Consumer medicine information

DBL Dobutamine Hydrochloride Injection

Dobutamine

BRAND INFORMATION

Brand name

DBL Dobutamine Hydrochloride Injection

Active ingredient

Dobutamine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Dobutamine Hydrochloride Injection.

What is in this leaflet

This leaflet answers some common questions about DBL Dobutamine Hydrochloride Injection.

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 being given DBL Dobutamine Hydrochloride Injection against the benefits they expect it will have for you.

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

Keep this leaflet in a safe place. You may need to read it again.

What DBL Dobutamine Hydrochloride Injection is used for

DBL Dobutamine Hydrochloride Injection is used in patients who require short-term treatment of heart failure following a heart attack or heart surgery.

DBL Dobutamine Hydrochloride Injection acts directly on the heart muscle to increase the force of each contraction.

Your doctor may have prescribed this medicine for another reason.

Ask your doctor if you have any questions about why DBL Dobutamine Hydrochloride Injection has been prescribed for you.

There is no evidence that DBL Dobutamine Hydrochloride Injection is addictive.

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

Before you are given DBL Dobutamine Hydrochloride Injection

When you must not be given it

You must not be given DBL Dobutamine Hydrochloride Injection if you have an allergy to dobutamine or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to DBL Dobutamine Hydrochloride Injection 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.

You should not be given DBL Dobutamine Hydrochloride Injection if you have any of the following medical conditions:

  • a heart condition called idiopathic hypertrophic sub aortic stenosis (a narrowing of an artery coming from the heart).

DBL Dobutamine Injection is not recommended in children as the safety and effectiveness of dobutamine in children have not been established.

If you are not sure whether you should be given DBL Dobutamine Hydrochloride Injection, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant. DBL Dobutamine Hydrochloride Injection is not recommended for use during pregnancy. If there is a need to consider dobutamine during pregnancy, your doctor will discuss with you the benefits and risks of being given it.

Tell your doctor or pharmacist if you are breast-feeding or plan to breast-feed. It is not known whether DBL Dobutamine Hydrochloride Injection passes into breast milk. Your doctor or pharmacist will discuss the possible risks and benefits of being given dobutamine while you are breast-feeding.

Tell your doctor or pharmacist if you have or have had any medical conditions, especially the following:

  • high blood pressure
  • fast or irregular heart beat
  • other heart problems.
  • low potassium levels (hypokalaemia)

If you have not told your doctor or pharmacist about any of the above, tell them before you start being given DBL Dobutamine Hydrochloride Injection.

Taking other medicines

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

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

  • some general anaesthetics, such as halothane
  • beta-blockers, a type of medication used for heart and blood pressure problems.

These medicines may be affected by DBL Dobutamine Hydrochloride Injection, or may affect how well it works. You may need different amounts of your medicine, or you may need to take or use different medicines. Your doctor or pharmacist will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while being given DBL Dobutamine Hydrochloride Injection.

How DBL Dobutamine Hydrochloride Injection is given

How much is given

Your doctor will decide what dose of dobutamine you will receive. This depends on your condition and other factors, such as your weight.

How it is given

DBL Dobutamine Hydrochloride Injection is given as a slow injection into a vein (via a ‘drip’). It must only be given by a doctor or nurse.

If you take too much (overdose)

As DBL Dobutamine Hydrochloride Injection is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any side effects after being given DBL Dobutamine Hydrochloride Injection, immediately tell your doctor or nurse or call the Poisons Information Centre (telephone 13 11 26 in Australia for advice.

Symptoms of a dobutamine overdose include the side effects listed below in the ‘Side Effects’ section, but are usually of a more severe nature.

Side effects

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

It helps most people with heart failure, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

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

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

  • nausea and vomiting
  • headache

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

  • chest pain (such as angina pain)
  • shortness of breath
  • pain or tenderness at the injection site
  • fast or irregular heart beat
  • signs of an allergic reaction, such as those listed at the start of the leaflet.
  • tremors or shaking
  • feeling anxious or nervous

These may be serious side effects. You may need urgent medical attention.

Other side effects not listed above may occur in some patients.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

After you have been given DBL Dobutamine Hydrochloride Injection

Storage

DBL Dobutamine Hydrochloride Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25C.

Product description

What it looks like

DBL Dobutamine Hydrochloride Injection is a clear, colourless or slightly yellow solution.

Ingredients

Active ingredients:

  • dobutamine hydrochloride

Other ingredients:

  • sodium metabisulfite
  • water for injection

DBL Dobutamine Hydrochloride Injection does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

DBL Dobutamine Hydrochloride Injection is supplied by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Dobutamine Hydrochloride Injection is supplied as:

  • 250 mg /20 mL vials. AUST R 46451

This leaflet was updated in:
October 2020

Published by MIMS December 2020

BRAND INFORMATION

Brand name

DBL Dobutamine Hydrochloride Injection

Active ingredient

Dobutamine

Schedule

S4

 

1 Name of Medicine

Dobutamine hydrochloride.

2 Qualitative and Quantitative Composition

Each 20 mL vial of DBL Dobutamine Hydrochloride Injection contains dobutamine hydrochloride 280.2 mg (250 mg dobutamine equivalent) and sodium metabisulfite 4.4 mg.
Dobutamine hydrochloride is a white to practically white, crystalline powder. It is sparingly soluble in water and methyl alcohol; soluble in alcohol.

Excipient with known effect.

Sodium metabisulfite.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
DBL Dobutamine Hydrochloride Injection is a sterile solution.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Dobutamine Hydrochloride Injection is indicated in 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/min (see Table 1). On rare occasions, infusion rates up to 40 microgram/kg/min 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 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 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.

Method of administration.

DBL Dobutamine Hydrochloride Injection must be diluted to at least 50 mL at the time of administration in 5% glucose injection or 0.9% sodium chloride injection. Although chemically stable for 24 hours, prepared solutions should be used immediately after dilution.
Do not add DBL Dobutamine Hydrochloride Injection to 5% sodium bicarbonate injection or any other strongly alkaline solutions. Dobutamine hydrochloride should not be used in conjunction with other agents or diluents containing sodium bisulfite.

4.3 Contraindications

DBL Dobutamine Hydrochloride Injection is contraindicated in patients with idiopathic hypertrophic subaortic stenosis and previous hypersensitivity to dobutamine.

4.4 Special Warnings and Precautions for Use

Increase in heart rate or blood pressure.

Dobutamine may cause a marked increase in heart rate or blood pressure, especially systolic pressure. Approximately 10 percent of patients in clinical studies have had rate increases of 30 beats/minute or more, and about 7.5 percent have had a 50 mmHg or greater increase in systolic pressure. Reduction of dosage usually reverses these effects promptly. Because dobutamine 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.

Ectopic activity.

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

Anaesthetics.

The myocardium may be sensitised to the effect of dobutamine by cyclopropane or halogenated hydrocarbon anaesthetics, and these should be avoided.
DBL Dobutamine Hydrochloride Injection solution contains sodium metabisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people.
During the administration of dobutamine, 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.
Hypovolaemia should be corrected with suitable volume expanders before treatment with dobutamine is instituted.
In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to instituting therapy with dobutamine.
Animal studies indicate that dobutamine may be ineffective if the patient has recently received a beta-blocking drug. In such a case, the peripheral vascular resistance may increase.
No improvement may be observed in the presence of marked mechanical obstruction, such as severe valvular aortic stenosis.
There is concern that any agent which increases contractile force and heart rate may increase the size of an infarction by intensifying ischaemia but it is not known whether dobutamine does so in man. However, animal studies have shown that massive doses of 30 mg/kg/min infused for 72 hours have produced irreversible myocardial damage.
Dobutamine, like other beta-agonists, can produce a mild reduction in serum potassium concentration, rarely to hypokalemic levels. Accordingly, consideration should be given to monitoring serum potassium.

Use in the elderly.

No data available.

Paediatric use.

The safety and efficacy of dobutamine for use in children have not been studied.

Effects on laboratory tests.

No abnormal laboratory values attributable to dobutamine have been observed.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There was no evidence of interactions with other medicines in clinical studies in which dobutamine was administered concurrently with other medicines, including digitalis preparations, frusemide, spironolactone, lignocaine, glyceryl trinitrate, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid and paracetamol. 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 medicine is used alone.
Beta-blocker therapy, cyclopropane or halogenated hydrocarbon anaesthetics.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
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 fetus.
 It is not known if dobutamine is distributed into breast milk. The decision of whether or not to treat lactating women with dobutamine should take into account the potential harmful effects to the infant.

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 per minute have been noted in most patients (see Section 4.4 Special Warnings and Precautions for Use regarding exaggerated chronotropic and pressure effects). Approximately 5 percent 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.

Miscellaneous uncommon effects.

The following adverse effects have been reported in 1 to 3 percent of 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 hypokalaemic levels.
Hypersensitivity reactions including rash, fever, eosinophilia and bronchospasm.
As with other catecholamines, decreases in serum potassium concentrations have occurred, rarely to hypokalaemic levels (see Section 4.4 Special Warnings and Precautions for Use).

Reaction at site of intravenous infusion.

Phlebitis has occasionally been reported. Local inflammatory changes have been described following inadvertent infiltration. Isolated cases of cutaneous necrosis have been reported.

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.

Signs and 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 = 2 minutes) because it is rapidly metabolised 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.
If the product is ingested, unpredictable absorption may occur from the mouth and the gastrointestinal tract.

Treatment.

Because the duration of action of dobutamine is short, reducing the rate of administration or temporarily discontinuing dobutamine therapy until the patient's condition stabilises is usually adequate. However, 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. 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 hemoperfusion have not been established as beneficial for an overdose of dobutamine hydrochloride.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Dobutamine hydrochloride is an inotropic agent whose primary activity results from stimulation of the beta-receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic and vasodilative effects. The drug is believed to be a direct agonist which, in animal studies, produces less increase in heart rate and less decrease in peripheral vascular resistance for a given inotropic effect than does isoprenaline.
In patients with depressed cardiac function, both dobutamine and isoprenaline increase the cardiac output to a similar degree. In the case of dobutamine, this increase is usually not accompanied by marked increases in heart rate (although tachycardia is occasionally observed), and the cardiac stroke volume is usually increased. In contrast, isoprenaline increases the cardiac index primarily by increasing the heart rate while stroke volume changes little or declines.
Facilitation of atrioventricular conduction has been observed in human electrophysiological studies in normal subjects and in patients with atrial fibrillation.
Systemic vascular resistance is usually decreased with administration of dobutamine. Occasionally, minimal vasoconstriction has been observed.
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.

Clinical trials.

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. Infusions of up to 72 hours have revealed no adverse effects other than those seen with shorter infusions.

5.2 Pharmacokinetic Properties

Metabolism.

The plasma half-life of dobutamine in humans is two minutes. The major routes of metabolism are methylation of the catechol and conjugation.

Excretion.

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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium metabisulfite, water for injections.

6.2 Incompatibilities

Dobutamine is incompatible with alkaline solutions such as sodium bicarbonate 5%.
Do not add DBL Dobutamine Hydrochloride Injection to 5% sodium bicarbonate injection or any other strongly alkaline solutions. Dobutamine hydrochloride should not be used in conjunction with other agents or diluents containing sodium bisulfite.

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

Store below 25°C. Protect from light.

Compatibilities.

DBL Dobutamine Hydrochloride Injection when diluted to 250 microgram/mL and 500 microgram/mL with 0.9% sodium chloride injection and 5% glucose injection, was found to be stable for 24 hours at room temperature and in the presence of fluorescent light.

6.5 Nature and Contents of Container

DBL Dobutamine Hydrochloride Injection (250 mg/20 mL) is available in single vial.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: (RS)-4-[2- [[3-(4-hydroxyphenyl)-1 -methylpropyl]amino]-ethyl] benzene-1,2-diol hydrochloride.
Molecular formula: C18H25NO3.HCl.
Molecular weight: 337.9.

CAS number.

49745-95-1.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes