dobu ahfs

7/23/2019 Dobu AHFS

1/15

Dobutamine (Systemic)

Introductory Information

Dobutamine is a synthetic sympathomimetic that is structurally related to dopamine and generally isconsidered a relatively selective 1-adrenergic agonist.

Class:12:12.08.08 Selective beta-1-Adrenergic Agonists; au100 (VA primary);

Brands*:Dobutrex

*also available generically

Generic Name:Dobutamine HydrochlorideCAS Number:49745-95-1

Uses

Cardiac Decompensation, Shock, and CHF

Used to increase cardiac output in the short-term treatment of cardiac decompensation caused bydepressed contractility from organic heart disease, cardiac surgical procedures, cardiac arrest(ACLS; see CPR under Uses), or acute MI (see MI under Uses).103, 107, 110, 111, a,b

May be particularly useful in the management of cardiogenic shock, including drug-inducedcardiogenic shock, in patients with normal DBP and SBP >100 mm Hg, since the drug provides the

best sympathomimetic support.104, 112

May be preferable to dopamine in the period immediately following cardiopulmonary bypasssurgery.b

Safety and efficacy in the long-term (e.g., exceeding 48 hours) treatment of CHF have not beenestablished.103, 107, 109, a,bPatients with NYHA class IV disease appear at particular risk of adverseeffects of long-term cAMP-dependent inotropic therapy.a

May be ineffective and potentially harmful in marked mechanical obstruction (e.g., severe valvularaortic stenosis).b

Should not be used alone in severely hypotensive patients (e.g., when SBP is

7/23/2019 Dobu AHFS

2/15

Arterial blood pressure may remain unchanged due to reflex peripheral vasodilation (baroreceptormediated) in response to increased stroke volume.110

Useful in the management of postresuscitation shock (e.g., when combined with dobutamine).110, c

MI

Although the manufacturers state that safety following MI has not been established, use incombination with dopamine in acute MI management is recommended by the ACC and AHA forthe management of heart failure and low-output syndromes associated with left ventriculardysfunction and for inotropic support following hypotension management associated with rightventricular ischemia.111

May be useful as an adjunct (to increase cardiac output) to volume replacement in patients with rightventricular infarction, since dopamine may increase pulmonary vascular resistance.b

Dosage and Administration

Administration

Usually administered by IV infusionb

Has also been administered by intraosseous infusion .110

V InfusionInfuse IV using an infusion pump or other apparatus to control the rate of flow and avoid inadvertent

administration of a bolus of drug.

107, a,b

Commercially available premixed dobutamine hydrochloride in 5% dextrose should be administeredonly by IV infusion via a suitable catheter or needle.107

Do not be use in series connections.107

When the commercially available IV infusion solution of dobutamine hydrochloride in 5% dextroseis used, the accompanying labeling should be consulted for proper methods of administration andother associated precautions.b

DilutionThe concentrate for injection mustbe diluted prior to administration; alternatively, commerciallyavailable diluted injections for IV infusion may be used.103,b

20 mL of the concentrate for injection should be diluted in at least 50 mL of diluent and 40 mL ofconcentrate should be diluted in at least 100 mL of diluent.b

The concentration used is individualized according to patient dosage and fluid requirements, butshould not exceed 5000 mcg (5 mg)/mL.103, 110, a,b

>Dilution of Concentrate for Injection for IV Infusion103, b

Amount ofConcentrate

Add (volume ofconcentrate)

To Compatible IV Solution(volume of solution)

To Make (final dilutionconcentration)

Page 2 of 15AHFS DI Essentials

7/30/2015mk:@MSITStore:F:\Kuliah%20Apoteker%2081\ebook\AHFS%202011.chm::/nymayn...

