DOBUTAMINE 250 mg Lyophilizate

Contents of the leaflet

1. Leaflet attached to the packaging: patient information
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet:
2. What is Dobutamine TZF and what is it used for
   1. Indications for use
3. Important information before using Dobutamine TZF
   1. When not to use Dobutamine TZF
   2. Warnings and precautions
   3. Children
   4. Dobutamine TZF and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
4. How to use Dobutamine TZF
   1. Recommended dose
   2. Adults
   3. Use in children and adolescents
   4. Use of a higher than recommended dose of Dobutamine TZF
   5. Missing a dose of Dobutamine TZF
5. Possible side effects
   1. Reporting side effects
6. How to store Dobutamine TZF
7. Contents of the pack and other information
   1. What Dobutamine TZF contains
   2. What Dobutamine TZF looks like and what the pack contains
   3. Packaging
   4. Marketing authorization holder and manufacturer
   5. Date of last revision of the leaflet:
   6. Information intended exclusively for healthcare professionals
   7. Method of administration
   8. Method of preparing the solution
   9. Pharmaceutical incompatibilities

Leaflet attached to the packaging: patient information

DOBUTAMINE TZF 250 mg, lyophilisate for solution for infusion
Dobutamine hydrochloride

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is Dobutamine TZF and what is it used for

Dobutamine, the active substance of Dobutamine TZF, is a synthetic catecholamine. The drug increases the strength of the heart muscle contraction, slightly accelerates heart rate and atrioventricular conduction.

Indications for use

Dobutamine is used in acute heart failure occurring in cardiogenic shock, myocardial infarction, after cardio-surgical procedures.
Children and adolescents
Dobutamine TZF is indicated in children and adolescents (from newborns to 18 years), when positive inotropic action is required in patients with reduced cardiac output in hypoperfusion states due to uncompensated heart failure after cardio-surgical procedures, in cardiomyopathy, in cardiogenic or septic shock.

2. Important information before using Dobutamine TZF

When not to use Dobutamine TZF

• If the patient is allergic to dobutamine or any of the other ingredients of this medicine (listed in section 6).
• If the patient has hypertrophic cardiomyopathy with left ventricular outflow tract obstruction.
• If the patient has a condition called hypertrophic obstructive cardiomyopathy.

Warnings and precautions

Dobutamine TZF is administered only as an intravenous infusion by appropriately qualified medical personnel. During intravenous infusion of dobutamine, medical personnel monitor heart rate and rhythm, blood pressure, ECG recording, diuresis, and infusion rate.
Dobutamine may accelerate heart rate, increase systolic blood pressure, or exacerbate arrhythmia.
In such cases, the doctor should reduce the dose of the medicine or temporarily discontinue dobutamine administration.
Dobutamine may increase ventricular ectopic beats, but ventricular tachycardia or fibrillation rarely occurs. Since dobutamine facilitates atrioventricular conduction, in patients with atrial flutter or fibrillation, a rapid ventricular response may occur.
Particular caution should be exercised when administering dobutamine to patients with myocardial infarction. Significant acceleration of heart rate or increase in blood pressure may increase myocardial ischemia and cause angina pectoris and ST-segment elevation on the electrocardiogram.
Inotropic agents, including dobutamine, do not improve hemodynamics in most patients with mechanical obstruction of ventricular filling or (and) outflow. This applies to patients with cardiac tamponade, aortic stenosis, and idiopathic hypertrophic subaortic stenosis.
In patients who received beta-adrenergic receptor blockers before dobutamine treatment, a slight peripheral vasoconstriction may occur.
The use of dobutamine as an alternative to exercise tests is not recommended in patients with unstable angina, bundle branch block, valvular heart disease, aortic outflow obstruction, or other cardiac conditions that may be inappropriate for dobutamine stress testing.
A potential complication of myocardial infarction may be heart rupture. The risk of heart rupture (septal and free wall) is influenced by factors such as the location and time of infarction.
Sometimes, during dobutamine administration, a decrease in blood pressure is observed. In such cases, usually reducing the dose of the medicine or interrupting the infusion causes a rapid increase in blood pressure to baseline values. However, occasionally, more serious medical intervention may be required, and blood pressure normalization may not be rapid.
Dobutamine should be administered with great caution to patients with significantly reduced blood pressure with cardiogenic shock (mean arterial blood pressure below 70 mmHg).
In patients with reduced circulating blood volume, before starting treatment, the circulating blood volume should be supplemented.
Persistent low blood pressure or a steady decrease in blood pressure during dobutamine use, despite normal right ventricular filling pressure and cardiac output, may be an indication for the administration of peripheral vasoconstrictor drugs, such as dopamine or norepinephrine.
Patients with renal failure before taking the medicine should inform their doctor about it before taking the medicine.

