Consumer medicine information

DBL Sterile Cardioplegia Concentrate

Procaine hydrochloride; Magnesium chloride hexahydrate; Potassium chloride

BRAND INFORMATION

Brand name

DBL Sterile Cardioplegia Concentrate

Active ingredient

Procaine hydrochloride; Magnesium chloride hexahydrate; Potassium chloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Sterile Cardioplegia Concentrate.

What is in this leaftet

This leaflet answers some common questions about DBL™ Sterile Cardioplegia Concentrate. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given DBL™ Sterile Cardioplegia Concentrate against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

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

What DBL™ Sterile Cardioplegia Concentrate is used for

This medicine is used in open-heart surgery. This medicine contains magnesium and potassium which stop the heart beating and minimise the energy requirements of the heart during surgery. It also contains procaine which protects the heart muscle and helps stop the heart beating during the surgery. Procaine also helps prevent disturbances in heart rhythm straight after the surgery.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

Before you are given DBL™ Sterile Cardioplegia Concentrate

When you must not be given it

You must not be given DBL™ Sterile Cardioplegia Concentrate if you have an allergy to:

  • procaine or other similar local anaesthetics
  • para-aminobenzoic acid or its derivatives (used as preservatives and in sunscreens)

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

You must not be given DBL™ Sterile Cardioplegia Concentrate if you

  • have myasthenia gravis, a disease with severe weakness of the muscles
  • have been told you have a heartbeat conduction defect
  • are taking medicines called anticholinesterases such as pyridostigmine
  • are taking medicines from a group of antibiotics, known as sulfonamides

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have any allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have ever had any other medical conditions, including:

  • liver disease
  • kidney disease
  • an overactive thyroid gland (hyperthyroidism)
  • if you or anyone in your family has had a dangerously high body temperature brought on by general anaesthesia

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given Sterile Cardioplegia Concentrate.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and DBL™ Sterile Cardioplegia Concentrate may interfere with each other. These include:

  • medicines which are used to treat myasthenia gravis, such as pyridostigmine
  • acetazolamide, a medicine used to treat glaucoma, fluid retention and certain rare types of epilepsy (fits)
  • medicines used to help you sleep or to treat anxiety or depression
  • strong pain relievers
  • diuretics (fluid tablets) such as triamterene, spironolactone and amiloride
  • angiotensin converting enzyme (ACE) inhibitors, medicines for high blood pressure and some other heart conditions
  • medicines containing potassium
  • cyclosporin, a medicine used to reduce the activity of the body's immune system
  • a group of antibiotics for treating infections, known as sulfonamides
  • hyaluronidase, used for bruising and preventing skin reactions to chemotherapy
  • neuromuscular blocking agents, medicines used to relax muscles.

Although it is unlikely, these medicines may be affected by DBL™ Sterile Cardioplegia Concentrate or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or to avoid while being given DBL™ Sterile Cardioplegia Concentrate.

How DBL™ Sterile Cardioplegia Concentrate is given

How much is given

Your doctor will decide how much DBL™ Sterile Cardioplegia Concentrate you will receive and how long you will receive it for. This depends on the type of open-heart surgery you are receiving and other factors such as your weight and height.

How it is given

DBL™ Sterile Cardioplegia Concentrate is diluted with Ringer's Injection before use and infused through the heart.

It must only be given by a person trained in open-heart surgery.

If you receive too much (overdose)

As DBL™ Sterile Cardioplegia Concentrate is given to you in hospital under the supervision of your doctor, it is unlikely that you will receive too much. Your doctor has information on how to recognise and treat an overdose.

Ask your doctor if you have any concerns.

Side Effects

Tell your doctor or nurse as soon as possible if you do not feel well after you have been given DBL™ Sterile Cardioplegia Concentrate. This medicine helps most people undergoing open-heart surgery, but it may have unwanted side effects in some people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Tell your doctor or nurse immediately if you notice any of the following after the surgery:

  • nausea
  • muscle twitching, tremors or convulsions (fits)
  • irregular or slow heartbeat.

Tell your doctor or nurse if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Ask your doctor to answer any questions you may have about possible side effects.

Your doctor will monitor you closely during the surgery for any side effects.

After you are given DBL™ Sterile Cardioplegia Concentrate

Storage

DBL™ Sterile Cardioplegia Concentrate will generally be stored in the pharmacy or on the ward. It is kept in a cool, dry place, where the temperature stays below 25°C.