7/23/2019 Dobu AHFS

3/15

Rate of AdministrationAvoid bolus administration.b

Rate of IV infusion varies according to individual dose requirements titrated to response.103, 107, 110,a,b

Initiate at a slow rate (e.g., 0.5-1 mcg/kg per minute) and carefully adjust at intervals of a fewminutes according to response;busually 2-20 mcg/kg per minute is needed.103, 107, 110, a,b

250 mg 20 mL 1 L 250 mcg (0.25 mg)/mL250 mg 20 mL 500 mL 500 mcg (0.5 mg)/mL250 mg 20 mL 250 mL 1000 mcg (1 mg)/mL250 mg 20 mL 50 mL 5000 mcg (5 mg)/mL

ntraosseous AdministrationWhen IV administration is not possible, dobutamine may be given by intraosseous infusion for

emergency uses such as CPR.110, 112

Limit intraosseous administration to personnel well trained in the technique.100

Place a cannula in a noncollapsible marrow venous plexus; such access often can be achieved in 30-60 seconds.100Use a rigid needle, preferably a specially designed intraosseous or Jamshidi-type

bone marrow needle; a styleted needle is preferred to prevent obstruction of the needle with corticalbone.100

Insert the intraosseous needle into the anterior tibial bone marrow; alternatively, the distal femur,

medial malleolus, or anterior superior iliac spine can be used.100In older children and adults,intraosseous cannulas also have been inserted successfully into the distal radius or ulna in addition tothe proximal tibia.100

Successful placement outside the hospital (e.g., by emergency medical services) generally is moredifficult in older than in younger children.100

Onset of action and systemic concentrations are comparable to those achieved with intravascularadministration.100, 112

DilutionSame as those for IV infusion. (See Dilution under IV Infusion.)

Rate of AdministrationIntraosseous infusion rates are the same as those for IV infusion.100 (See Rate of Administrationunder IV Infusion.)

Administration RisksComplications are uncommon (less than 1% of patients), and include tibial fracture, lower-extremitycompartment syndrome, extravasation, and osteomyelitis; careful technique can minimize therisk.100Local effects on bone marrow and bone growth appear to be minimal.100Risk of

microscopic pulmonary fat and bone marrow emboli does not appear to be increased.100

Dosage



7/23/2019 Dobu AHFS

4/15

Available as dobutamine hydrochloride; dosage expressed in terms of dobutamine.103, 107, a,b

Hemodynamic end points rather than a specific dose should be used to optimize therapy.110, 112

Individual response to dobutamine is variable, and infusion rate should be titrated to achieve the

desired clinical response.b

Rate and duration should be carefully adjusted according to patient response as indicated by heartrate, BP, urine flow, peripheral perfusion, presence of ectopic heartbeats, and, whenever possible, bymeasurement of central venous or pulmonary wedge pressure and cardiac output.103, 107, a,b

Pediatric Patients

Pharmacokinetics and clinical responses to specific doses vary widely.110

Usually initiate slowly (e.g., 0.5-1 mcg/kg per minute).b

Cardiac Decompensation and Shock>IV or Intraosseous

Usually, 2-20 mcg/kg per minute is needed to increase cardiac output.110,b

CPR>IV or Intraosseous

Usually, 2-20 mcg/kg per minute is needed to increase cardiac output.110, 112,b

MI>IV or Intraosseous


dultsIndividual response to dobutamine is variable, and infusion rate should be titrated to achieve thedesired clinical response.103, 107, 110, a,b

Initiate at a slow rate (e.g., 0.5-1 mcg/kg per minute) and carefully adjust at intervals of a fewminutes according to response.b

Dobutamine has been infused for up to 72 hours without decreased effectiveness.b

Cardiac Decompensation and Shock>IV or Intraosseous


CPR>IV or Intraosseous


MI>IV or Intraosseous


Prescribing Limits



7/23/2019 Dobu AHFS

5/15

Pediatric PatientsIV or IntraosseousDosages >20 mcg/kg per minute may produce tachycardia and ventricular ectopy and could induceor exacerbate myocardial ischemia.104, 112

dults

IV or IntraosseousDosages >20 mcg/kg per minute often increase heart rate by more than 10%, and such increasespotentially could induce or exacerbate myocardial ischemia.104, 112

Rarely, dosages as great as 40 mcg/kg per minute,103, 107, 112but these may substantially increaseadverse effects, (e.g., tachycardia, hypotension) and usually should be avoided.104, 112

Special Populations

Hepatic Impairment

No specific hepatic dosage recommendations.a

Renal Impairment

No specific renal dosage recommendations.a

Geriatric PatientsInitiate therapy at lower end of usual range because of age-related decreases in hepatic, renal, and/orcardiac function and concomitant disease and drug therapy.108However, geriatric patients mayexhibit a substantially decreased response.110, 112

Cautions

Contraindications

Idiopathic hypertropic subaortic stenosis.Known hypersensitivity to dobutamine hydrochloride or any ingredient in the formulation.103, 106,107, a,b

Solutions containing dextrose may be contraindicated in patients with known allergy to corn orcorn products.107, a

Warnings/Precautions

WarningsCardiovascular EffectsMarked increases in heart rate and BP (especially systolic pressure) can occur.103, a,bHeart rate of30 beats per minute or an increase in systolic BP of 50 mm Hg reported.b

Cardiovascular effects are usually dose related, and dosage should be reduced or the infusiontemporarily discontinued if such effects occur.b

Patients with preexisting hypertension are at increased risk of an exaggerated pressor response.103, a,b

Patients with atrial fibrillation should be digitalized because of the risk of developing a rapidventricular response.103, a,b



7/23/2019 Dobu AHFS

6/15

Ectopic ActivityCan precipitate or exacerbate ventricular ectopic activity; rarely, causes ventricular tachycardia.103

Sensitivity ReactionsHypersensitivity Reactions

Hypersensitivity, including skin rash, fever, eosinophilia, and bronchospasm, have been reportedoccasionally.103, 107

SulfitesSome formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxisand life-threatening or less severe asthmatic episodes) in certain susceptible individuals.102, 103, 106,107, a,b

CornDextrose-containing solutions may be contraindicated in patients who are sensitive to corn or corn

products.107, a

General PrecautionsHypovolemiaHypovolemia should be corrected with an appropriate plasma volume expander before initiatingdobutamine.103, 107, a,b

MIClinical experience insufficient to rule out possibility of intensified or extended myocardialischemia; use with extreme caution following MI.103, 107, a,b (See MI under Uses.)

Cardiac Mechanical ObstructionNo benefit may be apparent in the presence of marked mechanical obstruction (e.g., severe valvularaortic stenosis).103, 107, a

Monitoring ParametersMonitor ECG, BP and, when possible, cardiac output and pulmonary wedge pressure.103, 107, a,b

May produce slight reductions in serum potassium concentrations and hypokalemia may occurrarely; monitor serum potassium concentrations.b

Specific Populations

PregnancyCategory B.103, a

LactationNot known whether dobutamine is distributed into human milk.103Caution if used in nursingwomen.103

Pediatric UseMay increase cardiac output and systemic pressure in pediatric patients of all age groups.103, 107Such increases generally are seen at lower infusion rates than those associated with substantial

tachycardia.103, 107

Premature neonates: May be less effective in increasing systemic BP without causing unduetachycardia, and dobutamine has not been shown to provide any additional benefit when



7/23/2019 Dobu AHFS

7/15

administered to such infants who are already receiving optimal dopamine therapy.103, 107

Geriatric UseInsufficient experience in patients 65 years of age to determine whether geriatric patients responddifferently than younger adults; some clinical experience showed no differences.a

Use with caution since renal, hepatic, and cardiovascular dysfunction and concomitant disease orother drug therapy are more common in this age group.108, aHowever, geriatric patients generallyhave a substantially reduced response to dobutamine.110, 112

Common Adverse Effects

Ectopic heartbeats, increased heart rate, elevations in BP, hypotension, phlebitis, local inflammatorychanges.103, a,b

Interactions

No evidence of interactions in clinical studies when used with atropine, cardiac glycosides (digoxin),furosemide, heparin, lidocaine, morphine, nitrates, potassium chloride, or spironolactone.103, 103, a

Specific Drugs

Pharmacokinetics

Absorption

Drug Interaction Comments

-Adrenergic blocking agents

Cardiac effects of dobutamine are antagonized,resulting in predominant -adrenergic effects andincreased peripheral resistance; dobutamine may

be ineffective103, a,b

Useconcomitantlywith cautionb

Anesthetics, general (e.g.,halogenated hydrocarbons[e.g., halothane],cyclopropane)

May increase cardiac irritability, resulting inventricular arrhythmias with usual dobutaminedosesb

Useconcomitantlywith cautionb

Sodium nitroprussidePotentiated effects on cardiac output and

pulmonary wedge pressurea

Onset

Onset occurs within 2 minutes after initiation of IV infusion; peaks within 10 minutes.b

Duration

Effects cease shortly after infusion discontinuance.b

Distribution

Extent

Not known if dobutamine crosses the placentabor is distributed into milk.103,b

Elimination



7/23/2019 Dobu AHFS

8/15

etabolismMetabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) to an inactivecompound, 3-O-methyldobutamine, and by conjugation with glucuronic acid.b

Elimination RouteConjugates of dobutamine and 3-O-methyldobutamine excreted mainly in urine and to a minor

extent in feces.b

Half-life

About 2 minutes.a,b

Stability

Storage

ParenteralPink discoloration indicates slight oxidation of the drug; however, there is no important loss of

potency if administered within the recommended time period.b

Store at 15-30C.b

Solutions of dobutamine hydrochloride in 5% dextrose should be protected from excessive heat orfreezing and stored at room temperature (25C); however, brief exposure of the solutions totemperatures up to 40C does not adversely affect the products.107

Solutions diluted for IV infusion should be used within 24 hours; unused portions should bediscarded.b

Concentrate for Injection for IV Infusion15-30C.103,b

Injection for IV Infusion25C; may be exposed briefly to temperatures up to 40C.aDo not freeze.a

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Incompatible with strongly alkaline solutions.103, a,b

Should not be used in conjunction with other drugs or diluents containing both sodium bisulfite andethanol.103,b

Parenteral

Solution CompatibilityHIDStable for 24 hours in dextrose 5 or 10%, dextrose 5% in sodium chloride 0.45 or 0.9%, dextrose 5%in lactated Ringers injection, IsolyteM with 5% dextrose, lactated Ringers, Normosol-M with5% dextrose, Osmitrolin water, sodium chloride 0.9%, and sodium lactate (1/6) M.103

CompatibleDextrose 2.5% in half-strength Ringers injection, lactated



7/23/2019 Dobu AHFS

9/15

Drug CompatibilityAdditives should not be introduced into the injection containers.a, 107

Since dobutamine dosage must be titrated according to response, other drugs generally should not beadded to the infusion fluid.c

Dextrose 5% in Ringers injection, lactatedDextrose 2.5% in sodium chloride 0.45%Dextrose 5% in sodium chloride 0.45 or 0.9%Dextrose 5% in waterRingers injection, lactated

Sodium chloride 0.45 or 0.9%IncompatibleSodium bicarbonate 5%

>Admixture CompatibilityHIDCompatibleAmiodarone HClAtracurium besylateAtropine sulfateCiprofloxacinDopamine HClEnalaprilatEpinephrine HCl

FlumazenilHydralazine HClIsoproterenol HClLidocaine HClMeperidine HClMeropenemMetaraminol bitartrateMorphine sulfate

Nitroglycerin

Norepinephrine bitartratePhentolamine mesylatePhenylephrine HClProcainamide HClPropranolol HClRanitidine HClZidovudineIncompatibleAcyclovir sodium

AlteplaseAminophyllineBumetanide



7/23/2019 Dobu AHFS

10/15

Calcium gluconateDiazepamDigoxinFurosemideMagnesium sulfate

Phenytoin sodiumPotassium phosphatesSodium bicarbonateVariableBretylium tosylateCalcium chlorideHeparin sodium

Nitroglycerin with sodium nitroprussidePotassium chloride

Verapamil HCl

>Y-Site CompatibilityHID

CompatibleAlcohol 10% in dextrose 5%AmifostineAmiodarone HClArgatrobanAtracurium besylate

