ISUPREL Solution for injection Ref.[8252] Active ingredients: Isoprenaline

Isoprenaline injection should generally be started at the lowest recommended dose. This may be gradually increased if necessary while carefully monitoring the patient.

Isoprenaline injection, by increasing myocardial oxygen requirements while decreasing effective coronary perfusion, may have a deleterious effect on the injured or failing heart. Most experts discourage its use as the initial agent in treating cardiogenic shock following myocardial infarction. However, when a low arterial pressure has been elevated by other means, isoprenaline injection may produce beneficial haemodynamic and metabolic effects.

In a few patients, presumably with organic disease of the A-V node and its branches, isoprenaline has been reported, paradoxically to worsen heart block or precipitate Adams-Stokes seizures during normal sinus rhythm or transient heart block.

Particular caution is necessary in administering isoprenaline injection to the elderly and patients with coronary insufficient, ischaemic heart disease, hypertension, aneurysms, diabetes or hyperthyroidism, and in patients sensitive to sympathomimetic amines.

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 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 ECG suggests myocardial ischaemia, cardiac enzymes including cardiac-specific CPK-MB isoenzyme levels should be determined.

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 vasoactive drugs. 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, Isuprel may be given.

In addition to the routine monitoring of systemic blood pressure, heart rate, urine flow, and the 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 Isuprel 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 Isuprel sufficient to increase the heart rate to a 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. Care is required when sympathomimetic agents are given to patients with diabetes mellitus or closed angle glaucoma.

Paediatric population

Dosage has not been established in children (see section 4.2).

Adrenaline

Isuprel and adrenaline should not be administered simultaneously because both medicines are direct cardiac stimulants and their combined effects may induce serious arrhythmias. The medicines may, however, be administered alternately provided a proper interval has elapsed between doses.

Anaesthetics

Isuprel should be used with caution, if at all, when potent inhalational anaesthetics such as halothane and cyclopropane are employed because of potential to sensitise the myocardium to effects of sympathomimetic amines.

Antidepressants, tricyclic or Maprotiline

Concurrent use may potentiate cardiovascular effects of isoprenaline and phenylephrine, possibly resulting in arrhythmias, tachycardia or severe hypertension or hyperpyrexia.

Beta-adrenergic blocking agents

Concurrent use with isoprenaline may result in mutual inhibition of therapeutic effects; beta-blockade may antagonise beta-2-adrenergic bronchodilating effects of isoprenaline; use of a cardioselective beta-2-adrenergic blocker, such as acebutolol, atenolol, or metoprolol, at low doses may reduce antagonism of the bronchodilating effect.

CNS Stimulants

Concurrent use with isoprenaline may result in additive CNS stimulation to excessive levels, which may cause unwanted effects such as nervousness, irritability, insomnia, or possibly convulsions or cardiac arrhythmias; close observation is recommended.

Digitalis Glycosides

Concurrent use with isoprenaline and phenylephrine may increase the risk of cardiac arrhythmias; caution and electrocardiographic monitoring are very important if concurrent use is necessary.

Levodopa

Concurrent use with isoprenaline and phenylephrine may increase the possibility of cardiac arrhythmias; dosage reduction of the sympathomimetic is recommended.

Nitrates

Concurrent use with isoprenaline and phenylephrine may reduce the antianginal effects of these medications.

Sympathomimetics

Concurrent use may increase the cardiovascular effects of either the other sympathomimetics or isoprenaline and phenylephrine and the potential for side effects.

Thyroid hormones

Concurrent use may increase the effects of either these medications or isoprenaline and phenylephrine; thyroid hormones enhance risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease; dosage adjustment is recommended, although problem is reduced in euthyroid patients.

MAOI’s, Chlorpromazine

Isoprenaline should not be used with chlorpromazine or monoamine oxidase inhibitors since the effects of isoprenaline may be magnified.

Xanthines/Corticosteroids

Caution should be maintained when using continuous intravenous isoprenaline infusions in conjunction with intravenous methyl xanthines (aminophylline, theophylline) and intravenous corticosteroids. The use of isoprenaline 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.

Fertility

No data available.

Pregnancy

Category A.

Medicines which have been taken by a large number of pregnant women of childbearing age without any proven increase in the frequency of malformation or other direct or indirect harmful effects on the foetus having been observed.

There has been no clinical evidence of teratogenic effects attributable to Isuprel in more than 25 years use of the medicine. Isoprenaline may delay the second stage of labour by inhibiting contraction of the uterus. However, before administration of any medicine to pregnant or lactating women, or women of childbearing potential, the expected benefit of the medicine should be carefully weighed against the possible risk to the mother or child.

Lactation

It is unknown whether isoprenaline hydrochloride is excreted into breast milk. Caution should be exercised in administering to a nursing mother.

No data available.

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

CNS: Nervousness, headache, dizziness, restlessness, tension, fear of excitement, and rarely, nausea, vomiting, tinnitus, light headedness and asthenia.

Cardiovascular: Tachycardia, palpitations, angina, Adams-Stokes attacks, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias and pulmonary oedema. In a few patients, presumably with organic disease of the AV node and its branches, isoprenaline hydrochloride injection has been reported to precipitate Adams-Stokes seizures during normal sinus rhythm or transient heart block.

Other: Hot flashes, flushing of the skin, sweating, mild tremors, weakness.

These effects disappear quickly and usually do not require discontinuation of treatment with Isuprel. No cumulative effects have been reported. Pulmonary oedema has been reported in a patient extremely intolerant to all sympathomimetic drugs.

The following effects to isoprenaline hydrochloride have been reported in healthy adult controls undergoing upright tilt testing:

^* P=0.03 (difference between patients vs. controls)

Toxicity

The oral LD₅₀ of isoprenaline in mice is 3,850mg/kg ± 1,190mg/kg of pure drug in solution.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

No data available.