Product Description

What it looks like

DBL™ Sterile Cardioplegia Concentrate is a clear, colourless solution supplied in glass ampoules

Ingredients

Each mL of DBL™ Sterile Cardioplegia Concentrate contains:

  • magnesium chloride hexahydrate 162.5 mg,
  • potassium chloride 59.5 mg
  • and procaine hydrochloride 13.64 mg as the active ingredients.

This medicine also contains:

  • water for injection.

DBL™ Sterile Cardioplegia Concentrate does not contain gluten, sucrose, tartrazine or any other azo dyes.

Sponsor

DBL™ Sterile Cardioplegia Concentrate is supplied by:

Australian Sponsor:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number : 1800 675 229
www.pfizer.com.au

DBL™ Sterile Cardioplegia Concentrate is available in the following presentation:

  • 20mL ampoules x 5
    AUST R 16365

This leaflet was prepared in August 2019.

Published by MIMS December 2019

BRAND INFORMATION

Brand name

DBL Sterile Cardioplegia Concentrate

Active ingredient

Procaine hydrochloride; Magnesium chloride hexahydrate; Potassium chloride

Schedule

S4

 

1 Name of Medicine

Magnesium chloride hexahydrate, potassium chloride, procaine hydrochloride.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

Magnesium chloride hexahydrate.

CAS Registry number is 7791-18-6.

Potassium chloride.

CAS Registry number is 7447-40-7.

Procaine hydrochloride.

CAS Registry number is 51-05-8.

2 Qualitative and Quantitative Composition

DBL Sterile Cardioplegia Concentrate contains magnesium chloride hexahydrate 3.25 grams (16 mmol), potassium chloride 1.19 grams (16 mmol), procaine hydrochloride 272.8 milligrams (1 mmol) and water for injections to 20 mL. The pH is 4.0 to 6.0.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

DBL Sterile Cardioplegia Concentrate is a sterile, clear, colourless solution for injection.
Magnesium chloride hexahydrate exists as colourless, odourless, deliquescent or hygroscopic crystals or flakes. It is very soluble in water, and freely soluble in alcohol. The chemical formula of magnesium chloride hexahydrate is MgCl2.6H2O. Its molecular weight is 203.3.
Potassium chloride is a white crystalline or granular powder, or odourless, colourless, cubical, elongated or prismatic crystals. It is very soluble in water, and practically insoluble in alcohol and dehydrated alcohol. The chemical formula of potassium chloride is KCl. Its molecular weight is 74.55.
Procaine hydrochloride is a white crystalline powder, or small colourless or white odourless crystals. It is very soluble in water, soluble in alcohol, slightly soluble in chloroform, and practically insoluble in ether. The chemical formula of procaine hydrochloride is C13H20N2O2.HCl. Its molecular weight is 272.8. For further detailed information on procaine hydrochloride, see the Product Information document on Procaine Hydrochloride Injection.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Cardiac surgery is most easily performed while the heart is still and relaxed, in a bloodless environment. Cardioplegia solution is used, usually in combination with cardiac hypothermia, to produce rapid and complete diastolic arrest. Cardioplegia solution aims to minimise myocardial energy requirements during arrest, prevent ischaemic damage which may be caused by the absence of coronary blood flow during the arrest phase, and to minimise or prevent reperfusion injury when coronary blood flow is restored.
In addition to inducing and maintaining arrest, the chemical components of the cardioplegia solution can counteract the specific cellular effects of ischaemia, and the cellular events that may occur during reperfusion.
Magnesium prevents cellular potassium and magnesium loss, conserving magnesium for its role as an enzymatic cofactor. Magnesium appears to counteract the effects of calcium in excitation-contraction coupling, resulting in reduced energy consumption. Magnesium ions also have a weak arresting action on the heart.
Potassium induces rapid diastolic arrest by blocking the inward sodium current and initial phases of cellular depolarisation. Cellular energy stores (adenosine triphosphate and creatine phosphate) are thereby preserved for post-ischaemic activity.
Procaine has a protective effect on the myocardium. Laboratory studies in rats have shown this to be additive to the protective effects of potassium and magnesium. Procaine may help induce arrest and reduce reperfusion arrhythmias.
DBL Sterile Cardioplegia Concentrate must be diluted with Ringer's injection before use, at a rate of 20 mL per L (see Section 4.2 Dose and Method of Administration). Ringer's injection contains approximately 144 mmol/L of sodium ions, 4 mmol/L of potassium ions, 2 mmol/L of calcium ions and 152 mmol/L of chloride ions. Each litre of diluted cardioplegia solution will, therefore, contain approximately 144 mmol of sodium ions, 20 mmol of potassium ions, 2 mmol of calcium ions, 16 mmol of magnesium ions, 200 mmol of chloride ions and 1 mmol of procaine hydrochloride.
Calcium ions (contained in Ringer's injection) help maintain the integrity of the cell membrane and prevent the condition known as the "calcium paradox" from occurring during reperfusion.
Sodium ions (contained in Ringer's injection) and chloride ions do not have a specific role in producing cardiac arrest, but result in a solution with a similar composition to that of normal extracellular fluid. Sodium ions are also essential for controlling calcium movements and ensuring that intracellular calcium is kept at the diastolic resting level. The inclusion of sodium enables the electroneutral sodium-calcium exchange to be maintained.
The hyperosmolarity of the cardioplegia solution minimises the myocardial oedema which occurs during ischaemia and reperfusion.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

