ISOPRENALINE

What it is

ISOPRENALINE MACURE is an injection solution containing 1 mg of isoprenaline hydrochloride in 5 mL (1:5000). It is a clear, colourless or pale yellow solution for injection. Isoprenaline hydrochloride acts primarily on the heart, and on the smooth muscle of bronchi, skeletal muscle vasculature and gastrointestinal tract.

Approved indications

— Mild or transient episodes of heart block that do not require electric shock or pacemaker therapy. — Serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation). — Use in cardiac arrest until electric shock or pacemaker therapy, the treatments of choice, are available. — 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.

Dosing overview

ISOPRENALINE MACURE should generally be started at the lowest recommended dose and the rate of administration gradually increased if necessary while carefully monitoring the patient. The usual route of administration is by intravenous infusion or bolus intravenous injection. In dire emergencies, the drug may be administered by intracardiac injection. If time is not of the utmost importance, initial therapy by intramuscular or subcutaneous injection is preferred. For shock and hypoperfusion states, the recommended adult dosage via intravenous infusion is 5 mL (1 mg) diluted in 500 mL of 5% Glucose Injection at 0.5 microgram per minute (0.25 mL to 2.5 mL of diluted solution), with rates over 30 microgram per minute used in advanced stages of shock. The rate of infusion should be adjusted on the basis of heart rate, central venous pressure, systemic blood pressure and urine flow. If the heart rate exceeds 110 beats per minute, it may be advisable to decrease or temporarily discontinue the infusion. For heart block, Adams-Stokes attacks and cardiac arrest, adult bolus intravenous injection dosing is 0.02 mg to 0.06 mg initially, with a subsequent dose range of 0.01 mg to 0.2 mg; intravenous infusion uses 10 mL of solution 1:5000 (2 mg) diluted in 500 mL of 5% Glucose Injection at 5 microgram per minute; intramuscular dosing is 0.2 mg initially with subsequent doses of 0.02 mg to 1 mg; subcutaneous dosing is 0.2 mg initially with subsequent doses of 0.15 mg to 0.2 mg; and intracardiac dosing is 0.02 mg. For bronchospasm occurring during anaesthesia, adult bolus intravenous injection dosing is 0.01 mg to 0.02 mg initially, and the initial dose may be repeated when necessary. Elderly patients may be more sensitive to the effects of sympathomimetics and lower doses may be required.

Key safety warnings

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. If evidence of hypoperfusion persists after adequate volume replacement, isoprenaline hydrochloride may be given. Doses of isoprenaline hydrochloride sufficient to increase the heart rate to more than 130 beats per minute may induce ventricular arrhythmia. 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. 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.

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.

Regulatory history

ISOPRENALINE MACURE received first approval on 26 April 2022 and was first included in the Australian Register of Therapeutic Goods on that date.