SUMMARY CMI

ISOPRENALINE MACURE 1 mg/5 mL

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ISOPRENALINE MACURE?

ISOPRENALINE MACURE contains the active ingredient isoprenaline hydrochloride. ISOPRENALINE MACURE is primarily used to treat heart block and cardiac arrest. It may also be used to help you breathe when your airways spasm and contract; or in combination with other medicines when your body is not getting enough blood flow (shock). For more information, see Section 1. Why am I using Isoprenaline Macure? in the full CMI.

2. What should I know before I use ISOPRENALINE MACURE?

Do not use if you have ever had an allergic reaction to isoprenaline or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Isoprenaline Macure? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Isoprenaline Macure and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ISOPRENALINE MACURE?

• Your doctor will decide what dose you will receive. The dosage will depend on your condition.
• A doctor or nurse will usually prepare and administer the injection.
• Follow all instructions given to you by your doctor or pharmacist.

More instructions can be found in Section 4. How is Isoprenaline Macure given? in the full CMI.

5. What should I know while using ISOPRENALINE MACURE?

For more information, see Section 5. What should I know while using Isoprenaline Macure? in the full CMI.

6. Are there any side effects?

Some unwanted effects may occur when being treated with Isoprenaline Macure. These include nervousness, headache, dizziness or light-headedness, restlessness, palpitations, sweating, mild tremors, weakness, hot flushes, flushing of the skin, fast heart-beat, ringing in the ears, nausea and vomiting.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

ISOPRENALINE MACURE 1 mg/5 mL

Active ingredient: isoprenaline hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using Isoprenaline Macure. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Isoprenaline Macure.

Where to find information in this leaflet:

1. Why am I using Isoprenaline Macure?
2. What should I know before I use Isoprenaline Macure?
3. What if I am taking other medicines?
4. How is Isoprenaline Macure given?
5. What should I know while using Isoprenaline Macure?
6. Are there any side effects?
7. Product details

1. Why am I using Isoprenaline Macure?

Isoprenaline Macure contains the active ingredient isoprenaline hydrochloride. Isoprenaline Macure belongs to a group of medicines called synthetic sympathomimetic amines. Isoprenaline Macure helps improve the efficiency with which your heart pumps blood around your body. It works by strengthening your heart muscles and increasing the heartbeat rate. Isoprenaline Macure also helps your airway muscles relax.

Isoprenaline Macure is primarily used to treat heart block and cardiac arrest. It may also be used to help you breathe when your airways spasm and contract; or in combination with other medicines when your body is not getting enough blood flow (shock). Isoprenaline Macure is intended to be used in hospitals only.

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 available only with a doctor's prescription.

2. What should I know before I use Isoprenaline Macure?

Warnings

You must not be given Isoprenaline Macure if you have an allergy to:

• isoprenaline, or any of the ingredients listed at the end of this leaflet.
• Always check the ingredients to make sure you can use this medicine.

Some of the symptoms of an allergic reaction may include

• Shortness of breath
• Wheezing 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 Isoprenaline Macure if you have any of the following:

• Faster than usual heart rate
• Fast, slow or irregular heart beat caused by too much of a type of medicine called cardiac glycoside such as digoxin (digitalis), a medicine used to treat irregular heart beats and heart failure
• Medicines used to treat unusual heart beat, such as inotropic therapy (e.g. adrenaline)
• Recently suffered a heart attack
• A feeling of tightness, pressure or heaviness in the chest.

Check with your doctor if you:

• Have or have had any other medical conditions:
  - Asthma
  - Diabetes
  - Hyperthyroidism
  - Convulsive disorders
  - Other heart conditions.
• Have ever had a reaction to a medicine affecting the heart and circulation (belonging to the sympathomimetic amine group).

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

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

Some medicines may interfere with Isoprenaline Macure and affect how it works.

Medicines that have a similar effect to Isoprenaline Macure on the heart and other parts of the body can have unwanted additive effects when taken at the same time as Isoprenaline Macure.

