Dopamine admeda 200

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DOPAMIN ADMEDA 200 (DOPAMINADMEDA 200)

Composition:

Active substance: dopamine;

One ampoule (10 ml) of concentrate contains 200 mg of dopamine hydrochloride;

1 ml of concentrate contains 20 mg of dopamine hydrochloride;

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

Pharmaceutical form. Concentrate for solution for infusion.

Pharmaceutical characteristics.

Main physicochemical properties: colorless or slightly yellowish clear liquid.

Pharmacotherapeutic group.

Non-glycoside cardiotonic agents. Adrenergic and dopaminergic agents.

ATC code C01CA04.

Pharmacological properties.

Pharmacodynamics. Dopamine belongs to the catecholamines and has a positive inotropic effect. Its effects are dose-dependent. At low doses, it dilates renal and mesenteric blood vessels.

The drug produces the following pharmacological effects:

• increased systolic volume and cardiac output due to enhanced myocardial contractility;
• increased coronary, cerebral, and mesenteric blood flow; increased renal blood flow combined with increased diuresis and enhanced excretion of sodium and potassium as a result of stimulation of specific dopaminergic receptors (urine osmolality usually does not decrease);
• reduced (or unchanged) peripheral vascular resistance when administered at low doses (1.5–3.5 mcg/kg/min);
• increased peripheral vascular resistance when administered at high doses (over 10 mcg/kg/min).

Pharmacokinetics. The elimination half-life of dopamine after intravenous administration is less than 5 minutes. Dopamine is metabolized to inactive metabolites in the liver, kidneys, and plasma; 85% of dopamine is excreted in urine within 24 hours.

Clinical characteristics.

Indications.

Shock states or conditions threatening to develop into shock:

• heart failure caused by acute myocardial infarction (cardiogenic shock);
• postoperative shock states;
• severe infections (septic shock);
• hypersensitivity reactions (anaphylactic shock);
• pronounced decrease in arterial pressure (severe hypotension) of any etiology.

Contraindications.

Hypersensitivity to dopamine or to any other component of the drug. Pheochromocytoma, closed-angle glaucoma, hyperthyroidism, prostate hypertrophy with residual urine syndrome, tachyarrhythmia, ventricular fibrillation, hypovolemia (before starting treatment with Dopamine Admeda 200, circulating blood volume deficit must be corrected). Avoid anesthesia with cyclopropane and halogenated hydrocarbons.

Interaction with other medicinal products and other forms of interaction.

Administration of dopamine should be avoided in patients undergoing inhalational anesthesia with cyclopropane or halogenated hydrocarbons due to their potential to provoke arrhythmias.

Concomitant use of dopamine and ergot alkaloids may lead to excessive constriction of peripheral vessels and development of gangrene.

Patients who are currently receiving or have received monoamine oxidase inhibitors (MAOIs) within the previous 2 weeks should be given a significantly lower dose of dopamine. The initial dose should not exceed one-tenth (1/10) of the usual dose.

Concomitant use of dopamine with tricyclic antidepressants and phenytoin may result in hypotension and bradycardia.

Concomitant use of dopamine and diuretics may produce additive and enhanced diuretic effects.

ß-adrenoblockers, such as propranolol and metoprolol, counteract the cardiac-stimulating effects of dopamine.

α-adrenoreceptor blockers counteract the peripheral vasoconstrictive effects of dopamine.

Concomitant use of dopamine and guanethidine enhances the sympathomimetic effect of dopamine.

Simultaneous administration of dobutamine and dopamine may result in increased arterial pressure, while ventricular filling pressure decreases or remains unchanged.

Catechol-O-methyltransferase (COMT) inhibitors, such as entacapone, may potentiate the chronotropic and arrhythmogenic effects of catecholamines, including dopamine. The clinical significance of this potentiating interaction is not established. Patients who have received entacapone therapy within 1–2 days prior to dopamine administration should be given lower doses of the drug.

Special precautions.

Particular attention should be paid to patients with organic heart and blood vessel disorders, for example:

• patients with ischemic heart disease and angina pectoris;
• patients with arterial occlusive diseases (e.g., atherosclerosis, thromboembolism, Raynaud’s disease, frostbite, diabetic microangiopathy, or Buerger’s disease);
• patients with arrhythmias.

Hypovolemia should be corrected before initiating dopamine infusion. In acute myocardial infarction complicated by shock, low doses of Dopamine Admeda 200 should be used.

If a disproportionate increase in diastolic pressure (i.e., marked reduction in cardiac stroke volume) occurs, the infusion rate should be reduced and the patient should remain under physician supervision, as this may result from increased peripheral vascular resistance.

Patients with a history of peripheral vascular disease must be carefully monitored for any changes in skin color or temperature of the extremities.

Glucose solution should be used with caution in patients with diabetes mellitus.

After gastrointestinal surgery, and in patients with hemorrhagic diathesis, there is a risk of bleeding due to redistribution of blood flow.

Dopamine administration, even at low doses, should be initiated gradually to prevent undesirable arterial hypotension, which usually resolves after increasing the infusion rate.

The infusion rate must be continuously adjusted according to changes in the patient’s condition, diuresis, cardiac output, and arterial pressure. If a patient receiving dopamine develops an increase in diastolic arterial pressure (i.e., a noticeable decrease in pulse pressure amplitude), the infusion rate should be reduced and the patient should be closely observed for signs of vasoconstrictor activity.

Once cardiac function and arterial pressure have stabilized, the dose may need to be reduced to ensure optimal diuresis.

Dopamine infusion should be administered with continuous monitoring of heart rate, arterial pressure, ECG, and diuresis; monitoring of cardiac stroke volume, ventricular filling pressure, central venous pressure, and pulmonary artery pressure is also recommended.

During prolonged parenteral therapy, regardless of the patient’s clinical status, cardiac output, or laboratory findings, regular monitoring of electrolyte and acid-base balance, as well as liver and kidney function, is required.

If excessive elevation of diastolic arterial pressure, reduced diuresis, or arrhythmias occur, the dopamine dose should be reduced.

To prevent extravasation, dopamine should be administered into a large vein. Accidental infiltration into surrounding tissues may cause necrosis. In case of extravasation, necrosis can be prevented by local infiltration of the affected area with phentolamine.

Dopamine must not be administered intraarterially or as a bolus injection.

Due to dopamine administration, especially in patients with occlusive peripheral vascular disease and/or disseminated intravascular coagulation (DIC), severe vasoconstriction may occur, leading to skin necrosis and gangrene. Close monitoring of such patients is essential; if signs of peripheral ischemia appear, dopamine infusion must be stopped immediately. Careful monitoring is also required in patients with impaired renal or hepatic function.

In comatose patients, airway patency must be ensured.

Use during pregnancy or breastfeeding.

The drug is not used during pregnancy due to insufficient data on its safety and efficacy.

Use during breastfeeding is considered safe, as the drug is inactivated upon entering the infant’s body during feeding and has a very short half-life.

Effect on the ability to drive or operate machinery.

Dopamine Admeda 200 is administered under inpatient conditions and has a very short half-life. After hospital discharge, there is no potential for the drug to affect reaction speed when driving or operating machinery.

Administration and dosage.

The dosage of Dopamine Admeda 200 is determined individually by a physician, taking into account the severity of shock, the patient's response to dopamine therapy, and any adverse effects. To achieve the desired hemodynamic effect of dopamine, the dose for each patient should be carefully titrated.

Prior to initiating therapy, circulating blood volume must be restored. Essential supportive measures, such as monitoring electrolyte balance, should not be neglected during dopamine administration.

Unless otherwise directed by the physician, the following dosages are recommended: for patients who are likely to respond to moderate cardiovascular support, dopamine may be administered at an initial dose of 2–5 mcg/kg body weight per minute.

In critically ill patients, the initial dose should be 5 mcg/kg and, if necessary, may be gradually increased (e.g., every 15–30 minutes) to 5–10 mcg/kg body weight per minute, up to a maximum dose of 20–50 mcg/kg body weight per minute.

In most patients, satisfactory clinical response is achieved with dopamine doses below 20 mcg/kg body weight per minute. Administration of doses exceeding 20 mcg/kg body weight per minute may be associated with reduced renal blood flow.

In cases of increased cardiac failure, dopamine should be administered as an infusion at a dose not exceeding 50 mcg/kg body weight per minute.

If doses higher than 50 mcg/kg body weight per minute are required, urine output (diuresis) should be monitored.

It is preferable to increase the infusion rate using lower concentration solutions rather than administering more concentrated solutions.

The tables below indicate the infusion rates for various dosages and initial concentrations.

When 1 ampoule of dopamine is diluted to 50 mL of infusion solution, 1 mL of the resulting solution contains 4000 mcg of dopamine hydrochloride.

If 1 ampoule of dopamine is diluted to 500 ml of infusion solution, 1 ml of this solution contains 400 mcg of dopamine hydrochloride.

The duration of treatment depends on the patient's clinical condition and is determined by the physician.

Before initiating dopamine therapy in patients with hypovolemia, blood volume should be restored. Since dopamine improves atrioventricular conduction, cardiac glycosides should be administered prior to dopamine in patients with atrial fibrillation and rapid ventricular response.

In the treatment of unconscious patients, airway patency must be monitored due to the risk of aspiration. For patients with increased preload and afterload, additional nitroglycerin is recommended to reduce cardiac workload.

