دوبوتامین
Dobutamine (Dobutamine)
دوبوتامین

نام ژنریک

Dobutamine HCl

شکل دارویی

اشكال دارويي:


Injection, solution: 12.5 mg/ml, 20ml


Injection, Powder, Lyophilized: 250mg

موارد مصرف

موارد و مقدار مصرف


براي افزايش برونده قلب در درمان كوتاهمدت نارسايي جبران نشده قلب ناشي از كاهش قدرت انقباضي.


بزرگسالان: مقدار mcg/kg/min 10-5/2 انفوزيون وريدي ميشود. به ندرت، ممكن است در صورت نياز تا mcg/kg/min 40 انفوزين شود. مقدار مصرف بايد براساس پاسخ بيمار به دقت تنظيم شود.


مكانيسم اثر


اثر اينوتروپيك : دو بوتامين با تحريك انتخابي گيرندههاي آدرنرژيك قدرت انقباضي ميوكارد و حجم ضربه اي و در نتيجه، برونده قلب را
افزايش مي دهد (يك اثر اينوتروپيك مثبت در بيماران داراي قلب سالم يا بيماران مبتلا به نارسايي احتقاني قلب). مقادير درماني اين دارو موجب كاهش مقاومت محيطي (كاهش پس بار) و كاهش فشار ناشي از پر شدن بطن
(كاهش پيشبار) مي شود و ممكن است هدايت گره دهليزي ـ بطني (AV) را تسهيل كند.


فشار خون سيستوليك و فشار نبض ممكن است تغيير نكند يا ‌به دليل افزايش برونده قلب، افزايش يابد. افزايش قدرت انقباضي ميوكارد موجب افزايش جريان خون عروق كرونر و مصرف اكسيژن ميوكارد مي شود.


ضربان قلب معمولاً تغيير نميكند، ‌ولي مصرف مقادير زياد دارو موجب
بروز اثرات كرونوتروپيك مي شود. دوبوتامين ظاهراً بر روي گيرندههاي دوپامينرژيك تأثيري نمي گذارد. همچنين، اين دارو سبب گشاد شدن
عروق مزانتريك يا كليوي نمي شود. با اين وجود، ‌افزايش برونده قلب
ناشي از دارو ممكن است موجب بهبود جريان خون كليوي و افزايش ميزان
دفع ادرار شود.

موارد منع مصرف

تداخل دارويي


مصرف همزمان با بيهوش كننده هاي هيدروكربنه استنشاقي، بخصوص هالوتان، ‌ممكن است احتمال بروز آريتمي بطني را افزايش دهد.


داروهاي اكسي توسيك ممكن است باعث هايپرتانسيون پايدار شود از مصرف همزمان خودداري كنيد.


ضد افسردگيهاي سه حلقه‌اي ممكن است اثرات اين دارو را افزايش دهد. با احتياط استفاده كنيد.


داروهاي مسدود كننده بتا آدرنرژيك ممكن است اثرات قلبي دوبوتامين را
خنثي كرده و موجب افزايش مقاومت محيطي و غالب آمدن اثرات آلفا آدرنرژيك شوند.


در صورت مصرف همزمان با گوانتيدين، ممكن است اثر كاهنده فشارخون گوانتيدين كاهش يابد، ولي اثر بالابرنده فشارخون دوبوتامين توسط گوانتيدين افزايش يابد و به افزايش فشار خون و آريتمي قلبي منجر شود.


مصرف همزمان با نيتروپروسايد ممكن است موجب افزايش برونده قلب و كاهش فشار گوهاي شريان ريوي (Pulmonary Wedge Pressure) شود.


از نظر تئوري، ‌آلكالوئيدهاي روولفيا (رزرپين) ممكن است سبب طولاني شدن اثرات دوبوتامين شوند (افزايش بيش از حد حساسيت ناشي از دنرواسيون).

موارد قابل توجه

-

تداخل دارویی

عوارض جانبي


قلبي ـ عروقي : ضربان نا به جاي قلب، افزايش ضربان قلب، آنژين
صدري، غيراختصاصي درد قفسه سينه، طپش قلب، زيادي فشار خون، PVC، افت فشار خون.


دستگاه گوارش: ‌ تهوع، استفراغ.


تنفسي: اپيزودهاي حملهاي آسم، تنگينفس.


ساير عوارض: تنگي نفس، سردرد، آنافيلاکسي، فلبيت.


توجه : در صورت بروز واكنشهاي ناشي از حساسيت مفرط به داروي يا سولفيتها‌ و يا بروز آريتمي قلبي، بايد مصرف دارو قطع شود.


