibitors and ARBs: Concomitant use with ZYNRELEF in elderly, volume-depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function.
Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effect
Use in specific populations
Infertility: NSAIDs are associated with reversible infertility. Consider avoidance of ZYNRELEF in women who have difficulties conceiving.
Severe Hepatic Impairment: Only use if benefits are expected to outweigh risks; monitor for signs of worsening liver function.
Severe Renal Impairment: Not recommended
Store ZYNRELEF kits at 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. If ZYNRELEF vials are removed from the kit, store them at controlled room temperature. Protect from light during storage.
bupivacaine and meloxicam
