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

14 mL (400 mg/12 mg)

7 mL (200 mg/6 mg)

Step 1: Prepare components

STERILE

Open all components onto sterile field. Reminder: Prepare all syringes provided in kit, and do not substitute any of the components. Only withdraw 7 mL of ZYNRELEF into each syringe. For the 400-mg dose (14 mL total) fill 2 syringes, each with 7 mL.

Note: Vial contains overfill to account for amount that remains in the vial, vial spike, applicator, and syringe during drug withdrawal and administration.

Do not inject ZYNRELEF.

400-mL kit components; 2 syringes, 2 needle-free tips, 2 tip caps, 1 vented vial spike.

2-person team recommended: 1 sterile, 1 nonsterile

Step 2: Prepare vial

NONSTERILE

  1. Flip cap off of vial and place onto stable, nonsterile surface. Do not remove the stopper from the vial or attempt to pour the vial contents into a sterile cup.
  2. Cleanse septum with alcohol wipe.
  3. Hold the vial in place for safe insertion of the vented vial spike.
Green “nonsterile” hand holding ZYNRELEF vial on stable, nonsterile surface.

The contents of the ZYNRELEF vial are sterile. The vial exterior is not sterile. Follow your facility’s standard operating procedures regarding aseptic and sterile preparation.

Step 3: Remove protective sheath

STERILE

  1. Remove blue protective sheath from vented vial spike.
  2. Remove Luer cap.
Blue, “sterile” hands, removing protective sheath from vented vial spike and removing Luer cap.

Step 4: Attach vented vial spike

STERILE

  1. Hold the vented vial spike by the adapter neck to maintain sterility of the vented vial spike and sterile person.
  2. Push the spike through the septum until it snaps into place.

NONSTERILE

Hold the vial in place on a firm, flat surface while the sterile person attaches spike.
Blue “sterile” hand snapping vented vial spike down onto ZYNRELEF vial, held by green “nonsterile” hand on nonsterile surface.

Step 5: Prepare syringe

STERILE

Fill the syringe with 7 mL of air before attaching to the vented vial spike. Reminder: Air from syringe will be pushed into the vial at Step 7 after the vial has been inverted and product has filled the neck of the vial.
Blue “sterile” hands holding syringe from ZYNRELEF kit, filling syringe with 7 mL of air.

Doing this will improve withdrawal time.

Step 6: Prepare for withdrawal

STERILE

Attach the air-filled syringe to the vented vial spike.
  • Avoid moving the plunger rod up and down at any point in the withdrawal process

NONSTERILE

Hold the vial in place until the syringe is attached.
Blue “sterile” hand attaching air-filled syringe to the vial spike with green “nonsterile” hand holding ZYNRELEF vial.

Do not push air into the vial at any point this step.

Step 7: Withdraw product

STERILE

  1. Invert the vial using the syringe.
  2. Allow product to fill the neck of the vial before pushing air into the vial.
  3. Push air into vial and wait for the air bubble to rise.
  4. Withdraw indicated amount of product.
    • Small air bubbles in the syringe are normal
    • ZYNRELEF is viscous and specially formulated to coat the affected area. It may take a few minutes to withdraw.

NONSTERILE

You may assist the sterile person with inverting the vial if necessary, by holding the nonsterile vial.
Green “nonsterile” hand inverting the ZYNRELEF vial with blue “sterile” hands withdrawing ZYNRELEF into syringe.

Step 8: Repeat with second syringe if needed

STERILE

  1. Return vial to nonsterile surface.
  2. Remove syringe from vial and attach Luer lock applicator.
  3. Place syringe on sterile surface.
  4. Repeat steps 5 to 7 with second syringe if needed.

NONSTERILE

Hold the vial in place for attachment of second syringe.
Blue “sterile” hand attaching second syringe to vented vial spike held by green “nonsterile” hand.

Do not inject ZYNRELEF.

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. 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.

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.