مسموميت و درمان


مصرف بيش از حد دارو ممكن است باعث تحريك پذيري و عصبانيت، بي‌حالي، ‌تغيير در فشار خون، تهوع، استفراغ، اضطراب، طپش قلب، ‌سردرد، آنژين قلبي، تنگي نفس، ‌ايسكمي ميوكارد و فيبريلاسيون بطني شود. درمان شامل كاهش دوز يا در صورت امكان قطع دارو است. آريتمي را در صورت وجود با پروپرانولول درمان نماييد.

مکانیزم اثر

عوارض جانبي


قلبي ـ عروقي : ضربان نا به جاي قلب، افزايش ضربان قلب، آنژين
صدري، غيراختصاصي درد قفسه سينه، طپش قلب، زيادي فشار خون، PVC، افت فشار خون.


دستگاه گوارش: ‌ تهوع، استفراغ.


تنفسي: اپيزودهاي حملهاي آسم، تنگينفس.


ساير عوارض: تنگي نفس، سردرد، آنافيلاکسي، فلبيت.


توجه : در صورت بروز واكنشهاي ناشي از حساسيت مفرط به داروي يا سولفيتها‌ و يا بروز آريتمي قلبي، بايد مصرف دارو قطع شود.


مسموميت و درمان


مصرف بيش از حد دارو ممكن است باعث تحريك پذيري و عصبانيت، بي‌حالي، ‌تغيير در فشار خون، تهوع، استفراغ، اضطراب، طپش قلب، ‌سردرد، آنژين قلبي، تنگي نفس، ‌ايسكمي ميوكارد و فيبريلاسيون بطني شود. درمان شامل كاهش دوز يا در صورت امكان قطع دارو است. آريتمي را در صورت وجود با پروپرانولول درمان نماييد.

فارماكوكینتیك

موارد منع مصرف و احتياط


موارد منع مصرف: تنگي ايديوپاتيك هيپرتروفيك زير آئورتي و يا حساسيت مفرط شناخته شده نسبت به دارو.


موارد احتياط: تاكيكاردي ضربان نابجا، استنوز آئورت، فيبريلاسيون دهليزي، بيماران پس از MI، مصرف همزمان با MAOI و حساسيت به بي سولفيتسديم.

سایر اطلاعات

طبقه بندي فارماكولوژيك: آدرنرژيك، آگونيست 1‌.


طبقه‌‌بندي درماني: محرك قلبي (آدرنرژيك ـ1‌ آگونيست).


طبقه‌بندي مصرف در بارداري: رده B


نام‌هاي تجاري: Cardiject


ملاحظات اختصاصي


علاوه بر ملاحظات مربوط به تمامي آدرنرژيكها، ‌رعايت موارد زير نيز توصيه مي شود:


1- قبل از مصرف دوبوتامين، ‌كمي حجم خون را بايد با مصرف حجيم‌كننده هاي پلاسما درمان كرد.


2- الكتروكارديوگرام، فشارخون، برونده قلبي ‌و فشارگوهاي شريان ريوي بيمار (از طريق فشار وريد مركزي و يا كاتتر Swan-Ganz) پيگيري گردد.


3- در بيماران مبتلا به فيبريلاسيون دهليزي، قبل از شروع درمان با دوبوتامين، ‌بايد يك گليكوزيد ديژيتال مصرف شود (دوبوتامين هدايت دهليزي ـ بطني را افزايش مي دهد).


4- با مصرف اين دارو، ‌فشار خون سيستوليك در اكثر بيماران تا mmHg20-10 و در بعضي ديگر تا mmHg50 يا بيشتر افزايش مي يابد.


ضربان قلب در اكثر بيماران 15-5 ضربان در دقيقه و در بعضي ديگر تا 30 ضربان در دقيقه يا بيشتر افزايش مي يابد. ضربان زودرس بطني (PVC) نيز ممكن است در حدود پنج درصد از بيماران بروز نمايد. در صورت بروز اين موارد، كاهش مقدار مصرف ممكن است لازم باشد.


5- مقدار مصرف بايد براساس نيازها و پاسخ باليني بيمار تنظيم شود. دارو بايد به صورت انفوزيون وريدي، ‌توسط يك پمپ انفوزيون يا دستگاه ديگري كه سرعت جريان را كنترل كند، ‌مصرف گردد.


6- غلظت محلول انفوزيون نبايد از mg/ml15 تجاوز نمايد. محلول بايد
طي 24 ساعت مصرف شود. سرعت و مدت انفوزيون براساس پاسخ بيمار تعيين مي شود.


7- صورتي رنگ شدن محلول دوبوتامين ناشي از اكسيداسيون جزئي دارو است، ولي قدرت دارويي آن به طور قابل توجهي كاهش نمي يابد.


8- دوبوتامين با محلولهاي قليايي (بيكربنات سديم) ناسازگاري دارد.


