Physicians Total Care, Inc.Physicians Total Care, Inc.Dobutamine HydrochlorideDobutamine HydrochlorideDOBUTAMINE HYDROCHLORIDEDOBUTAMINEDEXTROSE MONOHYDRATEWATERSODIUM METABISULFITEEDETATE DISODIUMHYDROCHLORIC ACIDSODIUM HYDROXIDEFlexible Plastic ContainerRx onlyDESCRIPTIONDobutamine in 5% Dextrose Injection, USP is a sterile,
nonpyrogenic, prediluted solution of dobutamine hydrochloride and dextrose in
water for injection. It is administered by intravenous infusion.Each 100 mL contains dobutamine hydrochloride equivalent to 50 mg, 100 mg,
200 mg, or 400 mg of dobutamine; dextrose, hydrous 5 g in water for injection,
with sodium metabisulfite 25 mg and edetate disodium, dihydrate 10 mg added as
stabilizers; osmolar concentration, respectively, 260, 263, 270, or 284
mOsmol/liter (calc.). The pH is 3.0 (2.5 to 5.5). May contain hydrochloric acid
and/or sodium hydroxide for pH adjustment. Dobutamine in 5% Dextrose Injection,
USP is oxygen sensitive.Dobutamine Hydrochloride, USP is chemically designated
(±)-4-[2-[[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl]-pyrocatechol
hydrochloride. It is a synthetic catecholamine.Dextrose, USP is chemically designated D-glucose monohydrate (C6H12O6• H2O), a hexose sugar freely soluble in water. It has the
following structural formula:Water for Injection, USP is chemically designated H2O.The flexible plastic container is fabricated from a specially formulated CR3
plastic material. Water can permeate from inside the container into the overwrap
but not in amounts sufficient to affect the solution significantly. Solutions in
contact with the plastic container may leach out certain chemical components
from the plastic in very small amounts; however, biological testing was
supportive of the safety of the plastic container materials. Exposure to
temperatures above 25°C/77°F during transport and storage will lead to minor
losses in moisture content. Higher temperatures lead to greater losses. It is
unlikely that these minor losses will lead to clinically significant changes
within the expiration period.image of dobutamine hcl chemical structureimage of dextrose chemical structureCLINICAL PHARMACOLOGYDobutamine is a direct-acting inotropic agent whose primary
activity results from stimulation of the β-receptors of the heart while
producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and
vasodilative effects. It does not cause the release of endogenous
norepinephrine, as does dopamine. In animal studies, dobutamine produces less
increase in heart rate and less decrease in peripheral vascular resistance for a
given inotropic effect than does isoproterenol.In patients with depressed cardiac function, both dobutamine and
isoproterenol increase the cardiac output to a similar degree. In the case of
dobutamine, this increase is usually not accompanied by marked increases in
heart rate (although tachycardia is occasionally observed), and the cardiac
stroke volume is usually increased. In contrast, isoproterenol increases the
cardiac index primarily by increasing the heart rate while stroke volume changes
little or declines.Facilitation of atrioventricular conduction has been observed in human
electrophysiologic studies and in patients with atrial fibrillation.Systemic vascular resistance is usually decreased with administration of
dobutamine. Occasionally, minimum vasoconstriction has been observed.Most clinical experience with dobutamine is short-term, not more than several
hours in duration. In the limited number of patients who were studied for 24,
48, and 72 hours, a persistent increase in cardiac output occurred in some,
whereas output returned toward baseline values in others.The onset of action of Dobutamine in 5% Dextrose Injection, USP is within 1
to 2 minutes; however, as much as 10 minutes may be required to obtain the peak
effect of a particular infusion rate.The plasma half-life of dobutamine in humans is 2 minutes. The principal
routes of metabolism are methylation of the catechol and conjugation. In human
urine, the major excretion products are the conjugates of dobutamine and
3-O-methyl dobutamine. The 3-O-methyl derivative of dobutamine is inactive.Alteration of synaptic concentrations of catecholamines with either reserpine
or tricyclic antidepressants does not alter the actions of dobutamine in
animals, which indicates that the actions of dobutamine are not dependent on
presynaptic mechanisms.The effective infusion rate of dobutamine varies widely from patient to
patient, and titration is always necessary (see DOSAGE AND ADMINISTRATION). At
least in pediatric patients, dobutamine-induced increases in cardiac output and
systemic pressure are generally seen, in any given patient, at lower infusion
rates than those that cause substantial tachycardia. (See Pediatric Use under
PRECAUTIONS.)INDICATIONS AND USAGEDobutamine in 5% Dextrose Injection, USP is indicated when
