DOBUTAMINE HYDROCHLORIDE

INDICATIONS AND USAGE Dobutamine Hydrochloride in 5% Dextrose Injection is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients 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 risks of hospitalization and death. Patients with NYHA Class IV symptoms appeared to be at particular risk.

DOSAGE AND ADMINISTRATION Recommended Dosage Dobutamine Hydrochloride in 5% Dextrose Injection is administered intravenously through a suitable intravenous catheter or needle. A calibrated electronic infusion device is recommended for controlling the rate of flow in mL/hour or drops/minute. Infusion of dobutamine should be started at a low rate (0.5-1.0 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 2-20 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 in mL/hour for dobutamine hydrochloride concentrations of 1,000, 2,000 and 4,000 mcg/mL are in Table 2. This container system may be inappropriate for the dosage requirements of pediatric patients under 30 kg. Other dosage forms may be more appropriate. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Dobutamine Hydrochloride in 5% Dextrose Injection solutions 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. 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. Do not add supplementary medications to Dobutamine Hydrochloride in 5% Dextrose Injection. Do not administer Dobutamine Hydrochloride in 5% Dextrose Injection simultaneously with solutions containing sodium bicarbonate or strong alkaline solutions.

CONTRAINDICATIONS Dobutamine Hydrochloride in 5% Dextrose Injection is contraindicated in patients with idiopathic hypertrophic subaortic stenosis and in patients who have shown previous manifestations of hypersensitivity to dobutamine. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

WARNINGS Increase in Heart Rate or Blood Pressure Dobutamine Hydrochloride in 5% Dextrose Injection 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 reverses these effects. Because dobutamine 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. In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to institution of therapy with Dobutamine in D 5 W. Ectopic Activity Dobutamine Hydrochloride in 5% Dextrose Injection 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 Hydrochloride in 5% Dextrose Injection 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. Solutions containing dextrose should not be administered through the same administration set as blood, as this may result in pseudoagglutination or hemolysis. The intravenous administration of solutions may cause fluid overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of the injections. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentration of the injections. Excess administration of potassium-free solutions may result in significant hypokalemia.

Drug Interactions 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. 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.

ADVERSE REACTIONS Increased Heart Rate, Blood Pressure, and Ventricular Ectopic Activity 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). Approximately 5% of adult 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. Stress Cardiomyopathy Stress cardiomyopathy has been reported with dobutamine in association with cardiac stress testing. 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% of adult patients: 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 values.

Pregnancy 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.