INFORMATION FOR HEALTH PROFESSIONALS
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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 milligrams/5 mL in a clear glass ampoule. The pH of the solution is approximately 4. It must be diluted before use.
Dopamine hydrochloride can stimulate alpha, beta and dopamine receptors. At infusion rates of 0.5 to 2 micrograms/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 micrograms/kg/min, beta1-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 micrograms/kg/min, alpha-receptors are activated, causing vasoconstriction, and both systolic and diastolic pressures increase.
Dopamine does not cross the blood-brain barrier and so does not activate dopamine receptors in the brain.
Cardiovascular effects of dopamine at various infusion rates
| 0.5 to 2 micrograms/kg/min. | 2-10 micrograms/ kg/min. | Over 10 micrograms/kg/min. | |
|---|---|---|---|
| *Low but needs monitoring | |||
| Cardiac output | no change | increase | increase |
| Stroke volume | no change | increase | increase |
| Heart rate | no change | there is an initial increase followed by a decrease toward normal rate as infusion continues. | |
| Myocardial contractility | no change | increase | increase |
| Potential for excessive myocardial oxygen demands | low* coronary blood flow increased | low* coronary blood flow increased | data unavailable |
| Potential for tachyarrhythmias | low* | low* | moderate |
| Total systemic vascular resistance | slight decrease to no change | no change to slight increase | increase |
| Renal blood flow | increase | increase | decrease |
| Urine output | increase | increase | decrease |
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 minutes 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.
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.
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 15cm H2O, or pulmonary wedge pressure
14 to 18mm Hg.
The rate of administration should be controlled in order to prevent inadvertent bolus administration: constant evaluation of therapy should be undertaken (ie. 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.
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 milligrams 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.
Aseptically transfer DBL® Sterile Dopamine Concentrate into the intravenous solution as per the table below:
| Strength milligrams/5 mL |
Volume mL |
Intravenous solution volume mL |
Final concentration micrograms/mL |
|---|---|---|---|
| 200 | 5 | 250 | 800 |
| 200 | 5 | 500 | 400 |
In patients in whom greater fluid load is undesirable, an alternative regimen is
suggested:
| Strength milligrams/5 mL |
Volume mL |
Intravenous solution volume mL |
Final concentration micrograms/mL |
|---|---|---|---|
| 200 | 10 | 250 | 1600 |
| 200 | 20 | 500 | 1600 |
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 per 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 micrograms/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.
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 mm Hg.
Begin administration of diluted solution at doses of 2 to 5 micrograms/kg/min in patients who are likely to respond to modest increments of heart force and renal perfusion (see table under PHARMACOLOGY for physiological effects at various doses).
In more seriously ill patients, begin administration of diluted solution at doses of 5 micrograms/kg/min and increase gradually using 5 to 10 micrograms/kg/min increments up to 20 to 50 micrograms/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 micrograms/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 micrograms/kg/min.
Treatment of all patients requires constant evaluation of therapy in terms of the blood volume, augmentation of myocardial contractility and distribution of peripheral perfusion. 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 micrograms/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 micrograms/kg/min, increasing the dose as the urine flow increases to a usual maintenance dose of 1 to 3 micrograms/kg/min. The infusion rate should be reduced if the diastolic blood pressure or heart rate increases.
It is not recommended for use in children as safety and efficacy in this age group has not been established.
No variation in dosage is suggested for geriatric patients. However, close monitoring is required for blood pressure, urine flow, and peripheral tissue perfusion.
Dopamine is metabolised in the tissues and blood by MAO and COMT. Since the effect of impaired liver function is not known, close monitoring is advisable.
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.
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.
NOTE: Dopamine should not be added to sodium bicarbonate and other alkaline solutions (see PRECAUTIONS ) 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 injection has been shown to be stable for 24 hours when 200 milligrams is diluted in 250 mL or 500 mL of the following intravenous fluids:
However, as with all intravenous admixtures, dilution should be made just prior to administration.
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:
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:
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.
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.
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.
Administration of dopamine is contraindicated in the following cases:
Patients who are taking monoamine oxidase inhibitors or who have taken them within the last two to three weeks require a substantially reduced starting dose, ie about 1/10th the usual dose (see Interactions with other drugs ).
Dopamine should not be added to alkaline diluents (see Compatibilities/incompatibilities ).
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 mm Hg.
Excessive dosage may be indicated by a disproportionate rise in diastolic pressure (ie a marked decrease in pulse pressure). The infusion rate should be decreased or ceased.
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 (eg. 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 milligrams 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.
If a disproportionate rise in the diastolic pressure (ie. a marked decrease in the pulse pressure) is observed, the infusion rate should be decreased or suspended and the patient observed closely, unless such an effect is required.
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 non-asthmatic people.
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.
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.
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 breast-feeding mothers unless the expected benefits outweigh any potential risks.
Dopamine Hydrochloride may be likely to produce minor or moderate adverse effects that may impair the patient's ability to concentrate and react and therefore constitute a risk in the ability to drive and use machines.
The genotoxic potential of dopamine has not been evaluated. Long term studies in animals have not been performed to evaluate the carcinogenic potential of dopamine. Studies in animals have not been performed to assess the effects of dopamine on fertility.
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.
Biochemical abnormalities - Azotaemia.
Cardiovascular - Aberrant ventricular conduction, bradycardia, widened QRS complex, hypertension. Gangrene of the feet has occurred in a few patients with pre-existing vascular disease. A few cases of peripheral cyanosis have been reported in patients receiving dopamine.
Nervous System - Piloerection, anxiety.
Gangrene of feet has occurred following doses of 10 to 14 micrograms/kg/min and higher and in a few patients with pre-existing vascular disease (see PRECAUTIONS ).
Fatal ventricular arrhythmias have been reported on rare occasions. Extravasation of dopamine may cause necrosis and sloughing of surrounding tissue (see DOSAGE AND ADMINISTRATION ).
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.
Monoamine oxidase (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 1/10thof 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.
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 PRECAUTIONS ).
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.
Dopamine or its metabolites may interfere with urine tests for amino acids or catecholamines and also with tests for detecting uric acid or urobilinogen.
Excessive elevation of blood pressure could be expected from accidental overdose (see ADVERSE REACTIONS ).
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.
See Dosage and Administration.
See Dosage and Administration.
See Dosage and Administration, IV fluid.
Store below 30°C. Protect from light.
Prescription Medicine.
DBL® Sterile Dopamine Concentrate is available in ampoules in the following strength:
200 milligrams dopamine hydrochloride/5 mL
Dopamine hydrochloride is a naturally occurring biochemical catecholamine precursor of noradrenaline and adrenaline.
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 chemical name of dopamine hydrochloride is 4-(2-aminoethyl) benzene-1,2-diol hydrochloride and its chemical structure is:
C8H11NO2 · HCl
MW 189.6
CAS 51-61-6
Hospira NZ Limited
23 Haining Street
Te Aro
Wellington
New Zealand
23 May 2008
DBL® is a registered trade mark of Hospira Australia Pty Ltd.