parenteral therapy is necessary for inotropic support in the short-term treatment of cardiac decompensation due to
depressed contractility resulting either from organic heart disease or from
cardiac surgical procedures. Experience with intravenous dobutamine in
controlled trials does not extend beyond 48 hours of repeated boluses and/or
continuous infusions.Whether given orally, continuously intravenously, or intermittently
intravenously, neither dobutamine nor any other cyclic-AMP-dependent inotrope
has been shown in controlled trials to be safe or effective in the long-term
treatment of congestive heart failure. In controlled trials of chronic oral
therapy with various such agents, symptoms were not consistently alleviated, and
the cyclic-AMP-dependent inotropes were consistently associated with increased
risks of hospitalization and death. Patients with NYHA Class IV symptoms
appeared to be at particular risk.CONTRAINDICATIONSDobutamine in 5% Dextrose Injection, USP is contraindicated in
patients with idiopathic hypertrophic subaortic stenosis and in patients who
have shown previous manifestations of hypersensitivity to dobutamine.Dextrose solutions without electrolytes should not be administered
simultaneously with blood through the same infusion set because of the
possibility that pseudoagglutination of red cells may occur.WARNINGSIncrease in Heart Rate or Blood Pressure
Dobutamine hydrochloride may cause a marked increase in heart rate or blood
pressure, especially systolic pressure. Approximately 10% of adult patients in
clinical studies have had rate increases of 30 beats/minute or more, and about
7.5% have had a 50-mm Hg or greater increase in systolic pressure. Usually,
reduction of dosage promptly reverses these effects.Because dobutamine facilitates atrioventricular conduction, patients with
atrial fibrillation are at risk of developing rapid ventricular response. In
patients who have atrial fibrillation with rapid ventricular response, a
digitalis preparation should be used prior to institution of therapy with
dobutamine. Patients with pre-existing hypertension appear to face an increased
risk of developing an exaggerated pressure response.Ectopic ActivityDobutamine may precipitate or exacerbate ventricular ectopic activity, but it
rarely has caused ventricular tachycardia.HypersensitivityReactions suggestive of hypersensitivity associated with administration of
Dobutamine in 5% Dextrose Injection, USP, including skin rash, fever,
eosinophilia, and bronchospasm, have been reported occasionally.Additive medications should not be delivered via this solution.Dobutamine in 5% Dextrose Injection, USP 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.PRECAUTIONSDuring the administration of dobutamine, 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 Dobutamine in 5% Dextrose
Injection, USP.Hypovolemia should be corrected with suitable volume expanders
before treatment with Dobutamine in 5% Dextrose Injection, USP is
instituted.Animal studies indicate that dobutamine may be ineffective if the
patient has recently received a β-blocking drug. In such a case, the peripheral
vascular resistance may increase.No improvement may be observed in the presence of marked
mechanical obstruction, such as severe valvular aortic stenosis.Dobutamine, like other β-agonists, can produce a mild reduction
in serum potassium concentration, rarely to hypokalemic levels. Accordingly,
consideration should be given to monitoring serum potassium.Excess administration of potassium-free solutions may result in
significant hypokalemia.The intravenous administration of these solutions can cause fluid and/or
solute overloading resulting in dilution of serum electrolyte concentrations,
overhydration, congested states or pulmonary edema.Avoid bolus administration of the drug. (See DOSAGE AND
ADMINISTRATION.)Clinical evaluation and periodic laboratory determinations are necessary to
monitor changes in fluid balance, electrolyte concentrations and acid-base
balance during prolonged parenteral therapy or whenever the condition of the
patient warrants such evaluation.Solutions containing dextrose should be used with caution in patients with
known subclinical or overt diabetes mellitus.Dobutamine in 5% Dextrose Injection, USP may exhibit a pink color
that, if present, will increase with time. This color change is due to slight
oxidation of the drug, but there is no significant loss of potency during the
time of administration. Do not administer unless solution is clear and container
is undamaged. Discard unused portion. Usage Following Acute Myocardial
Infarction: Clinical experience with dobutamine 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 does so.Drug Interactions:There was no evidence of drug interactions in clinical studies in
which dobutamine hydrochloride 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. 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.Carcinogenesis, Mutagenesis, Impairment of
