DOBUTAMINE HCL
DESCRIPTION:
Dobutrex(R) Solution (Dobutamine Hydrochloride Injection) is 1,2-benzenediol, 4-
(2-((3-(4-hydroxyphenyl)-1-methylpropyl)amino)eth yl)-, hydrochloride, ()-.
It is a synthetic catecholamine.
Molecular Formula: C18H23NO3.HCl
Molecular Weight: 337.85
The clinical formulation is supplied in a sterile form for intravenous use only.
Each mL contains 12.5 mg (41.5 micromol) dobutamine, 0.24 mg sodium bisulfite
(added during manufacture), and water for injection, q.s. Hydrochloric acid
and/or sodium hydroxide may have been added during manufacture to adjust the pH.
ACTIONS/CLINICAL PHARMACOLOGY:
CLINICAL PHARMACOLOGY
Pharmacodynamics - DOBUTREX is a direct acting inotropic agent whose primary
activity results from stimulation of cardiac adrenargic receptors: it produces comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilator effects.In contrast with dopamine, it does not release norepinephrine and its actions are not dependent on norepinephrine stores in the heart. In animal studies, DOBUTREX produces less increase in the heart rate and less decrease in peripheral vascular resistance for given inotropic effect than does isoproterenol.In humans, DOBUTREX 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 myocardial contractility.
Heart rate is not increased significantly by the usual dosage of DOBUTREX+ADs- however,significant tachycardia may occur with high doses (usually greater than 101-+ADs-S/kg/min).
Arterial blood pressure usually is not changed significantly by DOBUTREX 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 preexisting arterial hypertension, even those who are normotensive at the time, seem more susceptible to sustaining a pressor response.
In animals, DOBUTREX 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 DOBUTREX. DOBUTREX has been shown to prevent or to revert partially the decrease in cardiac output that occurs in patients during mechanical ventilation with positive and expiratory pressure (PEEP).
DOBUTREX does not act at dopamine receptors +ADs- thus it does not selectively dilate renal or splanchnic vessels. DOBUTREX may improve renal blood flow, glomerular filtration rate, urine flow, and sodium excretion by increasing cardiac output and by nonselective vasodilatation.
DOBUTREX also exhibits inotropic effects in children, but the hemodynamic response is somewhat different than that in adults. Although cardiac output increases in children,there is a tendency for systemic yascular resistance and ventricular filling pressure to decrease less and for heart rate and arterial blood pressure to increase more in children than in adults. Pulmonary wedge pressure may increase during infusion of DOBUTREX in children 12 months of age or younger.Facilitation of atrioventriculai conduction has been observed during administration ofDOBUTREX in human electrophysiologic studies and in patients with atrial fibrillation.
Like all inotropic agents, DOBUTREX increases myocardial oxygen consumption.
DOBUTREX 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 +ADs-
b) -changes in afterload, generally proportional to changes in systolic blood pressure +ADs-
c) -changes in heart rate.When the use of an inotropic agent in a patient with a failing, dilated heart results in ventricular diameter, oxygen demand may increase only slightly or not at all provided afterload and heart rate do not increase markedly in general. DOBUTREX 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 the infusion of DOBUTREX, 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 DOBUTREX. In some instances, myocardial lactate extraction has decreased. Net lactate production has been reported in a few patients +ADs- this has occurred especially when heart rate and/or arterial blood pressure have increased excessively during infusion of DOBUTREX, or when ventricular dysfunction was not present prior to the administration of DOBUTREX.In patients with angina pectoris who do not have heart failure, infusions of DOBUTREX 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 ischemia. 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 arrhythmia's were not increased in patients with acute myocardial infarction who were treated with DOBUTREX for 24 hours, as compared to similar patients who did not receive DOBUTREX. In animals, administration of DOBUTREX shortly after the ligation of coronary arteries reduces infarct size, when compared to controls receiving saline solution or dopamine. In other animals with experimental infarction who were given DOBUTREX at doses that increased both heart rate and myocardial contractility, there were electrocardiographic signs of increased ischemia. Recent studies in animals suggest that functional deterioration and possible enlargement of experimental myocardial lesions during the administration of inotropic drugs including DOBUTREX is related to their chronotropic effect rather than to the positive inotropism. When
DOBUTREX was infused at doses that produced significant inotropic effect with a
minimal increase in heart rate, there was no evidence of enhanced myocardial damage.
Infusions of DOBUTREX for less than one hour in patients with congestive heart failure increase cardiac output and decrease pulmonary wedge pressure, however,hemodynamic improvements are not accompanied by increases in exercise tolerance.
By contrast, longer infusions (upto 72 hours) or infusions that are repeated at regular intervals over several weeks or months do increase exercise tolerance and improve clinical status. This is true (even though) resting ventricular function is not always augmented. The mechanism of the sustained improvement in ventricular function following prolonged or intermittent infusions of DOBUTREX is not understood.
However, in studies involving prolonged infusions of DOBUTREX in humans,
mitochondrial ultrastructural and biochemical changes have been reported, suggesting a basis for the protracted amelioration.
DOBUTREX has been used in combination with dopamine. In general, the combination does not increase cardiac output more than does an equivalent dose of DOBUTREX alone. However, the combination of DOBUTREX and dopamine :
a) -increases systemic arterial pressure (which would b3 beneficial to hypotensive patients).
b) -increases renal blood flow, urine flow, and sodium excretion.
c) -prevents the increase in ventricular filling pressure that tends to occur with dopamine alone, thus decreasing the risk of pulmonary congestion and edema,especially in patients with compromised ventricular function.
DOBUTREX has also been used in combination with other vasodilators such as
nitroglycerin or nitroprusside especially in patients with ischemic heart disease. This combination potentiates the increment in cardiac output and the decrement in systemic vascular resistance and ventricular filling pressure observed with either drug alone. The heart rate, blood pressure product is either minimally increased or not changed by the concomitant administration of DOBUTREX and a vasodilator.
DOBUTREX is a p-adrenergic agonist. Accordingly, its effects may be counteracted by P-adrenergic receptor antagonists. During treatment with p-antagonists, low doses of DOBUTREX will manifest varying degrees of (x-adrenergic activity, such as vasoconstriction. Because the interaction between both DOBUTREX and the antagonists on the P-receptors is reversible, these two drug classes will compete among themselves. Thus, higher doses of DOBUTREX will progressively counteract the effect of p-adrenergic receptor antagonists.
Pharmacokinetics - Although the onset of action of DOBUTREX is within 1 to 2
minutes, as much as 10 minutes may be required to reach steady state plasma
concentrations and peak effects with any given infusion rate. Steady state plasma concentrations are linearly related to infusion rates. At an infusion rate of 5 g/(kg/min)the mean plasma concentration is approximately 100 ng/ml in patients with congestive heart failure.
Plasma clearance of DOBUTREX in humans is 2.4 I / min / m2 , the volume of
distribution is about 20+ACU- of body weight, and plasma elimination half-time is less than 3 minutes.
The principal routes of disposition include methylation followed by conjugation.
Metabolites are eliminated by renal and biliary mechanisms. In human urine, the major excretion products include conjugates of dobutamine and 3-0- methyl dobutamine.The 3-0- methyl derivative is inactive.
Partial tolerance to DOBUTREX develops during prolonged continuous infusions and becomes statistically significant at 72 hours. The cardiac output response to a constant infusion of DOBUTREX at 72 hours is over 70+ACU- of that obtained at the end of 2 hours in patients with congestive heart failure. This phenomenon may be caused by a decrease (down-regulation) in the number of P-adrenargic receptors.
Alteration of synaptic concentrations of catecholamines with either reserpine or tricyclic antidepressants does not alter the actions of DOBUTREX in animals. DOBUTREX acts directly, and its effects are not dependent on presynaptic mechanises.