همچنين اين دارو نبايد با داروهايي مانند هپارين، هيدروكورتيزون سدي مسوكسينات، سفازولين، سفالوتين خنثي، سفاماندول يا ‌پنيسيلين مخلوط شده يا از طريق يك وريد مصرف شوند.


روش تجويز: براي تجويز از عروق بزرگ و پمپ انفوزيون استفاده كند. با سفازولين، ‌هپارين، پنيسيلين و هيدروكورتيزون از يك مسير تزريق نشود.


نكات قابل توصيه به بيمار


در صورت بروز هرگونه عوارض جانبي به خصوص تنگينفس و سردرد به پزشک اطلاع دهيد.


مصرف در سالمندان: در افراد سالخورده مقادير مصرف كمتري توصيه مي‌شود، ‌زيرا بيماران سالخورده ممكن است نسبت به اثرات دارو حساستر باشند.


مصرف در كودكان: مصرف اين دارو در كودكان توصيه نمي‌شود. بي‌ضرري و اثربخشي دارو در كودكان ثابت نشده است.


دارو باعث افزايش برونده قلبي و فشار خون سيستميك مي شود.


مصرف در شيردهي: ترشح دوبوتامين در شير مشخص نيست و مصرف اين دارو در مادراني که به کودکان خود شير مي‌دهند بايد با احتياط همراه باشد.

Dobutamine (Dobutamine)

Dobutamine
Injection USP

DRUG DESCRIPTION

Dobutamine Injection USP is (±)-4-[2-[[3-(p-Hydroxyphenyl)-1-methylpropyl]amino]ethyl]-pyrocatechol hydrochloride. It is a synthetic catecholamine.

Dobutamine Structural Formula Illustration

Molecular Formula: C18H23NO3•HCl
Molecular Weight: 337.84

The clinical formulation is supplied in a sterile form for intravenous use only. Each mL contains: Dobutamine hydrochloride, equivalent to 12.5 mg (41.5 µmol) dobutamine; Sodium Bisulfite 0.28 mg (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 (2.5 to 5.5).

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Dobutamine is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of adults with 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 risk of hospitalization and death. Patients with NYHA Class IV symptoms appeared to be at particular risk.

DOSAGE AND ADMINISTRATION

Note–Do not add dobutamine to 5% Sodium Bicarbonate Injection or to any other strongly alkaline solution. Because of potential physical incompatibilities, it is recommended that dobutamine not be mixed with other drugs in the same solution. Dobutamine should not be used in conjunction with other agents or diluents containing both sodium bisulfite and ethanol.

Preparation and Stability – At the time of administration, dobutamine 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% Dextrose Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 10% Dextrose Injection, Isolyte®M with 5% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose in Lactated Ringer's Injection, Normosol®-M in D5-W, 20% Osmitrol® in Water for Injection, 0.9% Sodium Chloride Injection, or Sodium Lactate Injection. Intravenous solutions should be used within 24 hours.

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. Rates of infusion (mL/h) for dobutamine concentrations of 500 mcg/mL, 1000 mcg/mL, and 2000 mcg/mL necessary to attain various delivery rates of dobutamine (mcg/kg/min) for patients of different weights are given in Table 1.

Table 1: Dobutamine Injection USP Infusion Rate (mL/h) for 500 mcg/mL concentration

Drug Delivery Rate
(mcg/kg/ min)
Patient Body Weight (kg)
5 10 20 30 40 50 60 70 80 90 100 110
0.5 0.3 0.6 1.2 1.8 2.4 3 3.6 4.2 4.8 5.4 6 6.6
1 0.6 1.2 2.4 3.6 4.8 6 7.2 8.4 9.6 10.8 12 13.2
2.5 1.5 3 6 9 12 15 18 21 24 27 30 33
5 3 6 12 18 24 30 36 42 48 54 60 66
7.5 4.5 9 18 27 36 45 54 63 72 81 90 99
10 6 12 24 36 48 60 72 84 96 108 120 132
12.5 7.5 15 30 45 60 75 90 105 120 135 150 165
15 9 18 36 54 72 90 108 126 144 162 180 198
17.5 10.5 21 42 63 84 105 126 147 168 189 210 231
20 12 24 48 72 96 120 144 168 192 216 240 264

Dobutamine Injection USP Infusion Rate (mL/h) for 1000 mcg/mL concentration

Drug Delivery Rate
(mcg/kg/ min)
Patient Body Weight (kg)
5 10 20 30 40 50 60 70 80 90 100 110
0.5 0.1 0.3 0.6 0.9 1.2 1.5 1.8 2.1 2.4 2.7 3 3.3
1 0.3 0.6 1.2 1.8 2.4 3 3.6 4.2 4.8 5.4 6 6.6
2.5 0.7 1.5 3 4.5 6 7.5 9 10.5 12 13.5 15 16.5
5 1.5 3 6 9 12 15 18 21 24 27 30 33
7.5 2.2 4.5 9 13.5 18 22.5 27 31.5 36 40.5 45 49.5
10 3 6 12 18 24 30 36 42 48 54 60 66
12.5 3.7 7.5 15 22.5 30 37.5 45 52.5 60 67.5 75 82.5
15 4.5 9 18 27 36 45 54 63 72 81 90 99
17.5 5.2 10.5 21 31.5 42 52.5 63 73.5 84 94.5 105 115.5
20 6 12 24 36 48 60 72 84 96 108 120 132