Fertility:Studies to evaluate the carcinogenic or mutagenic potential of
dobutamine or the potential of the drug to affect fertility adversely have not
been performed.PregnancyPregnancy Category B: Reproduction studies performed in rats and
rabbits have revealed no evidence of harm to the fetus due to dobutamine. The
drug, however, has not been administered to pregnant women and should be used
only when the expected benefits clearly outweigh the potential risks to the
fetus.Pediatric Use:Dobutamine has been shown to increase cardiac output and systemic
pressure in pediatric patients of every age group. In premature neonates,
however, dobutamine is less effective than dopamine in raising systemic blood
pressure without causing undue tachycardia, and dobutamine has not been shown to
provide any added benefit when given to such infants already receiving optimal
infusions of dopamine.Geriatric Use:Clinical studies of dobutamine did not include sufficient numbers
of subjects aged 65 and over being treated for acute cardiac decompensation to
determine whether they respond differently from younger subjects. Other reported
clinical experience suggests that the incidence of significant hypotension is a
function of both dose and age, older individuals having a greater incidence of
hypotension. In general, dose selection for an elderly patient should be
cautious, usually starting at the low end of the dosing range, reflecting the
greater frequency of decreased hepatic, renal or cardiac function, and of
concomitant disease or other drug therapy.ADVERSE REACTIONSIncreased 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 to15 beats/minute have been noted in
most patients (see WARNINGS regarding exaggerated
chronotropic and pressor effects). Approximately 5% 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 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.Miscellaneous Uncommon Effects: The following adverse
effects have been reported in 1% to 3% ofpatients: nausea, headache, anginal
pain, nonspecific chest pain, palpitations, and shortness of breath.Administration of dobutamine, like other catecholamines, has been associated
with decreases in serum potassium concentrations, rarely to hypokalemic levels
(See PRECAUTIONS).OVERDOSAGEOverdoses 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 (T½ = 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 dobutamine on the myocardium may cause hypertension,
tachyarrhythmias, myocardial ischemia, and ventricular fibrillation. Hypotension
may result from vasodilation.If the product is ingested, unpredictable absorption may occur from the mouth
and the gastrointestinal tract.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 dobutamine hydrochloride 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. 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: 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 dobutamine
hydrochloride.DOSAGE AND ADMINISTRATIONDo NOT add sodium bicarbonate or other
alkalinizing substance, since dobutamine is inactivated in alkaline solution.
Dobutamine in 5% Dextrose Injection, USP is administered only intravenously via
a suitable catheter or needle infusion. The less concentrated 0.5 mg/mL solution
may be preferred when fluid expansion is not a problem. The more concentrated
1 mg/mL, 2 mg/mL, or 4 mg/mL solutions may be preferred in patients with fluid
retention or when a slower rate of infusion is desired.Recommended Dosage: Infusion of dobutamine should be
started at a low rate (0.5 to 1.0 mcg/kg/min) and titrated at intervals of a few
minutes, guided by the patient’s response, including systemic blood pressure,
urine flow, frequency of ectopic activity, heart rate, and (whenever possible)
measurements of cardiac output, central venous pressure, and/or pulmonary
capillary wedge pressure. In reported trials, the optimal infusion rates have
varied from patient to patient, usually 2 to 20 mcg/kg/min but sometimes
slightly outside of this range. On rare occasions, infusion rates up to 40
mcg/kg/min have been required to obtain the desired effect. For the infusion
rates necessary to achieve various delivery rates (mcg/kg/min) for patients of
different weights, refer to the Dobutamine Infusion Rate (mL/hr) charts
below.Rate of Administration: When administering dobutamine
(or any potent medication) by continuous intravenous infusion, it is advisable
to use a precision volume control I.V. set.Each patient must be individually titrated to the desired hemodynamic
response to dobutamine. 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.As with all potent intravenously administered drugs, care should be taken to
control the rate of infusion so as to avoid inadvertent administration of a
bolus of the drug.Parenteral drug products should be visually inspected for particulate matter
and discoloration prior to administration, whenever solution and container
permit (see PRECAUTIONS).
