Consumer medicine information

DBL Sterile Dopamine Concentrate

Dopamine hydrochloride

BRAND INFORMATION

Brand name

DBL Sterile Dopamine Concentrate

Active ingredient

Dopamine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Sterile Dopamine Concentrate.

What is in this leaflet

This leaflet answers some common questions about DBL Sterile Dopamine Concentrate.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given DBL Sterile Dopamine Concentrate against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet in a safe place. You may need to read it again.

What DBL Sterile Dopamine Concentrate is used for

Dopamine acts in different ways, depending on the dose given. At low doses, dopamine increases blood flow to the kidneys. At higher doses, it increases the blood flow to the muscles and can increase the heart’s pumping efficiency.

Dopamine may be used to increase low blood pressure in people who have:

  • experienced a heart attack
  • a severe infection
  • lost blood during an accident
  • kidney failure
  • problems after surgery.

Dopamine may be used to help the heart pump better in some people with congestive heart failure.

Your doctor may have prescribed DBL Sterile Dopamine Concentrate for another reason.

Ask your doctor if you have any questions about why DBL Sterile Dopamine Concentrate has been prescribed for you.

There is no evidence that dopamine is addictive.

This medicine is available only with a doctor’s prescription.

Before you are given DBL Sterile Dopamine Concentrate

When you must not be given it

You must not be given DBL Sterile Dopamine Concentrate if you have an allergy to dopamine or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

You should not be given dopamine if you have any of the following medical conditions:

  • adrenal gland tumour (phaeochromocytoma)
  • fast or irregular heart beat (arrhythmia, ventricular fibrillation)
  • overactive thyroid gland (hyperthyroidism).
  • liver disease
  • kidney disease

You should not be given dopamine if:

  • you are being given certain anaesthetics at the same time
  • you are currently using ergotamine, a medicine used to treat migraines.

If you are not sure whether you should be given dopamine, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • sulfites
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant. If it is necessary for you to be given dopamine, your doctor will discuss the risks and benefits of using it during pregnancy.

Tell your doctor if you are breast-feeding or plan to breast-feed. Your doctor will discuss the possible risks and benefits of you being given dopamine during breast-feeding.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • hardening of the blood vessels
  • Raynaud’s disease, where the fingers become white and very painful when cold
  • diabetes
  • frostbite
  • high blood pressure.

If you have not told your doctor about any of the above, tell them before you are given dopamine.

Taking other medicines

Tell your doctor or pharmacist if you are using any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and dopamine may interfere with each other. These include:

  • some anaesthetic agents
  • ergotamine, methysergide and dihydroergotamine (medicines used to prevent or treat migraines)
  • some heart and blood pressure tablets, including digoxin, prazosin, beta-blockers such as propranolol and metoprolol, calcium channel blockers and glyceryl trinitrate
  • antidepressants (MAO inhibitors, tricyclic antidepressants)
  • haloperidol or droperidol (medicines used to treat some mental illnesses)
  • medicines used to control seizures (fits), such as phenytoin.

These medicines may be affected by dopamine, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines. Your doctor or pharmacist will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while being given dopamine.

How DBL Sterile Dopamine Concentrate is given

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight.

How it is given

DBL Sterile Dopamine Concentrate is diluted and given slowly as an infusion (a drip) into a vein. This medicine should only be given by a doctor, nurse or other trained person.

If you take too much (overdose)

As DBL Sterile Dopamine Concentrate is given to you in hospital under the supervision of your doctor, it is very unlikely that you will receive an overdose. Symptoms of a dopamine overdose include the effects listed below in the ‘Side Effects’ section but are usually of a more severe nature.

While you are being given DBL Sterile Dopamine Concentrate

Things you must do

Tell any other doctors, dentists and pharmacists who treat you that you have been given dopamine.

Be sure to keep all of your doctor’s appointments so that your progress can be checked. Your doctor will check your progress and may want to take some tests from time to time. This helps to prevent unwanted side effects.

Things to be careful of

Be careful driving or operating machinery until you know how this medicine affects you.

If you are feeling dizzy or drowsy do not drive, operate machinery, or do anything else that could be dangerous.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being given dopamine or soon after the injection. Dopamine may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • dizziness
  • nausea
  • vomiting
  • headache
  • anxiety.

These are the more common side effects of dopamine and are usually mild.

Tell your doctor or nurse immediately if you notice any of the following:

  • cold or tingling feet which may indicate problems with blood circulation
  • chest pain
  • irregular or rapid heart beat
  • difficulty breathing.