DBL Sterile Cardioplegia Concentrate should not be absorbed systemically if it is used as recommended. However, systemic absorption could occur if large volumes of diluted cardioplegia solution are instilled and allowed to return to the heart lung machine without venting from the right heart.
Procaine is an ester type local anaesthetic which is poorly absorbed from mucous membranes, but is readily absorbed if it is administered parenterally.

Metabolism.

After absorption, procaine is rapidly hydrolysed by plasma cholinesterase to para-aminobenzoic acid and diethylaminoethanol; some may also be metabolised in the liver.

Excretion.

About 80% of the para-aminobenzoic acid is excreted unchanged or conjugated in the urine. About 30% of the diethylaminoethanol is excreted in the urine, while the remainder is metabolised in the liver. Procaine is 6% bound to plasma proteins and less than 2% is excreted unchanged in the urine.
Magnesium salts are mainly excreted in the urine following parenteral administration. About 25 to 30% of magnesium is protein bound. Potassium is mainly excreted by the kidneys; it is secreted in the distal tubules in exchange for sodium or hydrogen ions. Some potassium is excreted in the faeces and small amounts may also be excreted in sweat.

5.3 Preclinical Safety Data

Genotoxicity.

Magnesium and potassium are natural constituents of human tissues and fluids, and no evidence of mutagenic potential exists. No information is available on the mutagenicity of procaine hydrochloride.

Carcinogenicity.

Magnesium and potassium are natural constituents of human tissues and fluids, and no evidence of carcinogenic potential exists. No information is available on the carcinogenicity of procaine hydrochloride.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Sterile Cardioplegia Concentrate is indicated for use in combination with ischaemia and hypothermia to induce cardiac arrest during open-heart surgery and to preserve the myocardium during asystole.

4.3 Contraindications

DBL Sterile Cardioplegia Concentrate must not be used unless it has been diluted with Ringer's injection prior to use.
Use of DBL Sterile Cardioplegia Concentrate is contraindicated in patients who are hypersensitive to procaine.
As procaine is metabolised to produce para-aminobenzoic acid, it should be used with caution in patients who are allergic to para-aminobenzoic acid or its derivatives such as preservatives and sunscreens. Cross sensitivity can occur between procaine and other local anaesthetics of the para-aminobenzoic acid ester type, para-aminobenzoic acid and hydroxybenzoate preservatives.
Procaine hydrochloride is contraindicated in patients:
with low plasma cholinesterase levels or who are receiving anticholinesterases;
with myasthenia gravis, severe shock or impaired cardiac conduction;
receiving sulfonamides.

