Dobutamin Admeda (Solution) Instructions for Use

Marketing Authorization Holder

Admeda Arzneimittel, GmbH (Germany)

Manufactured By

Haupt Pharma Wulfing, GmbH (Germany)

ATC Code

C01CA07 (Dobutamine)

Active Substance

Dobutamine (Rec.INN registered by WHO)

Dosage Form

Dobutamine Admeda

Infusion solution 250 mg/50 ml: amp. 1 pc.

Dosage Form, Packaging, and Composition

Infusion solution from colorless to slightly yellowish, transparent.

Excipients: cysteine hydrochloride monohydrate, citric acid monohydrate, sodium chloride, sodium hydroxide, water for injections.

50 ml – ampoules of colorless glass (1) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenomimetic. Cardiotonic

Pharmacotherapeutic Group

Cardiotonic agent of non-glycoside structure

Pharmacological Action

Cardiotonic agent of non-glycoside nature.

The positive inotropic effect is associated with stimulation of myocardial beta₁-adrenergic receptors. It has a weak stimulating effect on beta₂– and alpha₁-adrenergic receptors. It causes a moderate positive chronotropic effect. Heart rate does not increase significantly when prescribed in usual doses; at high doses (infusion rate of 10 mcg/kg/min), pronounced tachycardia may be observed. It increases stroke and minute volumes of blood, reduces left ventricular end-diastolic pressure, systemic vascular resistance and vascular resistance in the pulmonary circulation.

Systemic blood pressure does not change significantly, because the increase in stroke volume is offset by a decrease in systemic vascular resistance. Both an increase and a decrease in blood pressure are possible. Patients with arterial hypertension who have normal blood pressure during drug administration are more prone to a vasopressor reaction.

It reduces the filling pressure of the heart ventricles, increases coronary blood flow and myocardial oxygen supply, and improves AV conduction. Like all inotropic drugs, Dobutamine increases myocardial oxygen consumption. By increasing the minute volume of blood, it increases renal perfusion and increases the excretion of sodium ions and water.

In children, an increase in stroke volume is accompanied by a less pronounced decrease in systemic vascular resistance and ventricular filling pressure; a more pronounced increase in heart rate and an increase in blood pressure are noted. A decrease in the concentration of catecholamines in the synapses under the influence of reserpine or tricyclic antidepressants practically does not affect the action of dobutamine (it has a direct action, and its effectiveness does not depend on presynaptic mechanisms).

Onset of action – after 1-2 minutes, if the infusion rate is low – up to 10 minutes; duration of action – less than 5 minutes.

Partial tolerance to dobutamine may develop during prolonged continuous infusions for 72 hours.

Pharmacokinetics

Volume of distribution – 20% of body weight.

It is metabolized in the liver with the participation of catechol-O-methyltransferase to inactive metabolites. The main metabolite is 3-O-methyldobutamine.

Clearance – 2.4 l/min/m², T_1/2 – about 2 minutes. It is excreted by the kidneys in the form of metabolites.

Indications

Acute heart failure:

• Acute myocardial infarction;
• Cardiogenic shock;
• Consequences of heart surgery.

As an auxiliary agent

• Temporary maintenance treatment of patients with chronic heart failure receiving conventional treatment;
• Acute heart failure of non-cardiogenic origin (including in septic shock);
• Low minute volume of blood against the background of artificial lung ventilation with positive end-expiratory pressure.

ICD codes

Dosage Regimen

Dobutamine Admeda should be dosed individually!

For adults

The infusion rate required to increase the minute volume of blood is 2.5-10 mcg/kg/min. In rare cases, an infusion rate of up to 40 mcg/kg/min is used.

For children

Doses between 1 and 15 mcg/kg/min are used (the minimum effective dose for children is often higher than for adults, while the maximum dose for children is lower than for adults).

At doses greater than or equal to 7.5 mcg/kg/min, the greatest number of adverse events (especially tachycardia) was observed.

The required dose for children must be accurately calculated to account for the presumably smaller therapeutic range in childhood.

Tables for determining intravenous dosages for different types of administration and different initial concentrations

Before discontinuing Dobutamine Admeda, it is necessary to gradually reduce its dose!

Instructions for preparation of infusion solution

Dobutamine Admeda in the form of a solution for intravenous administration in 50 ml ampoules for use undiluted in infusion drips. Alternatively, the drug can be pre-diluted. For this, 5% dextrose (glucose) solution, physiological saline, Ringer’s lactate solution can be used. For intravenous use only.

Due to the short elimination half-life, Dobutamine should be administered intravenously continuously.

During the administration of Dobutamine Admeda, heart rhythm, blood pressure, urine output, infusion volume and infusion rate should be monitored. If possible, during the infusion, the minute cardiac output, central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) should be monitored.

Duration of use

The duration of intravenous administration depends on clinical symptoms and is determined by the doctor.

Special instruction

With continuous use of the drug for more than 72 hours, a tolerance phenomenon may develop, which makes it necessary to increase the dosage of the drug.

