DOBUTAMINE

Dobutamine Injection USP is (±)-4-[2-[[3-( p -Hydroxyphenyl)-1-methylpropyl]amino]ethyl]-pyrocatechol hydrochloride. It is a synthetic catecholamine. Molecular Formula: C 18 H 23 NO 3 •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 metabisulfite 0.26 mg, 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). structure

Dobutamine 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 risk of hospitalization and death. Patients with NYHA Class IV symptoms appeared to be at particular risk.

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 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 Patient Body Weight (kg) (mcg/kg/min) 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 Patient Body Weight (kg) (mcg/kg/min) 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 Patient Body Weight (kg) (mcg/kg/min) 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.

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

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 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. Reactions at Sites of Intravenous Infusion Phlebitis 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 adult patients: nausea, headache, anginal pain, nonspecific 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 ).

Animal studies indicate that dobutamine may be ineffective if the patient has recently received a ß-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.