Zynrelef: Uses, Side Effects and Dosage

Serious Warnings And Precautions

What is ZYNRELEF used for?

ZYNRELEF is a local analgesic used in adults to reduce pain after:

• removal of bunions,
• groin hernia repair, and
• total knee replacement.

ZYNRELEF is applied into the wound at the end of surgery.

How does ZYNRELEF work?

ZYNRELEF is a combination of two drugs that work together to reduce pain: bupivacaine, a local anesthetic, and meloxicam, a nonsteroidal anti-inflammatory drug (NSAID).

What are the ingredients in ZYNRELEF?

Medicinal ingredients: Bupivacaine and meloxicam.

Non-medicinal ingredients: Dimethyl sulfoxide, maleic acid, triacetin, tri(ethylene glycol) poly(orthoester) or TEG-POE.

ZYNRELEF comes in the following dosage forms:

It comes in 4 vial sizes:

• 400 mg bupivacaine and 12 mg meloxicam (14 mL in 20 mL single-dose vial)
• 300 mg bupivacaine and 9 mg meloxicam (10.5 mL in 20 mL single-dose vial)
• 200 mg bupivacaine and 6 mg meloxicam (7 mL in 10 mL single-dose vial)
• 60 mg bupivacaine and 1.8 mg meloxicam (2.3 mL in 10 mL single-dose vial)

ZYNRELEF should not be given to you if:

• you are allergic to bupivacaine and/or meloxicam or any of the other ingredients of this medicine;
• you are allergic to other local anesthetics of the same class as bupivacaine (such as lidocaine, mepivacaine, prilocaine, levobupivacaine, and ropivacaine);

• you develop any of the following after taking aspirin or other NSAIDs:

  • wheezing, chest tightness, breathlessness (asthma);
  • nasal blockage due to swellings in the lining of your nose (nasal polyps);
  • skin rashes/nettle rash (urticaria) or serious skin reactions;
  • sudden skin or mucosal swelling, such as swelling around the eyes, face, lips, mouth, or throat, possibly making breathing difficult (angioneurotic oedema);
• you require a local anesthetic during childbirth (paracervical block);
• you are having heart bypass surgery (coronary artery bypass graft);
• you have severe heart failure;
• you have severe liver problems;
• you have severe kidney failure and not receiving dialysis;

• you are pregnant and in a later stage of pregnancy (28 weeks or later).

To help avoid side effects and ensure proper use, talk to your healthcare professional before you are given ZYNRELEF. Talk about any health conditions or problems you may have, including if you:

• have heart problems, previous stroke, or think that you might be at risk of these conditions;
• have ever had bleeding from your stomach or gastrointestinal tract, a stomach ulcer, or inflammation of the stomach (gastritis);
• have asthma or diabetes;
• have liver problems;
• have kidney problems;
• have a genetic blood disorder (methemoglobinemia);
• are pregnant, breastfeeding, or if you may be pregnant or are planning to have a baby.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with ZYNRELEF:

• medicines used to treat an uneven heart beat (arrhythmia), such as procainamide, disopyramide, mexiletine, and flecainide;
• medicines to treat heart and kidney diseases (such as ACE inhibitors, angiotensin receptor blockers, or beta-blockers);
• aspirin;
• any diuretic medicine (“water tablets”);
• lithium, which is used to treat mood disorders;
• blood thinners such as warfarin;
• non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates (e.g., diflunisal, salsalate) used to treat pain following your surgery;
• serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) to treat depression;
• digoxin used to treat heart problems or heart failure;
• methotrexate used to treat certain types of cancer;
• cyclosporine used as an immunosuppressant medication;
• pemetrexed used to treat pleural mesothelioma and lung cancer.

Tell your healthcare professional if you are on medications for any health condition, even if they are not related to your surgery, because they may interact with medications used for your surgery.

How to take ZYNRELEF:

• ZYNRELEF is applied once by your healthcare professional during surgery.

Usual Dose:

Your healthcare professional will determine the correct dose for you depending on the type of surgery you are having.

Overdose:

Serious side effects from ZYNRELEF may need special treatment and the healthcare professional treating you is trained to deal with these situations.

Tell your healthcare professional immediately if you experience any of these early signs or symptoms:

• feeling dizzy or light-headed;
• numbness of the lips and around the mouth;
• numbness of the tongue;
• hearing problems;
• problems with your vision.

More serious side effects from being given too much ZYNRELEF include problems with your speech, twitching of your muscles, tremors, trembling, fits (seizures), and loss of consciousness. If any of these occur, seek medical help immediately.

Missed Dose:

ZYNRELEF is only given as a single dose during surgery. Therefore, you will not miss a dose.

What are possible side effects from using ZYNRELEF?

These are not all the possible side effects you may have when taking ZYNRELEF. If you experience any side effects not listed here, tell your healthcare professional.

Sudden life-threatening allergic reactions (such as anaphylaxis). If you think that ZYNRELEF is causing an allergic reaction, tell your healthcare professional immediately. Symptoms may include:

• sudden onset of rash;
• itching or lumpy rash (hives);
• swelling of the face, lips, tongue, or other parts of the body;
• shortness of breath, wheezing, or difficulty breathing.

Life-threatening skin reactions. Tell your healthcare professional immediately if you experience:

• reddish target-like spots, red welts, or purple areas on your stomach, chest, back, mouth, throat, eyes, nose, or genitals;
• peeling or blistering of the skin;
• flu-like symptoms.

Potentially life-threatening serious skin reactions have been reported with the medicines in ZYNRELEF.

Gastrointestinal bleeding or ulcers. Tell your healthcare professional immediately if you experience:

• black colored stools;
• blood in your stool;
• stomach pain.

Gastrointestinal bleeding or ulcers may sometimes be severe and potentially fatal, especially in the elderly.

Serious side effects and what to do about them

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

Storage:

Store at room temperature (15 - 25°C) in original carton.

Protect from light and moisture.

Keep out of reach and sight of children.

If you want more information about ZYNRELEF:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website: (https://health-products.canada.ca/dpd-bdpp/index-eng.jsp) or the manufacturer’s website [https://www.ZYNRELEF.com], or calling 1-844-437-6611.

ZYNRELEF® is a registered trademark of Heron Therapeutics, Inc.

Copyright © 2022 – 2023 Heron Therapeutics, Inc. All rights reserved.

Last Revised: June 1, 2023