Adverse Reactions

More often – headache, nausea, vomiting; less often – angina pectoris, bradycardia, shortness of breath, increase or decrease in blood pressure, palpitations, tachycardia, ventricular arrhythmia (when administered in high doses); rarely – hypokalemia, slight vasoconstriction (in patients who have undergone a course of treatment with beta-blockers), myocardial ischemia, myocardial infarction, cardiac arrest, myocardial dystrophy, slight decrease in pulmonary capillary pressure (in children), increase in pulmonary capillary pressure (in children under 1 year); very rarely – decreased platelet aggregation (temporarily), frequent urge to urinate (when administering large doses), fever, eosinophilia, bronchospasm.

Local reactions phlebitis (as a result of careless venipuncture), skin rash.

Contraindications

• Presence of a mechanical obstruction to the filling or outflow from the heart ventricles (cardiac tamponade, pericarditis, hypertrophic obstructive cardiomyopathy, severe aortic stenosis);
• Hypovolemia;
• With simultaneous use of MAO inhibitors;
• Pheochromocytoma;
• Ventricular arrhythmias (including ventricular fibrillation);
• Increased sensitivity to the drug.

With caution myocardial infarction (high doses of dobutamine may increase heart rate and myocardial contractility and, by increasing myocardial oxygen demand, exacerbate ischemia), metabolic acidosis, hypercapnia, hypoxia, tachyarrhythmia, atrial fibrillation, pulmonary hypertension, hypovolemia, occlusive vascular diseases (arterial thromboembolism, atherosclerosis, thromboangiitis obliterans (Buerger’s disease), cold injury, including frostbite, diabetic endarteritis, Raynaud’s disease), closed-angle glaucoma, pregnancy, lactation period, children under 18 years of age.

Use in Pregnancy and Lactation

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

If it is necessary to carry out treatment during breastfeeding, then in this case breastfeeding should be discontinued for the duration of treatment.

Pediatric Use

Use with caution in children under 18 years of age.

Special Precautions

Solutions containing Dobutamine may give a pink color, the intensity of which will increase over time (due to its oxidation, but there is no significant loss of activity or increase in toxicity).

Constant monitoring of blood pressure, ventricular filling pressure, central venous pressure, pulmonary artery pressure, heart rate, ECG, stroke volume, body temperature and diuresis, serum potassium concentration is necessary.

If treatment with dobutamine causes a significant increase in heart rate and/or an increase in blood pressure, the dose of dobutamine should be reduced or the drug should be temporarily discontinued.

If blood pressure remains low or continues to decrease during drug administration, despite adequate end-diastolic pressure and minute volume of blood, the possibility of using dopamine or norepinephrine should be considered.

In some cases, in chronic heart failure in the stage of decompensation, along with dobutamine, the administration of peripheral vasodilators (including sodium nitroprusside, nitroglycerin) is indicated. The issue of using dobutamine in coronary heart disease should be decided in each individual case.

When conducting a continuous infusion lasting 72 hours or more, tolerance may develop, so higher doses may be required to maintain the initial effect.

Dobutamine is not recommended as an adjunctive therapy for hypovolemic shock.

When determining the concentration of chloramphenicol by HPLC in the presence of dobutamine, distortion of results is possible.

Overdose

Symptoms loss of appetite, nausea, vomiting, tremor, anxiety, palpitations, tachycardia, tachyarrhythmia, ventricular fibrillation, excessive increase in blood pressure, myocardial ischemia, cardialgia, headache, shortness of breath.

Treatment discontinuation of intravenous administration, if necessary, tracheal intubation to ensure lung ventilation and blood oxygenation. With an excessive increase in blood pressure – intravenous administration of short-acting alpha-blockers, with ventricular tachyarrhythmia – propranolol or lidocaine. In case of accidental oral intake – activated charcoal (gastric lavage and induction of vomiting are more effective). Hemodialysis and peritoneal dialysis, forced diuresis, hemoperfusion using activated charcoal are ineffective.

Drug Interactions

Dobutamine in combination with dopamine increases blood pressure, increases renal blood flow, sodium excretion and diuresis, prevents an increase in ventricular filling pressure, and reduces the risk of pulmonary circulation overload and pulmonary edema.

It reduces the hypotensive effect of diuretics and antihypertensive drugs (including rauwolfia alkaloids).

Nitrates contribute to an increase in minute volume of blood, a decrease in systemic vascular resistance and ventricular filling pressure (a weakening of the antianginal, pressor effects, and a decrease in blood pressure is possible).

Alpha-blockers and drugs with alpha-blocking activity reduce the pressor effect. Beta-blockers in small doses contribute to arterial constriction; in high doses they exhibit antagonism, reduce the positive inotropic effect, and an increase in systemic vascular resistance may be observed.

Concomitant use with ACE inhibitors leads to the appearance of heart pain and arrhythmias, with MAO inhibitors (including furazolidone, procarbazine, selegiline) – to life-threatening conditions (hypertensive crisis, hemorrhagic stroke, arrhythmias).

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

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

Cardiac glycosides enhance (mutually) the inotropic effect and the risk of arrhythmia (caution should be exercised).

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 (requires a reduction in the dose of the sympathomimetic).

Thyroid hormones enhance (mutually) the effect and the associated risk of coronary insufficiency (especially with coronary atherosclerosis).

Pharmaceutically incompatible with 5% sodium bicarbonate solution or any other alkaline solution, as well as with solutions containing sodium bisulfite or ethanol.

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

Storage Conditions

List B. At room temperature not exceeding 25°C (77°F) in a dry, light-protected place. Do not freeze. Store the medicine out of the reach of children!

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.