CARDIOPLEXOL SOLUTION FOR CARDIOPLEGIA

2. What you need to know before using Cardioplexol

Do not use Cardioplexol

Warnings and Precautions

If you have severe myasthenia, administration of this medication may increase muscle weakness.

If you have a deficiency of a specific enzyme (pseudocholinesterase), the active principle may have increased effects (toxic symptoms).

At the end of this package leaflet, in the section "Information intended exclusively for healthcare professionals," additional information is provided regarding the use and handling by qualified personnel.

Children and Adolescents

The safety and efficacy of this medication in children and adolescents have not been established. No data are available.

Other Medications and Cardioplexol

Tell your doctor or nurse if you are using, have recently used, or may need to use any other medication.

Cardioplexol ready-to-use solution should not be mixed with other medications.

Especially inform your doctor if you are using muscle relaxants, sulfonamides (antibiotics), or cholinesterase inhibitors such as physostigmine (medications for treating Alzheimer's disease).

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or nurse before using this medication.

Pregnancy and Breastfeeding

There are no data on the use of this medication in pregnant or breastfeeding women. If you are pregnant, this medication will only be administered if clearly indicated.

Driving and Using Machines

Not applicable

3. How to use Cardioplexol

This medication will be administered to you during surgery only by qualified and trained personnel in open-heart surgery.

This solution is intended only for use during cardiopulmonary bypass when coronary circulation is isolated from systemic circulation.

Continuous electrocardiographic monitoring is essential to detect changes in myocardial activity during surgery.

Adequate equipment for defibrillation of the heart, as well as inotropic support medications, should be available.

Your doctor will evaluate the correct dose for you during surgery

Method of administration:

The product is indicated only for intracoronary use.

Injection of this cardioplegic solution should only be performed by trained cardiac surgeons familiar with its preparation and administration.

If you use more Cardioplexol than you should

It is very unlikely that you will be administered an overdose. You will be given this medication in the hospital under the supervision of your doctor. Your doctor has information on how to recognize and treat an overdose and will apply supportive measures to maintain cardiocirculatory and respiratory function in case of actual overdose.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the packaging and package leaflet of the medication to the healthcare professional.

If you have any questions about the use of this medication, ask your doctor or nurse.

4. Possible Side Effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

The undesirable effects observed in patients who received this medication are inherent to open-heart surgery and include myocardial infarction, electrocardiographic abnormalities, arrhythmias such as ventricular fibrillation. Spontaneous recovery from cardioplegic cardiac arrest may be delayed and subsequently require the use of a pacemaker. Defibrillation may be necessary to restore rhythmic cardiac contractile function. In a clinical trial, the following side effects were classified as at least possibly related to this medication:

Uncommon (may affect up to 1 in 100 people): death, medication error.

Unknown (frequency cannot be estimated from available data): arrhythmia, heart failure, myocardial infarction, delayed effect of the medication.

Reporting Side Effects

If you experience any side effects, consult your doctor or nurse, even if they are not listed in this package leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Cardioplexol

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

Do not use this medication after the expiration date stated on the box, vial, and syringe after EXP. The expiration date is the last day of the month indicated.

Do not use this medication unless the solutions are transparent and the packaging is intact.

Do not store above 25°C. Do not freeze.

After reconstitution (mixing of Solution A and Solution B), the solution can be stored in its original glass vial at 2-8°C for one hour before transferring it to the administration syringe by aspiration. Once removed from the vial, use within 15 minutes.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Cardioplexol

• The active ingredients are:

Cardioplexol Solution A: contains (95 ml): magnesium sulfate heptahydrate 4g (16.2 mmol), potassium chloride 0.746g (10.0mmol), xylitol 4.5g (29.6 mmol) Cardioplexol Solution B: contains (5 ml): procaine hydrochloride 0.3 g (1.1 mmol)

Cardioplexol ready-to-use solution (composed of Solution A and Solution B) 100 ml contains:

• The other excipients are:

Cardioplexol Solution A: citric acid monohydrate, sodium hydroxide (for pH adjustment), water for injectable preparations

Cardioplexol Solution B: hydrochloric acid (for pH adjustment), water for injectable preparations.