INDICATIONS
DOBUTREX is indicated when inotropic support is necessary for the treatment of
patients with hypoperfusion states in whom cardiac output is insufficient to meet circulatory demands. DOBUTREX 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 edema. Conditions which may precipitate such situations include the following hypoperfusion states-Initially cardiac in origin :
1) Acute heart failure
-Acute myocardial infarction
-Cardiogenic shock
-Following cardiac surgery
- Drug induced depression of cardiac contractility such as that which occurs in
excessive (3-adrenergic receptor blockade
2) Chronic heart failure
-Acute decompensation of chronic congestive heart failure
-Temporary inotropic support in advanced chronic congested heart failure, as an
adjunct to therapy with conventional oral inotropic agents, systemic vasodilators, and diuretics
Initially noncardiac in origin :
1) Acute hypoperfusion states secondary to trauma, surgery, sepsis, or hypovolemia when mean arterial pressure is above 70 mmHg and pulmonary capillary wedge pressure is 18 mm Hg or greater, with inadequate response to volume repletion and increased ventricular filling pressure.
2) Low cardiac output secondary to mechanical ventilation with positive end-expiratory pressure (PEEP)
DOBUTREX may be used as a substitute for physical exercise in stress testing in the diagnosis of coronary artery disease. When DOBUTREX 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 ,patient should be subjected to the same close monitoring that is mandatory in standard exercise stress tests,including continuous electrocardiographic monitoring.
CONTRAINDICATIONS:
Dobutrex Solution is contraindicated in patients with idiopathic hypertrophic
subaortic stenosis and in patients who have shown previous manifestations of
hypersensitivity to Dobutrex Solution.
WARNINGS:
1. Increase In Heart Rate Or Blood Pressure- -Dobutrex Solution may cause a
marked increase in heart rate or blood pressure, especially systolic pressure.
Approximately 10+ACU- of patients in clinical studies have had rate increases of 30
beats/minute or more, and about 7.5+ACU- have had a 50 mm Hg or greater increase in
systolic pressure. Usually, reduction of dosage promptly reverses these effects.
Because dobutamine hydrochloride facilitates atrioventricular conduction,
patients with atrial fibrillation are at risk of developing rapid ventricular
response. Patients with preexisting hypertension appear to face an increased
risk of developing an exaggerated pressor response.
2. Ectopic Activity--Dobutrex Solution may precipitate or exacerbate ventricular
ectopic activity, but it rarely has caused ventricular tachycardia.
3. Hypersensitivity--Reactions suggestive of hypersensitivity associated with
administration of Dobutrex Solution, including skin rash, fever, eosinophilia,
and bronchospasm, have been reported occasionally.
4. Dobutrex Solution 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.
PRECAUTIONS:
GENERAL--1. DURING THE ADMINISTRATION OF DOBUTREX(R) SOLUTION, AS WITH ANY
ADRENERGIC AGENT, ECG AND BLOOD PRESSURE SHOULD BE CONTINUOUSLY MONITORED. IN
ADDITION, PULMONARY WEDGE PRESSURE AND CARDIAC OUTPUT SHOULD BE MONITORED
WHENEVER POSSIBLE TO AID IN THE SAFE AND EFFECTIVE INFUSION OF DOBUTREX
SOLUTION.
2. Hypovolemia should be corrected with suitable volume expanders before
treatment with Dobutrex Solution is instituted.
3. No improvement may be observed in the presence of marked mechanical
obstruction, such as severe valvular aortic stenosis.
Usage Following Acute Myocardial Infarction- -Clinical experience with Dobutrex
Solution following myocardial infarction has been insufficient to establish the
safety of the drug for this use. There is concern that any agent that increases
contractile force and heart rate may increase the size of an infarction by
intensifying ischemia, but it is not known whether dobutamine hydrochloride does
so.
Laboratory Tests--Dobutamine, like other beta2-agonists, can produce a mild
reduction in serum potassium concentration, rarely to hypokalemic levels.
Accordingly, consideration should be given to monitoring serum potassium.
Drug Interactions--Animal studies indicate that dobutamine may be ineffective if
the patient has recently received a beta-blocking drug. In such a case, the
peripheral vascular resistance may increase.
