Dobutamine

Description

DESCRIPTION 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

What Is Dobutamine Used For?

INDICATIONS AND USAGE 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.

Dosage and Administration

DOSAGE AND ADMINISTRATION 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...

Side Effects (Adverse Reactions)

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 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 ).

Drug Interactions

Drug Interactions 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.

Contraindications

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

Pregnancy and Breastfeeding

Pregnancy-Teratogenic Effects-Pregnancy Category B 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. 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.

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 is administered to a nursing woman. If a mother requires dobutamine treatment, breastfeeding should be discontinued for the duration of the treatment.

Overdosage

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 ß-receptor stimulation. The duration of action of dobutamine is generally short (T 1/2 = 2 minutes) because it is rapidly metabolized by catechol-0-methyltranferase. 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...

How Supplied

HOW SUPPLIED Dobutamine Injection USP, 20 mL single dose vial contains dobutamine hydrochloride, equivalent to 250 mg dobutamine per 20 mL; ten vials per carton. NDC 0143-9141-10 . Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 April 2024 PIN612-WES/2