NEOATRICON Solution for infusion Ref.[114544] Active ingredients: Dopamine

Avoid co-infusion with other medicinal products.

Mono-amine oxidase (MAO) inhibitors

To avoid potentiation patients who have been treated with MAO inhibitors prior to dopamine hydrochloride should be given reduced doses of dopamine hydrochloride (see sections 4.2, 4.5 and 5.2).

Monitoring of volume, electrolyte and diastolic blood pressure

Vasopressors, including dopamine hydrochloride, are generally not indicated in hypovolemic shock. Once adequate fluid resuscitation has been initiated, vasopressor therapy may be considered in specific cases where blood pressure remains severely low despite adequate fluid resuscitation. Dopamine hydrochloride should be chosen if inotropic, chronotropic, vasoconstrictive effects and an increase in peripheral venous resistance is required. However, the use of vasopressors in haemorrhagic or hypovolemic shock should be approached cautiously and under close monitoring.

Excess administration of potassium-free solutions may result in significant hypokalaemia.

If a disproportionate rise in diastolic pressure (i.e. a marked decrease in pulse pressure) is observed, the infusion rate should be decreased and the patients observed carefully for further evidence of predominant vasoconstriction activity, unless such an effect is desired.

Constant evaluation of therapy in terms of blood volume, augmentation of cardiac contractility, and distribution of peripheral perfusion and urinary output is required for patients of any age.

Monitoring of potential cardiac adverse reactions

Careful monitoring should be performed for dysrhythmia and tachycardia and if present consideration should be given to reducing the infusion rate or discontinuing dopamine hydrochloride if clinically appropriate. Any reversible causes of tachycardia such as volume depletion, hypoxia or pain should be corrected and tachycardia should be controlled.

Peripheral vascular disease

Patients should be closely monitored for any changes in colour or temperature of the skin of the extremities. If change of skin colour or temperature occurs and is thought to be the result of compromised circulation to the extremities, the benefits of continued dopamine hydrochloride infusion should be weighed against the risk of possible necrosis. These changes may be reversed by decreasing the rate or discontinuing the infusion. Even at low doses, dopamine hydrochloride can cause skin necrosis; the risk is particularly high in patients with disorders of acral circulation and when higher doses are administered (≥10 μg/kg/min).

Because of variable, age-dependent clearance, titrate dose slowly and deliberately, particularly in neonates. Neonates may be more sensitive to vasoconstrictive effects.

Subcutaneous, intramuscular or intra-arterial administration must be avoided, as the vasoconstrictor effect may result in tissue damage.

Extravasation

Dopamine hydrochloride should be infused into a large vein whenever possible to prevent the possibility of infiltration of perivascular tissue adjacent to the infusion site. Extravasation may cause necrosis and sloughing of the surrounding tissue. Ischaemia can be reversed by infiltration of the affected area with a vasodilator. A syringe with a fine hypodermic needle should be used to liberally infiltrate the ischaemic area as soon as extravasation is noted.

Renal and hepatic impairment

The clearance of dopamine hydrochloride is affected by renal and hepatic dysfunction – decreasing by 2-fold in the presence of either. In younger children, particularly neonates, clearance is highly variable, close monitoring is advised.

Withdrawal effect

Dopamine hydrochloride infusion should be withdrawn gradually, to avoid unnecessary hypotension. It may be necessary to decrease the dose of dopamine hydrochloride gradually while expanding blood volume with IV fluids to prevent a recurrence of hypotension. Sudden cessation of dopamine hydrochloride infusion may result in marked hypotension. See also weaning instructions in section 4.2.

Septic shock

Based on signals of an increased mortality with the first line use of dopamine in paediatric and adult patients with septic shock, first line administration of dopamine in paediatric patients with sepsis is not recommended.

Cardiac surgery

Dopamine hydrochloride is selectively used in paediatric patients with low cardiac output syndrome (LCOS) and low systemic vascular resistance (SVR) to improve cardiac output. Its use in patients with elevated SVR or elevated pulmonary vascular resistance (PVR) is generally limited due to the potential to worsen vascular resistance abnormalities. The decision to administer dopamine hydrochloride in cardiac surgery should always be made based on the patient’s specific clinical condition.