Medicines that may increase the effect of Isoprenaline Macure include:

• Adrenaline (epinephrine) or digitalis, medicines used to stimulate the heart
• Anaesthetics that are inhaled such as halothane and cyclopropane
• Medicines used to treat certain mental conditions such as chlorpromazine or monoamine oxidase inhibitors
• Doxapram, a class of medicine used in intensive care to increase respiratory rate
• A group of medicines called methyl xanthines (aminophylline, theophylline) or corticosteroids given via the vein (intravenously) in combination with a slow injection of isoprenaline
• Other medicines that stimulate the nervous system such as sympathomimetics or thyroid hormone products
• Medicines combined with sulphates (such as salicylamide) when given at the same time as isoprenaline
• Entacapone, a class of medicine used for Parkinson's disease.

Medicines that may be affected by Isoprenaline Macure include:

• Medicines used to treat certain mental conditions such as tricyclic antidepressants
• Ergotamine, a class of medicines used to treat acute migraines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Isoprenaline Macure.

4. How is Isoprenaline Macure given?

How much is given

• Your doctor will decide what dose you will receive.
  The dosage will depend on your condition.

How it is given

• Isoprenaline Macure will normally be given to you as an injection into the vein.
• Isoprenaline Macure may also be given to you as an injection under the skin, muscle or heart.
• The doctor will carefully monitor your heart rate while you are being given Isoprenaline Macure.

If you are given too much Isoprenaline Macure

As Isoprenaline Macure is given to you under the supervision of a doctor, it is very unlikely that you will receive too much. However, if you experience any severe side effects after being given Isoprenaline Macure, you may need urgent medical attention.

You should immediately:

• contact your doctor or nurse, or
• go to the Emergency Department at your nearest hospital.

In case of overdose, immediately phone the Poisons Information Centre (by calling 13 11 26).

Symptoms of Isoprenaline Macure overdose can include faster or extra heart beats, changes in blood pressure and chest pain. Symptoms of overdose can also include the side effects listed below in the ‘Side effects’ section, but are usually more severe in nature.

5. What should I know while using Isoprenaline Macure?

Things you should do

Call your doctor straight away if you:

• Are pregnant while being given this medicine.

Remind your doctor, nurse or pharmacist that you have been given Isoprenaline Macure if you:

• Are about to be started on any new medicine
• Are going into surgery. It may affect other medicines used during surgery.
• Are about to have any blood tests. It may interfere with the results of some tests.

Remind any doctor, dentist or pharmacist who treat you that you have been given Isoprenaline Macure.

Keep all of your doctor's appointments so that your progress can be checked.

Getting out of bed or standing up

• If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.
• Standing up slowly, especially when you get up from bed or chairs will help your body get used to the change in position and blood pressure.
• If this problem continues or gets worse, talk to your doctor.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Isoprenaline Macure affects you.

Isoprenaline Macure may cause dizziness and light-headedness in some people.

If you have any of these symptoms, do not drive, use any machines or tools, or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may worsen dizziness or light-headedness.

Looking after your medicine

• Store refrigerated (between 2 – 8°C).

Each ampoule of Isoprenaline Macure is intended for single use in one patient only. Discard any residue.

Your doctor or pharmacist is responsible for storing Isoprenaline Macure.

They are also responsible for disposing of any unused Isoprenaline Macure properly.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Some unwanted effects may occur when being treated with Isoprenaline Macure. These include:

• Nervousness
• Headache, dizziness or light-headedness
• Restlessness
• Palpitations, sweating
• Mild tremors, weakness
• Hot flushes, flushing of the skin
• Fast heart beat
• Ringing in the ears (tinnitus)
• Nausea and vomiting.

Tell your doctor, nurse or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is only available with a doctor's prescription.

What Isoprenaline Macure contains

Do not take this medicine if you are allergic to any of these ingredients.

What Isoprenaline Macure looks like

Isoprenaline Macure is a clear, colourless or pale yellow solution for injection. It is available as 5 mL amber glass ampoules in packs of 5 (AUST R 370377).

Who distributes Isoprenaline Macure

Juno Pharmaceuticals Pty Ltd
42 Kelso Street,
Cremorne
VIC – 3121
Australia
www.junopharm.com.au

This leaflet was prepared in April 2022

Published by MIMS May 2023

1 Name of Medicine

Isoprenaline hydrochloride.