These may be serious side effects. You may need urgent medical attention. Serious side effects are rare.

Other side effects not listed above may occur in some patients. Tell your doctor, pharmacist or nurse if you notice anything that is making you feel unwell.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After you are given DBL Sterile Dopamine Concentrate

Storage

DBL Sterile Dopamine Injection Concentrate will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 30C.

Product description

What it looks like

DBL Sterile Dopamine Concentrate is a sterile, clear colourless to pale yellow liquid in a glass ampoule.

Each 5 mL ampoule contains 200 milligrams of dopamine hydrochloride.

It is available in packs of 5 ampoules.

Ingredients

Active ingredients:

  • Dopamine hydrochloride.

Other ingredients

  • Water for Injection
  • Sodium metabisulfite.

DBL Sterile Dopamine Concentrate does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian Registration Number:

AUST R 16378

This leaflet was updated in:
August 2021.

™ Trademark

© Pfizer Australia Pty Ltd 2021

Published by MIMS October 2021

BRAND INFORMATION

Brand name

DBL Sterile Dopamine Concentrate

Active ingredient

Dopamine hydrochloride

Schedule

S4

 

1 Name of Medicine

Dopamine hydrochloride.

2 Qualitative and Quantitative Composition

Dopamine hydrochloride is a naturally occurring biochemical catecholamine precursor of noradrenaline and adrenaline. The chemical name of dopamine hydrochloride is 4-(2-aminoethyl) benzene-1,2-diol hydrochloride and has the chemical formula C8H11NO2.HCl.
DBL Sterile Dopamine Concentrate is a sterile solution of Dopamine Hydrochloride BP in water for injection, containing 1% sodium metabisulfite. The strength supplied is 200 mg/5 mL in a clear glass ampoule.

Excipient with known effect.

Sodium metabisulfite.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dopamine hydrochloride is a white, odourless powder, freely soluble in water and soluble in alcohol. It is sensitive to light, alkalis, iron salts and oxidising agents. The pH of the solution is approximately 4. It must be diluted before use.

4 Clinical Particulars

4.1 Therapeutic Indications

For the correction of haemodynamic imbalance present in:
Acute hypotension or shock associated with myocardial infarction, endotoxic septicaemia, trauma and renal failure.
As an adjunct after open heart surgery, where there is persistent hypotension after correction of hypovolaemia.
In chronic cardiac decompensation as in congestive failure.

4.2 Dose and Method of Administration

Warning.

Dopamine is a potent drug. It must be diluted before administration. Do not add to alkaline solutions such as sodium bicarbonate, as these inactivate dopamine.
In appropriate cases, restoration of blood volume with plasma, whole blood, or a suitable plasma expander, should be instituted prior to administration: central venous pressure should be 10 to 15 cm H2O, or pulmonary wedge pressure 14 to 18 mmHg.

Dosage.

Adult.

When appropriate, increase blood volume with a suitable plasma expander, whole blood or plasma until central venous pressure is 10 to 15 cm H2O or pulmonary wedge pressure is 14 to 18 mmHg.
Begin administration of diluted solution at doses of 2 to 5 microgram/kg/min in patients who are likely to respond to modest increments of heart force and renal perfusion (see Section 5 Pharmacological Properties, Table 3) for physiological effects at various doses).
In more seriously ill patients, begin administration of diluted solution at doses of 5 microgram/kg/min and increase gradually using 5 to 10 microgram/kg/min increments up to 20 to 50 microgram/kg/min as needed. In patients who do not respond to these doses with adequate arterial pressures or urine flow, additional increments may be employed in an effort to produce an appropriate arterial pressure and central perfusion. If doses of dopamine in excess of 50 microgram/kg/min are required, it is suggested that urine output be checked frequently. Should urine flow begin to decrease in the absence of hypotension, reduction of dosage should be considered. Once optimal haemodynamic effects have been achieved, the lowest dose that maintains these effects should be used. Multiclinic trials have shown that more than 50% of the patients were satisfactorily maintained on doses of dopamine less than 20 microgram/kg/min.
Treatment of all patients requires constant evaluation of therapy in terms of the blood volume, augmentation of myocardial contractility, distribution of peripheral perfusion and urinary output. Dosage should be adjusted according to the patient's response with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indices for decreasing or temporarily suspending the dosage.
Care must be taken in patients with cardiac decompensation to avoid alpha-adrenoceptor induced vasoconstriction and increased afterload. These patients should be started on a dose of 1 to 2 microgram/kg/minute and the rate of infusion increased with caution. Patients with occlusive vascular disease should also be commenced on a similar low dose.
For patients with severe, refractory, chronic congestive heart failure who are to be treated for a short period of time with dopamine, it is recommended that the infusion rate be commenced at a rate of 0.5 to 2 microgram/kg/min, increasing the dose as the urine flow increases to a usual maintenance dose of 1 to 3 microgram/kg/min. The infusion rate should be reduced if the diastolic blood pressure or heart rate increases.