Instances of increased pulmonary arterial pressure

Dopamine hydrochloride can increase pulmonary vascular resistance, particularly at higher doses. When administering dopamine hydrochloride in patients with increased pulmonary arterial pressure, close haemodynamic monitoring is recommended and doses above 10 μg/kg/min should be avoided. In acute pulmonary hypertension dopamine hydrochloride should only be administered if considered necessary based on an individual assessment of the haemodynamic and clinical state of the patient.

Risk of intraventricular haemorrhage (IVH)/subependymal bleed

To mitigate the risk of IVH/subependymal bleed, blood pressure and hemodynamic status of infants receiving dopamine hydrochloride should be closely monitored by healthcare professionals in the neonatal intensive care unit (NICU). Dose adjustments should be made as needed to maintain stable blood pressure and minimize the risk of adverse reactions such as t achycardia, extravasation at injection site, disproportionate rise in diastolic pressure, chest pain, palpitations, hypotension. The overall management of IVH/subependymal bleed should involve supportive care and measures to address potential risk factors beyond vasoactive medicinal products.

Risk of infection

The potential unfavourable effects of dopamine hydrochloride on the risk of infection should be considered, particularly when used in high doses or for prolonged periods. The decision to use dopamine hydrochloride or any vasoactive medicinal product should be individualized, taking into account the patient’s clinical condition, infection risk, and potential benefits of treatment. Close monitoring and infection prevention measures are essential in managing patients receiving dopamine hydrochloride.

Narrow angle glaucoma

Dopamine is not recommended in patients with narrow angle glaucoma.

Alkalizing substances

If sodium bicarbonate is simultaneously indicated to treat acidosis, it should be given through a separate infusion line from a separate container or administration set.

Laboratory test interferences

Infusion of dopamine hydrochloride suppresses pituitary secretion of thyroid stimulating hormone (TSH), and prolactin (see section 4.8). Dopamine hydrochloride-induced decrease of TSH may interfere with early diagnosis of congenital hypothyroidism, which is characterized by high TSH levels in connection with low T4. It is therefore recommended to test all new-borns for TSH and T4 values not only at primary screening, but also after dopamine hydrochloride discontinuation.

Dopamine hydrochloride may lead to false positive results when urinary catecholamine excretion is determined.

Prolactin

Dopamine hydrochloride is known to reduce serum prolactin (see section 4.6).

Excipients with known effect

Contains sodium metabisulfite which may rarely cause severe hypersensitivity reactions and bronchospasm.

This medicinal product contains less than 1 mmol of sodium (23 mg) per dose, and therefore is essentially sodium free.

Anaesthetics

The myocardium is sensitised by cyclopropane or halogenated hydrocarbon anaesthetics, and these medicinal products are contraindicated with dopamine hydrochloride (see section 4.3). This interaction applies both to pressor activity and cardiac beta adrenergic stimulation.

Alpha and beta blockers

It is not recommended to use dopamine with alpha and beta blockers. The cardiac effects of dopamine hydrochloride are antagonised by β-adrenergic blocking agents such as propranolol acebutolol, atenolol, bisoprolol, nadolol, nebivolol, and metoprolol, and the peripheral vasoconstriction caused by high doses of dopamine hydrochloride is antagonised by α adrenergic blocking agents (e.g. doxazosin, prazosin, terazosin).

MAO inhibitors

It is not recommended to use dopamine with MAO inhibitors. MAO inhibitors (e.g. isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline, linezolid) potentiate the effect of dopamine hydrochloride and its duration of action. Patients who have been treated with MAO inhibitors prior to administration of dopamine hydrochloride will therefore require a substantially reduced dose (see sections 4.2, 4.4 and 5.2).