Dobutamine Infusion Rate (mL/hr) Chart Using 500 mcg/mL
Concentration
Patient Body Weight (kg)
Infusion rate (mcg/kg/min)
5
10
20
30
40
50
60
70
80
90
100
110
120
2.5
1.5
3
6
9
12
15
18
21
24
27
30
33
36
5
3
6
12
18
24
30
36
42
48
54
60
66
72
7.5
4.5
9
18
27
36
45
54
63
72
81
90
99
108
10
6
12
24
36
48
60
72
84
96
108
120
132
144
12.5
7.5
15
30
45
60
75
90
105
120
135
150
165
180
15
9
18
36
54
72
90
108
126
144
162
180
198
216
17.5
10.5
21
42
63
84
105
126
147
168
189
210
231
252
Dobutamine Infusion Rate (mL/hr) Chart Using 1000 mcg/mL
Concentration
Patient Body Weight (kg)
Infusion rate (mcg/kg/min)
5
10
20
30
40
50
60
70
80
90
100
110
120
2.5
0.75
1.5
3
4.5
6
7.5
9
10.5
12
13.5
15
16.5
18
5
1.5
3
6
9
12
15
18
21
24
27
30
33
36
7.5
2.25
4.5
9
13.5
18
22.5
27
31.5
36
40.5
45
49.5
54
10
3
6
12
18
24
30
36
42
48
54
60
66
72
12.5
3.75
7.5
15
22.5
30
37.5
45
52.5
60
67.5
75
82.5
90
15
4.5
9
18
27
36
45
54
63
72
81
90
99
108
17.5
5.25
10.5
21
31.5
42
52.5
63
73.5
84
94.5
105
115.5
126
Dobutamine Infusion Rate (mL/hr) Chart Using 2000 mcg/mL
Concentration
Patient Body Weight (kg)
Infusion rate (mcg/kg/min)
30
40
50
60
70
80
90
100
110
120
2.5
2.25
3
3.75
4.5
5.25
6
6.75
7.5
8.25
9
5
4.5
6
7.5
9
10.5
12
13.5
15
16.5
18
7.5
6.75
9
11.25
13.5
15.75
18
20.25
22.5
24.75
27
10
9
12
15
18
21
24
27
30
33
36
12.5
11.25
15
18.75
22.5
26.25
30
33.75
37.5
41.25
45
15
13.5
18
22.5
27
31.5
36
40.5
45
49.5
54
17.5
15.75
21
26.25
31.5
36.75
42
47.25
52.5
57.75
63
Dobutamine Infusion Rate (mL/hr) Chart Using 4000 mcg/mL
Concentration
Patient Body Weight (kg)
Infusion rate (mcg/kg/min)
30
40
50
60
70
80
90
100
110
120
2.5
1.125
1.5
1.875
2.25
2.625
3
3.375
3.75
4.125
4.5
5
2.25
3
3.75
4.5
5.25
6
6.75
7.5
8.25
9
7.5
3.375
4.5
5.625
6.75
7.875
9
10.125
11.25
12.375
13.5
10
4.5
6
7.5
9
10.5
12
13.5
15
16.5
18
12.5
5.625
7.5
9.375
11.25
13.125
15
16.875
18.75
20.625
22.5
15
6.75
9
11.25
13.5
15.75
18
20.25
22.5
24.75
27
17.5
7.875
10.5
13.125
15.75
18.375
21
23.625
26.25
28.875
31.5
INSTRUCTIONS FOR USETo OpenTear outer wrap at notch and remove solution container. Some opacity of the
plastic due to moisture absorption during the sterilization process may be
observed. This is normal and does not affect the solution quality or safety. The
opacity will diminish gradually.Preparation for Administration(Use aseptic technique)Close flow control clamp of administration set.Remove cover from outlet port at bottom of container.Insert piercing pin of administration set into port with a
twisting motion until the set is firmly seated. NOTE:
See full directions on administration set carton.Suspend container from hanger.Squeeze and release drip chamber to establish proper fluid level
in chamber.Open flow control clamp and clear air from set. Close
clamp.Attach set to venipuncture device. If device is not indwelling,
prime and make venipuncture.Regulate rate of administration with flow control
clamp.WARNING: Do not use flexible container in series
connections.HOW SUPPLIEDDOBUTamine in 5% Dextrose Injection, USP is supplied in 250 and
500 mL LifeCare® flexible containers as follows:List No. 2347 − 500 mg DOBUTamine in 5% Dextrose Injection, USP 250 mLNDC 54868-5777-0 Store at 20 to 25ºC (68 to 77ºF). [See USP Controlled Room Temperature.]
Protect from freezing. June, 2006
Printed in USA
EN-1227
Hospira, Inc., Lake Forest, IL 60045 USA
Relabeling of "Additional" barcode label by: Physicians Total Care, Inc. Tulsa, OK 74146 PRINCIPAL DISPLAY PANEL500 mg DOBUTamine in 5% Dextrose Injection, USP 250 mLimage of package label