New Zealand - English - Medsafe (Medicines Safety Authority)
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NEW ZEALAND DATA SHEET
DBL™ Dobutamine Hydrochloride Injection
QUALITATIVE AND QUANTITATIVE COMPOSITION
Dobutamine Hydrochloride Injection is a sterile solution containing in each 20 mL
vial, Dobutamine Hydrochloride USP 280.2
mg (250 mg Dobutamine equivalent) and
Sodium Metabisulfite BP 4.4 mg.
Excipient(s) with known effect
For the full list of excipients, see section 6.1.
Solution for injection
Dobutamine hydrochloride is a white to practically white, crystalline powder. It is sparingly
soluble in water and methyl alcohol; soluble in alcohol.
4.1 Therapeutic indications
Dobutamine hydrochloride is indicated when inotropic support is necessary for the treatment
circulatory demands. Dobutamine hydrochloride is also indicated when inotropic support is
required for the treatment of patients in whom abnormally increased ventricular filling
pressures introduce the risk of pulmonary congestion and oedema. Conditions which may
precipitate such situations include the following hypoperfusion states:
Initially cardiac in origin
A. Acute heart failure
Acute myocardial infarction
Following cardiac surgery
Medicine-induced depression of cardiac contractility such as that which occurs in
excessive β-adrenergic receptor blockade.
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B. Chronic heart failure
Acute decompensation of chronic congestive heart failure
Temporary inotropic support in advanced chronic congestive heart failure, as an
adjunct to therapy with conventional oral inotropic agents, systemic vasodilators, and
Initially noncardiac in origin
Acute hypoperfusion states secondary to trauma, surgery, sepsis, or hypovolaemia
when mean arterial pressure is above 70-mm Hg and pulmonary capillary wedge
pressure is 18-mm Hg or greater, with inadequate response to volume repletion and
increased ventricular filling pressure
Low cardiac output secondary to mechanical ventilation with positive end-expiratory
Dobutamine hydrochloride may be used as a substitute for physical exercise in stress testing
in the diagnosis of coronary artery disease. When dobutamine hydrochloride is used for this
purpose, as is the case when exercise is used for stress testing, patients should be informed of
the potential risks involved in the test. In addition, patients should be subjected to the same
close monitoring that is mandatory in standard exercise stress tests, including continuous
4.2 Dose and method of administration
continuous intravenous infusion. Following the initiation of a constant rate infusion, or upon
approximately 10 minutes. Thus, loading doses or bolus injections are not necessary and are
The rate of infusion needed to increase cardiac output has ranged from 2.5 to 10 mcg/kg/min
in the majority of patients. Frequently, doses up to 20 mcg/kg/min are required for adequate
haemodynamic improvement. On rare occasions, infusion rates up to 40 mcg/kg/min have
The rate of administration and the duration of therapy should be adjusted according to the
parameters such as heart rate and rhythm, arterial pressure, and, whenever possible, cardiac
output and measurements of ventricular filling pressures (central venous, pulmonary capillary
wedge, and left atrial), and signs of pulmonary congestion and organ perfusion (urine flow,
skin temperature, and mental status).
Concentrations up to 5,000 mg/L have been administered to humans (250 mg/50 mL). The
final volume administered should be determined by the fluid requirements of the patient.
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advisable to decrease the dosage gradually.
Most reports on dobutamine hydrochloride have expressed the dose in relation to body mass,
for example, mcg/kg/min. This practice is useful to relate doses in infants and children to
those in adults. Among adults, body mass has little influence on the effect of dobutamine
hydrochloride; since the dosage of dobutamine hydrochloride should be titrated in each
patient, adults may be as easily dosed with mcg/min units. The dosage of dobutamine
hydrochloride may be initiated at 100 to 200 mcg/min and increased gradually to 1000 to
2000 mcg/min or greater, depending on the clinical and haemodynamic response of the
Rates of Infusion Based on Concentration of Dobutamine Hydrochloride
The rates of fluid infusion that are required to deliver specific dosages are a function of the
concentration of dobutamine hydrochloride in the infusate. The following table provides a
guideline of infusion rates (mL/kg/min) required for 3 frequently used concentrations of
dobutamine hydrochloride (250, 500, and 1000 mg/L) in order to deliver the medicine
dosages (mcg/kg/min) which are indicated in the left hand column of the table.
