Dobutamine sandoz

Package leaflet: Information for the user

Dobutamin Sandoz, 250 mg, powder for solution for infusion
Dobutaminum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

1. What Dobutamin Sandoz is and what it is used for
2. Important information before using Dobutamin Sandoz
3. How to use Dobutamin Sandoz
4. Possible side effects
5. How to store Dobutamin Sandoz
6. Contents of the package and other information

1. What Dobutamin Sandoz is and what it is used for

Dobutamin Sandoz contains the active substance dobutamine, which acts on the heart muscle, increasing the force of its contraction.
Dobutamin Sandoz is used:

• in adults, when it is necessary to increase the force of contraction of the heart muscle in patients with myocardial infarction, heart diseases, after heart surgery, or during shock;
• in children (from newborns to 18 years of age), when it is necessary to increase the force of contraction of the heart muscle in patients with decompensated heart failure, after heart surgery, with heart muscle diseases, and in shock.

2. Important information before using Dobutamin Sandoz

When not to use Dobutamin Sandoz
if the patient:

• is allergic to dobutamine or mannitol;
• has phaeochromocytoma;
• is taking medicines from the group known as monoamine oxidase inhibitors (MAOIs).

Warnings and precautions
Talk to your doctor before starting treatment.
Exercise caution if:

• the patient has acute myocardial infarction,
• the patient has undergone heart transplantation,
• the patient suffers from asthma,
• the patient has heart disease, including unstable ischaemic heart disease,
• the patient has high blood pressure,
• the patient has severe hypotension due to cardiogenic shock,
• the patient's condition does not allow for significant physical exertion.

Before administering dobutamine, the doctor will, if necessary, correct hypovolaemia (insufficient blood volume in the circulatory system) by administering whole blood or plasma.

Cases of sudden drop in blood pressure have been reported occasionally during treatment with dobutamine.

If excessive increase in heart rate, rise in systolic blood pressure or occurrence of cardiac arrhythmias occurs, the doctor will reduce the dose of dobutamine or temporarily discontinue the drug.

In heart failure associated with acute or chronic myocardial ischaemia, the doctor will monitor the patient's cardiac function and blood pressure during dobutamine treatment.

Children
Tachycardia and increased blood pressure occur more frequently and are more pronounced in children than in adults. There are reports of reduced cardiovascular responsiveness to dobutamine in newborns, and the blood pressure-lowering (hypotensive) effect appears to be observed more often in adults than in young children. Therefore, the doctor will closely monitor dobutamine administration in children.

Dobutamin Sandoz and other medicines
Inform your doctor about all medicines currently used or recently taken, as well as any medicines the patient plans to use. This also includes medicines available without a prescription.

Dobutamin Sandoz and other concomitantly administered medicines may interact and affect each other's actions and the occurrence of adverse effects.

Be sure to inform your doctor if the patient is taking any of the following medicines:

• beta-blocking agents (medicines used in the treatment of hypertension and certain heart conditions);
• glyceryl trinitrate, sodium nitroprusside (vasodilating medicines);
• dopamine;
• monoamine oxidase inhibitors (MAOIs).

If the patient is to undergo a procedure under general anaesthesia, it is essential to inform the anaesthesiologist about dobutamine treatment.

If in doubt about which medicines are listed or whether the patient is taking them, consult a doctor, pharmacist, or nurse.

Pregnancy and breastfeeding

If a woman is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.

Pregnancy
There is insufficient evidence on the safety of dobutamine use during pregnancy in humans. It is not known whether dobutamine crosses the placenta. The medicine may be used in pregnant women only if the potential benefits to the mother outweigh the risks to the foetus and if no safer alternative treatment is available.

Breastfeeding
It is not known whether dobutamine passes into human milk; therefore, caution should be exercised. If dobutamine treatment is necessary during breastfeeding, interruption of breastfeeding during treatment is recommended.

Driving and operating machinery
Patients in whom this medicine impairs psycho-physical performance should not drive vehicles or operate machinery.