AztreonamBivalirudinBretylium tosylateCalcium chlorideCalcium gluconateCiprofloxacinCladribineClarithromycinDexmedetomidine HClDiazepamDiltiazem HClDocetaxelDopamine HClDopamine HCl with lidocaine HClDopamine HCl with nitroglycerinDopamine HCl with sodium nitroprussideDoxorubicin HCl liposome injectionEnalaprilatEpinephrine HClEtoposide phosphateFamotidine



7/23/2019 Dobu AHFS

11/15

Fenoldopam mesylateFentanyl citrateFluconazoleGemcitabine HClGranisetron HCl

Haloperidol lactateHetastarch in lactated electrolyte injection (Hextend)Hydromorphone HClInamrinone lactateInsulin, regular (Humulin R)Labetalol HClLevofloxacinLidocaine HClLidocaine HCl with dopamine HCl

Lidocaine HCl with nitroglycerinLidocaine HCl with sodium nitroprussideLinezolidLorazepamMagnesium sulfateMeperidine HClMilrinone lactateMorphine sulfate

Nicardipine HClNitroglycerinNitroglycerin with dopamine HClNitroglycerin with lidocaine HClNitroglycerin with sodium nitroprussideNorepinephrine bitartrateOxaliplatinPancuronium bromidePotassium chloridePropofolRanitidine HClRemifentanil HClSodium nitroprussideSodium nitroprusside with dopamine HClSodium nitroprusside with lidocaine HClSodium nitroprusside with nitroglycerinTacrolimusTheophyllineThiotepaTirofiban HCl

VasopressinVecuronium bromide



7/23/2019 Dobu AHFS

12/15

Actions

The main effect of therapeutic doses is cardiac stimulation.bPrincipally a selective, direct stimulatory effect on 1-adrenergic receptors, but the mechanisms of

action are complex.100, 101, 110

In therapeutic doses, also mild 2-a nd1-adrenergic receptor agonist effects.b

1-Adrenergic effects exert a potent positive inotropic effect, resulting in increased myocardial

contractility and cardiac output.110,b

Increased left ventricular filling pressure decreases in CHF.b, 110

Therapeutic doses cause decreased peripheral resistance; however, systolic blood pressure andpulse pressure may remain unchanged or be increased because of augmented cardiac output.b

Usual doses do not substantially change heart rate.bCoronary blood flow and myocardial oxygen consumption are usually increased because ofincreased myocardial contractility.b

May facilitate AV conduction and shorten or cause no important change in intraventricularconduction.b

Pulmonary vascular resistance may decrease if it is elevated initially and mean pulmonary arterypressure may decrease or remain unchanged.bUnlike dopamine, dobutamine does not seem to affect dopaminergic receptors and causes no renalor mesenteric vasodilation; however, urine flow may increase because of increased cardiac output.

Advice to Patients

ZidovudineIncompatibleAcyclovir sodiumAlteplaseAminophylline

Amphotericin B cholesteryl sulfate complexCefepime HClFoscarnet sodiumIndomethacin sodium trihydrateLansoprazolePantoprazole sodiumPemetrexed disodiumPhytonadionePiperacillin sodium-tazobactam sodium

Thiopental sodiumWarfarin sodiumVariableCefepime HCICeftazidimeFurosemideHeparin sodiumMidazolam HCl



7/23/2019 Dobu AHFS

13/15

Importance of informing clinicians of existing or contemplated concomitant therapy, includingprescription and OTC drugs.a,bImportance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

Importance of informing patients of other important precautionary information.a,b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects insome individuals; consult specific product labeling for details.