Appearance of the Product and Container Contents

Cardioplexol - Solution A: 100 ml Type I glass vial. The vial is sealed with a rubber stopper, a flip-off aluminum cap, and a polypropylene safety cap.

Cardioplexol – Solution B: 5 ml single-use BD Sterifill SCF Crystal Clear Polymer (CCP) syringe.

The vial (containing Solution A) is placed in a transparent plastic box (polycarbonate) along with the aluminum bag containing the pre-filled syringe (containing Solution B) and a sterile 18 G stainless steel needle.

The plastic box is inserted into a cardboard box that is sealed with a sticker.

Marketing Authorization Holder and Manufacturer

MIT Gesundheit GmbH

Thaerstrabe 4a

47533 Kleve

Germany

Manufacturer

Biokanol Pharma GmbH

Kehler Str. 7

76437 Rastatt

Germany

This Medicinal Product is Authorized in the Member States of the European Economic Area under the Following Names:

Date of the Last Revision of thisLeaflet:04/2024

Other Sources of Information

Detailed information on this medicinal product is available on the website of the {Spanish Agency for Medicines and Health Products (AEMPS)} (http://www.aemps.gob.es/)

----------------------------------------------------------------------------------------------------------------------------------

This Information is Intended Only for Healthcare Professionals:

Posology and Method of Administration

Only by intracoronary route, only during extracorporeal circulation when coronary circulation is isolated from systemic circulation.

The injection of the Cardioplexol solution for cardioplegia must be performed only by trained surgeons accustomed to its preparation and administration.

Continuous electrocardiographic monitoring is essential to detect changes in cardiac electrical activity during surgery.

Adequate equipment for defibrillating the heart after cardioplegia, as well as inotropic support medications, should be readily available.

Posology

Initial Dose:

The usual initial dose is a single injection of 100 ml of the ready-to-use solution. The ready-to-use solution consists of 95 ml of electrolyte solution (Solution A) and 5 ml of procaine solution (Solution B).

The solution should be administered immediately after aortic clamping and injected rapidly (within 10-15 seconds). If the heart does not stop beating within 10-15 seconds, it is essential to check for possible causes that would require immediate adaptation.

These checks include:

• Is the aortic ventilation cannula still open?

If so, it is likely that the cardioplegic solution has been directly eliminated. In this case, close or disconnect the ventilation and administer a new initial dose of the ready-to-use solution.

• Is the aortic clamp properly placed?

If the clamp is not totally occlusive, retrograde blood flow will compromise the action of the cardioplegic solution. In such a case, reposition the aortic clamp and administer a new initial dose of the ready-to-use solution.

• Is there an unrecognized aortic valve insufficiency?

In this case, the ready-to-use solution should be administered directly into the coronary ostia using an appropriate coronary cannula.

• Is there ventricular hypertrophy?

If so, administer a complementary dose of 50 - 100 ml (total injection volume = 150 - 200 ml).

If none of these possible causes apply and the heart has not stopped beating, administer an additional dose of 50 - 100 ml of the ready-to-use solution.

Maintenance Dose:

Cardioplegic protection should be repeated if the ischemic period needs to be prolonged. Normally, a second dose of 100 ml of the ready-to-use solution should be administered 45 minutes after aortic clamping and thereafter every 30 minutes until the heart has been reperfused.

If it is anticipated that the additional ischemic period will be less than 30 minutes, the additional dose may be reduced to 50 ml. In other situations or in the case of ventricular hypertrophy, it is recommended to administer a complete additional dose of 100 ml.

Table 1

Pediatric Population:

The safety and efficacy of Cardioplexol in children and adolescents have not been established. No data are available.

Special Populations

Cardiac Hypertrophy or Other Situations with Enlarged Heart:

Although not specifically studied, current clinical knowledge indicates that the initial dose should be increased to 150 - 200 ml. Each subsequent dose should be 100 ml and should be administered punctually (as described in Table 1)

Aortic Valve Insufficiency:

In case of aortic valve insufficiency with a severity grade >1, injection of the ready-to-use solution into the aortic root is contraindicated, as the amount of ready-to-use solution reaching the coronary vasculature may be insufficient. Instead, the doses of the ready-to-use solution should be injected directly into the coronary ostia using an appropriate coronary cannula.

Renal Function Impairment:

No dose adjustment is necessary.

Hepatic Function Impairment:

No dose adjustment is necessary.

Elderly (from 65 years):

No dose adjustment is necessary.

Method of Administration:

To obtain detailed information on the preparation of the ready-to-use cardioplegic solution, refer to"Preparation of the Ready-to-Use Cardioplegic Solution".

The product is indicated only for intracoronary use. The injection of Cardioplexol solution for cardioplegia must be performed only by trained cardiac surgeons accustomed to its preparation and administration. The intracoronary injection (initial and maintenance doses) is administered with the ready-to-use solution refrigerated at 2-8°C.

The individual components of Cardioplexol - Solution A and Solution B - must not be administered separately.

Administration:

• The surgeon takes the first 50 ml syringe and connects it via the Luer lock to the 3-way connector of the aortic cardioplegia cannula.
• The syringe is kept vertical and a few ml of blood are aspirated from the cannula to verify the connection and complete the de-airing of the cannula.
• The aorta is cross-clamped.
• The entire contents of this first syringe with the ready-to-use solution are manually injected rapidly (in approximately 5 seconds) into the aortic root.
• The empty syringe is disconnected and immediately replaced by the second 50 ml syringe.
• After de-airing, the contents of the second syringe are administered rapidly (in approximately 5 seconds) in the same manner.

Precaution:

• It is recommended to monitor the aortic valve by transesophageal echocardiography during OR anesthesia after induction of anesthesia to verify the competence of the aortic valve. In case of aortic valve insufficiency (severity grade >1), the ready-to-use solution of Cardioplexol should be administered directly into the coronary ostia and not into the aortic root.
• Ensure that the aortic clamp is properly placed and that the aorta is completely occluded.
• Ensure that the aortic vent is closed before injecting the cardioplegic solution into the aortic root.
• The injection should be started without delay once the aorta is clamped.
• The contents of both 50 ml syringes with the ready-to-use solution should be administered rapidly (within 10-15 seconds).

Preparation of the Ready-to-Use Cardioplegic Solution

The Cardioplexol ready-to-use solution must be prepared by qualified personnel for this type of procedure (e.g., cardiotechnician, surgical nurse).

Before administration, the sealed box containing the two components should be refrigerated at 2-8°C for at least 3 hours to reach the correct temperature. Since it may be necessary to administer additional doses of Cardioplexol, at least 2 additional sealed boxes of this medicinal product should be stored in the refrigerator during the procedure.

The sterile injection of Solution B (supplied in the syringe) into the vial containing Solution A produces the ready-to-use solution of this medicinal product.

Preparation by Qualified Personnel:

• Open the aluminum bag containing the 5 ml syringe (Solution B).
• Connect the needle (18 G needle) supplied with Cardioplexol
• Remove the aluminum cap covering the rubber stopper of the vial (Solution A).
• Disinfect the rubber stopper.
• Puncture the rubber stopper with the needle and inject the 5 ml of contents of the syringe (Solution B) into the vial (Solution A).
• Remove the syringe and its needle.
• Gently shake the vial while keeping the rubber stopper sterile.
• Present the vial to the qualified personnel so that they can easily puncture the rubber stopper.

Preparation by Qualified Personnel:

• Obtain 2 sterile Luer-lock syringes of 50 ml.
• Connect one syringe to a 14 G needle.
• Puncture the vial presented by the qualified personnel (careful, the vial itself is not sterile).
• Aspirate 50 ml of the Cardioplexol ready-to-use solution into the syringe.
• Disconnect the syringe from the needle.
• Connect the second syringe to the needle and aspirate the remaining 50 ml of the Cardioplexol ready-to-use solution.
• Disconnect the syringe from the needle (which remains with the vial and is discarded by the qualified personnel).
• Carefully de-air the 2 syringes.
• Keep the 2 syringes on the table ready to be used by the surgeon.

Precaution:

• The mixture of Solution A (95 ml vial) and Solution B (5 ml syringe) should be performed no earlier than 30 minutes before the surgeon administers it.
• The ready-to-use solution (Solution A and Solution B mixed) can be stored in the original glass vial at 2-8°C for 1 hour.
• Once transferred to the two 50 ml syringes, the ready-to-use solution should be injected into the coronary arteries within 15 minutes.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.