Preliminary studies indicate that the concomitant use of dobutamine and
nitroprusside results in a higher cardiac output and, usually, a lower pulmonary
wedge pressure than when either drug is used alone.
There was no evidence of drug interactions in clinical studies in which Dobutrex
Solution was administered concurrently with other drugs, including digitalis
preparations, furosemide, spironolactone, lidocaine, glyceryl trinitrate,
isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium
chloride, folic acid, and acetaminophen.
Carcinogenesis, Mutagenesis, Impairment Of Fertility--Studies to evaluate the
carcinogenic or mutagenic potential of Dobutrex Solution, or its potential to
affect fertility, have not been conducted.
Pregnancy--Teratogenic effects--Pregnancy Category-B--Reproduction studies
performed in rats at doses up to the normal human dose (10 mcgm/kg/min for 24 h,
total daily dose of 14.4 mg/kg) and in rabbits at doses up to twice the normal
human dose, have revealed no evidence of harm to the fetus due to Dobutrex
Solution. There are, however, no adequate and well- controlled studies in
pregnant women. Because animal reproduction studies are not always predictive of
human response, this drug should be used during pregnancy only if clearly
needed.
Labor And Delivery--The effect of Dobutrex Solution on labor and delivery is
unknown.
Nursing Mothers--It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
Dobutrex Solution is administered to a nursing woman. If a mother requires
Dobutrex Solution treatment, breast- feeding should be discontinued for the
duration of the treatment.
Pediatric Use--The safety and effectiveness of Dobutrex Solution for use in
children have not been studied.
DRUG INTERACTIONS:
Animal studies indicate that dobutamine may be ineffective if the patient has
recently received a beta-blocking drug. In such a case, the peripheral vascular
resistance may increase.
Interactions : Bretyliunn and halogenated hydrocarbon
anesthetic agents potentiate the risk of cardiac arryth
mias in a patient receiving dobutamine.
Dobutamine decreases serum potassium levels and
may aggravate hypokalemia in a patient receiving
intravenous frusemide. Alpha adrenoceptor antagonists
can aggravate hypotensive effect.
Preliminary studies indicate that the concomitant use of dobutamine and
nitroprusside results in a higher cardiac output and, usually, a lower pulmonary
wedge pressure than when either drug is used alone.
There was no evidence of drug interactions in clinical studies in which Dobutrex
Solution was administered concurrently with other drugs, including digitalis
preparations, furosemide, spironolactone, lidocaine, glyceryl trinitrate,
isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium
chloride, folic acid, and acetaminophen.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
Increased Heart Rate, Blood Pressure, And Ventricular Ectopic Activity--A 10- to
20-mm increase in systolic blood pressure and an increase in heart rate of 5 to
15 beats/minute have been noted in most patients (See Warnings regarding
exaggerated chronotropic and pressor effects). Approximately 5+ACU- of patients have
had increased premature ventricular beats during infusions. These effects are
dose related.
Hypotension--Precipitous decreases in blood pressure have occasionally been
described in association with Dobutrex Solution 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.
Miscellaneous Uncommon Effects--The following adverse effects have been reported
in 1+ACU- to 3+ACU- of patients: nausea, headache, anginal pain, nonspecific chest pain,
palpitations, and shortness of breath.
Isolated cases of thrombocytopenia have been reported.
Administration of Dobutrex Solution, like other catecholamines, can produce a
mild reduction in serum potassium concentration, rarely to hypokalemic levels
(See Precautions).
Longer-Term Safety--Infusions of up to 72 hours have revealed no adverse effects
other than those seen with shorter infusions.
OVERDOSAGE:
Overdoses of Dobutrex Solution have been reported rarely. The following is
provided to serve as a guide if such an overdose is encountered.
Signs And Symptoms--Toxicity from Dobutrex Solution is usually due to excessive
cardiac beta-receptor stimulation. The duration of action of Dobutrex Solution
is generally short (T1/2 +AD0- 2 minutes) because it is rapidly metabolized by
catechol-O-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 chronotropic
effects of Dobutrex Solution on the myocardium may cause hypertension,
tachyarrhythmias, myocardial ischemia, and ventricular fibrillation. Hypotension
may result from vasodilation.