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Medicine Delivery Rate
Infusion Delivery Rate
250 mg/L *
500 mg/L †
1000 mg/L ‡
* 250 mg/L of diluent
† 500 mg/L or 250 mg/500 mL of diluent
‡ 1000 mg/L or 250 mg/250 mL of diluent
Dobutamine Hydrochloride Injection when diluted to 250 micrograms/mL and 500
micrograms/mL with 0.9% Sodium Chloride Injection and 5% Glucose Injection, was found
to be stable for 24 hours at room temperature and in the presence of fluorescent light.
manifestations of hypersensitivity to dobutamine hydrochloride.
4.4 Special warnings and precautions for use
Increase in Heart Rate or Arterial Blood Pressure
Dobutamine hydrochloride may cause an increase in heart rate or blood pressure, especially
in systolic pressure. Approximately 10% of the patients in clinical studies have had rate
increments of 30 beats/min or more, and about 7.5% have had a 50-mm Hg or greater
increase in systolic pressure. Reduction of dosage usually reverses these effects promptly.
Patients with pre-existing hypertension are more likely to develop an exaggerated pressor
Increased Atrioventricular Conduction
Because dobutamine hydrochloride facilitates atrioventricular conduction, patients with atrial
flutter or fibrillation may develop rapid ventricular responses.
Dobutamine hydrochloride may precipitate or exacerbate ventricular ectopic activity; rarely
has it caused ventricular tachycardia or fibrillation.
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Impaired Ventricular Filling and Ventricular Outflow Obstruction
Inotropic agents, including dobutamine hydrochloride, do not improve haemodynamics in
most patients with mechanical obstruction that hinders either ventricular filling or outflow, or
both. Inotropic response may be inadequate in patients with markedly reduced ventricular
compliance. Such conditions are present in cardiac tamponade, valvular aortic stenosis, and
idiopathic hypertrophic subaortic stenosis. Beneficial inotropic effects may be seen in some
patients if the heart is dilated or under excessive effect of β-adrenergic receptor antagonists.
Reactions suggestive of hypersensitivity associated with the administration of dobutamine
Dobutamine Hydrochloride Injection contains sodium bisulfite, a sulfite that may
cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less
severe asthmatic episodes, in certain 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 in nonasthmatic people.
catecholamine, heart rate and rhythm, arterial blood pressure, and infusion rate should be
monitored closely. When initiating therapy, electrocardiographic monitoring is advisable
until a stable response is achieved.
No improvement may be observed in the presence of marked mechanical obstruction, such as
severe valvular aortic stenosis.
Usage for Heart Failure Complicating an Acute Myocardial Infarction
Although the treatment of heart failure and the reduction in cardiac diameter will decrease
myocardial oxygen consumption, there is still concern that the use of any inotropic agent may
increase myocardial oxygen demand and the size of an infarction by intensifying ischaemia.
myocardial infarction suggests that dobutamine hydrochloride does not have an adverse
effect on the myocardium when used in doses that do not cause excessive increments in heart
rate or arterial pressure. The dose of dobutamine hydrochloride should be titrated to prevent
an excessive increase in heart rate and systolic blood pressure.
Usage in Hypotension
When hypotension is largely attributable to decreased cardiac output and coincides with an
elevated ventricular filling pressure, the infusion of dobutamine hydrochloride may help
restore the pressure.
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As volume is replenished in the treatment of acute hypoperfusion states and there is an
increase in pulmonary wedge or central venous pressures but with no increase in cardiac
output and arterial pressure, dobutamine hydrochloride may improve output and help restore
the arterial pressure.
In general, when mean arterial blood pressure is less than 70-mm Hg in the absence of an
increased ventricular filling pressure, hypovolaemia may be present and would require
treatment with appropriate volume repleting solutions before dobutamine hydrochloride is
If arterial blood pressure remains low or decreases progressively during administration of
dobutamine hydrochloride despite adequate ventricular filling pressure and cardiac output,
consideration may be given to the concomitant use of a peripheral vasoconstrictor agent such
as dopamine or norepinephrine.
Dobutamine hydrochloride has been administered to children with low-output hypoperfusion
states resulting from decompensated heart failure, cardiac surgery, and cardiogenic and septic
quantitatively or qualitatively different in children as compared to adults ( see section 5.1).
Increments in heart rate and blood pressure appear to be more frequent and intense in
children. Pulmonary wedge pressure may not decrease in children, as it does in adults, or it
may actually increase, especially in infants less than one year old. Accordingly, the use of
dobutamine hydrochloride in children should be monitored closely, bearing in mind these
4.5 Interaction with other medicines and other forms of interaction
The potency of dobutamine hydrochloride may be decreased if the patient is given β-
dobutamine hydrochloride may become apparent, including peripheral vasoconstriction and
hypertension. Conversely, α-adrenergic blockade may make the β-1 and β-2 effects apparent,
resulting in tachycardia and vasodilatation.