Paediatric.

It is not recommended for use in children as safety and efficacy in this age group has not been established.

Geriatric.

No variation in dosage is suggested for geriatric patients.

Method of administration.

The rate of administration should be controlled in order to prevent inadvertent bolus administration: constant evaluation of therapy should be undertaken (i.e. blood volume, ECG, arterial blood pressure, urine output, augmentation of myocardial contractility and distribution of peripheral perfusion. Measurement of central venous pressure and pulmonary wedge pressure and cardiac output are also helpful). Dopamine should be administered into a large vein (preferably of the antecubital fossa) to reduce the risk of extravasation into surrounding tissue which may cause necrosis.

Antidote for peripheral ischaemia following extravasation.

To prevent sloughing and necrosis in ischaemic areas, the area should be infiltrated as soon as possible with 10 to 15 mL of sodium chloride intravenous infusion 0.9% containing from 5 to 10 mg of phentolamine, an adrenergic blocking agent. A syringe with a fine hypodermic needle should be used, and the solution liberally infiltrated throughout the ischaemic area. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperaemic changes if the area is infiltrated within 12 hours. Therefore, phentolamine should be given as soon as possible after the extravasation is noted.

Suggested dilution.

Aseptically transfer DBL Sterile Dopamine Concentrate into the intravenous solution as shown in Table 1.
In patients in whom greater fluid load is undesirable, an alternative regimen is suggested in Table 2.

Rate of administration.

Dopamine, after dilution, is administered intravenously through a suitable intravenous catheter or needle. An intravenous drip chamber or other suitable metering device is essential for controlling the rate of flow in drops/minute. Each patient must be individually titrated to the desired haemodynamic and/or renal response with dopamine. In titrating to the desired increase in systolic blood pressure, the optimum dosage rate for renal response may be exceeded thus necessitating a reduction in rate after the haemodynamic condition is stabilised.
Administration at rates greater than 50 microgram/kg/minute has safely been used in advanced circulatory decompensation states. If unnecessary fluid expansion is of concern, adjustment of drug concentration may be preferred over increasing the flow rate of a less concentrated dilution.

Compatibilities.

Dopamine has been reported to be compatible with the following: sodium chloride 0.9%, glucose 5%, glucose 5% and sodium chloride 0.9%, glucose 5% in sodium chloride 0.45%, glucose 5% in lactated Ringer's solution, sodium lactate 1/6 M injection, lactated Ringer's injection.
It is recommended that, if dopamine is administered with other drugs, a 'piggyback' administration set or administration into a second injection site is used to avoid mixing of potent drugs with dopamine.

IV fluids.

Dopamine injection has been shown to be stable for 24 hours when 200 mg is diluted in 250 mL or 500 mL of the following intravenous fluids: sodium chloride infusion 0.9%, glucose 5% injection, glucose 5% and sodium chloride infusion 0.9%, 5% glucose in lactated Ringer's solution, 1/6 M sodium lactate injection, lactated Ringer's injection.
However, as with all intravenous admixtures, dilution should be made just prior to administration.

Antibiotics.

Dopamine has been found to be chemically and physically stable for 24 hours (at 23° to 25°C and exposed to light) with the following antibiotics: kanamycin sulfate (500 mg/250 mL 5% glucose admixture), tetracycline hydrochloride (250 mg/250 mL 5% glucose admixture), carbenicillin disodium (1.0 g/250 mL 5% glucose admixture), chloramphenicol sodium succinate (1.0 g/250 mL 5% glucose admixture), cephalothin sodium neutral (1.0 g/250 mL 5% glucose admixture) (see note below), oxacillin (500 mg/250 mL 5% glucose) (see note below).
Because of loss of potency of the antibiotic at 24 hours the following admixtures of antibiotics and dopamine in 5% glucose solution should be administered within six hours of mixing: gentamicin sulfate (80 mg/250 mL 5% glucose), cephalothin sodium (1.0 g/250 mL 5% glucose), penicillin G potassium (5,000,000 units/250 mL 5% glucose).

Note.