2 Qualitative and Quantitative Composition

Isoprenaline Macure injection solution contains 1 mg of isoprenaline hydrochloride in 5 mL (1:5000).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clear, colourless or pale yellow solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy.
For serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation). (See Section 4.3 Contraindications.)
For use in cardiac arrest until electric shock or pacemaker therapy, the treatments of choice, are available. (See Section 4.3 Contraindications.)
For bronchospasm occurring during anaesthesia.
As an adjunct to fluid and electrolyte replacement therapy and the use of other drugs and procedures in the treatment of hypovolaemic and septic shock, low cardiac output (hypoperfusion) states, congestive heart failure and cardiogenic shock. (See Section 4.4 Special Warnings and Precautions for Use.)

4.2 Dose and Method of Administration

Dosage.

Recommended dosage for adults with shock and hypoperfusion states.

Recommended dosage for adults with heart block, Adams-Stokes attacks and cardiac arrest.

Recommended dosage for adults with bronchospasm occurring during anaesthesia.

Method of administration.

Elderly patients.

4.3 Contraindications

Use of isoprenaline hydrochloride is contraindicated in patients with tachyarrhythmias; tachycardia or heart block caused by digitalis intoxication; ventricular arrhythmias which require inotropic therapy; recent myocardial infarction; angina pectoris; hypersensitivity to isoprenaline or to any of the excipients in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Isoprenaline hydrochloride infusions may produce an increase in myocardial work and oxygen consumption. These effects may be detrimental to myocardial metabolism and functioning in patients in cardiogenic shock secondary to coronary artery occlusion and myocardial infarction.
In a few patients, presumably with organic disease of the A-V node and its branches, isoprenaline hydrochloride has been reported, paradoxically, to precipitate Adams-Stokes seizures during normal sinus rhythm or transient heart block.
Adequate filling of the intravascular compartment by suitable volume expanders is of primary importance in most cases of shock, and should precede the administration of isoprenaline. In patients with normal cardiac function, determination of central venous pressure is a reliable guide during volume replacement. If evidence of hypoperfusion persists after adequate volume replacement, isoprenaline hydrochloride may be given.
In addition to the routine monitoring of systemic blood pressure, heart rate, urine flow, and electrocardiograph, the response to therapy should also be monitored by frequent determinations of the central venous pressure and blood gases. Patients in shock should be closely observed during isoprenaline hydrochloride administration. If the heart rate exceeds 110 beats per minute, it may be advisable to decrease the infusion rate or temporarily discontinue the infusion. Determinations of cardiac output and circulation time may also be helpful. Doses of isoprenaline hydrochloride sufficient to increase the heart rate to more than 130 beats per minute may induce ventricular arrhythmia. If the cardiac rate increases sharply, patients with angina pectoris may experience anginal pain until the cardiac rate decreases.
If ventricular hyperexcitability (extrasystoles, polymorphic extrasystoles or sustained ventricular tachycardia) should occur, the dosage should be reduced and the electrocardiogram monitored.
Appropriate measures should be taken to ensure adequate ventilation. Careful attention should be paid to acid-base balance and to the correction of electrolyte disturbances.
In cases of shock associated with bacteraemia, suitable antimicrobial therapy is, of course, imperative.
There are case reports of occasional fatal cardiac dysrhythmia and myocardial necrosis at autopsy as a result of intravenous isoprenaline. ECG changes and serum CPK-MB level elevation consistent with transient myocardial ischaemia and abnormal echocardiographic findings suggestive of myocardial dysfunction have been documented with the use of intravenous isoprenaline hydrochloride infusion for the treatment of severe asthma exacerbations in children. Care should be taken to ensure that oxygen is always administered during isoprenaline infusions in patients with asthma. Heart rate, blood pressure, arrhythmias and evidence of myocardial ischaemia by ECG should be monitored. Arterial blood gases should also be monitored carefully and PaO₂ maintained above 60 torr. Where the ECG suggests myocardial ischaemia, cardiac enzymes including cardiac specific CPK-MB isoenzyme levels should be determined.
The dosage of isoprenaline hydrochloride should be carefully adjusted in patients with cardiovascular disorders (particularly coronary insufficiency, ischaemic heart disease, hypertension and arrhythmias), diabetes or hyperthyroidism. Administration of the medicinal product should be avoided in cases of uncontrolled hyperthyroidism.
Caution when used on patients under the effect of digitalis (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Caution in cases of convulsive disorders.
Caution when using in patients sensitive to sympathomimetic amines or who respond to sympathomimetic amines in an unusual manner.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Isoprenaline hydrochloride should not be given simultaneously with adrenaline (epinephrine) or digitalis because both drugs are direct cardiac stimulants and their combined effects may induce serious arrhythmias. The drugs may, however, be administered alternately, provided a proper interval has elapsed between doses.
Isoprenaline hydrochloride should be used with caution, if at all, when potent inhalational anaesthetics such as halothane and cyclopropane are employed, because of their potential to sensitise the myocardium to the effects of sympathomimetic amines.
Isoprenaline should not be used with chlorpromazine or monoamine oxidase inhibitors since the effects of isoprenaline may be magnified.
Doxapram and MAOIs may cause a risk of severe hypertension. Hypertension may occur because of the high vasopressor effect of sympathomimetic vasoconstrictors (e.g. oxytocin).
Caution should be maintained when using continuous intravenous isoprenaline hydrochloride infusions in conjunction with intravenous methyl xanthines (aminophylline, theophylline) and intravenous corticosteroids. The use of isoprenaline hydrochloride with aminophylline and corticosteroids may be additive in cardiotoxic properties and can lead to myocardial necrosis and death. Severe cardiac symptoms of sympathetic overactivation, i.e. hypertension, tachycardia, arrhythmias, seizures, myocardial ischaemia, and fatal myocardial necrosis, have been reported.
Isoprenaline toxicity increases when administered at the same time as other cardiotonics or drugs stimulating the central nervous system (such as sympathomimetics or thyroid hormone products).
Isoprenaline may worsen cardiovascular side effects of tricyclic antidepressants such as imipramine.
The simultaneous administration of isoprenaline and drugs combined with sulphates, such as salicylamide, may exacerbate the pharmacological effects of isoprenaline.
Administration of entacapone may enhance the effect of isoprenaline.
Isoprenaline hydrochloride may increase the risk of ergotism, if given together with ergotamine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

