Consumer medicine information

DOBUTAMINE SANDOZ

Dobutamine

BRAND INFORMATION

Brand name

Dobutamine Sandoz

Active ingredient

Dobutamine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DOBUTAMINE SANDOZ.

What is in this leaflet

This leaflet answers some common questions about Dobutamine Sandoz. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Dobutamine Sandoz against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Dobutamine Sandoz is used for

The name of your medicine is Dobutamine Sandoz. It contains the active ingredient dobutamine hydrochloride.

This medicine belongs to a group of medicines called adrenergic stimulants.

This medicine is used to treat heart failure following a heart attack or heart surgery. Dobutamine Sandoz works by helping the heart to beat more strongly.

Ask your doctor if you have any questions about why this medicine has been prescribed for you Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor’s prescription.

Dobutamine Sandoz is not recommended for use in children. The safety and effectiveness of Dobutamine Sandoz in children have not been established.

Before you are given Dobutamine Sandoz

When you must not be given it

Do not use Dobutamine Sandoz if you have an allergy to dobutamine or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not use Dobutamine Sandoz if you have a heart condition known as idiopathic hypertrophic subaortic stenosis.

This medicine should not be used after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have an allergy to sodium metabisulfite.

Tell your doctor if you have or have had any medical conditions, including:

  • high or low blood pressure
  • any heart problems
  • asthma

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding or intend to breast-feed. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given Dobutamine Sandoz.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Dobutamine Sandoz may interfere with each other. These include:

  • some medicines used to treat high blood pressure.
  • some medicines used to treat heart problems
  • some anaesthetics
  • some adrenergic agents (adrenaline-like agents)

These medicines may be affected by Dobutamine Sandoz or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How Dobutamine Sandoz is given

Dobutamine Sandoz is given as a slow injection into a vein. Dobutamine Sandoz is a concentrated injection which will be diluted before being injected.

Dobutamine Sandoz will be given to you in hospital by highly trained medical personnel.

Your doctor will decide on the dose and how long you will receive Dobutamine Sandoz. This will depend on your condition, whether you are taking any other medicines and how well you respond to the medicine.

If you are given too much (overdose)

If you have been given too much Dobutamine Sandoz your doctor has information on how to recognise and treat an overdose.

If you have been given too much Dobutamine Sandoz you may experience symptoms such as loss of appetite, nausea, vomiting, tremor, anxiety, headache, shortness of breath, fast heart beat or chest pain.

However, immediately telephone your doctor or the Poisons Information Centre on 13 11 26 for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have been given too much Dobutamine Sandoz. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using Dobutamine Sandoz

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given Dobutamine Sandoz

Tell any other doctors, dentists, and pharmacists who are treating you that you are using this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine. It may affect other medicines used during surgery.

If you are about to have any blood tests tell your doctor that you are having Dobutamine Sandoz. It may interfere with the results of some tests.

If you become pregnant while using this medicine, tell your doctor immediately.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given Dobutamine Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • nausea
  • headache
  • fever
  • pain, redness or swelling at the site of the injection
  • dizziness, lightheadedness

The above list includes the more common side effects of your medicine. They are usually mild.

Tell your doctor or nurse immediately if you notice any of the of the following:

  • shortness of breath, wheezing or difficulty breathing
  • skin rash, itching or hives
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • swelling of the hands or feet
  • chest pain
  • fast heart beat
  • feeling faint
  • bleeding or bruising more easily than normal

The above list includes serious side effects which may require urgent medical attention. Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell. Other side effects not listed above may also occur in some people.

Do not be alarmed by this list of side effects. You may not experience any of them.

After using Dobutamine Sandoz

Storage

Dobutamine Sandoz will be stored on the pharmacy or on the ward in a cool dry place where the temperature stays below 25°C.

Disposal

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Dobutamine Sandoz is a clear colourless solution which is supplied in colourless glass ampoules. It is available in packs of 1, 5 or 10.