Treatment--To obtain up-to-date information about the treatment of overdose, a
good resource is your certified Regional Poison Control Center. Telephone
numbers of certified poison control centers are listed in the Physicians' Desk
Reference (PDR). In managing overdosage, consider the possibility of multiple
drug overdoses, interaction among drugs, and unusual drug kinetics in your
patient.
The initial actions to be taken in a Dobutrex Solution overdose are
discontinuing administration, establishing an airway, and ensuring oxygenation
and ventilation. 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.
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. If the product is ingested,
unpredictable absorption may occur from the mouth and the gastrointestinal
tract. Absorption of drugs from the gastrointestinal tract may be decreased by
giving activated charcoal, which, in many cases, is more effective than emesis
or lavage+ADs- consider charcoal instead of or in addition to gastric emptying.
Repeated doses of charcoal over time may hasten elimination of some drugs that
have been absorbed. Safeguard the patient's airway when employing gastric
emptying or charcoal.
Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion
have not been established as beneficial for an overdose of Dobutrex Solution.
DOSAGE AND ADMINISTRATION:
Note--Do not add Dobutrex Solution to 5+ACU- Sodium Bicarbonate Injection or to any
other strongly alkaline solution. Because of potential physical
incompatibilities, it is recommended that Dobutrex Solution not be mixed with
other drugs in the same solution. Dobutrex Solution should not be used in
conjunction with other agents or diluents containing both sodium bisulfite and
ethanol.
Reconstitution And Stability--At the time of administration, Dobutrex Solution
must be further diluted in an IV container to at least a 50-mL solution using
one of the following intravenous solutions as a diluent: 5+ACU- Dextrose Injection,
5+ACU- Dextrose and 0.45+ACU- Sodium Chloride Injection, 5+ACU- Dextrose and 0.9+ACU- Sodium
Chloride Injection, 10+ACU- Dextrose Injection, Isolyte(R) M with 5+ACU- Dextrose
Injection, Lactated Ringer's Injection, 5+ACU- Dextrose in Lactated Ringer's
Injection, Normosol(R)-M in D5-W, 20+ACU- Osmitrol(R) in Water for Injection, 0.9+ACU-
Sodium Chloride Injection, or Sodium Lactate Injection. Intravenous solutions
should be used within 24 hours.
Recommended Dosage--The rate of infusion needed to increase cardiac output
usually ranged from 2.5 to 15 mcgm/kg/min (see Table 1). On rare occasions,
infusion rates up to 40 mcgm/kg/min have been required to obtain the desired
effect.
Tolerance to effects of dobutamine develops within 72 hrs.Short term intermittent infusion are therefore more useful.injection insulin should not be mixed with dobutamine solution.
Table 1
Dobutrex Solution Infusion Rate(mL/kg/min)
for Concentrations of 250, 500, and 1,000 mcgm/mL
Infusion Delivery Rate
Drug Delivery ----------------------------------------------------
Rate 250 mcgm/mL+ACo- 500 mcgm/mL+ACoAKg- 1,000 mcgm/mL+ACoAKg-/+ACo-
(mcgm/kg/min) (mL/kg/min) (mL/kg/min) (mL/kg/min)
-------------- ------------ ------------- ----------------+AAAAAA-
2.5 0.01 0.005 0.0025
5 0.02 0.01 0.005
7.5 0.03 0.015 0.0075
10 0.04 0.02 0.01
12.5 0.05 0.025 0.0125
15 0.06 0.03 0.015
------------------------------------------------------------------------
+ACo-250 mcgm/mL of diluent
+ACoAKg-500 mcgm/mL or 250 mg/500 mL of diluent
+ACoAKg-/+ACo-1,000 mcgm/mL or 250 mg/250 mL of diluent
------------------------------------------------------------------------
Rates of infusion in mL/h dor Dobutrex Solution concentrations of 500 mcg/mL,
1,000 mcg/mL, and 2,000 mcg/mL are given in Table 2.
