NURSING

Indication and limitations of use

ZYNRELEF is indicated in adults for instillation to produce postsurgical analgesia for up to 72 hours after soft tissue and orthopedic procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided.

Limitations of Use: Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large 4 or more level spinal, and head and neck procedures.

Reducing your patients’ need for opioids

Nurses can play a critical role in advocating for their patients when it comes to postoperative pain management and reducing opioid use during recovery.

One important tactic in minimizing the use of opioids following surgery is the use of local anesthetics as the foundation for postoperative pain management.1 However, most local anesthetics inconsistently provide pain relief beyond 12 to 24 hours, in part because the inflammatory process inhibits their ability to penetrate the nerve cell membrane.2-7 With severe pain often lasting beyond 24 hours, we rely on opioids to pick up where local anesthetics leave off.8-10

In Phase 3 trials of bunionectomy and herniorrhaphy, ZYNRELEF patients experienced greater pain relief through 72 hours—when pain is most severe—and superior reduction in opioid use compared to patients who received the current standard of care, bupivacaine HCl solution.1,10-12 This makes ZYNRELEF the first and only product to demonstrate superiority over bupivacaine HCl solution in Phase 3 studies.1,11,12

In The HOPE Project, most patients were highly satisfied with their multimodal analgesic regimen at day 15.13

Preparing ZYNRELEF14

Vial Access Needle (7 mL & 14 mL) Preparation Video

Step 1: Prepare Components

NON STERILE

  1. Check packaging for damage or tears.
  2. Open all components onto the sterile field.

Do not substitute any of the components.

Step 2: Prepare Vial Access Needle

STERILE

  1. In the sterile field, separate VAN into two pieces – base and shroud.
  2. If the two pieces are locked together, twist and pull apart at the same time.

Step 3: Prepare Vial

NON-STERILE

  1. Flip cap off of vial.
  2. Cleanse septum with alcohol wipe.
  3. Place non-sterile vial into base of sterile VAN.

Do not remove the stopper or attempt to pour the vial contents.

Do not touch base of VAN.

Step 4: Attach Vial Access Needle Shroud

STERILE

  1. Position shroud above vial.
  2. Insert needle into the septum of the vial.
  3. Push down firmly on the shroud until the shroud “snaps” into the base and the needle is fully inserted

Ensure shroud is fully connected to the base to avoid compromising sterility.

Step 5: Prepare syringe

STERILE

  1. Attach the provided syringe to the top (Luer) of the VAN shroud.

Note: Air does not need to be pushed into the vial.

Repeat steps 5-7 for more than one syringe.

Step 6: Invert Syringe

STERILE

  1. Invert syringe and VAN as pictured above.
  2. Wait until the drug product fills the neck of the vial to cover drug inlet.

Note: Drug inlet is at the base of the needle, not at the tip.

Step 7: Withdraw product

STERILE

  1. Using a continuous motion, slowly withdraw the desired amount of ZYNRELEF from the vial.

Note: It is normal for there to be air bubbles in the syringe.

Note: Product is very thick. It may take approximately 30 seconds to withdraw per syringe.

Note: Pushing or pumping the plunger rod up and down at any point may prolong the withdrawal process.

Step 8: Attach Luer Lock Applicator

STERILE

  1. Remove syringe from VAN and attach Luer lock applicator.
    1. If product is prepared in advance of surgery, attach only the blue tip cap to the syringe until ready for application.
    2. Before administration, remove the blue tip cap and attach the Luer lock applicator.
  2. Place syringe on sterile surface.

Note: Vial contains overfill to account for amount that remains in the components

Resources for you

FDA Approval Letter

FDA Approval Letter

Preparation and Administration Poster

Preparation and Administration Poster

Find Additional Resources  

Register for updates

Registering will put you at the front of the line to receive updates on the availability of ZYNRELEF and tools/resources.

Sign Up Today

Important Safety Information and Indication

Indication

ZYNRELEF is indicated in adults for instillation to produce postsurgical analgesia for up to 72 hours after soft tissue and orthopedic procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided.

Limitations of Use: Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large 4 or more level spinal, and head and neck procedures.

Important Safety Information

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
  • ZYNRELEF is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
  • NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Contraindications

ZYNRELEF is contraindicated in patients with a known hypersensitivity (eg, anaphylactic reactions and serious skin reactions) to any amide local anesthetic, NSAIDs, or other components of ZYNRELEF; with 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); undergoing obstetrical paracervical block anesthesia; or undergoing CABG.

Warnings and Precautions

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 medication 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 failure.

Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs.

Risk of Joint Cartilage Necrosis and Degeneration with Unapproved Intra-articular Use: Animal studies evaluating the effects of ZYNRELEF following intra-articular administration in the knee joint demonstrated cartilage necrosis and degeneration.

Chondrolysis: Limit exposure to articular cartilage due to the potential risk of chondrolysis.

Methemoglobinemia: Cases have been reported with local anesthetic use.

Serious Skin Reactions: NSAIDs, including meloxicam, can cause serious skin adverse reactions. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening. If symptoms present, evaluate clinically.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): If symptoms are present, evaluate clinically.

Fetal Toxicity: Due to the risk of oligohydramnios/fetal renal dysfunction and premature closure of the ductus arteriosus with NSAIDs, limit use of ZYNRELEF between about 20 to 30 weeks gestation, and avoid use after about 30 weeks.

Hematologic Toxicity: Monitor hemoglobin and hematocrit in patients with any signs or symptoms of anemia.

Drug Interactions

Drugs That Interfere with Hemostasis: Monitor patients for bleeding who are using ZYNRELEF with drugs that interfere with hemostasis (eg, warfarin, aspirin, SSRIs/SNRIs). 

ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), or Beta-Blockers: Use with ZYNRELEF may diminish the antihypertensive effect of these drugs. Monitor blood pressure.

ACE Inhibitors and ARBs: 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 effects.

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.

Adverse Reactions

Most common adverse reactions (incidence ≥5%) in controlled clinical trials with ZYNRELEF are soft tissue procedures: vomiting and orthopedic procedures: constipation and headache.

Report side effects to Heron at 1-844-437-6611 or to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication

ZYNRELEF is indicated in adults for instillation to produce postsurgical analgesia for up to 72 hours after soft tissue and orthopedic procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided.

Limitations of Use: Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large 4 or more level spinal, and head and neck procedures.

Please see full Prescribing Information, including Boxed Warning and updated Warnings and Precautions for serious skin reactions caused by nonsteroidal anti-inflammatory drugs (NSAIDs).

References: 1. ZYNRELEF [package insert]. San Diego, CA: Heron Therapeutics Inc; 2024. 2. Data on file. DRG physician survey. San Diego, CA: Heron Therapeutics Inc; 2017. 3. 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. 4. 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. 5. 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. 6. Exparel [package insert]. San Diego, CA: Pacira Pharmaceuticals Inc; 2021. 7. 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. 8. Hill MV, McMahon ML, Stucke RS, Barth RJ Jr. Wide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg. 2017;265(4):709-714. doi:10.1097/SLA.0000000000001993. 9. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6):e170504. doi:10.1001/jamasurg.2017.0504. 10. Svensson I, Sjöström B, Haljamäe H. Assessment of pain experiences after elective surgery. J Pain Symptom Manage. 2000;20(3):193-201. doi:10.1016/S0885-3924(00)00174-3. 11. 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. 12. 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. 13. Fanikos J, Minkowitz H, Reinhorn M, Quart B. HTX-011 as the foundation of a non-opioid, multimodal analgesic regimen reduces the need for opioids following herniorrhaphy in a real-world study. Poster presented at: American Society of Health-System Pharmacists 2019 Midyear Clinical Meeting & Exhibition; December 9, 2019; Las Vegas, NV. 14. ZYNRELEF [instructions for use]. San Diego, CA: Heron Therapeutics Inc; 2024.