DOBUTAMINE

Route of Administration:

For intravenous use only. 45% Sodium Chloride Intravenous Infusion BP Sodium Lactate Intravenous Infusion BP For example, diluting to 250 ml or 500 ml will provide the following concentrations for administration: 250 ml contains 1,000 micrograms/ml of dobutamine 500 ml contains 500 micrograms/ml of dobutamine The prepared solution should be used within 24 hours.

5 mg/ml concentrate for solution for infusion is administered as a continuous intravenous infusion. After dilution, it should be administered through an intravenous needle or catheter using an IV drip chamber or other suitable metering device to control the rate of flow.

5 to 10 micrograms/kg/minute. 5 micrograms/kg/minute will produce a response. Rarely, up to 40 micrograms/kg/minute may be required. The rate of administration and the 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. 5 mg/ml concentrate for solution for infusion 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. 5 mg/ml concentrate for solution for infusion should only be given with an infusion pump, to ensure accurate dosage.

Cardiac stress testing (Adult population only) 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 > 3 mm ST segment depression or any ventricular arrhythmia. The infusion should also be terminated if heart rate reaches the age/sex maximum, systolic blood pressure rises above 220 mm Hg or any side effects occur.

Paediatric population For all paediatric age groups (neonates to 18 years) an initial dose of 5 micrograms/kg/minute, adjusted according to clinical response to 2 – 20 micrograms/kg/minute is recommended. 0 micrograms/kg/minute will produce a response.

There is reason to believe that the minimum effective dosage for children is higher than for adults. Caution should be taken in applying high doses, because there is also reason to believe that the maximum tolerated dosage for children is lower than the one for adults.

5 micrograms/kg/minute, but reducing or termination of the rate of dobutamine infusion is all that is required for rapid reversal of undesirable effects. A great variability has been noted between paediatric patients in regard to both the plasma concentration necessary to initiate a hemodynamic response (threshold) and the rate of hemodynamic response to increasing plasma concentrations, which demonstrates that the required dose for children cannot be determined a priori and should be titrated in order to allow for the supposedly smaller “therapeutic width” in children.

9%. Infuse higher concentration solutions through central venous catheter only. Dobutamine intravenous infusion is incompatible with bicarbonate and other strong alkaline solutions.

Neonatal intensive care:

Dilute 30 mg/kg body weight to a final volume of 50 mL of infusion fluid. 5 mL/hour provides a dose of 5 micrograms/kg/minute.

Adult population Infusions for up to 72 hours have revealed no adverse effects other than those seen with shorter infusions. 5 mg/ml concentrate for solution for infusion 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 Nervous system disorders Common: Headache Not known: Paraesthesia, tremor, myoclonic spasm.

Myoclonus has been reported in patients with severe renal failure receiving dobutamine Cardiac disorders / vascular 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.

Children: pronounced increase of heart rate and/or blood pressure as well as a lower decrease of the pulmonary capillary pressure than adults. Increase of pulmonary capillary pressure in children under 1.

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.

4) 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 Paediatric population The undesirable effects include elevation of systolic blood pressure, systemic hypertension or hypotension, tachycardia, headache, and elevation of pulmonary wedge pressure leading to pulmonary congestion and edema, and symptomatic complaints.

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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Adult population If an undue increase in heart rate or systolic blood pressure occurs, or if an arrhythmia is precipitated, the dose of dobutamine should be reduced or the drug should be discontinued temporarily. 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. Particular care is required when administering dobutamine to patients with acute myocardial infarction, as any significant increase in heart rate or excessive increases 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.

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. 3) 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. 5 mg/ml concentrate for solution for infusion, 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.

5 mg/ml concentrate for solution for infusion should be used with caution in the presence of severe hypotension complicating cardiogenic shock (mean arterial pressure less than 70 mm Hg). Hypovolaemia should be corrected when necessary with whole blood or plasma before administering dobutamine.

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.

5 mg/ml concentrate for solution for infusion contains sodium metabisulfite. Sulfites may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible […]

• Hypersensitivity to dobutamine, sodium metabisulfite 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