Dobutamine hameln

Package leaflet: Information for the user

Dobutamin hameln 12.5 mg/ml concentrate for solution for infusion
Dobutaminum
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• If the patient experiences any adverse reactions, including those not listed in this leaflet, inform your doctor or nurse immediately. See section 4.

Table of contents

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

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

Dobutamin hameln belongs to a group of medicines called catecholamine amines. It acts by increasing the heart's pumping efficiency. It strengthens the heart's pumping action, increases blood flow throughout the body, and dilates veins and arteries.

Dobutamin hameln is used:

• in the treatment of heart failure (decompensated heart failure) when the heart does not beat strongly enough (reduced contractility),
• in heart failure associated with very low blood pressure (hypotension),
• to detect reduced blood flow to the heart (cardiac stress testing).

Children and adolescents
Dobutamin hameln may be used in children and adolescents (from newborns up to 18 years of age) when a positive inotropic effect is required in patients with reduced cardiac output due to hypoperfusion resulting from uncompensated heart failure following cardiothoracic surgery, cardiomyopathy, cardiogenic or septic shock.

2. Important information before using Dobutamin hameln

When not to use Dobutamin hameln:

• if the patient has a hypersensitivity (allergy) to dobutamine or to any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction may include: rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue. If the patient has previously experienced such symptoms.
• if the patient has aortic valve stenosis or blood vessel narrowing that prevents the heart from filling or ejecting blood properly (this will be diagnosed by a physician).
• if the patient has low circulating blood volume (hypovolemia).
• if the patient has high blood pressure due to a tumor near the kidney (phaeochromocytoma).

Dobutamin hameln should not be used for detecting reduced blood flow to the heart if the patient has certain heart or blood vessel diseases.

Warnings and precautions

Before starting treatment with Dobutamin hameln, discuss this with your doctor.
You should discuss with your doctor if:

• the patient has asthma and is allergic to sulfites,
• the patient has severe coronary heart disease,
• the patient has acute (sudden) heart failure.

Children

Increased heart rate and elevated 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 a blood pressure-lowering (hypotensive) effect appears to be observed more often in adults than in young children. Therefore, the doctor will closely monitor the use of dobutamine in children.
Caution should be exercised when administering high doses of dobutamine to children.
The doctor will carefully adjust the required dose for the child.

Dobutamin hameln and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to use.
It is essential to inform the doctor, as the following medicines may affect the action of Dobutamin hameln:

• beta-blockers (medicines used to treat high blood pressure and irregular heartbeat),
• alpha-blockers (medicines used to treat high blood pressure and benign prostatic hyperplasia),
• vasodilators (medicines that dilate blood vessels, used in the treatment of angina or severe heart failure),
• antidiabetic medicines (medicines used in diabetes),
• ACE inhibitors (medicines used to treat high blood pressure and heart failure),
• dopamine (used to increase heart rate and blood pressure),
• inhaled anesthetics,
• entacapone (a medicine used in the treatment of Parkinson's disease).

The doctor will decide whether dobutamine administration is beneficial for the patient.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Dobutamine should not be given to pregnant women unless medically justified.
If dobutamine treatment is necessary during breastfeeding, breastfeeding should be discontinued for the duration of treatment.

Driving and operating machinery

If in any doubt, consult your doctor or pharmacist.

Dobutamin hameln contains sodium metabisulfite (E223). This medicine may rarely cause severe hypersensitivity reactions and bronchospasm.

Dobutamin hameln contains sodium
The medicine contains less than 1 mmol of sodium (23 mg) per 1 ml; therefore, the medicine is considered "sodium-free".

3. How to use Dobutamin hameln

Dobutamin hameln must be administered only by qualified medical personnel under conditions where emergency equipment is available.
Dosage
The required infusion rate depends on the patient's response to treatment and the occurrence of adverse reactions. The physician determines the dose of dobutamine for each patient and adjusts the infusion flow rate and duration accordingly.
Dosage in adults:
Most patients respond to a dose of 2.5–10 micrograms of dobutamine per kg of body weight per minute. A dose of up to 40 micrograms of dobutamine per kg of body weight per minute may be administered.
Dosage in children and adolescents:
In children and adolescents (from newborns 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, response may be achieved with a lower dose of 0.5 to 1.0 microgram/kg body weight/min.
This dose should be determined taking into account the presumed narrower therapeutic window in children.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Possible adverse reactions include:

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

• increased heart rate
• chest pain
• heart rhythm disturbances
• abnormal result of cardiac function test (ST-segment elevation on electrocardiogram) during dobutamine stress test

