DOBUTAMINE

INDICATIONS AND 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 AND 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 Drug Delivery Rate Infusion Delivery Rate 250 mcg/mL 250 mcg/mL of diluent 500 mcg/mL 500 mcg/mL or 250 mg/500 mL of diluent 1,000 mcg/mL 1,000 mcg/mL or 250 mg/250 mL of diluent (mcg/kg/min) (mL/kg/min) (mL/kg/min) (mL/kg/min) 2.5 0.01 0.005 0.0025 5 0.02 0.01 0.005 7.5 0.03 0.015 0.0075 10 0.04 0.02 0.01 12.5 0.05 0.025 0.0125 15 0.06 0.03 0.015 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 Drug Delivery Rate (mcg/kg/min) Dobutamine Infusion Rate (mL/h) for 500 mcg/mL concentration Patient Body Weight (kg) 30 40 50 60 70 80 90 100 110 2.5 9 12 15 18 21 24 27 30 33 5 18 24 30 36 42 48 54 60 66 7.5 27 36 45 54 63 72 81 90 99 10 36 48 60 72 84 96 108 120 132 12.5 45 60 75 90 105 120 135 150 165 15 54 72 90 108 126 144 162 180 198 Drug Delivery Rate (mcg/kg/min) Dobutamine Infusion Rate (mL/h) for 1,000 mcg/mL concentration Patient Body Weight (kg) 30 40 50 60 70 80 90 100 110 2.5 4.5 6 7.5 9 10.5 12 13.5 15 16.5 5 9 12 15 18 21 24 27 30 33 7.5 13.5 18 22.5 27 31.5 36 40.5 45 49.5 10 18 24 30 36 42 48 54 60 66 12.5 22.5 30 37.5 45 52.5 60 67.5 75 82.5 15 27 36 45 54 63 72 81 90 99 Drug Delivery Rate (mcg/kg/min) Dobutamine Infusion Rate (mL/h) for 2000 mcg/mL concentration Patient Body Weight (kg) 30 40 50 60 70 80 90 100 110 2.5 2 3 4 4.5 5 6 7 7.5 8 5 4.5 6 7.5 9 10.5 12 13.5 15 16.5 7.5 7 9 11 13.5 16 18 20 22.5 25 10 9 12 15 18 21 24 27 30 33 12.5 11 15 19 22.5 26 30 34 37.5 41 15 13.5 18 22.5 27 31.5 36 40.5 45 49.5 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.

CONTRAINDICATIONS 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.

ADVERSE REACTIONS 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.

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, nitroglycerin, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid, and acetaminophen.

DESCRIPTION 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: C 18 H 23 NO 3 • HCl structural formula dobutamine hydrochloride

OVERDOSAGE Overdoses of dobutamine have been reported rarely. The following is provided to serve as a guide if such an overdose is encountered. Signs and Symptoms − Toxicity from dobutamine is usually due to excessive cardiac β-receptor stimulation. The duration of action of dobutamine is generally short (T 1/2 = 2 minutes) because it is rapidly metabolized by catechol-O-methyltransferase. 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 hemo-perfusion have not been established as beneficial for an overdose of dobutamine.

HOW SUPPLIED/STORAGE & HANDLING DOBUTAMINE INJECTION, USP is supplied in the following dosage forms. NDC 51662-1337-1 DOBUTAMINE INJECTION, USP 250mg PER 20mL VIAL NDC 51662-1337-2 DOBUTAMINE INJECTION, USP 250mg PER 20mL VIAL in a Pouch NDC 51662-1337-3 Case of 10, DOBUTAMINE INJECTION, USP 250mg PER 20mL VIAL in a Pouch HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms Dobutamine Injection, USP is supplied in 20 mL single-dose glass vials containing 250 mg dobutamine, as the hydrochloride as follows: Store at 20 to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] HOW SUPPLIED