There has been no overt indication of medicine interactions in clinical studies in which
dobutamine hydrochloride was administered concurrently with other medicines, including
isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid,
and acetaminophen. Pharmacodynamic interactions with dopamine and vasodilators are
described in the see section 5.1.
Dobutamine, like other β
-agonists, can produce a mild reduction in serum potassium
concentration, rarely to hypokalaemic levels. Accordingly, consideration should be given to
monitoring serum potassium.
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4.6 Fertility, pregnancy and lactation
No data available.
Reproduction studies performed in rats at doses up to 3.5 times the normal human dose (10
mcg/kg/min for 24 h, total daily dose of 14.4 mg/kg) and in rabbits at doses up to 2 times the
normal human dose have revealed no evidence of harm to the foetus or teratogenic effects
due to dobutamine hydrochloride. Since there are no adequate and well-controlled studies in
pregnant women, and since animal reproduction studies are not always predictive of human
response, dobutamine hydrochloride should not be used during pregnancy unless the potential
benefits outweigh the potential risks to the foetus.
It is not known whether this medicine is excreted in human milk. Because many medicines
are excreted in human milk, caution should be exercised when dobutamine hydrochloride is
administered to a nursing woman. If a mother requires dobutamine treatment, breastfeeding
should be discontinued for the duration of the treatment.
4.7 Effects on ability to drive and use machinery
Dobutamine Hydrochloride Injection 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.
4.8 Undesirable effects
Heart Rate, Blood Pressure, and Ventricular Ectopic Activity
A 10- to 20-mm Hg increase in systolic blood pressure and an increase in heart rate of 5 to 15
beats/minute have been noted in many patients ( see section 4.4). Approximately 5% of
patients have had increased premature ventricular beats during infusions of dobutamine
hydrochloride. These effects are usually dose related.
Precipitous decreases in blood pressure have occasionally been described in association with
dobutamine therapy. Decreasing the dose or discontinuing the infusion typically results in
rapid return of blood pressure to baseline values. In rare cases, however, intervention may be
required and reversibility may not be immediate.
Reactions at Sites of Intravenous Infusion
Phlebitis has occasionally been reported. Local inflammatory changes have been described
following inadvertent infiltration. Isolated cases of cutaneous necrosis (destruction of skin
tissue) have been reported.
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Miscellaneous Uncommon Effects
The following adverse effects have been reported in 1% to 3% of patients: nausea, headache,
anginal pain, nonspecific chest pain, palpitations, and shortness of breath. Isolated cases of
thrombocytopenia have been reported.
Administration of Dobutamine, like other catecholamines, can produce a mild reduction in
serum potassium concentration, rarely to hypokalaemic levels ( see section 4.4).
Infusions for up to 72 hours have revealed no adverse effects other than those seen with
shorter infusions. There is evidence that partial tolerance develops with continuous infusions
of dobutamine hydrochloride for 72 hours or more; therefore, higher doses may be required
to maintain the same effects.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It
Overdoses of dobutamine have been reported rarely. The following is provided to serve as a
guide if such an overdose is encountered.
Signs and Symptoms
Toxicity from dobutamine hydrochloride is usually due to excessive cardiac β-receptor
stimulation. The duration of action of dobutamine hydrochloride is generally short (T
minutes) because it is rapidly metabolised by catechol-0-methyltransferase. The symptoms of
toxicity may include anorexia, nausea, vomiting, tremor, anxiety, palpitations, headache,
shortness of breath, and anginal and nonspecific chest pain. The positive inotropic and
tachyarrhythmias, myocardial ischaemia, and ventricular fibrillation. Hypotension may result
from vasodilation. If the product is ingested, unpredictable absorption may occur from the
mouth and the gastrointestinal tract.
In managing overdosage, consider the possibility of multiple medicine overdoses, interaction
among medicines, and unusual medicine kinetics in your patient.
The initial actions to be taken in a dobutamine hydrochloride overdose are discontinuing
Resuscitative measures should be initiated promptly. Severe ventricular tachyarrhythmias
may be successfully treated with propranolol or lidocaine. Hypertension usually responds to a
reduction in dose or discontinuation of therapy.
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Protect the patient's airway and support ventilation and perfusion. If needed, meticulously
monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum
electrolytes, etc. Absorption of medicines from the gastrointestinal tract may be decreased by
giving activated charcoal, which, in many cases, is more effective than emesis or lavage;
consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal
over time may hasten elimination of some medicines that have been absorbed. Safeguard the
patient's airway when employing gastric emptying or charcoal.