Dobutamine Injection USP Infusion Rate (mL/h) for 2000 mcg/mL concentration

Drug Delivery Rate
(mcg/kg/ min)
Patient Body Weight (kg)
5 10 20 30 40 50 60 70 80 90 100 110
0.5 0.07 0.1 0.3 0.4 0.6 0.7 0.9 1 1.2 1.3 1.5 1.6
1 0.1 0.3 0.6 0.9 1.2 1.5 1.8 2.1 2.4 2.7 3 3.3
2.5 0.4 0.7 1.5 2 3 4 4.5 5 6 7 7.5 8
5 0.7 1.5 3 4.5 6 7.5 9 10.5 12 13.5 15 16.5
7.5 1.1 2.2 4.5 7 9 11 13.5 16 18 20 22.5 25
10 1.5 3 6 9 12 15 18 21 24 27 30 33
12.5 1.9 3.7 7 11 15 19 22.5 26 30 34 37.5 41
15 2.2 4.5 9 13.5 18 22.5 27 31.5 36 40.5 45 49.5
17.5 2.6 5.2 10.5 15.7 21 26.2 31.5 36.7 42 47.2 52.5 57.7
20 3 6 12 18 24 30 36 42 48 54 60 66

Concentrations of up to 5,000 mcg/mL have been administered to humans (250 mg/50 mL).The final volume administered should be determined by the fluid requirements of the patient.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Dobutamine Injection USP, 20 mL single dose vial contains dobutamine hydrochloride, equivalent to 250 mg dobutamine per 20 mL; ten vials per carton. NDC 55390-560-90.

Store at controlled room temperature, 15° to 30°C (59° to 86°F) [see USP].

Manufactured by: Ben Venue Laboratories, Inc., Bedford, Ohio 44146. Manufactured for: Bedford Laboratories™, Bedford, OH 44146. June 2005.

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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% 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 InfusionPhlebitis 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% to 3% of patients: nausea, headache, anginal pain, non-specific 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 hypokalemic levels (see PRECAUTIONS).

Read the Dobutamine (dobutamine) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

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.

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 dobutamine 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.

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Increase in Heart Rate or Blood Pressure

Dobutamine 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 preexisting hypertension appear to face an increased risk of developing an exaggerated pressor response.

Ectopic Activity

Dobutamine may precipitate or exacerbate ventricular ectopic activity, but it rarely has caused ventricular tachycardia.

Hypersensitivity

Reactions suggestive of hypersensitivity associated with administration of dobutamine including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally.

Dobutamine 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 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.
  2. Hypovolemia should be corrected with suit-able volume expanders before treatment with dobutamine 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 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.

Laboratory Tests – Dobutamine, like other β2-agonists, can produce a mild reduction in serum potassium concentration, rarely to hypokalemic levels. Accordingly, consideration should be given to monitoring serum potassium.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to evaluate the carcinogenic or mutagenic potential of dobutamine, or its potential to affect fertility, have not been conducted.

Pregnancy

Teratogenic Effects–Pregnancy Category BReproduction studies performed in rats at doses up to 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 twice the normal human dose, have revealed no evidence of harm to the fetus due to dobutamine. 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 dobutamine 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 dobutamine is administered to a nursing woman. If a mother requires dobutamine treatment, breastfeeding should be discontinued for the duration of the treatment.

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

Of the 1893 patients in clinical studies who were treated with dobutamine, 930 (49.1%) were 65 and older. No overall differences in safety or effectiveness were observed between these and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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 drug therapy.

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Overdoses of dobutamine have been reported rarely. The following is provided to serve as a guide if such an overdose is encountered.

Signs and SymptomsToxicity from dobutamine is usually due to excessive cardiac β-receptor stimulation. The duration of action of dobutamine is generally short (T1/2= 2 minutes) because it is rapidly metabolized by catechol-0-methyltranferase. 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.

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 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; 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.

CONTRAINDICATIONS

Dobutamine is contraindicated in patients with idiopathic hypertrophic subaortic stenosis and in patients who have shown previous manifestations of hypersensitivity to dobutamine.

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Dobutamine 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 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 PRECAUTIONS, Pediatric Use).

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last reviewed on RxList: 11/22/2010
This monograph has been modified to include the generic and brand name in many instances.

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