Children

Tachycardia and increased blood pressure occur more frequently and are more pronounced in children than in adults. There are reports of lower sensitivity of the cardiovascular system of newborns to dobutamine, and it seems that hypotensive action (low blood pressure) is observed more frequently in adults than in young children.
Therefore, the use of dobutamine in children should be carefully monitored.
Consult a doctor, even if the above warnings refer to situations that have occurred in the past.
It is recommended to consult a doctor, even if the above warnings refer to situations that have occurred in the past.

Dobutamine TZF and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, as well as medicines you plan to take.
Some medicines may interact with dobutamine, which can reduce the effectiveness of the medicines used or cause dangerous side effects. This applies in particular to:

• halogenated general anesthetics;
• entacapone (a medicine used in patients with Parkinson's disease and movement disorders);
• β-adrenolytics (a group of medicines that act antagonistically on β1 and β2 adrenergic receptors, used, among others, in hypertension, coronary heart disease, arrhythmias, hyperthyroidism, glaucoma, and anxiety disorders).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Dobutamine TZF may be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Driving and using machines

Not applicable.

3. How to use Dobutamine TZF

Dobutamine TZF is intended for use only in a hospital setting, under the strict control of a doctor.
Dobutamine should be administered only as an intravenous infusion.
The medicine can only be administered by qualified medical personnel.

Recommended dose

Adults

Usually, a dose of 2.5 micrograms/kg/min to 10 micrograms/kg/min is used. In some patients, a dose of 0.5 micrograms/kg/min is sufficient. The need to use dobutamine in higher doses, sometimes up to 40 micrograms/kg/min, occurs very rarely.

Use in children and adolescents

In children and adolescents (from newborns to 18 years), the initial dose is recommended to be 5 micrograms/kg/min, adjusted to clinical response in the range of 2 to 20 micrograms/kg/min.
Occasionally, a response is obtained after administration of a small dose, ranging from 0.5 to 1.0 micrograms/kg/min. The dose required for children cannot be determined in advance. It should be calculated taking into account the presumably narrower than in adults therapeutic range.
If you feel that the action of the medicine is too strong or too weak, consult your doctor.
The prepared dobutamine solution should be used within 24 hours.
The method of administering the medicine and preparing the solution is given at the end of the leaflet, in the section "Information intended exclusively for healthcare professionals".

Use of a higher than recommended dose of Dobutamine TZF

Symptoms of dobutamine overdose are rare.
As a result of an overdose, the following symptoms may occur: loss of appetite, nausea, vomiting, muscle tremors, increased anxiety, palpitations, headaches, shallow breathing, and chest pain or atypical chest pain. Additionally, dobutamine may cause increased blood pressure and cardiac arrhythmias (ventricular tachyarrhythmias, up to ventricular fibrillation). A decrease in blood pressure may occur.
If the above symptoms occur, the medicine should be discontinued immediately and a doctor should be consulted.

Missing a dose of Dobutamine TZF

The medicine is administered in a hospital, so missing a dose at a certain time is rather unlikely.

4. Possible side effects

Like all medicines, Dobutamine TZF can cause side effects, although not everybody gets them.
In patients receiving dobutamine infusion for more than 72 hours, tolerance to the medicine may develop. To maintain the effect of dobutamine at the same level, it may be necessary to gradually increase the doses.
Very common(occurring in more than 1 in 10 patients)

• accelerated heart rate
• chest pain
• heart rhythm disturbances.

Common(occurring in 1 to 10 in 100 patients)

• headache
• increased or decreased blood pressure
• vasoconstriction (vasospasm)
• angina pectoris
• palpitations
• symptoms similar to asthma (bronchospasm), shortness of breath
• dyspnea
• increased white blood cell count (eosinophilia)
• inhibition of blood clot formation
• skin rash
• increased body temperature
• phlebitis (at the injection site).

Uncommon(occurring in 1 to 10 in 1,000 patients)

• ventricular tachycardia
• ventricular and atrial contractions (ventricular fibrillation, atrial fibrillation)
• myocardial infarction (myocardial infarction).

Rare(occurring in less than 1 in 10,000 patients)

• bradycardia (slow heart rate)
• cardiac arrest
• insufficient blood supply to the heart (myocardial ischemia)
• low potassium levels (hypokalemia), in some cases, the doctor may consider monitoring potassium levels
• skin spots (purpura), skin necrosis at the site of intravenous dobutamine administration
• constriction of blood vessels supplying the heart (coronary vasoconstriction).

Frequency not known- frequency cannot be determined from available data

• chest pain caused by stress (stress-induced cardiomyopathy)
• allergic reactions (hypersensitivity reactions), including rash, fever, increased white blood cell count (eosinophilia), and symptoms similar to asthma (bronchospasm)
• muscle spasms (clonic spasms) in patients receiving dobutamine with severe renal impairment
• ectopic rhythm (a type of arrhythmia)
• abnormal heart function test results (ST-segment elevation on ECG)
• myocarditis (eosinophilic myocarditis) in patients after heart transplantation)
• heart block (obstruction of the left ventricular outflow tract)
• heart rupture
• anxiety
• nausea (nausea)
• tingling (paresthesia)
• tremor
• increased need to urinate
• feeling of heat
• short, rapid muscle contractions (myoclonic contractions)
• heart function disorders (stress cardiomyopathy, also known as takotsubo syndrome), manifested by chest pain, shortness of breath, dizziness, fainting, irregular heartbeat, occurring during dobutamine stress echocardiography.

Impaired left ventricular outflow was observed during stress echocardiography.
In very rare cases, during dobutamine stress testing, heart rupture with fatal outcome was observed.
Eosinophilic myocarditis was observed in patients with a transplanted heart who received multiple medications such as dobutamine or other inotropic agents before transplantation.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products.
Aleje Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Dobutamine TZF

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

6. Contents of the pack and other information

What Dobutamine TZF contains

The active substance of the medicine is dobutamine in the form of dobutamine hydrochloride.
One vial contains 250 mg of dobutamine in the form of dobutamine hydrochloride.
The other ingredients are: mannitol.
To achieve the appropriate pH value, 0.1 mol/l hydrochloric acid solution is used.

What Dobutamine TZF looks like and what the pack contains

White or almost white lyophilisate in the form of a disk or its fragments of different sizes.

Packaging

1 or 25 vials in a cardboard box

Marketing authorization holder and manufacturer

Tarchomińskie Zakłady Farmaceutyczne "Polfa" S.A.
ul. A. Fleminga 2
03-176 Warsaw
Phone number: (22) 811-18-14
To obtain more detailed information, contact the marketing authorization holder.

Date of last revision of the leaflet:

Information intended exclusively for healthcare professionals

Method of administration

Dobutamine is administered only as a continuous intravenous infusion using precision dosing devices.
The infusion rate and duration of use should be adjusted according to the patient's heart rate and rhythm, taking into account hemodynamic parameters (blood pressure, ventricular filling pressure, central venous pressure, pulmonary artery occlusion pressure, cardiac output, or cardiac index).
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 (maximum 5 mg/ml with fluid restriction).
Administration of solutions with higher concentrations is only allowed through central venous access.
Dobutamine infusion solution is incompatible with solutions containing bicarbonates and other strongly alkaline solutions.
Dobutamine hydrochloride should not be mixed with substances or solutions containing ethanol or sodium metabisulfite.

Method of preparing the solution

To a vial containing 250 mg of dobutamine, 20 ml of water for injection or 20 ml of 5% glucose solution should be added. The resulting solution, after shaking, should be diluted by introducing it into 250 ml or 500 ml of one of the following infusion solutions: 5% glucose solution, 0.9% sodium chloride solution, or 5% glucose solution in 0.9% sodium chloride solution in a 1:1 ratio. The prepared solution, depending on the volume of the diluent used, has the following concentrations:
250 ml of infusion solution - 1000 micrograms of dobutamine per 1 ml.
500 ml of infusion solution - 500 micrograms of dobutamine per 1 ml.
Dobutamine solutions can be stored for 24 hours at a temperature of 2°C to 8°C (refrigerator). They also maintain physical and chemical stability for 24 hours at room temperature.
Note: The change in color of the solution stored at room temperature to a slightly pinkish color does not affect the physical and chemical stability of the medicine.

Pharmaceutical incompatibilities

The dobutamine solution should not be mixed with other medicines.
5% sodium bicarbonate solutions or other strongly alkaline solutions should not be added to dobutamine solutions.
Dobutamine hydrochloride should not be mixed with substances or solutions containing ethanol or sodium metabisulfite.