STERILE DOBUTAMINE HYDROCHLORIDE

This is a potent drug. The solution must be diluted to at least 50ml before administration and may then be administered by intravenous infusion. Alkaline solutions such as 5% sodium bicarbonate should not be added to dobutamine hydrochloride because the drug will be inactivated.

45% sodium chloride intravenous infusion BP Sodium lactate intravenous infusion BP. If not required immediately, the diluted solution may be stored for up to 24 hours in a refrigerator. Dobutamine should be administered as a continuous infusion because of its short half-life.

A suitable metering device is required in the infusion system to control the rate of flow and this should be adjusted to the optimum patient response and monitored constantly in the light of the individual patient's response. 5 to 10 micrograms/kg/minute.

5 micrograms/kg/minute will elicit a response. Up to 40 micrograms/kg/minute may occasionally be required. The rate of administration and duration of therapy should be adjusted according to the patient's response as determined by heart rate, blood pressure, urine flow and, if possible, measurement of cardiac output.

It is advisable to reduce the dosage of dobutamine hydrochloride gradually rather than abruptly stopping therapy. Side-effects which are dose related, are infrequent when dobutamine hydrochloride is administered at rates below 10 micrograms/kg/minute.

Rates as high as 40 micrograms/kg/minute have been used occasionally without significant adverse effects. The final volume administered should be determined by the fluid requirements of the patient. Concentrations as high as 5,000 micrograms/ml have been used in patients on a restricted fluid intake.

High concentrations of dobutamine should be given with an infusion pump, to ensure accurate dosage. Cardiac stress testing When used as an alternative to exercise for cardiac stress testing the recommended dose is an incremental increase of 5 micrograms/kg/minute from 5 up to 20 micrograms/kg/minute, each dose being infused for 8 minutes.

Continuous ECG monitoring is essential and the infusion terminated in the event of >3mm ST segment depression or any ventricular arrhythmia. The infusion should also be terminated if heart rate reaches the age/sex maximum, systolic blood pressure rise above 220mm HG or any side effects occur.

Children The safety and efficacy of dobutamine hydrochloride therapy in children have not been established. Method of administration: intravenous infusion.

Infusions for up to 72 hours have revealed no adverse effects other than those seen with shorter infusions. There is evidence that partial tolerance develops with continuous infusions of dobutamine solution for 72 hours or more; therefore, higher doses may be required to maintain the same effects.

Evaluation of undesirable effects is based on the following frequency scale:

Very common: ≥ 1/10 Common: ≥ 1/100 to < 1/10 Uncommon: ≥ 1/1,000 to < 1/100 Rare: ≥ 1/10,000 to < 1/1,000 Very rare: < 1/10,000 Not known cannot be estimated from the available data Immune system disorders: Not Known: Hypersensitivity reactions including rash, fever, eosinophilia and bronchospasm, have been reported.

4 Special warnings and other precautions for use).

Blood and lymphatic system disorders:

Common: Eosinophilia, inhibition of thrombocyte aggregation (only when continuing infusion over a number of days) Metabolism and nutrition disorders: Very rare: Hypokalaemia Consideration should be given to monitoring serum potassium.

Cardiac disorders:

Very common: Increase of the heart rate by ≥ 30 beats/min Common: Blood pressure increase of ≥ 50 mmHg. Patients suffering from arterial hypertension are more likely to have a higher blood pressure increase. Blood pressure decrease, ventricular dysrhythmia, dose-dependent ventricular extrasystoles.

Increased ventricular frequency in patients with atrial fibrillation. These patients should be digitalised prior to dobutamine infusion. Vasoconstriction in particular in patients who have previously been treated with beta receptor blockers.

Anginal pain, palpitations Uncommon:

Ventricular tachycardia, ventricular fibrillation Very rare: Bradycardia, myocardial ischaemia, myocardial infarction, cardiac arrest Not known: Electrocardiogram ST segment elevation Decrease in pulmonary capillary pressure Eosinophilic myocarditis has been noted in explanted hearts of patients who had undergone treatment with multiple medications including dobutamine or other inotropic agents prior to transplantation.

4) Vascular disorders: Hypertension. 5 Interactions). 5 Interactions).

Nervous system disorders:

Common: Headache Not known: Paraesthesia, tremor, myoclonic spasm. Myoclonus has been reported in patients with severe renal failure receiving dobutamine Gastrointestinal disorders Not known: Nausea Psychiatric disorders Not known: Restlessness, feeling of heat and anxiety Renal and urinary disorders Not known: Urinary urgency Dobutamine stress echocardiography Cardiac disorders / vascular disorders Very common: Pectoral anginal discomfort, ventricular extra- systoles with a frequency of > 6/min Common: Supraventricular extrasystoles, ventricular tachycardia Uncommon: Ventricular fibrillation, myocardial infarction Very rare: Occurrence of a second degree atrioventricular block, coronary vasospasms.

Hypertensive/hypotensive blood pressure decompensation, occurrence of an intracavitary pressure gradient, palpitations Not known: Stress cardiomyopathy Left ventricular outflow tract obstruction Fatal cardiac rupture Respiratory system, thoracic and mediastinal disorders Common: Bronchospasm, shortness of breath Gastrointestinal disorders Common: Nausea Skin and subcutaneous tissue disorders Common: Exanthema Very rare: Petechial bleeding Musculoskeletal and connective tissue disorders Common: Chest pain Renal and urinary disorders Common: Increased urgency at high dosages of infusion General disorders and administration site conditions Common: Fever, phlebitis at the injection site In case of accidental paravenous infiltration, local inflammation may develop.

Very rare:

Cutaneous necrosis Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

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The dose of dobutamine should be reduced or the drug should be discontinued temporarily if an undue increase in heart rate or systolic blood pressure occurs or if an arrhythmia is precipitated. Dobutamine may precipitate or exacerbate ventricular ectopic activity: rarely has it caused ventricular tachycardia or fibrillation.

Because dobutamine facilitates A-V conduction, patients with atrial flutter or fibrillation may develop rapid ventricular responses. Dobutamine should only be used with great care in patients with acute myocardial infarction because any significant increase in heart rate or excessive increase in arterial pressure that occur may intensify ischaemia and cause anginal pain and ST segment elevation.

Inotropic agents, including dobutamine, do not improve haemodynamics in most patients with mechanical obstruction that hinders either ventricular filling or outflow, or both. Inotropic response may be inadequate in patients with markedly reduced ventricular compliance.

Such conditions are present in cardiac tamponade, valvular aortic stenosis, and idiopathic hypertrophic subaortic stenosis. Minimal vasoconstriction has occasionally been observed, most notably in patients recently treated with a β-blocking drug.

The inotropic effect of dobutamine stems from stimulation of cardiac β1 receptors and this effect is prevented by β-blocking drugs. However, dobutamine has been shown to counteract the cardiodepressive effects of β-blocking drugs. Conversely, adrenergic blockade may make the β1 and β2 effects apparent, resulting in tachycardia and vasodilatation.

Dobutamine stress echocardiography Because of possible life-threatening complications, the administration of dobutamine for stress echocardiography should only be undertaken by a physician with sufficient personal experience of the use of dobutamine for this indication.

The use of dobutamine as an alternative to exercise for cardiac stress testing is not recommended for patients with unstable angina, bundle branch block, valvular heart disease, aortic outflow obstruction or any cardiac condition that could make them unsuitable for exercise stress testing.

Cardiac rupture is a potential complication of myocardial infarction. The risk of cardiac rupture (septal and free wall) may be influenced by a variety of factors including site of, and time since, infarct. There have been very rare, fatal reports of acute cardiac rupture during dobutamine stress testing.

These events have occurred during pre-discharge examination in patients hospitalised with recent (within 4-12 days) myocardial infarction. In the reported cases of free wall rupture, resting echocardiogram showed a dyskinetic and thinned inferior wall.

Patients considered at risk of cardiac rupture during dobutamine testing should therefore be carefully evaluated prior to testing. g. 8) dobutamine stress echocardiography must be stopped immediately. During the administration of dobutamine, as with any parenteral catecholamine, heart rate and rhythm, arterial blood pressure, and infusion rate should be monitored closely.

When initiating therapy, electrocardiographic monitoring is advisable until a stable response is achieved. Precipitous decreases in blood pressure have occasionally been described in association with dobutamine therapy, decreasing the dose or discontinuing the infusion typically results in rapid return of blood pressure to base-line values, but rarely intervention may be required and reversibility may not be immediate.

Dobutamine should be used with caution in the presence of severe hypotension complicating cardiogenic shock (mean arterial pressure less than 70mm HG). If hypovolaemia is present it should be corrected by administration of either whole blood or plasma before using dobutamine hydrochloride.

If arterial blood pressure remains low or decreases progressively during administration of dobutamine despite adequate ventricular filling pressure and cardiac output, consideration may be given to the concomitant use of a peripheral vasoconstrictor agent, such as dopamine or noradrenaline.

8). The administration of dobutamine for stress echocardiography should be only undertaken by a physician experienced with the procedure. The physician should be vigilant during the test and the recovery period and be prepared for appropriate therapeutic intervention during the test.

In the event of stress cardiomyopathy (Takotsubo syndrome) dobutamine should be stopped immediately. Sterile dobutamine hydrochloride concentrate contains sodium metabisulphite, Sulphites may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.

Sulphite sensitivity is seen more frequently in asthmatic than in non-asthmatic people. Also, the carton text shall contain the following statements: "Dilute to at […]

• Hypersensitivity to dobutamine, sodium metabisulphite or any of the other ingredients. • Phaeochromocytoma. •Dobutamine stress echocardiography Dobutamine must not be used for detection of myocardial ischaemia and of viable myocardium in case of: - recent myocardial infarction (within the last 30 days) - unstable angina pectoris - stenosis of the main left coronary artery - haemodynamically significant outflow obstruction of the left ventricle including hypertrophic obstructive cardiomyopathy - haemodynamically significant cardiac valvular defect - severe heart failure (NYHA III or IV) - predisposition for or documented medical history of clinically significant or chronic arrhythmia, particularly recurrent persistent ventricular tachycardia - significant disturbance in conduction - acute pericarditis, myocarditis or endocarditis - aortic dissection - aortic aneurysm - poor sonographic imaging conditions - inadequately treated / controlled arterial hypertension - obstruction of ventricular filling (constrictive pericarditis, pericardial tamponade) - hypovolaemia - previous experience of hypersensitivity to dobutamine