DOBUTAMINE

Dobutamine Injection, USP is a clear, practically colorless, sterile, nonpyrogenic solution of dobutamine hydrochloride for intravenous use only. Each milliliter contains 12.5 mg (41.5 µmol) dobutamine, as the hydrochloride and sodium metabisulfite, 0.2 mg added as antioxidant. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. pH is 3.3 (2.5 to 5.5). Dobutamine Hydrochloride, USP is chemically designated (±)-4-[2-[[3-(ρ-hydroxyphenyl)-1-methylpropyl] amino]ethyl]-pyrocatechol hydrochloride. It is a synthetic catecholamine. Molecular Weight: 337.85 Molecular Formula: C18H23NO3 • HCl STRUCTURE

INDICATIONS & USAGE Dobutamine Injection, USP 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. In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to institution of therapy with dobutamine hydrochloride.

DOSAGE & ADMINISTRATION Note − Do not add Dobutamine Injection, USP to 5% Sodium Bicarbonate Injection or to any other strongly alkaline solution. Because of potential physical incompatibilities, it is recommended that dobutamine hydrochloride not be mixed with other drugs in the same solution. Dobutamine hydrochloride 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 Injection, USP must be further diluted in an intravenous container to at least a 50 mL solution using one of the following intravenous solutions as a diluent: 5% Dextrose Injection, USP; 5% Dextrose and 0.45% Sodium Chloride Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; 10% Dextrose Injection, USP; 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, USP; or Sodium Lactate Injection, USP. Intravenous solutions should be used within 24 hours. Recommended Dosage − The rate of infusion needed to increase cardiac output usually ranged from 2.5 to 15 mcg/kg/min (see Table 1). On rare occasions, infusion rates up to 40 mcg/kg/min have been required to obtain the desired effect. Table 1 Dobutamine Infusion Rate (mL/kg/min) for Concentrations of 250, 500, and 1,000 mcg/mL Rates of infusion in mL/h for Dobutamine concentrations of 500 mcg/mL, 1,000 mcg/mL, and 2,000 mcg/mL are given in Table 2. Table 2 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. 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. DOSAGE 1 DOSAGE 2

Dobutamine hydrochloride is contraindicated in patients with idiopathic hypertrophic subaortic stenosis and in patients who have shown previous manifestations of hypersensitivity to Dobutamine Injection, USP solution.

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 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 patients: nausea, headache, anginal pain, nonspecific chest pain, palpitations, and shortness of breath. Isolated cases of thrombocytopenia have been reported. Administration of dobutamine hydrochloride, like other catecholamines, can produce a mild reduction in serum potassium concentration, rarely to hypokalemic levels (see PRECAUTIONS). Longer-Term Safety − Infusions of up to 72 hours have revealed no adverse effects other than those seen with shorter infusions.