No specific studies have been conducted to assess the direct effect of Isoprenaline Macure on the ability to drive and use machines. However, adverse effects of isoprenaline hydrochloride include dizziness which could affect the ability to drive or use machines. See Section 4.8 Adverse Effects (Undesirable Effects).

4.8 Adverse Effects (Undesirable Effects)

Serious effects to isoprenaline hydrochloride are infrequent. The following effects, however, have been reported:

CNS.

Cardiovascular.

Other.

Reporting suspected adverse effects.

4.9 Overdose

The acute toxicity of isoprenaline hydrochloride in animals is much less than that of adrenaline. Excessive doses in animals or humans can cause a striking drop in blood pressure, and repeated large doses in animals may result in cardiac enlargement and focal myocarditis.
In cases of accidental overdosage, as evidenced mainly by tachycardia or other arrhythmias, palpitations, angina, hypotension or hypertension, reduce rate of administration or discontinue isoprenaline hydrochloride until the patient's condition stabilises. Blood pressure, pulse, respiration and ECG should be monitored.
Very cautious use of a non-selective beta receptor antagonist should be considered if symptoms are very severe, but close monitoring of airway function would be essential. It is not known whether isoprenaline hydrochloride is dialysable.
The oral LD₅₀ of isoprenaline hydrochloride in mice is 3,850 mg/kg ± 1,190 mg/kg of pure drug in solution.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride, disodium edetate, sodium citrate dihydrate, citric acid monohydrate, water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. Isoprenaline Macure can be mixed with sodium chloride 9 mg/mL (0.9 %) solution for injection or glucose 50 mg/mL (5 %) solution for injection.

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 refrigerated (2°C - 8°C).
It is recommended that, to reduce microbiological contamination hazards, the diluted solutions should be prepared immediately prior to use and infusion commenced as soon as practicable after preparation of the mixture. Keep diluted solution at 25°C for not more than 24 hours. The diluted infusion solution should be used within 24 hours and any residue discarded.

6.5 Nature and Contents of Container

Isoprenaline hydrochloride injection 1 mg/5 mL clear, Type I amber glass ampoules: packaged into cartons containing 5 x 5 mL ampoules.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes