Dopamine Admeda (Concentrate) Instructions for Use

Marketing Authorization Holder

Admeda Arzneimittel, GmbH (Germany)

Manufactured By

Haupt Pharma Wulfing, GmbH (Germany)

ATC Code

C01CA04 (Dopamine)

Active Substance

Dopamine (Rec.INN registered by WHO)

Dosage Form

Dopamine Admeda

Concentrate for solution for infusion 20 mg/ml: 10 ml amp. 5 pcs.

Dosage Form, Packaging, and Composition

10 ml – ampoules (5) – cardboard holders (1) – cardboard packs.

Clinical-Pharmacological Group

Dopaminomimetic and adrenomimetic drug

Pharmacotherapeutic Group

Cardiotonic agent of non-glycoside structure

Pharmacological Action

Cardiotonic and hypertensive agent.

It stimulates beta-adrenergic receptors (in low and medium doses) and alpha-adrenergic receptors (in high doses). Improvement of systemic hemodynamics leads to a diuretic effect. It has a specific stimulating effect on postsynaptic dopamine receptors. In low doses (0.5-3 mcg/kg/min) it acts primarily on dopamine receptors, causing dilation of renal vessels, increasing renal blood flow, as well as glomerular filtration, sodium ion excretion and diuresis; mesenteric vessel dilation also occurs (this effect on renal and mesenteric vessels distinguishes dopamine from other catecholamines).

In low and medium doses (2-10 mcg/kg/min) it stimulates postsynaptic beta-adrenergic receptors, causing an increase in cardiac output. Systolic BP and pulse pressure may increase; while diastolic BP does not change or slightly increases. Total peripheral vascular resistance (TPR) usually does not change. Coronary blood flow and myocardial oxygen consumption generally increase.

In high doses (10 mcg/kg/min or more) additional stimulation of alpha-adrenergic receptors is noted, causing an increase in TPR and constriction of renal vessels (the latter may reduce the previously increased renal blood flow and diuresis). Both systolic and diastolic BP increase due to increased cardiac output and TPR.

The onset of therapeutic effect is within 5 minutes during IV administration and lasts for 10 minutes.

Pharmacokinetics

Dopamine is metabolized in the liver, kidneys, and blood plasma to form inactive metabolites; within 24 hours, 85% of the administered dose is excreted by the kidneys. About 25% of the dose is taken up by neurosecretory vesicles, where hydroxylation occurs and norepinephrine is formed. It is widely distributed in the body, slightly passes through the blood-brain barrier. Apparent volume of distribution (newborns) – 1.8 L/kg. Plasma protein binding – 50%, rapidly metabolized in the liver, kidneys, and blood plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) to inactive metabolites. T_1/2 – adults: from plasma – 2 min, from tissues – 9 min; newborns – 6.9 min (range 5-11 min). Excreted by the kidneys: 80% of the dose as metabolites within 24 hours, in small amounts – unchanged. Volume of distribution 0.9 L/kg.

Indications

• Shock of various origins (cardiogenic, postoperative, infectious-toxic, anaphylactic, hypovolemic/only after restoration of circulating blood volume);
• Acute cardiac and vascular failure in various pathological conditions.

ICD codes

Dosage Regimen

The drug is used only for IV administration.

The dose is selected individually and depends on the severity of shock, BP level, as well as the patient’s response to the therapy. The duration of administration depends on the clinical situation and should be determined by the doctor. The infusion rate should be individually selected to achieve the optimal patient response.

If possible, administration should be performed through a central venous catheter. The recommended initial dose of the drug is 2-5 mcg/kg/min. In case of severe patient condition, the initial dose should be 5 mcg/kg/min. If necessary, a gradual dose increase (every 15-30 minutes) by 5-10 mcg/kg of body weight per minute is possible. In most patients, a satisfactory condition can be maintained therapeutically using doses less than 20 mcg/kg/min. Doses exceeding this value may lead to reduced renal function and decreased renal blood flow. In case of acute cardiovascular failure, decompensation of cardiac activity, Dopamine Admeda is administered at a rate of more than 50 mcg/kg/min. Duration of use: the duration of infusions depends on the individual characteristics of the patient.