Dobutrex Solution Infusion Rate (mL/h) for
500 mcgm/mL concentration
Drug Delivery PATIENT BODY WEIGHT (KG)
Rate
(mcgm/kg/min) 30 40 50 60 70 80 90 100 110
----------------------------------------------------------------------------
2.5 9 12 15 18 21 24 27 30 33
5 18 24 30 36 42 48 54 60 66
7.5 27 36 45 54 63 72 81 90 99
10 36 48 60 72 84 96 108 120 132
12.5 45 60 75 90 105 120 135 150 165
15 54 72 90 108 126 144 162 180 198
----------------------------------------------------------------------------
Dobutrex Solution Infusion Rate (mL/h) for
1,000 mcgm/mL concentration
Drug Delivery PATIENT BODY WEIGHT (KG)
Rate
(mcgm/kg/min) 30 40 50 60 70 80 90 100 110
----------------------------------------------------------------------------
2.5 4.5 6 7.5 9 10.5 12 13.5 15 16.5
5 9 12 15 18 21 24 27 30 33
7.5 13.5 18 22.5 27 31.5 36 40.5 45 49.5
10 18 24 30 36 42 48 54 60 66
12.5 22.5 30 37.5 45 52.5 60 67.5 75 82.5
15 27 36 45 54 63 72 81 90 99
----------------------------------------------------------------------------
Dobutrex Solution Infusion Rate (mL/h) for
2,000 mcgm/mL concentration
Drug Delivery PATIENT BODY WEIGHT (KG)
Rate
(mcgm/kg/min) 30 40 50 60 70 80 90 100 110
----------------------------------------------------------------------------
2.5 2 3 4 4.5 5 6 7 7.5 8
5 4.5 6 7.5 9 10.5 12 13.5 15 16.5
7.5 7 9 11 13.5 16 18 20 22.5 25
10 9 12 15 18 21 24 27 30 33
12.5 11 15 19 22.5 26 30 34 37.5 41
15 13.5 18 22.5 27 31.5 36 40.5 45 49.5
----------------------------------------------------------------------------
The rate of administration and the duration of therapy should be adjusted
according to the patient's response as determined by heart rate, presence of
ectopic activity, blood pressure, urine flow, and, whenever possible,
measurement of central venous or pulmonary wedge pressure and cardiac output.
Concentrations up to 5,000 mcgm/mL have been administered to humans (250 mg/ 50
mL). The final volume administered should be determined by the fluid
requirements of the patient.
Intravenous drug should be inspected visually and should not be used if
particulate matter or discoloration is present.
Current version Changed to
Hypersensitivity
Reactions suggestive of hypersensitivity associated with the administration of DOBUTREX, including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally.
DOBUTREX solution contains sodium bisulfite, a sulfite that may
cause allergic-type reactiohs, 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.
PRECAUTIONS
General
1. During the administration of DOBUTREX , as with any parenteral 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.
2. Hypovolemia should be corrected before treatment with DOBUTREX is
instituted.
Current version Changed to
1. During the administration of DOBUTREX , as with any parenteral catecholamine,heart rate and rhythm, arterial blood pressure, and infusion rate should be
I monitored closely. When initiating therapy, electrocardiographic monitoring is advisable until a stable response is achieved.
2. Hypovolemia should be corrected before treatment with DOBUTREX is instituted.
3. The potency of DOBUTREX may be decreased if the patient is given (3-
adrenergic receptor antagonists. In such a case, the unopposed a-
agonist effects of DOBUTREX may become apparent, including
peripheral vasoconstrictionand hypertension. Conversely, a-adrenergic
blockade may make the (3-1 and (3-2 effects apparent, resulting in
tachycardia and vasodilation.
4. Dobutamine like other (3-2 agonists, can produce a mild reduction in
serum potassium concentration, rarely to hypokalemic levels.
Accordingly, consideration should be given to monitoring serum
potassium.