Dopamin Admeda 200 must be diluted before administration. The recommended diluents are:

• 0.9% sodium chloride solution;
• 5% glucose solution;
• Ringer's lactate solution.

The dilution volume is 1 ampoule per 250 ml or 500 ml of the recommended diluent.

Dopamine must not be added to 5% sodium bicarbonate solution or any other alkaline solution, as this leads to inactivation of the drug.

The infusion solution should be prepared immediately before use, using only clear solutions that do not change color after addition of Dopamin Admeda 200. Infusion should be administered, if possible, via a central venous catheter.

Ready-to-use infusion solutions containing Dopamin Admeda 200 are stable for the usual duration of infusion (at least 24 hours), except for mixtures with Ringer's lactate solution (stable for no more than 6 hours).

Children.

There is no information on the use of dopamine in children; therefore, the drug is not prescribed to this age group.

Overdose.

Symptoms of overdose are generally due to the sympathomimetic effects of dopamine.

When high doses are used, alpha-receptor stimulation increases in combination with beta-receptor antagonism, resulting in vasoconstrictive effects at the end.

Symptoms: excessive increase in arterial pressure, tachycardia, arrhythmia, increased left ventricular end-diastolic pressure leading to pulmonary edema, angina attacks (especially in patients with heart failure), non-specific chest pain, palpitations, nausea, vomiting, sensation of cold extremities, cyanosis.

Treatment: reduction of dose or temporary discontinuation of infusion, since the duration of dopamine action is very short. If these measures are insufficient, β-blockers or nitroglycerin should be administered.

Adverse Reactions.

Cardiovascular system: very common – arrhythmia (usually extrasystolic); rare – atrioventricular block, bradycardia, QRS complex widening, myocardial ischemia, arterial hypertension; very rare – supraventricular tachycardia, sinus tachycardia or ventricular tachycardia, increased ventricular pressure, palpitations, angina attacks, arterial hypotension, vasoconstriction; hand tremor.

Respiratory system: dyspnea.

Gastrointestinal tract: nausea, vomiting.

Nervous system: headache, restlessness, anxiety.

Skin: piloerection.

Other: increased blood urea levels, mydriasis, azotemia, bleeding, polyuria, hypersensitivity reactions.

With increasing dosage, there is a risk of elevated left ventricular end-diastolic pressure.

When high doses (20 mg/kg/min or higher) are administered, dopaminergic vasodilation in the visceral vascular bed may reverse to vasoconstriction due to stimulation of alpha-receptors, leading to reduced renal blood flow.

Even at low doses, skin necrosis and gangrene may occur; this risk exists in patients with circulatory disorders and when very high doses (10 mg/kg/min or more) are used.

In patients with a history of arterial occlusive disease (arteriosclerosis, arterial embolism, Raynaud's disease, cold injuries such as frostbite, diabetic microangiopathy, or Buerger's disease), any changes in skin color or skin temperature of the extremities should be carefully monitored. Changes in skin color or temperature may indicate worsening of skin circulation.

In patients with respiratory insufficiency, increased hypoxemia may occur, characteristic of increased blood flow through hypoventilated alveolar areas (intrapulmonary shunting).

Accidental infiltration of the drug into perivenous soft tissues may lead to tissue necrosis.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Since Dopamine Admeda 200 is not intended for repeated infusion from a single container, it contains no preservatives and must always be prepared for administration under optimal hygienic (aseptic) conditions immediately before infusion.

Physical and chemical stability during storage:

* Ratio of mixture components: content of 1 ampoule in 250 ml or 500 ml of infusion solution.

Incompatibility.

Dopamine is sensitive to alkaline agents. Therefore, it must not be mixed with alkaline solutions (pH above 7), such as sodium bicarbonate.

Alteplase and amphotericin B are unstable in the presence of dopamine.

In addition, physical-chemical incompatibility is known with acyclovir, alteplase, amikacin, amphotericin B, ampicillin, cephalothin, dacarbazine, ethylenediamine theophylline (euphylline), calcium theophyllinate solution (calcium euphylline solution), furosemide, gentamicin, heparin, iron salts, sodium nitroprusside, benzylpenicillin, tobramycin.

Packaging.

5 ampoules of 10 ml concentrate for solution for infusion in a cardboard pack.

Prescription category. Prescription only.

Manufacturer.

Haupt Pharma Wülfling GmbH.

Manufacturer's address and location of operations.

Betelner Landstrasse, 18, 31028, Gronau/Leine, Germany

Marketing Authorization Holder.

Admeda Arzneimittel GmbH.

Address of the Marketing Authorization Holder.

Trift 4, 23863 Nienwohld, Germany.