Dosages for drip administration (see Table No. 1)

If the contents of 1 ampoule of Dopamine Admeda 200 mg are dissolved in 50 ml of injection solution, 1 ml of such solution contains 4000 mcg of dopamine.

Table No. 1

After stabilization of the clinical situation, the drug should be withdrawn gradually. To enhance diuresis and obtain an inotropic effect (increase in myocardial contractility), it is administered at a rate of 100 – 250 mcg/min (1.5-3.5 mcg/kg/min) (low dose range). During intensive surgical therapy – 300-700 mcg/min (4-10 mcg/kg/min) (medium dose range); for septic shock – 750-1500 mcg/min (10.5-21 mcg/kg/min) (maximum dose range). To affect BP, an increase in dose to 500 mcg/min and more is recommended, or with a constant dose of Dopamine Admeda, norepinephrine is additionally prescribed at a dose of 5 mcg/min for a patient body weight of about 70 kg.

If cardiac arrhythmias occur, regardless of the doses used, further increase of the drug is contraindicated.

Children are administered at a dose of 4-6 (maximum 10) mcg/kg/min. Unlike adults, in children the dose should be increased gradually, i.e., starting from the smallest dose. Duration of use: the duration of infusions depends on the individual characteristics of the patient. There is positive experience with infusion duration up to 28 days.

Rules for solution preparation

For dilution, use: 0.9% sodium chloride solution, 5% dextrose (glucose) solution, Ringer’s lactate solution.

The infusion solution should be prepared immediately before use (solution stability is maintained for 24 hours, except for mixture with Ringer’s lactate solution – maximum 6 hours). The Dopamine Admeda drug solution should be clear and colorless.

Adverse Reactions

From the cardiovascular system: less frequently – angina pectoris, tachycardia or bradycardia, palpitations, chest pain, increase or decrease in BP, conduction disturbance, QRS complex widening (QRS – the first phase of the ventricular complex, reflecting the process of ventricular depolarization); vasospasm, increase in left ventricular end-diastolic pressure; when used in high doses – ventricular or supraventricular arrhythmia.

From the digestive tract: more frequently – nausea, vomiting, gastrointestinal bleeding.

From the CNS: more frequently – headache; less frequently – anxiety, motor restlessness, finger tremor.

Allergic reactions: in patients with bronchial asthma – bronchospasm, shock.

Other reactions: less frequently – dyspnea, azotemia, piloerection; rarely – polyuria (when administered in low doses).

Local reactions: if the drug gets under the skin – skin necrosis, subcutaneous tissue necrosis.

Contraindications

• Hypersensitivity to the components of the drug (including other adrenomimetics);
• Hyperthyroidism;
• Pheochromocytoma;
• Closed-angle glaucoma;
• Benign prostatic hyperplasia with clinical manifestations;
• Tachyarrhythmia;
• Ventricular fibrillation of the heart.

With caution: hypovolemia, coronary artery disease, angina pectoris, obliterating diseases of peripheral arteries (including atherosclerosis, arterial thromboembolism, obliterating thromboangiitis (Buerger’s disease), cold injury, diabetic endarteritis, Raynaud’s disease, frostbite), arrhythmias.

Use in Pregnancy and Lactation

Clinical data on the use of the drug in pregnant women are insufficient. Reproductive toxicity of dopamine was shown in animal studies.

During pregnancy, the drug should be used only if the intended benefit to the mother outweighs the potential risk to the fetus and/or child. There are no data on the penetration of dopamine into breast milk. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Pediatric Use

Children are administered at a dose of 4-6 (maximum 10) mcg/kg/min. Unlike adults, in children the dose should be increased gradually, i.e., starting from the smallest dose.

Special Precautions

The drug Dopamine Admeda is intended only for IV infusion and can only be used in diluted form!

In patients in a state of shock, hypovolemia must be corrected before drug administration by administering plasma and other blood-substituting fluids. The infusion rate should be constantly adjusted according to the patient’s condition. Infusion should be carried out under control of diuresis, heart rate, cardiac output, BP, ECG. A decrease in diuresis without a concomitant decrease in BP indicates the need to reduce the dose of Dopamine Admeda.

