Novel, Needle-Free Application

ZYNRELEF box with 400 mg vial next to it; needle-free applicator laying in front of vial and box; all components.

Instructions for use

ZYNRELEF is a viscous solution administered as a single-dose needle-free instillation to directly coat the affected tissue within the surgical site after final irrigation and suction and prior to suturing. The solution becomes more viscous when it comes into contact with moisture at the surgical site, allowing it to stay where it is placed. The active ingredients are released from the polymer and diffuse throughout the affected tissue.1,2

Administration

  • ZYNRELEF should not be administered with a needle. ZYNRELEF should only be administered with the syringe and Luer lock cone-shaped applicator provided in the ZYNRELEF kit.3
  • ZYNRELEF is applied into the surgical site following final irrigation and suction and prior to suturing. ZYNRELEF should only be applied after final irrigation and suction of each layer before closing, if multiple tissue layers are involved.3
  • ZYNRELEF is applied to the tissues within the surgical site that could result in pain generation. Use a sufficient amount to coat the tissues. For small spaces, ensure there is not an excess that could be expressed from the site during closure. Only apply ZYNRELEF to the tissue layers below the skin incision and not directly onto the skin.3
  • ZYNRELEF does not degrade sutures. When using monofilament sutures, use 3 or more knots as contact with ZYNRELEF may cause a single knot to loosen or untie.3
Visit the Resource Center to view detailed administration instructions for common surgical procedures.

View the Instructions for Use—14 mL.

View the Instructions for Use—7 mL.

Animation: Needle-free applicator applying ZYNRELEF into the surgical site.

ZYNRELEF kit contents, storage, and preparation

ZYNRELEF comes in a kit containing a ready-to-use vial and everything needed for needle-free application. Surgeons and PAs require no specialized training to administer ZYNRELEF.3

14-mL ZYNRELEF kit and components.

CAUTION: Do not substitute any of the components

  1. Vented Vial Spike
    • Sterile
  2. Luer Lock Syringe
    • Sterile
    • 2 syringes included in 14-mL kits
  3. Luer Lock Cone-Shaped Applicator
    • Sterile
    • 2 applicators included in 14-mL kits
  4. Tip Cap
    • Sterile
    • 2 caps included in 14-mL kits
  5. ZYNRELEF Vial
    • Contents sterile, exterior not sterile
  6. Instructions for Use

Storing the product

  • ZYNRELEF is room temperature stable for 36 months4
  • The ZYNRELEF kit carton is sized to fit in standard operating room automated dispensing cabinets, such as those manufactured by PyxisTM

For operating room preparation

Prepare product immediately prior to use and apply syringe tip cap until product delivery.3

Learn the step-by-step process of preparing ZYNRELEF.

ZYNRELEF kit contents, storage, and preparation

ZYNRELEF comes in a kit containing a ready-to-use vial and everything needed for needle-free application. Surgeons and PAs require no specialized training to administer ZYNRELEF.3

Hover or tap on the numbers for more information.

14-mL ZYNRELEF kit and components.

1. Vented Vial Spike

  • Sterile

2. Luer Lock Syringe

  • Sterile
  • 2 syringes included in 14-mL kits

3. Luer Lock Cone-Shaped Applicator

  • Sterile
  • 2 applicators included in 14-mL kits

4. Tip Cap

  • Sterile
  • 2 caps included in 14-mL kits

5. ZYNRELEF Vial

  • Contents sterile, exterior not sterile

6. Instructions for Use

Storing the product

  • ZYNRELEF is room temperature stable for 36 months4
  • The ZYNRELEF kit carton is sized to fit in standard operating room automated dispensing cabinets, such as those manufactured by PyxisTM

For operating room preparation

Prepare product immediately prior to use and apply syringe tip cap until product delivery.3

Learn the step-by-step process of preparing ZYNRELEF.

Dosing

Mixing with bupivacaine is not required to achieve efficacy with ZYNRELEF. Meloxicam potentiates the effects of bupivacaine over 72 hours without support from additional products. ZYNRELEF should not be mixed with water, saline, or other local anesthetics as the product will become very viscous and difficult to administer.1

Learn more about specific dosing recommendations by visiting the Resource Center.
Silhouette 3 vials labeled, “Liposomal Bupivacaine, Bupivacaine HCl Solution, and Normal Saline”; circled and crossed out.

Two vial volumes

  • Reduces average cost and waste to the facility
  • Use a sufficient amount to coat affected tissues1
  • Do not use more than is needed to coat tissues to prevent excess from being expressed from site during closure1
  • If excess does express from site, clean skin surface after suturing
14 mL (400 mg bupivacaine and 12 mg meloxicam) ZYNRELEF vial.

14–mL Vial Size

  • Total Knee Arthroplasty
    • up to 14 mL to deliver 400 mg/12 mg
  • Herniorrhaphy
    • up to 10.5 mL to deliver 300 mg/9 mg
7 mL (200 mg bupivacaine and 6 mg meloxicam) ZYNRELEF vial.

7 mL Vial Size

  • Bunionectomy
    • up to 2.3 mL to deliver 60 mg/1.8 mg

The recommended dose is based on the following factors1:

  • Size of the surgical site
  • Volume required to cover the tissues within the surgical site that could result in pain generation
  • Maximum total dose is 400 mg of bupivacaine/12 mg meloxicam (14 mL)

Contact your Heron representative

From answering questions about ZYNRELEF to providing updates on the reimbursement landscape, Heron representatives are here to help.

Contact Us

Important Safety Information and Indication

Indication

ZYNRELEF is indicated in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty.

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.

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 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 coronary artery bypass graft (CABG) surgery.

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.

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 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.

Adverse Reactions

Most common adverse reactions (incidence ≥10%) in controlled clinical trials with ZYNRELEF are constipation, vomiting, 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 soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty.

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.

Please see full Prescribing Information, including Boxed Warning.

References: 1. ZYNRELEF [package insert]. San Diego, CA: Heron Therapeutics Inc; 2021. 2. 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. 3. ZYNRELEF [instructions for use]. San Diego, CA: Heron Therapeutics Inc; 2021. 4. Roca R; Center for Drug Evaluation and Research. NDA approval letter: NDA 211988 (Zynrelef). Silver Spring, MD: US Food and Drug Administration; May 12, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2021/211988Orig1s000ltr.pdf. Accessed May 13, 2021.