It is recommended in the literature that cephalothin sodium, oxacillin sodium and gentamicin sulfate not be mixed with any other drug. It is considered that the recommendation should also include cephalothin sodium neutral. Although studies indicate that dopamine hydrochloride may be compatible with these drugs, their admixture produces a fixed combination of potent drugs. It is suggested that admixtures containing gentamicin sulfate, cephalothin sodium, cephalothin sodium neutral or oxacillin sodium should be avoided unless all other viable alternatives have been exhausted.

Other medicines.

Heparin sodium (50,000 units/250 mL 5% glucose) has been shown to be compatible with dopamine hydrochloride for 24 hours.
Lignocaine hydrochloride (1.0 g/250 mL 5% glucose) has been shown to be compatible with dopamine hydrochloride for 24 hours.
Mixing other drugs in dopamine infusion is not recommended, as sufficient evidence of compatibility is not available.

Incompatibilities.

See Section 6.2 Incompatibilities.

4.3 Contraindications

Administration of dopamine is contraindicated in the following cases:
Phaeochromocytoma: dopamine may release catecholamines into the circulation, producing an additive effect to an already abnormally high catecholamine level, and causing acute hypertension.
Atrial or ventricular tachyarrhythmias or ventricular fibrillation.
Concurrent use with cyclopropane and halogenated hydrocarbon anaesthetics (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Hyperthyroidism.
Concurrent use with ergotamine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Patients who are taking monoamine oxidase (MAO) inhibitors or who have taken them within the last two to three weeks require a substantially reduced starting dose, i.e. about 1/10th the usual dose (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Dopamine should not be added to alkaline diluents (see Section 4.2 Dose and Method of Administration; Section 6.2 Incompatibilities).

Hypovolaemia.

Hypovolaemia should be fully corrected prior to treatment with dopamine with a suitable plasma expander or whole blood or plasma until the central venous pressure is 10 to 15 cm H2O or the pulmonary wedge pressure is 14 to 18 mmHg.

Decreased pulse pressure.

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

Occlusive vascular disease.

Those patients with pre-existing peripheral vascular disease, such as that due to atherosclerosis, arterial embolism, Buerger's disease, Raynaud's disease, diabetic endarteritis or cold injury (e.g. frostbite), may be more susceptible to peripheral ischaemia and subsequent gangrene and should be observed carefully for any changes in colour or temperature of the skin in the extremities. If ischaemia occurs and is thought to be due to vasoconstriction, the benefits of the dopamine infusion should be weighed against the risks of possible necrosis. Ischaemia may be reversed by either decreasing the rate or discontinuing the infusion. Intravenous administration of phentolamine 5 to 10 mg may also reverse the ischaemia.
As with any cardiac stimulant, care should be exercised when administering dopamine to patients with cardiac ischaemia.
Acidosis, hypercapnia or hypoxia may reduce the effectiveness and/or increase the incidence of adverse effects of dopamine. These conditions should be corrected prior to or concurrently with administration of dopamine.
Pulmonary hypertension may be exacerbated due to dopamine induced pulmonary vasoconstriction. Where dopamine induced pulmonary hypertension has occurred, isoprenaline may be considered as an alternative inotropic agent.
Routine monitoring of blood pressure, ECG, cardiac status and renal output is necessary in all patients. Where possible, the cardiac output and pulmonary wedge pressure should also be measured.

Sulfite sensitivity.

DBL Sterile Dopamine Concentrate contains sodium metabisulfite, which may cause allergic type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than nonasthmatic people.

Hypotension.

Hypotension may occur when attempting to wean patients from dopamine and it may be necessary to substitute dopamine with another pressor agent or to expand blood volume whilst gradually reducing the infusion rate.

Extravasation.

Dopamine should be infused into a large vein whenever possible to prevent the possibility of extravasation into tissue adjacent to the infusion site. The infusion site should be continuously monitored for free flow. Extravasation may cause necrosis and sloughing of the surrounding tissue. A syringe with a fine hypodermic needle should be used to liberally infiltrate the ischemic area as soon as extravasation is noted.

Diabetes.

Glucose solutions should be used with caution in patients with known subclinical or overt diabetes mellitus.

Use in hepatic impairment.

Dopamine is metabolised in the tissues and blood by MAO inhibitors and COMT. Since the effect of impaired liver function is not known, close monitoring is advisable.

Use in renal impairment.

Dopamine and its metabolites are almost completely excreted in the urine. Since the effect of impaired renal function is not known, close monitoring of such patients is advisable.

Use in the elderly.

No variation in dosage is suggested for geriatric patients. Close monitoring is required for blood pressure, urine flow, and peripheral tissue perfusion.

Paediatric use.

It is not recommended for use in children as safety and efficacy in this age group has not been established.

Effects on laboratory tests.

Dopamine or its metabolites may interfere with urine tests for amino acids or catecholamines and also with tests for detecting uric acid or urobilinogen.
Infusion of dopamine suppresses pituitary secretion of thyroid stimulating hormone, and prolactin.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Alcohol.

No information available.

Food.

Not applicable.
Cyclopropane and halogenated anaesthetics sensitise the myocardium to the effects of dopamine. Dopamine should therefore be used with extreme caution with these drugs due to the potential for developing ventricular arrhythmias or hypertension.
MAO inhibitors potentiate the effect of dopamine and prolong its duration of action. Patients being treated, or who have been treated within the previous two to three weeks, with MAO inhibitors will, therefore, require a substantially reduced dosage of dopamine (the starting dose should be reduced to 1/10th of the usual dose or less).
Alpha- and beta-adrenergic receptor blocking drugs will interfere with the alpha- and beta-adrenergic responses induced by dopamine. The use of other pressor amines may be associated with complex interactions. The cardiac effects of dopamine are antagonized by β-adrenergic blocking agents such as propranolol and metoprolol, and the peripheral vasoconstriction caused by high doses of dopamine is antagonized by α-adrenergic blocking agents.
Hypotension may be observed with concurrent use of vasodilators such as glyceryl trinitrate, nitroprusside and calcium channel blockers.
In animal studies, large doses of butyrophenones blocked the dopaminergic mediated renal vasodilation. Whether this occurs in man is not known.
Tricyclic antidepressants may potentiate the cardiovascular effects of dopamine, possibly resulting in arrhythmias, tachycardia or severe hypertension or hyperpyrexia (see Section 4.4 Special Warnings and Precautions for Use).
Concurrent use of digitalis glycosides with dopamine may increase the risk of cardiac arrhythmias. Caution and close ECG monitoring are very important if concurrent use is necessary.
Concurrent use of methysergide or other ergot alkaloids with dopamine may result in excessive vasoconstriction and should be avoided. Ergot alkaloids or oxytocin may potentiate the pressor effect of dopamine and cause severe hypertension and rupture of cerebral blood vessels. Concurrent use of ergotamine with dopamine is not recommended as it may produce vascular ischaemia and gangrene.
Guanethidine may potentiate the pressor response to dopamine.
Concurrent use of intravenous phenytoin with dopamine may result in dose dependent, sudden hypotension and bradycardia and possibly cardiac arrest. If anticonvulsant therapy is necessary during administration of dopamine, an alternative to phenytoin should be considered. Caution is also advised with concurrent use of other hydantoins.
Also see Section 6.2 Incompatibilities.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies in animals have not been performed to assess the effects of dopamine on fertility.
(Category B3)
Category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have shown evidence of increased foetal damage, the significance of which is considered uncertain in humans.
It is not known whether dopamine crosses the placental barrier. In one animal study, the administration of dopamine to pregnant rats resulted in a decreased survival rate of the newborn, and cataract formation in the survivors. The benefits of using this product should be weighed against the possible risks to the foetus.
 It is not known if dopamine is excreted in breast milk, nor is the effect on the infant known. Dopamine is inactive when ingested orally, nonetheless it is not recommended for breastfeeding mothers unless the expected benefits outweigh any potential risks.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration. Patients should refrain from driving or using machines until they know that the medicinal product does not negatively affect these abilities.

4.8 Adverse Effects (Undesirable Effects)

Common reactions.

Adverse reactions have been observed in 19% of patients during clinical evaluation, however, only half of these were attributed to dopamine. Treatment was terminated in 5% of all patients due to adverse reactions.

Cardiovascular.

Ectopic beats, tachycardia, anginal pain, palpitation, hypotension, vasoconstriction.

Gastrointestinal.

Nausea, vomiting.

Nervous system.

Headache.

Respiratory.

Dyspnoea.

Less common reactions.

Biochemical abnormalities.

Azotaemia.

Cardiovascular.

Atrial fibrillation, aberrant ventricular conduction, bradycardia, widened QRS complex, hypertension, ectopic heartbeats. A few cases of peripheral cyanosis have been reported in patients receiving dopamine.

Nervous system.

Piloerection, anxiety.

Serious or life threatening reactions.

