Dobutamine Hydrochloride Injection

DOBUTAMINE HYDROCHLORIDE INJECTION

Novopharm

Inotropic

Action And Clinical Pharmacology: Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the b-receptors of the heart while producing less marked chronotropic, hypertensive, arrhythmogenic or vasodilatory effects. Dobutamine, unlike dopamine, does not cause the release of endogenous norepinephrine. No specific effect on the renal vasculature was observed. Dobutamine produces less increase in heart rate and less decrease in peripheral vascular resistance for a given inotropic effect than does isoproterenol as demonstrated in both animal and human studies.

The onset of action occurs within 1 to 2 minutes while the peak effect of a particular infusion may not be reached for 10 minutes. The plasma half-life in humans is 2 minutes.

Indications And Clinical Uses: In the treatment of adults with cardiac decompensation due to depressed contractility resulting from organic heart disease or following cardiac surgical procedures in which parenteral therapy is necessary for inotropic support.

Most clinical experience with dobutamine is short-term – up to several hours in duration. In the limited number of patients who were studied for 24, 48, and 72 hours, a persistent increase in cardiac output occurred in some, whereas the output of others returned toward base-line values.

Contra-Indications: Patients with idiopathic hypertrophic subaortic stenosis, in patients with pheochromocytoma, and in those patients with hypersensitivity to dobutamine.

Manufacturers’ Warnings In Clinical States: Dobutamine may cause a marked increase in blood pressure, especially systolic pressure or in heart rate. About 10% of patients in clinical studies have had rate increases of 30 beats/minute or more, while about 7.5% have had a 50 mmHg or greater increase in systolic pressure. There appears to be an increased risk in patients with pre-existing hypertension of developing an exaggerated pressor response. A reduction of dosage usually results in a prompt reversal of these effects.

Dobutamine may exacerbate or precipitate ventricular ectopic activity but has rarely caused ventricular tachycardia.

Following the administration of dobutamine, reactions suggestive of hypersensitivity including skin rash, fever, eosinophilia, and bronchospasm have been reported occasionally. Dobutamine injection contains sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms, in certain susceptible people.

A digitalis preparation should be used prior to instituting therapy with dobutamine in patients who have atrial fibrillation with rapid ventricular response. Patients with atrial fibrillation are at risk of developing rapid ventricular response because dobutamine facilitates atrioventricular conduction.

Dobutamine should not be used in the presence of ventricular fibrillation or uncorrected tachycardia.

There may be no improvement observed following dobutamine administration to patients with marked mechanical obstruction such as severe valvular aortic stenosis.

Minimal vasoconstriction has occasionally been observed, most notably in patients recently treated with a b-blocking drug. The inotropic effect of dobutamine is prevented by b-blocking drugs because the effect stems from stimulation of cardiac b1 receptors.

Precautions: General: During the administration of dobutamine, ECG, heart rate and blood pressure should be continuously monitored, as with any adrenergic agent. In addition, monitoring of cardiac output and pulmonary wedge pressure should be performed whenever possible to aid in the safe and effective infusion of dobutamine injection.

Caution should be exercised in order to prevent infiltration at the injection site.

Hypovolemia should be corrected with suitable volume expanders prior to the initiation of treatment with dobutamine.

Caution should be exercised when using dobutamine in patients with hyperthyroidism.

Dobutamine should be used with caution in patients receiving anesthetic agents such as halogenated hydrocarbons, or cyclopropane.

Dobutamine should be used with caution in patients taking concomitantly other sympathomimetic amines.

Dobutamine can produce a mild reduction in serum potassium concentration, like other b2-agonists, but rarely to hypokalemic levels. Accordingly serum potassium levels should be considered for monitoring.

Use Following Acute Myocardial Infarction: Clinical experience with dobutamine following myocardial infarction has been insufficient to establish the safety of this use. There is concern that any agent which increases contractile force and heart rate, such as dobutamine, may increase the size of an infarction by intensifying ischemia, but whether dobutamine does so or not is not known.

Pregnancy: Reproduction studies performed in rats and rabbits that have received dobutamine have revealed no evidence of impaired fertility or harm to the fetus. The drug has not been administered to pregnant women to date and should be used in such patients only when the expected benefits clearly outweigh the potential risks to the mother and fetus.

Children: Both the efficacy and safety of dobutamine for use in children have not been established.

Drug Interactions: Clinical 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.

No evidence of drug interactions was noted in clinical studies when dobutamine was administered concurrently with other drugs including furosemide and/or digitalis preparations, spironolactone, lidocaine, isosorbide dinitrate, glyceryl trinitrate, atropine, morphine, anticoagulants and potassium chloride supplements.

Adverse Reactions: Cardiovascular: The most common adverse reactions relate to the effect of dobutamine on the cardiovascular system.

An increase in heart rate of 5 to 15 beats/minute and a 10 to 20 mmHg increase in systolic blood pressure have been noted in most patients. (see Warnings regarding exaggerated chronotropic and pressor effects). About 5% of patients have had increased premature ventricular beats during infusions. These effects were dose-related.

Hypotension: There have been reports of precipitous decreases in blood pressure associated with dobutamine therapy. A reduction in dose or discontinuation of the drug is necessary to return the blood pressure to baseline levels. In some cases pressor support may be required.

Less commonly occurring effects relating to the cardiovascular system include, cardiac awareness, transient bigeminy, bradycardia, angina, nonspecific chest pain, palpitations, and shortness of breath.

Gastrointestinal: nausea, vomiting and bad taste.

CNS: headache, fatigue, anxiety, and paresthesia.

Hypersensitivity: rash, fever, eosinophilia and bronchospasm have been reported occasionally.

Miscellaneous: dyspnea, thrombocytopenia, pruritus, chill, and sweating were observed rarely. Phlebitis has been occasionally reported. Local inflammatory changes following inadvertent infiltration have also been reported.

Administration of dobutamine, like other catecholamines, has been associated with decreases in serum potassium concentrations, but rarely to hypokalemic values.

Long-Term Safety: Infusions of up to 72 hours have revealed no adverse effects other than those seen with shorter infusions.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: In case of overdosage, as evidenced by tachycardia or excessive blood pressure alteration, reduce the rate of administration, or temporarily discontinue dobutamine until the patient’s condition stabilizes. No additional remedial measures are usually necesssary because the duration of action of dobutamine is short.

Dosage And Administration: Note: Dobutamine is a potent drug. It is not for direct injection and must be diluted exactly as directed before administration to patients as an i.v. infusion (see Precautions).

The rate of infusion needed to increase cardiac output usually ranges from 2.5 to 10 µg/kg/min (see Table I). Some patients may respond to doses as low as 0.5 µg/kg/min whereas, on rare occasions, infusion rates up to 40 µg/kg/min have been required to obtain the desired effect.

Dobutamine is incompatible with alkaline solutions and should not be mixed with products such as 5% Sodium Bicarbonate Injection. Because of the occurrences of physical incompatibilities with some drugs and the potential for incompatibility with other drugs, it is recommended that dobutamine injection not be mixed with other drugs in the same solution. Dobutamine injection should not be used in conjunction with other agents or diluents containing both sodium bisulfite and ethanol.

Dobutamine injection must be further diluted at the time of administration to at least 50 mL prior to administration in an i.v. container with one of the following i.v. solutions: 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Sodium Lactate Injection. I.V. solutions should be used within 24 hours of preparation.

Solutions containing dobutamine may exhibit a color that, if present, will increase with time. This color change is due to slight oxidation of the drug, but there is no significant loss of potency during the reconstituted time periods stated above.

The diluted solution should be inspected visually for discoloration and particulate matter prior to administration. Discard unused portion.

The final volume administered should be determined by the fluid requirements of the patient.

The rate of administration and 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.

Availability And Storage: Each mL contains: dobutamine (as HCl) 12.5 mg. Nonmedicinal ingredients: sodium bisulfite 0.28 mg and water for injection. Sodium hydroxide and/or hydrochloric acid may be used for pH adjustment. Vials of 20 mL, cartons of 10. Store at room temperature (15 to 30°C).

DOBUTAMINE HYDROCHLORIDE INJECTION Novopharm Inotropic

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