Since Dopamine Admeda improves atrioventricular conduction, patients with atrial fibrillation and rapid ventricular response should be administered cardiac glycosides before prescribing Dopamine Admeda. During prolonged parenteral nutrition and in all cases (as indicated), circulating blood volume, water-electrolyte balance, acid-base status, liver and kidney function status should be regularly assessed.

MAO inhibitors, increasing the pressor effect of sympathomimetics, can cause headache, arrhythmia, vomiting and other manifestations of hypertensive crisis, therefore in patients who have received MAO inhibitors within the last 2-3 weeks, the initial doses of Dopamine Admeda should be no more than 10% of the usual dose.

Strictly controlled studies of the drug use in patients under 18 years of age have not been conducted (there are isolated reports of arrhythmias and gangrene associated with drug extravasation during intravenous administration in this group of patients). To reduce the risk of extravasation, it is recommended to administer the drug into large veins. To prevent tissue necrosis in case of extravasal drug entry, immediate infiltration with 10-15 ml of 0.9% sodium chloride solution with 5-10 mg of phentolamine should be performed.

Given the pharmacological properties of the drug, special attention should be paid to the inadmissibility of intra-arterial infusions and bolus injections!

Patients in a comatose state must have airway patency ensured.

Prescription of the drug against the background of occlusive diseases of peripheral vessels and/or a history of DIC syndrome can cause sharp and pronounced vasoconstriction, leading to skin necrosis and gangrene (careful monitoring should be carried out, and if signs of peripheral ischemia are detected, drug administration should be immediately stopped).

Overdose

Symptoms excessive increase in BP, tachycardia, tachyarrhythmias, increase in end-diastolic volume in the left ventricle with subsequent development of pulmonary edema, angina attack (especially in patients with coronary artery disease), nonspecific chest pain, palpitations, nausea, vomiting, spasm of peripheral arteries, cyanosis, ventricular extrasystole.

Treatment reduce the dose or temporarily stop intravenous infusion until the patient’s condition stabilizes, since Dopamine has a short half-life. In severe cases, the possibility of prescribing beta-blockers or nitroglycerin should be considered.

Drug Interactions

Dopamine is unstable in alkaline solutions (pH more than 7), for example, in sodium bicarbonate solution.

Compounds with which Dopamine is pharmaceutically incompatible: acyclovir, alteplase, amikacin, amphotericin B, ampicillin, cephalothin, dacarbazine citrate (due to the presence of cysteine), theophylline ethylenediamine (aminophylline), theophylline calcium solution (calcium aminophylline solution), furosemide, gentamicin, heparin, iron salts, nitroprusside, benzylpenicillin (penicillin G), tobramycin.

Sympathomimetic effect is enhanced by adrenergic stimulants, MAO inhibitors (including furazolidone, procarbazine, selegiline), guanethidine (increased duration and enhancement of cardiotonic and pressor effects); diuretic – diuretics; cardiotonic effect – inhalational agents for general anesthesia, hydrocarbon derivatives – such as cyclopropane, chloroform, enflurane, halothane, isoflurane, methoxyflurane (increased risk of severe atrial or ventricular arrhythmias), tricyclic antidepressants, including maprotiline (risk of cardiac arrhythmias, severe arterial hypertension or hyperpyrexia), cocaine, other sympathomimetics; weakened by – butyrophenones and beta-blockers (propranolol).

It weakens the hypotensive effect of guanadrel, guanethidine, mecamylamine, methyldopa, rauwolfia alkaloids (the latter prolong the effect of dopamine). With simultaneous use with levodopa – increased likelihood of arrhythmias; with thyroid hormones – possible enhancement of the action of both dopamine and thyroid hormones.

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.

Phenytoin may contribute to the development of arterial hypotension and bradycardia (depends on the dose and rate of administration); ergot alkaloids – vasoconstriction and development of gangrene.

Compatible with cardiac glycosides (possible increased risk of arrhythmias, additive inotropic effect, ECG monitoring required).

Reduces the antianginal effect of nitrates, which, in turn, may reduce the pressor effect of sympathomimetics and increase the risk of arterial hypotension (simultaneous use is allowed depending on the achievement of therapeutic effect).

Storage Conditions

Store in a light-protected place, out of reach of children, at a temperature not exceeding + 25°C (77°F). Do not freeze.

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.