3. How to use Dobutamin Sandoz

Dobutamin Sandoz is intended exclusively for use in a hospital setting under the close supervision of a physician.
The medicine may only be administered by qualified medical personnel.
The medicine is given exclusively by intravenous infusion (via drip).
The dosage of dobutamine is determined individually by the physician for each patient.
Detailed instructions are provided at the end of this leaflet, in the section intended for healthcare professionals.
The duration of treatment depends on the patient's clinical condition.
Administration of a dose higher than recommended of Dobutamin Sandoz
Since the medicine is administered by a doctor or nurse, it is unlikely that an excessive dose will be given.
However, if the patient feels that they have received too much medicine and experiences nausea, vomiting, loss of appetite, tremor, anxiety, palpitations, headache, chest pain, or shortness of breath, the doctor or nurse should be informed immediately.
Management in case of overdose is described at the end of the leaflet, in the section intended for healthcare professionals.
If you have any further questions regarding the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
The following adverse reactions may occur:

Very common adverse reactions (may occur in more than 1 in 10 people):

• Increased heart rate

Common adverse reactions (may occur in less than 1 in 10 people):

• Increased number of eosinophils in the blood, inhibition of platelet aggregation, headache, increased or decreased blood pressure, ventricular arrhythmias, extrasystoles, increased ventricular rate in patients with atrial fibrillation, vasoconstriction, angina pectoris, palpitations, bronchospasm, dyspnoea, nausea, rash, chest pain, increased frequency of urination, fever, phlebitis at the injection site, local inflammatory reaction due to inadvertent extravasation of the medicine

Uncommon adverse reactions (may occur in less than 1 in 100 people):

• Ventricular tachycardia, ventricular fibrillation

Very rare adverse reactions (may occur in less than 1 in 10,000 people):

• Decreased potassium levels in the blood (hypokalaemia), slowed heart rate (bradycardia), myocardial ischaemia, myocardial infarction, cardiac arrest, petechial haemorrhage, skin necrosis

Frequency not known (cannot be estimated from the available data):

• Decreased blood pressure in the pulmonary vessels, motor restlessness, sensation of heat and anxiety, disturbances in heart muscle function (stress-induced cardiomyopathy, also known as takotsubo syndrome), manifesting as chest pain, dyspnoea, dizziness, fainting, and irregular heartbeat, occurring during dobutamine use in stress echocardiography.

Children and adolescents
Adverse reactions in children include: increased systolic blood pressure, systemic hypertension or hypotension, increased heart rate (tachycardia), headache, increased pulmonary artery wedge pressure leading to pulmonary congestion and oedema, and associated symptoms.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Dobutamin Sandoz

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the stated month.
Store below 25 °C. Keep in the original packaging to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to safely dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Dobutamin Sandoz contains
The active substance is dobutamine. One vial contains 250 mg of dobutamine in the form of 280 mg
of dobutamine hydrochloride and mannitol.
What Dobutamin Sandoz looks like and contents of the pack
The pack consists of 1 vial with a rubber stopper and aluminium cap, placed in a cardboard box.
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl, Austria
Manufacturer
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany
For further information, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00

Information intended exclusively for healthcare professionals

Special warnings and precautions for use
If excessive increase in heart rate, systolic blood pressure elevation, or cardiac arrhythmias occur, the dose of dobutamine should be reduced or its administration temporarily discontinued.
Dobutamine may induce or exacerbate ventricular extrasystoles and rarely cause ventricular tachycardia or ventricular fibrillation. Since dobutamine facilitates atrioventricular conduction, a rapid ventricular response may develop in patients with atrial flutter or atrial fibrillation.
Particular caution is required when administering dobutamine to patients with acute myocardial infarction, as any significant increase in heart rate or excessive rise in arterial pressure may worsen myocardial ischemia and provoke angina pectoris as well as ST-segment elevation.
Inotropic agents, including dobutamine, do not improve hemodynamic parameters in most patients with mechanical obstruction impairing ventricular filling, ventricular outflow, or both. In patients with markedly reduced ventricular compliance, the inotropic response may be inadequate. This applies to cardiac tamponade, aortic valve stenosis, and idiopathic hypertrophic subaortic stenosis.
Occasionally, mild peripheral vasoconstriction has been observed, mainly in patients previously treated with beta-blockers before receiving dobutamine. The inotropic effect of dobutamine results from stimulation of cardiac beta-1 receptors and is antagonized by beta-blockers. It has been shown that dobutamine counteracts the cardiodepressive effects of beta-blocking drugs, but beta-1 and beta-2 adrenergic receptor blockade may lead to tachycardia and vasodilation.
During treatment with dobutamine, as with any parenterally administered catecholamine, heart rate, rhythm regularity, arterial blood pressure, and infusion rate must be closely monitored. Initial ECG monitoring is recommended until a stable therapeutic response is achieved.
Cases of sudden arterial hypotension have been reported occasionally in association with dobutamine therapy. Reducing the dose or discontinuing the infusion usually results in a rapid return of blood pressure to baseline values. However, in rare cases, medical intervention may be necessary, and blood pressure normalization may not occur quickly.
Dobutamine should be used cautiously in patients with severe hypotension in cardiogenic shock (mean arterial pressure below 70 mmHg).
Before administering dobutamine, hypovolemia should be corrected if necessary by administration of whole blood or plasma.
If arterial blood pressure remains low or continues to decrease despite adequate left ventricular filling pressure and cardiac output during dobutamine therapy, concomitant administration of peripheral vasoconstricting agents such as dopamine or noradrenaline may be considered.
During dobutamine treatment, local increases or decreases in coronary flow may occur, altering myocardial oxygen demand.
In patients with severe coronary artery disease, clinical symptoms may worsen, especially if tachycardia and/or increased arterial blood pressure occur during dobutamine therapy. Therefore, the indication for dobutamine use should be carefully evaluated in every patient with myocardial ischemia.
In heart failure associated with acute or chronic myocardial ischemia, significant increases in heart rate and/or arterial blood pressure should be avoided during dobutamine administration. Provocation of myocardial ischemia cannot be excluded, particularly in cases of relatively preserved ventricular function.
Dopamine is the drug of choice in the treatment of cardiogenic shock characterized by heart failure and reduced arterial blood pressure, as well as in septic shock.
In patients with impaired left ventricular function, elevated left ventricular filling pressure, and increased peripheral resistance, adding dobutamine to ongoing dopamine therapy is recommended.

Children and adolescents
Dobutamine has been administered to children with reduced cardiac output and hypoperfusion states due to decompensated heart failure following cardiothoracic surgery, cardiomyopathy, cardiogenic or septic shock. Some hemodynamic effects of dobutamine hydrochloride may differ quantitatively and qualitatively between children and adults. Tachycardia and increased arterial pressure occur more frequently and are more pronounced in children. Pulmonary capillary wedge pressure may not decrease as in adults but may even increase, especially in infants under 1 year of age. There are reports of reduced cardiovascular system sensitivity to dobutamine in neonates, and the hypotensive effect appears to be observed more frequently in adults than in young children. Therefore, dobutamine use in children should be carefully monitored, considering the above pharmacodynamic characteristics.

Dosage and method of administration
Dobutamine dosage should be individually adjusted for each patient.

Adults
In most patients, the desired response is achieved with a dobutamine dose of 2.5 to 10 micrograms/kg body weight/min. Dobutamine has occasionally been used at doses up to 40 micrograms/kg body weight/min.

Children and adolescents
In children of all age groups (from neonates to 18 years of age), an initial dose of 5 micrograms/kg body weight/min is recommended, adjusted according to clinical response within the range of 2 to 20 micrograms/kg body weight/min. Occasionally, a response is achieved with a low dose of 0.5 to 1.0 microgram/kg body weight/min. It has been demonstrated that the minimal effective doses in children are higher than in adults. Particular caution is required when using higher doses of dobutamine, as the maximum tolerated doses in pediatric treatment are lower than those used in adults. Most adverse effects (especially tachycardia) have been observed after administration of dobutamine at doses equal to or greater than 7.5 micrograms/kg body weight/min. Rapid resolution of adverse effects can be achieved by reducing the infusion rate or discontinuing the infusion.
Among pediatric patients, there is considerable variability in both the plasma concentration of dobutamine required to elicit a hemodynamic response (threshold) and the rate of hemodynamic response to increasing plasma concentration, indicating that the required dose cannot be predetermined and must be established considering the likely narrower therapeutic range compared to adults.

The following tables show the relationship between infusion rate and drug dosage.

Administration using syringe infusion pumps
Solution of 250 mg dobutamine (1 vial) in 50 ml*

* When using a twice higher concentration of dobutamine, i.e. 500 mg (2 vials) of dobutamine
in 50 ml of solvent, the infusion rate given in the table should be halved.
Administration using volumetric (drop) infusion devices
Solution of 250 mg dobutamine (1 vial) in 500 ml*

* When using a twice higher concentration of dobutamine, i.e. 500 mg (2 vials) of dobutamine in 500 ml of solvent or 250 mg of dobutamine in 250 ml of solvent, the infusion rate given in the table should be halved.
Method of administration
Due to its short half-life, dobutamine should be administered as a continuous intravenous infusion.
The desired intravenous infusion rate of dobutamine depends on the patient's response and the occurrence of adverse effects.
During administration of Dobutamin Sandoz, heart rate and rhythm, arterial blood pressure, urine output, and infusion rate should be carefully monitored. Whenever possible, cardiac output, central venous pressure, and pulmonary capillary wedge pressure should also be monitored during treatment. The duration of treatment depends on the patient's clinical condition.
Dobutamine should be discontinued by gradually reducing the administered dose.
Method of administration in children
To administer the medicinal product as a continuous infusion using an infusion pump, the solution should be diluted with 5% glucose solution or 0.9% sodium chloride solution to achieve a dobutamine concentration of 0.5 to 1 mg/ml (up to a maximum of 5 mg/ml when fluid volume must be limited). Administration of solutions with higher concentrations is permitted only via a central venous access.
The dobutamine infusion solution is incompatible with solutions containing carbonates and other strongly alkaline solutions.
Use in neonates under intensive medical care
Dilute a dose of 30 mg/kg body weight to a final volume of 50 ml of infusion solution. An infusion rate of 0.5 ml per hour provides a dose of 5 micrograms/kg body weight/minute.
Management in case of overdose
Dobutamine is rapidly metabolized and has a short duration of action (serum half-life is 2 to 3 minutes).
In case of overdose, the intravenous infusion should be stopped immediately. If necessary, supportive measures should be initiated under conditions of intensive medical supervision. Parameters of blood gas analysis and serum electrolyte concentrations should be monitored.
In cases of severe ventricular arrhythmias, lidocaine or beta-adrenergic blocking agents (e.g., propranolol) may be administered.
Angina pectoris should be treated with sublingual nitrate and (or) a beta-adrenergic blocking agent with the shortest possible duration of action administered intravenously (such as esmolol).
In cases of reactions associated with increased arterial blood pressure, it is usually sufficient to reduce the dose or stop the infusion.
Following accidental oral ingestion, absorption from the oral cavity or gastrointestinal tract is difficult to predict. After accidental oral intake, absorption may be reduced by administering activated charcoal, which is often more effective than emetics or gastric lavage.
In cases of dobutamine overdose, forced diuresis, peritoneal dialysis, hemodialysis, or hemoperfusion through carbon filters have not demonstrated benefit.
Pharmaceutical incompatibilities
Dobutamin Sandoz must not be mixed with the following substances:
alkaline solutions (e.g., sodium bicarbonate), solutions containing sodium metabisulfite and ethanol, acyclovir, aminophylline, bretylium, calcium chloride, calcium gluconate, cefamandole formate, sodium cephalothinate, sodium cefazolin, diazepam, digoxin, sodium ethacrynate, furosemide, sodium heparin, sodium succinate hydrocortisone, insulin, potassium chloride, magnesium sulfate, penicillin, phenytoin, streptokinase, and verapamil.
Dobutamin Sandoz must also not be administered using medical equipment (such as needles, syringes, infusion sets) previously used for these substances.
Instructions for preparation of the medicinal product for administration
Dobutamin Sandoz is intended for use as intravenous infusions after reconstitution and dilution.
The dry substance in the vial should be dissolved in 10 ml of water for injections. If the substance does not dissolve completely, an additional 10 ml of water for injections should be added.
Saline solutions should not be used for initial dissolution of the dry substance due to possible interference with ions present in the solvent and limited solubility of dobutamine.
For piercing the vial stopper before dissolving the drug, needles with a diameter not exceeding 0.8 mm should be used. The rubber stopper should be punctured vertically to avoid detachment of fragments which could enter the prepared solution.
Immediately before administration, the solution should be diluted (in 5% glucose solution, 0.9% sodium chloride solution, or Ringer's lactate solution) to the volume in which the product will be administered. Dilution should be performed immediately before use, and the solution must be used within 24 hours.
After reconstitution in 10 ml of water for injections and dilution in one of the following solutions: 5% glucose solution, 0.9% NaCl solution, or Ringer's lactate solution, the product remains stable for up to 24 hours when stored at 15–25 °C.
From a microbiological standpoint, the solution should be used immediately unless it was prepared under conditions that exclude the risk of microbial contamination. If the solution is not used immediately after preparation, the user is responsible for storage conditions and duration.