| DOBUTREX® |
|Dobutamine HCl |
|Action And Clinical Pharmacology: Dobutamine is a direct acting inotropic agent whose primary activity results from stimulation of the b-receptors of the heart while producing less marked chronotropic, hypertensive, arrhythmogenic or vasodilatory effects. It does not cause the release of endogenous norepinephrine as does dopamine. No specific effect on the renal vasculature has been observed. In both animal and human studies, dobutamine produces less increase in heart rate and less decrease in peripheral vascular resistance for a given inotropic effect than does isoproterenol.
The onset of action is within 1 to 2 minutes, the peak effect of a particular infusion may not be reached for 10 minutes. The plasma half-life in humans is 2 minutes.
Indications And Clinical Uses: The treatment of adults with cardiac decompensation due to depressed contractility resulting from organic heart disease or following cardiac surgical procedures in which parenteral therapy is necessary for inotropic support.
Most clinical experience with dobutamine is short-term - up to several hours in duration. In a limited number of patients who were studied for 24, 48 and 72 hours, a persistent increase in cardiac output occurred in some, whereas the output of others returned toward baseline values.
Contra-Indications: Patients with pheochromocytoma, idiopathic hypertrophic subaortic stenosis and hypersensitivity to dobutamine. tag_WarningWarnings
Manufacturers' Warnings In Clinical States: Dobutamine may cause a marked increase in heart rate or blood pressure, especially systolic pressure. About 10% of patients in clinical studies have had rate increases of 30 beats/minute or more, while about 7.5% have had a 50 mmHg or greater increase in systolic pressure. Patients with preexisting hypertension appear to have an increased risk of developing an exaggerated pressor response. Reduction of dosage usually reverses these effects promptly.
Dobutamine may precipitate or exacerbate ventricular ectopic activity but has rarely caused ventricular tachycardia.
Reactions suggestive of hypersensitivity associated with administration of dobutamine including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally. Dobutamine solution contains sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms, in certain susceptible people.
In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to instituting dobutamine therapy. Because dobutamine facilitates atrioventricular conduction, patients with atrial fibrillation are at risk of developing rapid ventricular response.
Dobutamine should not be used in the presence of uncorrected tachycardia or ventricular fibrillation.
No improvement may be observed in the presence of marked mechanical obstruction such as severe valvular aortic stenosis.
Minimal vasoconstriction has occasionally been observed, most notably in patients recently treated with a b-blocking drug. Because dobutamine's inotropic effects stem from stimulation of cardiac b1 receptors, this effect is, of course, prevented by b-blocking drugs.
Precautions: During dobutamine administration, monitor EKG, heart rate and blood pressure continuously. In addition, perform monitoring of pulmonary wedge pressure and cardiac output whenever possible to aid in the safe and effective infusion of dobutamine.
Caution should be exercised in order to prevent infiltration at the injection site.
Correct hypovolemia with suitable volume expanders before treatment with dobutamine.
Use with caution in patients with hyperthyroidism.
Use dobutamine with caution in patients receiving anesthetic agents, cyclopropane or halogenated hydrocarbons.
Dobutamine should be used with caution in patients taking concomitantly other sympathomimetic agents.
Dobutamine like other beta-2 agonists can produce a mild reduction in serum potassium concentration (rarely to hypokalemic levels). Accordingly, consideration should be given to monitoring serum potassium.
Usage following acute myocardial infarction: Clinical experience with dobutamine following myocardial infarction has been insufficient to establish the safety of this use. There is concern that any agent which increases contractile force and heart rate may increase the size of an infarction by intensifying ischemia, but whether dobutamine does so is not known.
Pregnancy: Reproduction studies (rats, rabbits) have revealed no evidence of impaired fertility or harm to the fetus due to dobutamine. To date, the drug has not been administered to pregnant women and should be used in such patients only when the expected benefits clearly outweigh the potential risks to the fetus and mother.
Children: Dobutamine's safety and efficacy for use in children have not been established.
Drug Interactions: Clinical 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.
No evidence of drug interactions were noted in clinical studies when dobutamine was administered concurrently with other drugs including digitalis preparations and/or furosemide, spironolactone, lidocaine, nitroglycerin, isosorbide dinitrate, morphine, atropine, anticoagulants and potassium chloride supplements.
Adverse Reactions: Cardiovascular: The most common adverse reactions relate to dobutamine's effect on the cardiovascular system.
A 10 to 20 mm Hg increase in systolic blood pressure and an increase in heart rate of 5 to 15 beats/minute have been noted in most patients. (See Warnings regarding exaggerated chronotropic and pressor effects). About 5% of patients have had increased premature ventricular beats during infusions. These effects are dose-related.
Hypotension: Precipitous decreases in blood pressure associated with dobutamine therapy have been reported. A reduction in dose or discontinuation of the drug is necessary to return the blood pressure to baseline levels. In some cases pressor support may be required.
Less common: cardiac awareness, transient bigeminy, bradycardia, angina, palpitations, nonspecific chest pain and shortness of breath.
Gastrointestinal: nausea, vomiting, bad taste.
CNS: headache, anxiety, fatigue, paresthesia.
Hypersensitivity: rash, fever, eosinophilia and bronchospasm have been reported occasionally.
Miscellaneous: rarely - dyspnea, thrombocytopenia, pruritus, chill, sweating. Phlebitis has been occasionally reported. Local inflammatory changes following inadvertent infiltration. Isolated cases of cutaneous necrosis (destruction of skin tissue) have been reported.
Administration of dobutamine, like other b2-agonists, has been associated with decreases in serum potassium concentrations, rarely to hypokalemic values.
Long-term Safety: Infusion of up to 72 hours have revealed no adverse effects other than those seen with shorter infusions.
Symptoms And Treatment Of Overdose: Symptoms: Excessive blood pressure alteration or tachycardia. tag_Treatment
Treatment: Reduce the rate of administration, or temporarily discontinue dobutamine until the patient's condition stabilizes. Because dobutamine's duration of action is short, no additional remedial measures are usually necessary.
Dosage And Administration: Dobutrex is a potent drug; it is not for direct injection and must be diluted exactly as directed before administration to patients as an i.v. infusion (see Precautions).
The infusion rate needed to increase cardiac output usually ranges from 2.5 to 10 µg/kg/min (see Table I). Some patients may respond to doses as low as 0.5 µg/kg/min whereas, on rare occasions, infusion rates up to 40 µg/kg/min have been required to obtain the desired effect.
Adjust the administration rate and duration of therapy 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.
Preparation and Stability: Dobutamine is incompatible with alkaline solutions and it should not be mixed with products such as 5% sodium bicarbonate injection, or to any other strongly alkaline solutions. Because of the occurrences of physical incompatibilities with some drugs and the potential for incompatibility with other drugs, 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.
At the time of administration dobutamine must be further diluted in an i.v. container to at least 50 mL using one of the following i.v. solutions as a diluent: 5% dextrose injection, 0.9% sodium chloride injection or sodium lactate injection. I.V. solutions should be used within 24 hours of preparation.
Solutions containing dobutamine may exhibit a 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 reconstituted time periods stated above.
Availability And Storage: Each mL of aqueous solution contains: dobutamine (as HCl) 12.5 mg. Nonmedicinal ingredients: sulfur dioxide 0.15 mg and water for injection. Hydrochloric acid and/or sodium hydroxide is used to adjust pH.