Dobutamine Hydrochloride

* available from one or more manufacturer, distributor, and/or repackager by generic(nonproprietary) name

Dobutamine Hydrochloride in Dextrose

* available from one or more manufacturer, distributor, and/or repackager by generic(nonproprietary) name

Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Leier CV, Unverferth DV. Dobutamine.Ann Intern Med. 1983; 99:490-6. [IDIS 176707][PubMed 6625384]

Routes Dosage Forms Strengths Brand Names Manufacturer

ParenteralFor injectionconcentrate, for IVinfusion

12.5 mg (ofdobutamine) permL*

Dobutamine Hydrochloridefor Injection (with sulfites)

Bedford,Hospira, Sicor

Dobutrex

Solution (withsodium bisulfite) Lilly

Routes DosageForms Strengths Brand Names Manufacturer

ParenteralInjection,for IVinfusion

0.5 mg (of dobutamine)per mL (125 or 250 mg)in 5% Dextrose*

Dobutamine in 5% DextroseInjection (with sulfites; Lifecare

[Braun, Hospira])

VariousManufacturers

1 mg (of dobutamine)per mL (250 or 500 mg)in 5% Dextrose*


[Hospira, McGaw]; Viaflex[Baxter])


2 mg (of dobutamine)per mL (500 mg) in 5%Dextrose*


[Hospira]; Viaflex[Baxter])


4 mg (of dobutamine)

per mL (1000 mg) in5% Dextrose*


[Hospira, Braun, McGaw];Viaflex[Baxter])

Various

Manufacturers



7/23/2019 Dobu AHFS

14/15

101. Ruffolo RR Jr. The mechanism of action of dobutamine.Ann Intern Med. 1984; 100:313-4.[IDIS 181321] [PubMed 6140893]

102. Food and Drug Administration. Sulfiting agents; labeling in drugs for human use; warningstatement: final rule [21 CFR Part 201].Fed Regist. 1986; 51:43900-5.

103. Eli Lilly and Company. Dobutrex

(dobutamine hydrochloride) solution prescribinginformation. Indianapolis, IN: 1999 Feb.

104. Emergency Cardiac Care Committee and Subcommittees, American Heart Association.Guidelines for cardiopulmonary resuscitation and emergency cardiac care.JAMA. 1992;268:2171-2302. [PubMed 1404767]

105. Robison-Strane SR, Bubik JS. Dobutamine-induced fever.Ann Pharmacother. 1992;26:1523-4. [IDIS 306620] [PubMed 1482808]

106. Gensia Laboratories, Inc. Dobutamine hydrochloride injection prescribing information.Irvine, CA; 1993 Apr.

107. Abbott Laboratories. Dobutamine in 5% dextrose injection prescribing information. NorthChicago, IL: 1998 Aug.

108. Food and Drug Administration. Dobutamine in 5% dextrose in flexible containers[September 1, 1999; Abbott]. MedWatch drug labeling changes. Rockville, MD; September1999. From FDA website ([Web]).

109. Food and Drug Administration. Dobutamine in 5% dextrose in plastic container [April 21,1999; Baxter]. MedWatch drug labeling changes. Rockville, MD; April 1999. From FDAwebsite ([Web]).

110. The American Heart Association in Collaboration with the International Liaison Committeeon Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergencycardiovascular care. Circulation. 2000; 102(Suppl I) I-132,I-328.

111. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management ofpatients with acute myocardial infarction: 1999 update: a report of the American College ofCardiology/American Heart Association Task Force on Practice Guidelines (Committee onManagement of Acute Myocardial Infarction). Circulation. 1999; 100:1016-30. [IDIS 437967][PubMed 10468535]

112. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation andemergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

pdh. Schilling McCann JA, Publisher. Pharmacists drug handbook. 2nd ed. Philadelphia, PA:Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society ofHealth-System Pharmacists; 2007:545-55.

a. Baxter Healthcare Corporation. Dobutamine hydrochloride in 5% injection prescribinginformation. Deerfield, IL; 2002 Jul.

b. AHFS drug information 2008. McEvoy GK, ed. Dobutamine. Bethesda, MD: American Societyof Health-System Pharmacists; 2008:1334-6



7/23/2019 Dobu AHFS

15/15

c. AHFS drug information 2008. McEvoy GK, ed. Dopamine. Bethesda, MD: American Societyof Health-System Pharmacists; 2008:1336-9


dobu ahfs

Documents