Forced diuresis, peritoneal dialysis, haemodialysis, or charcoal haemoperfusion have not
been established as beneficial for an overdose of dobutamine hydrochloride.
For advice on the management of overdose please contact the National Poisons Centre on
0800 POISON (0800 764766).
5.1 Pharmacodynamic properties
Mechanism of action
Dobutamine hydrochloride is a direct acting inotropic agent whose primary activity results
norepinephrine stores in the heart.
In animal studies, dobutamine hydrochloride produces less increase in heart rate and less
decrease in peripheral vascular resistance for a given inotropic effect than does isoproterenol.
In humans, dobutamine hydrochloride increases stroke volume and cardiac output and
decreases ventricular filling pressure and total systemic and pulmonary vascular resistances.
The ventricular function curve is shifted upwards and to the left as a reflection of increased
Heart rate is not increased significantly by the usual dosage of dobutamine hydrochloride;
Arterial blood pressure usually is not changed significantly by dobutamine hydrochloride
because the effect of the increase in cardiac output is balanced by the concomitant decrease in
peripheral vascular resistance. Both increments and decrements in arterial blood pressure
have been reported. Patients with pre-existing arterial hypertension, even those who are
normotensive at the time, seem more susceptible to sustaining a pressor response.
In animals, dobutamine hydrochloride has been shown to decrease pulmonary hypoxic
vasoconstriction. This may result in increased perfusion of poorly ventilated areas. This effect
may decrease arterial oxygen saturation in some patients, but to a lesser extent than with
dopamine or isoproterenol. Due to the increased cardiac output in such patients, oxygen
transport is generally increased by dobutamine hydrochloride. Dobutamine hydrochloride has
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been shown to prevent or to revert partially the decrease in cardiac output that occurs in
patients during mechanical ventilation with positive end-expiratory pressure (PEEP).
Dobutamine hydrochloride does not act at dopamine receptors; thus it does not selectively
dilate renal or splanchnic vessels. Dobutamine hydrochloride may improve renal blood flow,
glomerular filtration rate, urine flow, and sodium excretion by increasing cardiac output and
by nonselective vasodilatation.
Dobutamine hydrochloride also exhibits inotropic effects in children, but the haemodynamic
response is somewhat different than that in adults. Although cardiac output increases in
children, there is a tendency for systemic vascular resistance and ventricular filling pressure
to decrease less and for heart rate and arterial blood pressure to increase more in children than
hydrochloride in children 12 months of age or younger.
dobutamine hydrochloride in human electrophysiologic studies and in patients with atrial
consumption. Dobutamine hydrochloride also increases coronary blood flow and myocardial
oxygen supply. The changes in oxygen demand are dependent on several factors, including
the following: (a) changes in ventricular diameter, which, in turn, determines the level of wall
tension required to generate intraventricular pressure during systole; (b) changes in afterload,
generally proportional to changes in systolic blood pressure; and (c) changes in heart rate.
When the use of an inotropic agent in a patient with a failing, dilated heart results in a
decrease in ventricular diameter, oxygen demand may increase only slightly or not at all,
hydrochloride does not cause an imbalance between oxygen consumption and supply in either
animals or humans with heart disease. Increments in oxygen delivery have often exceeded the
augmentation in oxygen uptake during infusion of dobutamine hydrochloride, so that oxygen
saturation in coronary sinus blood increases. The arteriovenous extraction ratio of lactic acid,
an indirect evidence of unimpeded aerobic metabolism, is generally maintained during
administration of dobutamine hydrochloride. In some instances, myocardial lactate extraction
has decreased. Net lactate production has been reported in a few patients; this has occurred
especially when heart rate and/or arterial blood pressure have increased excessively during
infusion of dobutamine hydrochloride, or when ventricular dysfunction was not present prior
to the administration of dobutamine hydrochloride.
In patients with angina pectoris who do not have heart failure, infusions of dobutamine
hydrochloride have mimicked the effects of physical exercise, increasing myocardial oxygen
demand in excess of coronary oxygen supply, and thereby producing reversible clinical signs
of myocardial ischaemia. These signs have included anginal pain, ST segment depression,
thallium scintigraphic perfusion defects, and new wall motion abnormalities.
Myocardial infarct size and the incidence and severity of ventricular arrhythmias were not
increased in patients with acute myocardial infarction who were treated with dobutamine
hydrochloride for 24 hours, as compared to similar patients who did not receive dobutamine
hydrochloride. In animals, administration of dobutamine hydrochloride shortly after the
ligation of coronary arteries reduces infarct size, when compared to controls receiving saline