Gangrene of feet has occurred following doses of 10 to 14 microgram/kg/min and higher, and in a few patients with pre-existing vascular disease (see Section 4.4 Special Warnings and Precautions for Use).
Fatal ventricular arrhythmias have been reported on rare occasions. Extravasation of dopamine may cause necrosis and sloughing of surrounding tissue (see Section 4.2 Dose and Method of Administration).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Excessive elevation of blood pressure and vasoconstriction could be expected to occur due to the alpha-adrenergic actions of dopamine, especially in patients with a history of occlusive vascular disease (see Section 4.8 Adverse Effects (Undesirable Effects)).

Treatment.

In case of accidental overdose the rate of administration should be reduced or the infusion discontinued temporarily until the patient's condition stabilises. Since the duration of action of dopamine is quite short, no additional measures are usually necessary. If these measures fail to stabilise the patient's condition in a relatively short time, use of the short acting alpha-adrenergic blocking agent, phentolamine, should be considered.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Dopamine hydrochloride can stimulate alpha, beta and dopamine receptors. At infusion rates of 0.5 to 2 microgram/kg/min, dopamine receptors are selectively activated and blood pressure either does not change or decreases slightly. The most important effects are renal and mesenteric vasodilatation. Renal plasma flow, glomerular filtration rate and sodium excretion usually increase. At infusion rates of 2 to 10 microgram/kg/min, β1-receptors are activated and cardiac output and systolic blood pressure increase. The total peripheral resistance is relatively unchanged because of peripheral vasoconstriction (alpha effect) and muscle vasodilatation (beta effect). At infusion rates above 10 microgram/kg/minute, alpha-receptors are activated, causing vasoconstriction, and both systolic and diastolic pressures increase. (See Table 3.)
Dopamine does not cross the blood brain barrier and so does not activate dopamine receptors in the brain.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The steady state blood levels following intravenous infusion have not been determined in any species, nor has the time for these to be achieved.

Distribution.

Dopamine is widely distributed in the body.

Protein binding.

No information is available for humans or animals (however, dopamine is rapidly metabolised and excreted).

Metabolism.

Dopamine is metabolised in the liver, kidneys and plasma and the metabolites are excreted by the kidneys. The major routes of metabolism are deamination by monoamine oxidase, and formation of methylated and reduced derivatives by catechol-o-methyl transferase.
On infusion of 14C-labelled dopamine into humans, it was found that approximately 75% of the infused dopamine was rapidly converted into metabolites of dopamine, and 25% was synthesised into noradrenaline, and its metabolic products. Only a trace of unlabelled adrenaline was detected. The principal metabolite of dopamine was 3-methoxy-4-hydroxy phenylethanol (18.6% of an infused dose) and the principal metabolites of noradrenaline were normetanephrine and 3-4-dihydroxy-mandelic acid.

Excretion.

97% of the infused dose of 14C-labelled dopamine appeared in urine as metabolites. The metabolites of both dopamine and noradrenaline appear to be at least partially secreted (70% of an infused dose has been found to be secreted per 10 minute infusion period). The degree of active excretion of dopamine is about the same as for adrenaline and noradrenaline, and is inhibited by probenecid.

Onset of action.

5 minutes, with a duration of action of less than 10 minutes (in patients receiving monoamine oxidase inhibitors the duration of action may be as long as 1 hour).

Half-life.

Approximately 2 minutes after an intravenous bolus (due to rapid metabolism and excretion).

Clinical implication of pharmacokinetic data.

Dopamine should be given by continuous infusion because of the rapid metabolism and excretion of the drug.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of dopamine has not been evaluated.

Carcinogenicity.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of dopamine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium metabisulfate, water for injections.

6.2 Incompatibilities

Dopamine should not be added to sodium bicarbonate and other alkaline solutions (see Section 4.4 Special Warnings and Precautions for Use) as they will inactivate dopamine. If sodium bicarbonate is simultaneously indicated to treat acidosis, it should be given through a separate infusion line from a separate container.
Dopamine is incompatible with ampicillin or amphotericin B, so should not be mixed with either of these drugs.
Dopamine decomposes when mixed with ampicillin in 5% glucose solution, because the solution is alkaline. A precipitate forms immediately on mixing dopamine with amphotericin B in 5% glucose solution. Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

DBL Sterile Dopamine Concentrate is available in clear glass ampoules in the following strength:
200 mg dopamine hydrochloride/5 mL (cartons contain 5 ampoules).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

The chemical structure is:
MW: 189.6.

CAS number.

CAS 51-61-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4.

Summary Table of Changes