Dobutrex (Solution) Instructions for Use

Marketing Authorization Holder

Eli Lilly (Germany)

ATC Code

C01CA07 (Dobutamine)

Active Substance

Dobutamine (Rec.INN registered by WHO)

Dosage Form

Dobutrex

Infusion solution 250 mg/20 ml: vial 1 pc.

Dosage Form, Packaging, and Composition

20 ml – vials (1) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenomimetic. Cardiotonic

Pharmacotherapeutic Group

Cardiotonic agent of non-glycoside structure

Pharmacological Action

Beta₁-adrenomimetic. It has a positive inotropic effect, which is associated with an increase in the transmembrane calcium current within cardiomyocytes with an increase in their cAMP content as a result of beta-adrenergic stimulation and activation of G-protein adenylate cyclase.

It moderately increases heart rate, increases stroke and minute volume, reduces end-diastolic pressure in the left ventricle, and reduces total peripheral vascular resistance and vascular resistance of the pulmonary circulation. Systemic blood pressure does not change significantly, because the increase in stroke volume is offset by a decrease in total peripheral vascular resistance.

It reduces the filling pressure of the heart ventricles, increases coronary blood flow and helps improve myocardial oxygen supply. The increase in cardiac output can cause an increase in renal perfusion and an increase in the excretion of sodium and water.

In children, the increase in stroke volume observed under the influence of dobutamine is accompanied by a less pronounced decrease in total peripheral vascular resistance and ventricular filling pressure; at the same time, a more pronounced increase in heart rate and an increase in blood pressure are noted.

Pharmacokinetics

After intravenous administration, it is metabolized in the liver to inactive compounds. T_1/2 is about 2 min. It is excreted by the kidneys in the form of metabolites.

Indications

In adults

When inotropic support is necessary for acute decompensation of chronic heart failure, for short-term therapy of conditions caused by heart failure with low cardiac output, such as myocardial infarction, open-heart surgery, cardiomyopathy, septic shock and cardiogenic shock.

To increase or maintain the required volume of cardiac output during ventilation with positive end-expiratory pressure (PEEP).

As an alternative to physical activity during stress echocardiography.

In children of all age groups (from birth to 18 years)

When inotropic support is necessary against the background of low cardiac output and hypoperfusion in the following conditions: decompensated heart failure, upcoming heart surgery, cardiomyopathy, cardiogenic or septic shock.

ICD codes

Dosage Regimen

It is used as a continuous infusion. The dose and regimen are determined individually, depending on the indications, weight and age of the patient. The average dose for adults and elderly patients is from 2.5 to 10 mcg/kg/min.

When determining the rate of administration of dobutamine and its duration, one should focus on the patient’s condition, in particular, on the level of heart rate and heart rhythm, blood pressure, volume of urine output and others, and if possible, on the determination of minute cardiac output, central venous pressure and pulmonary capillary wedge pressure. Discontinuation of dobutamine should be gradual; abrupt cessation of infusion is not recommended.

For children of any age, the initial dose is 5 mcg/kg/min. To achieve a pharmacological effect, it is possible to increase to 20 mcg/kg/min.

In the pediatric population, high variability was observed between the plasma concentration of dobutamine at which the pharmacological effect was achieved and the level of hemodynamic response to the increase in concentration, so it is very difficult to calculate the dose in advance and it must be titrated individually for each patient, taking into account the narrower therapeutic range in this group.

Adverse Reactions

In adults

From the hematopoietic system: frequent – eosinophilia, decreased platelet aggregation (only with very long infusions over several days).

From the immune system: frequency unknown – hypersensitivity reactions, including skin rash, fever, eosinophilia and bronchospasm.

From the nervous system: frequent – headache; frequency unknown – paresthesia, tremor, myoclonic spasm (in patients with severe renal impairment).

From the psyche: frequency unknown – feeling of fatigue, sensation of heat, anxiety.

From the cardiovascular system: very frequent – increase in heart rate by >30 beats/min; frequent – increase in blood pressure by >50 mm Hg (especially in patients with a history of arterial hypertension), decrease in blood pressure, ventricular arrhythmia, dose-dependent increase in the number of ventricular extrasystoles, increase in ventricular rate in patients with atrial fibrillation (monitoring is required before starting and during infusion); vasoconstriction, especially in patients who have previously taken beta-blockers, angina pectoris, palpitations; infrequent – ventricular tachycardia, ventricular fibrillation; very rare – bradycardia, myocardial ischemia, myocardial infarction, cardiac arrest, ST segment elevation on ECG; frequency unknown – decrease in pulmonary capillary resistance; development of eosinophilic myocarditis in donor hearts that were subjected to therapy with dobutamine or another inotropic drug before transplantation.

From the digestive system: frequency unknown – nausea.

From the skin and subcutaneous tissues: frequent – skin redness; very rare – petechial bleeding.

From the urinary system: frequent – imperative urge to urinate when high doses are administered.

From metabolism: very rare – hypokalemia.

In children

Increase in systolic blood pressure, systemic hypo- or hypertension, tachycardia, headache; increase in pulmonary artery wedge pressure, leading to congestion, pulmonary edema; increase in pulmonary capillary resistance in children under 1 year of age.

Adverse reactions during dobutamine stress echocardiography

From the cardiovascular system: very frequent – ventricular extrasystoles with a frequency of more than 6/min, angina pectoris; frequent – supraventricular extrasystoles, ventricular tachycardia; infrequent – ventricular fibrillation, myocardial infarction; very rare – 2nd degree AV block, coronary artery spasm, palpitations, decompensation of hyper- or hypotension, occurrence of intracavitary pressure gradient; frequency unknown – stress cardiomyopathy, left ventricular outflow tract obstruction, cardiac rupture.

From the respiratory system: frequent – bronchospasm, shortness of breath.

From the digestive system: frequent – nausea.

From the skin and subcutaneous tissues: frequent – exanthema; very rare – petechial bleeding.

From the urinary system: increased frequency of imperative urge to urinate when high doses are administered.

Local reactions: frequent – phlebitis at the injection site; with accidental extravascular administration, a local inflammatory reaction is possible; very rare – skin necrosis.

Other: fever, agitation, headache, paresthesias, sensation of heat, anxiety, myoclonic spasm.

Contraindications

Hypersensitivity to dobutamine; ventricular arrhythmias (including ventricular fibrillation); pheochromocytoma; simultaneous use with MAO inhibitors; mechanical obstacles to the inflow/outflow of blood from the left ventricle (cardiac tamponade, constrictive pericarditis, hypertrophic obstructive cardiomyopathy, hemodynamically significant aortic stenosis); breastfeeding period. Conducting stress echocardiography (detection of myocardial ischemia) under the following conditions: recent myocardial infarction (within the last 30 days); unstable angina; stenosis of the left main coronary artery; hemodynamically significant narrowing of the left ventricular outflow tract, including hypertrophic obstructive cardiomyopathy; hemodynamically significant heart valve disease; severe heart failure (functional class III or IV according to NYHA classification); predisposition or history of clinically significant or chronic arrhythmias (especially ventricular tachycardia, severe AV conduction disorders (including bundle branch block); acute pericarditis, myocarditis or endocarditis; aortic dissection; aortic aneurysm; insufficient control of arterial hypertension; impaired ventricular filling (constrictive pericarditis, cardiac tamponade).

With caution: clinically significant tachyarrhythmias (for example, atrial fibrillation, ventricular ectopic activity, ventricular tachycardia), severe AV conduction disorders; severe arterial hypotension with cardiogenic shock (mean blood pressure less than 70 mm Hg); hypovolemia (should be corrected before starting dobutamine); acute myocardial infarction (significant increase in heart rate or blood pressure can provoke increased ischemia and cause angina or ST segment elevation); metabolic acidosis; hypoxia; hypercapnia; pulmonary hypertension; occlusive vascular diseases (arterial thromboembolism, atherosclerosis, thromboangiitis obliterans, cold injury, diabetic angiopathy, Raynaud’s disease); closed-angle glaucoma; pregnancy; children under 18 years of age.

Use in Pregnancy and Lactation

The use of dobutamine during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

Contraindicated for use during breastfeeding. If it is necessary to use dobutamine, breastfeeding should be discontinued.

Pediatric Use

It should be used with caution in children and adolescents under 18 years of age.

When using dobutamine in children, it is necessary to titrate the dose individually, taking into account the narrower therapeutic range in this group.

Geriatric Use

It is possible to use in elderly patients according to indications in recommended doses. Use with caution – to avoid worsening the course of concomitant diseases.

Special Precautions

When using dobutamine, as with any adrenergic agent, blood pressure (especially systolic) and heart rate values, as well as potentially possible heart rhythm disturbances, should be monitored. If they develop, the dose of dobutamine should be reduced or its use temporarily discontinued. If possible, wedge pressure and minute cardiac output should also be monitored.

The use of dobutamine in patients may lead to an increased need for insulin. Therefore, in patients with diabetes mellitus, at the beginning of dobutamine treatment, when changing the infusion rate, and when stopping the infusion, blood glucose levels should be monitored.

Dobutamine can provoke or enhance manifestations of ventricular ectopic activity. In rare cases, the development of ventricular tachycardia or fibrillation is possible, the risk of which increases in patients with pre-existing atrial flutter or fibrillation.

Since Dobutamine accelerates AV conduction, in patients with atrial fibrillation, the ventricular rate may increase, so in patients with this pathology and frequent ventricular systoles, appropriate correction of this condition must be carried out beforehand.