4.4 Special Warnings and Precautions for Use

DBL Sterile Cardioplegia Concentrate must be diluted with Ringer's injection before use. Do not use the solution unless it is clear and free from particulate matter. Discard any unused portion.
Cardioplegia solution must not be administered by intravenous injection. Cardioplegia solution should only be used for instillation into the coronary arteries during cardiopulmonary bypass, while the coronary circulation is isolated from the systemic circulation.
DBL Sterile Cardioplegia Concentrate should only be used by those who are trained in cardiac perfusion techniques and open heart surgery. Inotropic support drugs and appropriate defibrillation equipment should be readily available following use of the cardioplegia solution.
The cardioplegia solution should be cooled to 4°C prior to administration, thereby assisting in the reduction of cellular metabolism.
It is important to use sufficient cardioplegia solution (see Section 4.2 Dose and Method of Administration) to ensure that the myocardium is evenly cooled. This especially applies to areas distal to arterial obstruction in patients with coronary artery disease. Inadequate dosage may result in uneven cooling, incomplete arrest and ischaemic injury.
Maintenance of hypothermia is critical. Myocardial temperature and activity should be monitored continuously throughout the procedure.
Plasma magnesium and potassium levels may rise if large volumes of diluted cardioplegia solution are instilled and allowed to return to the heart lung machine without any venting from the right heart. Therefore, right heart venting is recommended.
DBL Sterile Cardioplegia Concentrate should be used with caution in acutely ill or debilitated patients, or patients with hyperthyroidism or other endocrine diseases, who may be more susceptible to the systemic toxicity of procaine.
Procaine should be used with caution in patients with a genetic predisposition to malignant hyperthermia as the safety of local anaesthetic agents in these patients has not been fully established. A standard protocol for the management of malignant hyperthermia should be available.

Use in hepatic impairment.

DBL Sterile Cardioplegia Concentrate should also be used with caution in patients with reduced hepatic blood flow (such as in liver disease), since the risk of systemic toxicity is increased due to decreased clearance of procaine.

Use in renal impairment.

DBL Sterile Cardioplegia Concentrate should also be used with caution in patients with renal disease, since the risk of systemic toxicity is increased due to decreased clearance of procaine.

Use in the elderly.

DBL Sterile Cardioplegia Concentrate should be used with caution in elderly, who may be more susceptible to the systemic toxicity of procaine.

Paediatric use.

DBL Sterile Cardioplegia Concentrate should be used with caution in very young, who may be more susceptible to the systemic toxicity of procaine.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

When used as recommended, systemic absorption of cardioplegia solution should not occur, and hence interactions between the cardioplegia solution and other medicines are unlikely. However, the following interactions could potentially occur if DBL Sterile Cardioplegia Concentrate is absorbed systemically.

Acetazolamide.

Acetazolamide may inhibit hydrolysis of procaine; concurrent administration may therefore theoretically extend the plasma half-life of procaine.

Anticholinesterase agents.

Anticholinesterase agents may inhibit procaine metabolism, leading to an increased risk of toxicity if procaine is used concurrently with anticholinesterase agents.

Antimyasthenic agents.

Procaine may antagonise the effects of antimyasthenic agents on skeletal muscle; concurrent use may, therefore, result in worsening of myasthenia gravis symptoms. Temporary dosage adjustment of antimyasthenic agents may be required.

CNS depressant medicines.

Concurrent use of procaine with CNS depressant medicines may result in enhanced CNS depressant effects.

Hyaluronidase.

Hyaluronidase may increase the diffusion rate of procaine hydrochloride, resulting in a decreased time of onset, but an increase in systemic toxicity.

Neuromuscular blocking agents.

Concurrent administration of procaine and neuromuscular blocking agents may prolong or enhance neuromuscular blockade. Magnesium salts may also interact with neuromuscular blocking agents.

Potassium-containing or potassium-sparing medicines.

Potassium salts should be used sparingly, if at all, in patients receiving medicines which increase serum potassium concentrations. Examples include potassium-sparing diuretics, angiotensin converting enzyme (ACE) inhibitors, cyclosporin, and potassium-containing medicines. Hyperkalaemia is more likely to occur in patients with renal impairment.

Sulfonamides.

Concurrent administration of procaine with sulfonamides may reduce the antibacterial action of the sulfonamide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No information is available on the effect on fertility of procaine hydrochloride.
(Category B2)
Category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformations or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Reproductive toxicity of DBL Sterile Cardioplegia Concentrate has not been studied in pregnant animals. It is known that procaine hydrochloride crosses the placenta. Magnesium and potassium are natural constituents of human tissues and fluids, and readily cross the placenta. The effect of DBL Sterile Cardioplegia Concentrate on the human foetus and reproductive capacity have not been established. DBL Sterile Cardioplegia Concentrate should be used in pregnant women only if unavoidable.
It is not known whether procaine hydrochloride is distributed into breast milk. Magnesium and potassium are natural constituents of human tissues and fluids, and are distributed into breast milk. There are no studies in lactating animals. Due to lack of data, its use in breastfeeding women is not recommended.