Phenytoin

Administration of IV phenytoin to patients receiving dopamine hydrochloride has resulted in hypotension, bradycardia and cardiac arrest; it is recommended that phenytoin should be used with extreme caution, if at all, in patients receiving dopamine hydrochloride.

Diuretic agents

It is not recommended to use dopamine with diuretic agents (e.g. bumetanide, torsemide, and furosemide). Dopamine hydrochloride may increase the effect of diuretic agents.

Ergot alkaloids

The combination of dopamine hydrochloride with ergot alkaloids (e.g., ergotamine) should be avoided because of the possibility of excessive peripheral vasoconstriction, increasing the risk of gangrene.

Tricyclic antidepressants and guanethidine

Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, nortriptyline) and guanethidine may potentiate the pressor response to dopamine hydrochloride.

Inactivation of dopamine hydrochloride by addition of alkalizing substances

Dopamine hydrochloride is inactivated in alkaline solution please refer to section 4.4 and section 6.2.

Metoclopramide

It is not recommended to use dopamine with metoclopramide as metoclopramide can impair the dopamine hydrochloride effect.

Blood glucose levels

Dopamine hydrochloride may increase the blood glucose level and may therefore interfere with antidiabetic medicinal products (e.g. meglitinides – repaglinide etc.; sulfonylureas – glipizide etc.). The metabolism of neonates can be very fragile; therefore, hypo- or hyperglycaemia is more common in this group. Metabolic parameters should be monitored during dopamine hydrochloride infusion, e.g. blood pressure and blood glucose.

Pregnancy

There are limited amount of data from the use of dopamine hydrochloride in pregnant woman. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Neoatricon is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

It is not known if dopamine hydrochloride is excreted in human milk. However, because of the short plasma half-life of dopamine hydrochloride at therapeutic doses no effects on the breastfed infants are anticipated. Therefore, Neoatricon can be used during breast-feeding. See section 4.4 for information on prolactin.

Fertility

No data available.

Not relevant.

Summary of the safety profile

Except for vasoconstrictive effects caused by inadvertent infusion of dopamine hydrochloride into the umbilical artery, adverse reactions unique to the paediatric population have not been identified.

Tabulated list of adverse reactions

The data in the following table is extracted from clinical studies and post-marketing experience pertaining to the adult population. The frequency of adverse events cannot be estimated in the paediatric population. The adverse reactions are listed below by SOC (System Organ Class) and by frequency, most frequent reactions first, with the following guidelines: 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) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 1. Adverse reactions identified in clinical studies and post-marketing:

^* Anaphylactic reactions and severe life-threatening asthmatic episodes may be due to Sodium metabisulphite sensitivity (see section 4.4).

Description of selected adverse reactions

Suppression of pituitary function

Due to activation of D2 receptors in the pituitary gland, dopamine suppresses the release of prolactin and thyroid-stimulating hormone (TSH), the latter resulting in a decrease of T4 release from the thyroid gland. Conversely, dopamine discontinuation may lead to a rebound effect with overshooting release of prolactin, TSH and T4.

Increase in hypoxemia

Dopamine may contribute to hypoxemia by several mechanisms, e.g. by ventilation-perfusion mismatch, i.e., increased blood flow even to hypoventilated alveolar areas (pulmonary “shunt” formation), specifically in ventilator-dependent patients. Moreover, dopamine may increase systemic oxygen consumption (VO2).

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. Avoid mixing with alkalis (including sodium bicarbonate), oxidizing agents or iron salts.

Do NOT add dopamine hydrochloride to sodium bicarbonate solution for injection, or other alkaline I.V. solutions.

Admixtures of ampicillin and dopamine in 5% glucose solution are alkaline and incompatible and result in decomposition of both drugs. They should not be admixed.

It is suggested that admixtures containing gentamicin sulphate, cephalothin sodium, cephalothin sodium neutral or oxacillin sodium should be avoided unless all other viable alternatives have been exhausted.

Admixtures of dopamine, amphotericin B in 5% glucose solution are incompatible as a precipitate forms immediately on mixing.