Inotropic drugs, including Dobutamine, do not improve hemodynamics in most patients with mechanical obstruction that impedes both filling and ejection of blood from the ventricles. In patients with a significant decrease in ventricular wall elasticity, it may also be problematic to achieve a noticeable inotropic effect. Such conditions are characteristic of cardiac tamponade, aortic valve stenosis and idiopathic hypertrophic subaortic stenosis.

In patients who have recently taken beta-blockers, slight vasoconstriction may be observed.

During intravenous administration of dobutamine, heart rate and rhythm, blood pressure and infusion rate should be carefully monitored. At the beginning of therapy, ECG monitoring is recommended until a stable response is obtained.

The use of dobutamine in hypovolemic shock is not recommended.

When using dobutamine, a situation may be observed when, despite adequate ventricular filling volumes and minute cardiac output, blood pressure does not increase or gradually decreases. In these cases, a drug that constricts peripheral vessels (such as dopamine or norepinephrine) should be added to the therapy.

Serum potassium levels should be monitored during dobutamine use.

Tolerance may develop with long-term (more than 72 hours) use of dobutamine.

Stress echocardiography should be performed by a specialist with appropriate experience in conducting stress tests specifically with dobutamine, with sufficient experience in ECG recording and intensive care, provided that blood pressure, heart rate and ECG are constantly monitored, in a specialized department equipped with the necessary equipment for emergency care (defibrillator, beta-blockers for intravenous administration, etc.). In rare cases, during dobutamine stress echocardiography, cardiac rupture was noted as a complication of myocardial infarction. The risk of rupture is associated with many factors, including the location of the infarction zone and the time that has passed since it. Patients at risk of rupture of the heart wall or septum must be examined before the test.

Use in pediatrics

In children, compared to the adult population, Dobutamine has a similar inotropic effect, but has a less pronounced effect on peripheral vascular resistance. Increased blood pressure and the development of tachycardia are more common in the pediatric population, and in children under 12 months of age, an increase in pulmonary capillary wedge pressure may also be observed. When prescribing dobutamine to children, the doctor must take into account the pharmacodynamic features in this age group.

Drug Interactions

With simultaneous use of beta-blockers and dobutamine in small doses, narrowing of arterial vessels is possible, due to the alpha-adrenomimetic activity of dobutamine. With simultaneous use of a beta-blocker and dobutamine in high doses, antagonistic interaction at the level of β-adrenergic receptors is possible.

With simultaneous use with cardiac glycosides, the inotropic effect is mutually enhanced, and the risk of arrhythmia development increases.

With simultaneous use with dipyridamole, there is a risk of developing severe arterial hypotension.

With simultaneous use with dopamine, systemic blood pressure increases, renal blood flow, sodium excretion and diuresis increase, while ventricular filling pressure does not increase (which is possible with the administration of dopamine alone).

With simultaneous use with nitroglycerin, sodium nitroprusside (especially in patients with coronary artery disease), minute cardiac output increases, total peripheral vascular resistance and ventricular filling pressure decrease.

With simultaneous use with theophylline, there is a risk of developing tachycardia.

Tolcapone inhibits COMT activity, so theoretically an increase in the plasma concentration of dobutamine and an increase in its side effects are possible.

With simultaneous use with ACE inhibitors, chest pain and arrhythmias were observed.

With simultaneous use with MAO inhibitors (including furazolidone, procarbazine, selegiline), there is a risk of developing life-threatening conditions (hypertensive crisis, hemorrhagic stroke, arrhythmias).

Inhalation anesthetics – hydrocarbon derivatives (including chloroform, enflurane, halothane, isoflurane, methoxyflurane) increase the risk of severe atrial or ventricular arrhythmias when using dobutamine (increase myocardial sensitivity to sympathomimetics).

Tricyclic antidepressants, maprotiline, cocaine, doxapram, guanadrel, guanethidine, enhance the pressor effect and the risk of developing cardiotoxic side effects.

With simultaneous use with dobutamine, ergometrine, ergotamine, methylergometrine, oxytocin increase the vasoconstrictor effect and the risk of ischemia and gangrene, as well as severe arterial hypertension, up to intracranial hemorrhage.

Levodopa increases the risk of arrhythmias (a reduction in the dose of the sympathomimetic is required).

With simultaneous use with thyroid hormones, mutual enhancement of action occurs, which increases the risk of developing coronary insufficiency (especially with coronary atherosclerosis).

Dobutamine is pharmaceutically incompatible with a 5% sodium bicarbonate solution or any other alkaline solution, as well as with solutions containing sodium bisulfite or ethanol, furosemide, ethacrynic acid (and its sodium salt), hydrocortisone sodium succinate, cefazolin sodium, cefamandole sodium, cephalothin sodium, penicillin G, procaine, heparin (and its salts), phenytoin sodium, human insulin, diazepam, aminophylline.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.