4.8 Adverse Effects (Undesirable Effects)

The use of cardioplegia solution during cardiac surgery has been associated with a number of intraoperative and perioperative risks, including myocardial infarction, electrocardiograph (ECG) abnormalities and arrhythmias (including ventricular fibrillation). Cardioplegia solutions may cause potential electrolyte and acid-base abnormalities (e.g. hyperkalaemia). Patients undergoing cardiac surgery should therefore be monitored closely for any adverse effects.
Spontaneous recovery may be delayed or absent after circulation is restored following chemically induced cardiac arrest. Defibrillation by electric shock may be required to restore normal cardiac function.
Plasma magnesium and potassium levels may rise if large volumes of cardioplegia solution are instilled and allowed to return to the heart lung machine without any venting from the right heart. This may lead to symptoms and signs of hypermagnesaemia and/or hyperkalaemia. This may lead to severe hypotension and metabolic acidosis (see Section 4.4 Special Warnings and Precautions for Use).
See Product Information for Procaine Hydrochloride Injection for further information on adverse effects due to systemic absorption of procaine.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

The following information is intended as a guide only. Dosage may vary, depending on perfusion technique being used and the preference and experience of the surgeon. The volume of solution administered into the aortic root may vary depending on the duration or type of open heart surgical procedure.
The solution may be administered at a rate of about 300 mL/m2 body surface area/minute, over a period of about 2 to 4 minutes.

Method of administration.

DBL Sterile Cardioplegia Concentrate must be diluted with Ringer's Injection prior to use.
DBL Sterile Cardioplegia Concentrate or diluted cardioplegia solution must not be administered by intravenous injection.
It is important to use sufficient cardioplegia solution to ensure that the myocardium is evenly cooled (see Section 4.4 Special Warnings and Precautions for Use).
DBL Sterile Cardioplegia Concentrate must be diluted before use, at a ratio of 20 mL to 1 litre of Ringer's injection. The solution must be cooled to 4°C prior to use. Any unused portion should be discarded.
Following institution of cardiopulmonary bypass and cross clamping of the ascending aorta, the cold, diluted cardioplegia solution is administered by rapid infusion into the aortic root.
External cardiac cooling helps to ensure that the heart remains continuously cold. This can be achieved by infusing a cold physiological solution into the pericardial sac. Warmed solution can be removed by suction and replaced by cold solution to ensure maintenance of hypothermia.
If myocardial electromechanical activity persists or recurs, administration of cold cardioplegia solution may be repeated at a rate of about 300 mL/m2/minute for a period of two minutes.
Diluted cardioplegia solution may be readministered every 20 to 30 minutes, or sooner if the myocardial temperature reaches 15 to 20°C, or if a return of cardiac activity is observed.
To reduce microbiological hazard, the solution should be used as soon as practicable after preparation. This product is for use in one patient only. Discard any remaining contents.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Excessive administration of cardioplegia solution may result in unnecessary dilation of coronary vessels and leakage into the perivascular myocardium, which may lead to tissue oedema. Any adverse effects should be treated symptomatically.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia), 0800 764 766 (New Zealand).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections.

6.2 Incompatibilities

DBL Sterile Cardioplegia Concentrate is potentially incompatible with aminophylline, amylobarbitone sodium, chloramphenicol, chlorothiazide sodium, magnesium sulphate, nitrofurantoin, phenobarbitone sodium, pentobarbitone, phenytoin sodium, quinalbarbitone sodium, sodium bicarbonate, sodium iodide, sulfadiazine, thiopentone and amphotericin due to the presence of procaine hydrochloride.
Procaine hydrochloride is also reported to be incompatible with amphotericin B, alkali hydroxides and their carbonates, alkaline solutions and iodine.
Potassium chloride is reported to be physically incompatible with amphotericin B, diazepam, ergotamine tartrate, methylprednisolone sodium succinate and phenytoin sodium.
Potassium chloride is also potentially incompatible with mannitol.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

DBL Sterile Cardioplegia Concentrate is supplied in 20 mL ampoules in a pack size of 5.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes