Zynrelef - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Zynrelef (60 mg + 1.8 mg) / 2.3 mL prolonged-release wound solution

Zynrelef (200 mg + 6 mg) / 7 mL prolonged-release wound solution

Zynrelef (400 mg + 12 mg) / 14 mL prolonged-release wound solution

bupivacaine/me­loxicam

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Zynrelef is and what it is used for

• 2. What you need to know before you are given Zynrelef

• 3. How you will be given Zynrelef

• 4. Possible side effects

• 5. How to store Zynrelef

• 6. Contents of the pack and other information

1. What Zynrelef is and what it is used for

Zynrelef contains the medicines bupivacaine and meloxicam.

• Bupivacaine belongs to a group of medicines called local anaesthetics.
• Meloxicam belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).

Zynrelef will be applied during surgery by your doctor.

Zynrelef is used in adults to reduce pain from small- to medium-sized surgical wounds after surgery.

2. What you need to know before you are given Zynrelef

You must not be given Zynrelef:

• if you are in your last trimester of pregnancy (30 weeks onwards). See section on pregnancy;
• if you are allergic to bupivacaine and/or meloxicam or any of the other ingredients of this

medicine (listed in section 6);

• if you are allergic to other local anaesthetics of the same class as bupivicaine (such as lidocaine, mepivacaine, prilocaine, levobupivacaine, and ropivacaine);
• if you have ever developed any of the following after taking acetyl salicylic acid, a

substance present in many medicines used to relieve pain and lower fever, as well as to prevent blood clotting, or other non-steroidal anti-inflammatories :

• – 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)

• during a heart bypass surgery (coronary artery bypass graft);
• if you have severe heart failure;
• if you have severe liver problems;
• if you have severe kidney failure and not receiving dialysis.

If you are not sure if any of the above applies to you, talk to your doctor before you are given Zynrelef.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before receiving Zynrelef:

• if you have heart problems, previous stroke or think that you might be at risk of these conditions because medicines such as meloxicam present in Zynrelef may be associated with a small increased risk of heart attack (“myocardial infarction”) or stroke.
• if you have ever had bleeding from your stomach or gastro-intestinal tract, a stomach ulcer, or inflammation of the stomach (gastritis) because medicines such as meloxicam present in Zynrelef may worsen these conditions.
• if you develop signs of skin reactions, especially within the first weeks after surgery. Your doctor will closely monitor skin reactions, and Zynrelef must never be administered to you again.
• if you have impaired kidney function or kidney disease.
• if you have impaired liver function or liver disease.
• if you have high potassium levels in your blood (hyperkalaemia).
• if you are having a surgery to fix a bunion in your foot because impaired wound healing has been observed in patients following this surgery. Your doctor should be aware to avoid the administration of an excess volume of Zynrelef.

Chondrolysis (breakdown of the cartilage) has been reported in patients receiving postoperative intra-articular continuous infusion of local anaesthetics (one of the ingredients of this medicine). Your doctor should be aware that Zynrelef is not intended to be used for administration via an intra-articular route.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before you are given Zynrelef.

Children and adolescents

Zynrelef is not recommended for use in children and adolescents below 18 years of age.

Other medicines and Zynrelef

Tell your doctor if you are taking, have recently taken or might take any other medicines. This is because Zynrelef can affect the way some medicines work.

In particular, tell your doctor or pharmacist if you are taking/have taken or are using any of the following:

• medicines used to treat an uneven heart beat (arrhythmia), such as lidocaine and mexiletine.

Your doctor needs to know about these medicines to be able to work out the correct dose of Zynrelef for you.

Also, tell your doctor if you are taking any of the following medicines:

• medicines to treat heart and kidney diseases (such as ACE inhibitors, angiotensin receptor

blockers, or beta-blockers);

• any diuretic medicine (“water tablets”). Your doctor may monitor your kidney function if you

are taking diuretics;

• lithium – used to treat mood disorders.

If you are in doubt about any of these medicines, ask your doctor.

Pregnancy, breast-feeding and fertility

Tell your doctor immediately if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby. Meloxicam, one of the medicines in Zynrelef, may make it more difficult to become pregnant. If you have difficulties conceiving or you are undergoing investigation for fertility, your doctor will decide if Zynrelef should be given to you.

Zynrelef must not be administered during the last three months of pregnancy because Zynrelef can have serious side effects on your unborn child, in particular heart, lung and kidney effects, even with only one administration. During the first 6 months of pregnancy, your doctor will decide if Zynrelef should be given to you. Zynrelef is not recommended during breast-feeding.

Driving and using machines

Zynrelef may have a very mild effect on your mental function and coordination, and may temporarily impair your locomotion and alertness. After you have been given Zynrelef, you should not drive or use tools or machines until after these effects wear off.

3. How you will be given Zynrelef

Zynrelef will be applied during surgery by your doctor.

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

Your doctor may decide to reduce the dose if you are elderly.

Your doctor will ensure you have the correct amount of pain relief at all times.

If you have been given too much Zynrelef

Serious side effects from getting too much Zynrelef need special treatment and the doctor treating you is trained to deal with these situations.

Seek medical help as soon as possible if you experience any of these early signs of being given too much Zynrelef:

• 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.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Important side effects to look out for:

Side effects reported in clinical studies for patients treated with Zynrelef were:

Very common (may affect more than 1 in 10 people):

• dizziness

Common (may affect up to 1 in 10 people):

• abnormally slow heart beat;
• low blood pressure;
• unpleasant body smell;
• infection of the skin (cellulitis);
• abnormal healing, including reopening of the wound, at the site of bunion surgery;
• swelling, redness, heat or infection at the site of surgery;
• swelling of your lower legs or hands;
• altered taste.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Zynrelef

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry date refers to the last day of that month.

Do not store above 25°C.

Store in the original package in order to protect from light and moisture.

Your doctor or the hospital will normally store Zynrelef and they are responsible for the quality of the medicine when it has been opened if it is not used immediately. The medicine should be visually inspected prior to use. The solution should only be used if it is clear, practically free from particles and if the container is undamaged. Your doctor will throw away the medicine appropriately.

6. Contents of the pack and other information

What Zynrelef contains

• – The active substances are bupivacaine and meloxicam. Each mL of solution contains 29.25 mg bupivacaine and 0.88 mg meloxicam.

• – Zynrelef prolonged-release solution is provided in the following doses:

• 60 mg/1.8 mg of bupivacaine/me­loxicam.
• 200 mg/6 mg of bupivacaine/me­loxicam.
• 400 mg/12 mg of bupivacaine/me­loxicam.

• – The other ingredients are DETOSU/triethylene glycol/triethylene glycol polyglycolide copolymer, triacetin, dimethyl sulfoxide and maleic acid.

What Zynrelef looks like and contents of the pack

Zynrelef is a prolonged-release wound solution for intralesional use (application to surgical site). It is a clear, pale yellow to yellow solution.

Each Zynrelef pack contains 1 × 10 mL or 1 × 20 mL single-use glass vial, contained in an individual carton and sterile individually packaged components for preparation and administration:

• 60 mg bupivacaine and 1.8 mg meloxicam: one 10 mL single-dose vial, 1 vented vial spike, one

• 3 mL Luer lock syringe, and 1 Luer lock applicator.

• 200 mg bupivacaine and 6 mg meloxicam: one 10 mL single-dose vial, 1 vented vial spike, one

12 mL Luer lock syringe, and 1 Luer lock applicator.

400 mg bupivacaine and 12 mg meloxicam: one 20 mL single-dose vial, 1 vented vial spike, two 12 mL Luer lock syringes, and 2 Luer lock applicators.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Heron Therapeutics, B.V.

Herengracht 500

1017 CB Amsterdam

Netherlands

Manufacturer

Millmount Healthcare Limited

Block-7, City North Business Campus

Stamullen K32 YD60

Co. Meath

Ireland

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website:

.

The following information is intended for healthcare professionals only:

INSTRUCTIONS FOR USE FOR ZYNRELEF

• 1. Zynrelef is intended for single-dose administration on­ly.

• 2. Zynrelef is supplied as a procedure pack consisting of a single-dose glass vial, and the following

sterile components: Luer lock syringe(s), a vented vial spike, and Luer lock applicator(s).

• 3. Zynrelef is a viscous solution that should only be prepared and administered with the components provided in the Zynrelef procedure pack.

• 4. The contents of the Zynrelef vial are sterile. The vial exterior is not sterile. Aseptic technique must be strictly observed throughout handling of the medicinal product to keep it free from microbial contamination.

Preparation

The following 3 procedure packs are available for Zynrelef:

Product Presentation	Syringe size	Number of syringes	Volume to withdraw per syringe a	Volume administered
60 mg/1.8 mg of bupivacaine/me­loxicam solution in a 10 mL vial	3 mL	1	2.3 mL	2.0 mL
200 mg/6 mg of bupivacaine/me­loxicam solution in a 10 mL vial	12 mL	1	7 mL	6.7 mL
400 mg/12 mg of bupivacaine/me­loxicam solution in a 20 mL vial	12 mL	2	7 mL (14 mL total)	13.5 mL

a Volume withdrawn includes Luer lock applicator hold-up volume.

Instructions for preparation and administration

For operating room preparation, it is recommended that a 2-person team prepares this product: one sterile (shown in blue) and one non-sterile (shown in green).

NON-STERILE

You may assist the sterile person with inverting the vial if necessary by holding the non-sterile vial.

This medicinal product should only be prepared immediately prior to use. This medicinal product cannot be prepared and stored in advance of use.

Administration Instructions – This information should be reviewed before using the medicinal product for the first time. Zynrelef should only be administered with the syringe and Luer lock applicator provided in the procedure pack.

• 1. Zynrelef is applied without a needle into the surgical site following final irrigation and suction and prior to suturing. Only apply Zynrelef after final irrigation and suction of each layer before closing, if multiple tissue layers are involved.

• 2. Using the Luer lock applicator attached to the syringe, apply Zynrelef to the tissues within the surgical site that could result in pain generation.

• 3. 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.

• 4. Only apply Zynrelef to the tissue layers below the skin incision and not directly onto the skin.

• 5. The amount of Zynrelef required depends upon the surgical area of tissue to be treated. The maximum total dose volume is approximately 14 mL. Zynrelef spreads easily and covers a large area.

• 6. Zynrelef does not degrade sutures. When using monofilament sutures, 3 or more knots are recommended as contact with Zynrelef may cause a single knot to loosen or untie.