Ingredients

Each ampoule of Dobutamine Sandoz contains 250mg of the active ingredient, dobutamine, as the hydrochloride salt. It also contains:

  • sodium metabisulfite
  • sodium hydroxide
  • hydrochloric acid
  • water for injections

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 634 500

This leaflet was revised in February 2016

Australian Register Number
AUST R 82994

Published by MIMS May 2017

BRAND INFORMATION

Brand name

Dobutamine Sandoz

Active ingredient

Dobutamine

Schedule

S4

 

1 Name of Medicine

Dobutamine hydrochloride.

2 Qualitative and Quantitative Composition

The active ingredient of Dobutamine Sandoz 250 mg/20 mL (as hydrochloride) concentrated injection is Dobutamine hydrochloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dobutamine Sandoz 250 mg/20 mL Concentrated Injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults who require short-term treatment of cardiac failure secondary to acute myocardial infarction, or cardiac surgery.

4.2 Dose and Method of Administration

Dosage.

The rate of infusion needed to increase cardiac output usually ranges from 2.5 to 10 microgram/kg/minute (see Table 1). On rare occasions, infusion rates up to 40 microgram/kg/minute have been required to obtain the desired effect. However, the possibility of intensifying myocardial ischaemia should be borne in mind and the lowest effective dose infused.
The rate of administration and the duration of therapy should be adjusted according to the patient's response, as determined by the following clinical indicators: haemodynamic parameters such as heart rate and rhythm, arterial pressure and, whenever possible, cardiac output and measurements of ventricular filling pressures (central venous, pulmonary artery wedge and left atrial) and signs of pulmonary congestion and organ perfusion (urine flow, skin temperature and mental status).
Concentrations up to 5,000 microgram/mL have been administered to humans (250 mg/50 mL). The final volume administered should be determined by the fluid requirements of the patient. Rather than abruptly discontinuing therapy with dobutamine hydrochloride, it is often advisable to decrease the dosage gradually.

Method of administration.

Reconstitution and stability.

Dobutamine Sandoz solution must be diluted at the time of administration to at least 50 mL in an intravenous container with one of the following solutions: glucose 5% injection, glucose 5% and sodium chloride 0.45% injection, glucose 5% and sodium chloride 0.9% injection, glucose 10% injection, lactated Ringer's injection, Normosol-M in D5W, Osmitrol 20% in water for injection, sodium chloride 0.9% injection or sodium lactate injection.
To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2-8°C for not more than 24 hours.
Parenteral drug products which are hazy, discoloured or contain visible particulate matter should be discarded. Solutions containing Dobutamine Sandoz may exhibit a pink colour that, if present, will increase with time. This colour change is due to slight oxidation of the drug, but there is no significant loss of potency during the reconstituted time periods stated above.

Administration.

Because of its short half-life, Dobutamine Sandoz must be administered as a continuous intravenous infusion. This is most reliably accomplished using a mechanical infusion pump or controller. Following the initiation of a constant rate infusion, or upon changing the rate, a steady-state dobutamine plasma concentration is achieved within approximately ten minutes. Thus, loading doses or bolus injections are not necessary and are not recommended.

Reactions at sites of intravenous infusion.

Phlebitis has occasionally been reported. Local inflammatory changes have been described following inadvertent infiltration.

4.3 Contraindications

Idiopathic hypertrophic subaortic stenosis. Previous manifestations of hypersensitivity to dobutamine or any of the excipients.

4.4 Special Warnings and Precautions for Use

During the administration of dobutamine, as with any adrenergic agent, ECG and blood pressure should be continuously monitored. In addition, pulmonary artery wedge pressure and cardiac output should be monitored whenever possible to aid in the safe and effective infusion of dobutamine.
Hypovolaemia should be corrected with suitable volume expanders before treatment with dobutamine is instituted.
Because positive inotropic therapy can be associated with increases in intrapulmonary shunting, attention to arterial blood gases during treatment with dobutamine is recommended.
In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to instituting therapy with dobutamine.
The potency of dobutamine may be decreased if the patient is given beta-adrenergic receptor antagonists. In such a case, the unopposed alpha-agonist effects of dobutamine may become apparent, including peripheral vasoconstriction and hypertension. Conversely, alpha-adrenergic blockade may make the beta1 and beta2 effects apparent, resulting in tachycardia and vasodilatation.
No improvement may be observed in the presence of marked mechanical obstruction, such as severe valvular aortic stenosis.
Dobutamine, like other beta2-agonists, can produce a mild reduction in serum potassium concentration, rarely to hypokalaemic levels. Accordingly, consideration should be given to monitoring serum potassium.

Increase in heart rate or blood pressure.

Dobutamine 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 mmHg or greater increase in systolic pressure. Reduction of dosage usually reverses these effects promptly. Patients with pre-existing hypertension are more likely to develop an exaggerated pressor response.

Increased atrioventricular conduction.

Because dobutamine facilitates atrioventricular conduction, patients with atrial flutter or fibrillation may develop rapid ventricular responses.

Ectopic activity.

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

Hypersensitivity.

Reactions suggestive of hypersensitivity associated with the administration of dobutamine, including skin rash, fever, eosinophilia and bronchospasm, have been reported occasionally.
Dobutamine Sandoz contains sodium metabisulfite, which may cause allergic type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people.

Anaesthetics.

The myocardium may be sensitised to the effect of dobutamine by cyclopropane or halogenated hydrocarbon anaesthetics, and these should be avoided.

Use for heart failure complicating an acute myocardial infarction.

Although the treatment of heart failure and the reduction in cardiac diameter will decrease myocardial oxygen consumption, there is still concern that the use of any positive inotropic agent may increase myocardial oxygen demand and the size of an infarction by intensifying ischaemia. Pertinent clinical data with dobutamine following acute myocardial infarction are limited but suggest that dobutamine does not have an adverse effect on the myocardium when used in doses that do not cause excessive increments in heart rate or arterial pressure. The dose of dobutamine should be titrated to prevent an excessive increase in heart rate and systolic blood pressure.

Cardiac rupture as a complication of myocardial infarction.

Cardiac rupture is a potential complication of myocardial infarction. The risk of cardiac rupture (septal and free wall) may be influenced by a variety of factors including site of and time since infarct. There have been very rare, fatal reports of acute cardiac rupture during dobutamine stress testing. These events have occurred during predischarge examination in patients hospitalised with recent (within 4 to 12 days) myocardial infarction. In the reported cases of free wall rupture, resting echocardiogram showed a dyskinetic and thinned inferior wall. Patients considered at risk of cardiac rupture during dobutamine testing should therefore be carefully evaluated.

Use in the elderly.

No data available.

Paediatric use.

Safety and efficacy for use in children have not been studied.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There was no evidence of drug interactions in clinical studies in which dobutamine was administered concurrently (but by separate routes or methods of administration) with other drugs, including digitalis preparations, frusemide, spironolactone, lignocaine, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid and paracetamol.
Preliminary studies in heart failure patients 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.
Studies on limited numbers of patients with heart failure demonstrate that the combination of dobutamine and glyceryl trinitrate results in a lower pulmonary wedge pressure than when dobutamine is used alone and a higher cardiac output than when glyceryl trinitrate is used alone.
Beta-adrenergic receptor antagonists, alpha-adrenergic receptor antagonists, cyclopropane or halogenated hydrocarbon anaesthetics (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies to evaluate its potential to affect fertility, have not been conducted.
(Category B2)
Reproduction studies performed in rats (15 mg/kg intravenously) and rabbits (30 mg/kg intravenously) have revealed no evidence of impaired fertility, harm to the foetus or teratogenic effects due to dobutamine hydrochloride. Since there are no adequate and well controlled studies in pregnant women, and since animal reproduction studies are not always predictive of human response, dobutamine hydrochloride should not be used during pregnancy unless the potential benefits outweigh the potential risks to the foetus.
 It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised. If a mother requires treatment with dobutamine, breastfeeding should be discontinued for the duration of the treatment.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Many of the adverse effects of dobutamine are a quantitative extension of the pharmacological actions. The following adverse effects have been reported.

Increased heart rate, blood pressure and ventricular ectopic activity.

A 10 to 20 mmHg increase in systolic blood pressure and an increase in heart rate of 5 to 15 beats/minute have been noted in most patients. (See Section 4.4 Special Warnings and Precautions for Use). Approximately 5% of patients have had increased premature ventricular beats during infusions. These effects are dose related and their occurrence may require that the dose be reduced.

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, shortness of breath, skin rash, fever, eosinophilia and bronchospasm. Isolated cases of thrombocytopenia have been reported.
Administration of dobutamine, like other catecholamines, can produce a mild reduction in serum potassium concentrations, rarely to hypokalaemic levels (see Section 4.4 Special Warnings and Precautions for Use).
There have been rare reports of fatal cardiac rupture during dobutamine stress testing.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdoses of dobutamine have been reported rarely. The following is provided to serve as a guide if such an overdose is encountered.

Symptoms.

Toxicity from dobutamine hydrochloride is usually due to excessive cardiac beta-receptor stimulation. The duration of action of dobutamine hydrochloride is generally short (t½ = two minutes) because it is rapidly metabolised by catechol-ortho-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 ischaemia and ventricular fibrillation. Hypotension may result from vasodilatation. If the product is ingested, unpredictable absorption may occur from the mouth and the gastrointestinal tract.

Treatment.

In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient. The initial actions to be taken in a dobutamine hydrochloride 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 lignocaine. 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. 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, haemodialysis or charcoal haemoperfusion have not been established as beneficial for an overdose of dobutamine hydrochloride.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Dobutamine is a synthetic catecholamine prepared as a 50:50 racemic mix of levo and dextro enantiomers. Animal studies have demonstrated that the levo stereoisomer is a partial alpha1-agonist with modest beta2-activity. The dextro stereoisomer is a beta1- and beta2-agonist with alpha1-blocking activity. These functional adrenoreceptor profiles are consistent with dobutamine's well described potent inotropic activity and typically mild vasodilatory action. The exact role each enantiomer plays in dobutamine's observed clinical effects, however, is unknown. It produces comparatively mild chronotropic, hypertensive and arrhythmogenic effects.
In contrast with dopamine, it does not release noradrenaline and its actions are not dependent on noradrenaline stores in the heart. In animal studies, dobutamine produces less increase in heart rate and less decrease in peripheral vascular resistance for a given inotropic effect than does isoprenaline.
Pretreatment of dogs with reserpine or desmethyl imipramine does not alter the actions of dobutamine. This provides strong experimental evidence that the drug is a direct agonist.
In patients with heart failure, dobutamine increases stroke volume and cardiac output, and decreases pulmonary artery wedge pressure and total systemic and pulmonary vascular resistances. Occasionally, minimal vasoconstriction has been observed. The increased stroke volume and decreased pulmonary artery wedge pressure are consistent with a shift in the ventricular function curve upward and to the left.
Dobutamine is typically less chronotropic than other inotropic catecholamines, like dopamine and isoprenaline. Significant tachycardia, however, may occur with increasing doses of dobutamine, particularly above 10 microgram/kg/minute.
Mean arterial pressure in patients with heart failure usually is not changed significantly by dobutamine because the effect of the increase in cardiac output is balanced by the concomitant decrease in peripheral vascular resistance. Both increments and decrements in arterial blood pressure have been reported. Patients with pre-existing arterial hypertension, even those who are normotensive at the time, seem more susceptible to sustaining a pressor response.
Dobutamine does not appear to act at dopamine receptors; thus it does not selectively dilate renal or splanchnic vessels. In patients with congestive heart failure from cardiomyopathy, dobutamine may improve renal blood flow, glomerular filtration rate, urine flow and sodium excretion by increasing cardiac output and by nonselective vasodilatation.
Facilitation of atrioventricular conduction has been observed during administration of dobutamine in human electrophysiological studies in normal subjects and in patients with atrial fibrillation.
Like all positive inotropic agents, dobutamine increases myocardial oxygen consumption. Dobutamine also increases coronary blood flow and myocardial oxygen supply. The changes in oxygen demand are dependent on several factors, including the following: level of wall tension required to generate intraventricular pressure during systole; changes in afterload, generally proportional to changes in systolic blood pressure; and changes in heart rate.
When the use of a positive inotropic agent in a patient with a failing, dilated heart results in a decrease in ventricular diameter, oxygen demand need not increase, provided afterload and heart rate do not increase markedly. In general, dobutamine does not cause an imbalance between oxygen consumption and supply in either animals or humans with heart disease. The arteriovenous extraction ratio of lactic acid, and indirect evidence of unimpeded aerobic metabolism, may be reduced during administration of dobutamine. In some instances net myocardial lactate extraction has become negative. Net lactate production has been reported in a few patients; this has usually occurred in patients with severe coronary artery disease especially when heart rate and/or arterial blood pressure have increased excessively during infusion of dobutamine, or in patients who respond poorly to the drug.
Myocardial infarct size and the incidence and severity of ventricular arrhythmias were not increased in patients with acute myocardial infarction who were treated with dobutamine for 24 hours, as compared to similar patients who did not receive dobutamine. In this study, dobutamine was titrated so that heart rate did not increase by more than 10% of baseline values or to a maximum of 120 beats/minute, whichever was less; and blood pressure did not exceed 130 mmHg. In animals, administration of dobutamine shortly after the ligation of coronary arteries reduces infarct size, when compared to controls receiving saline solution or dopamine. In other animals with experimental infarction who were given dobutamine at doses that increased both heart rate and myocardial contractility, there were electrocardiographic signs of increased ischaemia.
Recent studies in animals suggest that functional deterioration and possible enlargement of experimental myocardial lesions during the administration of positive inotropic drugs, including dobutamine, is related to their chronotropic effect rather than to the positive inotropism. When dobutamine was infused in dogs at doses that produced significant inotropic effect with a minimal increase in heart rate, there was no evidence of enhanced myocardial damage.
Dobutamine has been used in combination with dopamine. In general, the combination does not increase cardiac output more than does an equivalent dose of dobutamine alone. Whereas systemic blood pressure typically does not change significantly with dobutamine alone, this can be expected to increase with the addition of dopamine. Similarly, whereas dobutamine tends to increase renal blood flow in patients with heart failure in proportion to improvement in cardiac output, the addition of dopamine in doses up to 5 microgram/kg/minute will exert a further enhancement of renal blood flow. Finally, ventricular filling pressure, which can increase with dopamine therapy alone, tends either not to change or to decrease when dobutamine is given concomitantly. Avoiding such increases in ventricular filling pressure may be beneficial to the patient at risk of pulmonary congestion and oedema.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The onset of action is within one to two minutes; however, as much as ten minutes may be required to obtain the peak effect of a particular infusion rate. Steady state plasma concentrations are linearly related to infusion rates.

Distribution.

The volume of distribution is about 20% of bodyweight.

Metabolism.

The principle routes of disposition include methylation followed by conjugation. In human urine the major excretion products are the conjugates of dobutamine and 3-O-methyl dobutamine. The 3-O-methyl derivative of dobutamine is inactive.

Excretion.

Plasma clearance of dobutamine in humans is 2.4 L/minute/m2 and plasma elimination half-life is less than three minutes. Metabolites are eliminated by renal and biliary mechanisms.
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 baseline values. Infusions of up to 72 hours have revealed no adverse effects other than those seen with shorter infusions.

5.3 Preclinical Safety Data

Genotoxicity.

Studies to evaluate the mutagenic potential of dobutamine have not been conducted.

Carcinogenicity.

Studies to evaluate the carcinogenic potential of dobutamine have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium metabisulfite, water for injections, hydrochloric acid and/or sodium hydroxide to adjust pH.

6.2 Incompatibilities

Do not add Dobutamine Sandoz to sodium bicarbonate injection 5% or to any other strongly alkaline solution. Because of potential physical incompatibilities, it is recommended 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.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Concentrated Injection: Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Dobutamine Sandoz 250 mg/20 mL Concentrated Injection, 20 mL: 1's.

6.6 Special Precautions for Disposal

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The chemical name of dobutamine hydrochloride is (+/-)-4-[2-[[3- (para-hydroxyphenyl)-1- methylpropyl]-amino]ethyl]-pyrocatechol hydrochloride. Its molecular formula is C18H23NO3HCl (Molecular Weight: 337.84).

Chemical structure.

Its chemical structure is:

CAS number.

49745-95-1.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes