DOBUTAMINE 12.5 mg/mL Injection, Solution, Concentrate — NDC 0409-2344-01 (Billing 00409-2344-01)

WARNINGS 1. Increase in Heart Rate or Blood Pressure Dobutamine hydrochloride may cause a marked increase in heart rate or blood pressure, especially systolic pressure. Approximately 10% of 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 promptly reverses these effects. Because dobutamine hydrochloride facilitates atrioventricular conduction, patients with atrial fibrillation are at risk of developing rapid ventricular response. Patients with pre-existing hypertension appear to face an increased risk of developing an exaggerated pressor response.

2. Ectopic Activity Dobutamine hydrochloride may precipitate or exacerbate ventricular ectopic activity, but it rarely has caused ventricular tachycardia. 3.

Hypersensitivity Reactions suggestive of hyper-sensitivity associated with administration of Dobutamine Injection, USP, including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally. 4. Dobutamine Injection, USP contains sodium metabisulfite, 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.

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.

PRECAUTIONS General 1. During the administration of Dobutamine Injection, USP, as with any adrenergic agent, ECG and blood pressure should be continuously monitored. In addition, pulmonary wedge pressure and cardiac output should be monitored whenever possible to aid in the safe and effective infusion of dobutamine hydrochloride.

2. Hypovolemia should be corrected with suitable volume expanders before treatment with dobutamine hydrochloride is instituted. 3.

No improvement may be observed in the presence of marked mechanical obstruction, such as severe valvular aortic stenosis. Usage Following Acute Myocardial Infarction − Clinical experience with dobutamine hydrochloride following myocardial infarction has been insufficient to establish the safety of the drug for this use. There is concern that any agent that increases contractile force and heart rate may increase the size of an infarction by intensifying ischemia, but it is not known whether dobutamine hydrochloride does so.

Laboratory Tests – Dobutamine, like other β 2 -agonists, can produce a mild reduction in serum potassium concentration, rarely to hypokalemic levels. Accordingly, consideration should be given to monitoring serum potassium. 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility – Studies to evaluate the carcinogenic or mutagenic potential of dobutamine hydrochloride, or its potential to affect fertility, have not been conducted. Pregnancy – Teratogenic Effects − Reproduction studies performed in rats at doses up to the normal human dose (10 mcg/kg/min for 24 h, total daily dose of 14.4 mg/kg), and in rabbits at doses up to twice the normal human dose, have revealed no evidence of harm to the fetus due to dobutamine hydrochloride. There are, however, no adequate and well-controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Labor and Delivery – The effect of dobutamine hydrochloride on labor and delivery is unknown. Nursing Mothers – It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when dobutamine hydrochloride is administered to a nursing woman. If a mother requires dobutamine hydrochloride treatment, breastfeeding should be discontinued for the duration of treatment. Pediatric Use – The safety and effectiveness of Dobutamine Injection, USP for use in pediatric patients have not been studied.