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

• increase or decrease in blood pressure
• narrowing of blood vessels (vasoconstriction)
• irregular heartbeat (palpitations)
• rapid heartbeat (ventricular tachycardia)
• headache
• asthma-like symptoms (bronchospasm)
• shortness of breath
• increased number of white blood cells (eosinophilia)
• inhibition of blood clot formation
• increased need to urinate (at high doses)
• nausea
• rash (skin eruption)
• fever
• inflammation of the vein at the injection site (phlebitis)
• allergic reactions (hypersensitivity reactions), including skin rash
• inflammation of the heart muscle (eosinophilic myocarditis)

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

• uncontrolled contractions of the heart chambers (ventricular fibrillation)
• heart attack (myocardial infarction)
• uncontrolled contractions of the heart atria (atrial fibrillation)
• left ventricular outflow tract obstruction during dobutamine stress test
• severe allergic reactions (anaphylactic reactions) and severe, life-threatening asthmatic episodes, possibly due to hypersensitivity to sodium metabisulfite (see section 2).

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

• slow heartbeat (bradycardia)
• insufficient blood supply to the heart (myocardial ischemia)
• low potassium levels (hypokalemia)
• skin spots (petechial hemorrhage)
• cardiac conduction block
• narrowing of blood vessels supplying the heart (coronary artery spasm)
• black spots on the skin (skin necrosis)
• muscle jerks (myoclonus) in patients with severe renal failure receiving dobutamine
• fatal cardiac rupture during dobutamine stress test

Frequency unknown (cannot be estimated from available data):

• stress-induced chest pain (stress cardiomyopathy)
• disturbances in heart function (decrease in pulmonary capillary pressure)
• disturbances in heart muscle function (stress cardiomyopathy, also known as takotsubo syndrome), manifesting as chest pain, shortness of breath, dizziness, fainting, irregular heartbeat, occurring during dobutamine administration in stress echocardiography

Other observed adverse reactions:

• anxiety
• tingling (paresthesia)
• involuntary muscle contractions (tremor)
• feeling of warmth and restlessness
• muscle cramps

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, tell your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of 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 authorization holder.
By reporting adverse reactions, additional information on the safety of this medicine can be collected.

5. How to store Dobutamin hameln

• Keep this medicine out of 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.
• Do not use this medicine if you notice that the solution is not clear and free from solid particles, or if the packaging is damaged.
• This medicine does not require any special storage temperature conditions.
• Store the ampoules in the original packaging to protect from light.
• Do not freeze. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What Dobutamin hameln contains
The active substance is dobutamine.
1 ml of concentrate contains 12.5 mg of dobutamine.
One 20 ml vial of Dobutamin hameln contains 280 mg of dobutamine hydrochloride,
corresponding to 250 mg of dobutamine.
Other ingredients: sodium metabisulfite, hydrochloric acid 1N (for pH adjustment), and water for injections.

What Dobutamin hameln looks like and contents of the pack
Dobutamin hameln is a clear, colourless or slightly yellow concentrate for solution for infusion.
The immediate packaging consists of a vial made of colourless glass (type I) containing 20 ml of Dobutamin hameln.
The cardboard box contains 1, 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
hameln pharma gmbh
Inselstraße 1
31787 Hameln
Germany
Tel.: +49 171 766 2789

Manufacturer
Siegfried Hameln GmbH
Langes Feld 13
31789 Hameln
Germany

hameln rds s.r.o.
Horná 36
90001 Modra
Slovakia

This medicinal product is authorised in the European Economic Area countries under the following names:

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Information intended exclusively for medical professionals:
Medication Preparation Guide:
Dobutamin hameln 12.5 mg/ml concentrate for solution for infusion
Full information on indications and other details can be found in the Summary of Product Characteristics.
1. Dosage and Administration
The dose of Dobutamin hameln should be individually adjusted.
The required infusion rate depends on the patient's response to treatment and the occurrence of adverse effects.
Dosage
Dosage in adults:
Clinical experience indicates that most patients respond to doses of 2.5–10 micrograms of dobutamine/kg body weight/min. In individual cases, doses up to 40 micrograms of dobutamine/kg body weight/min have been used.
Dosage in children and adolescents:
In children and adolescents (from newborns 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 may be achieved with a low dose of 0.5 to 1.0 microgram/kg body weight/min.
It has been demonstrated that the minimal effective dose in children is higher than in adults. Particular caution is required when using higher doses, as the maximum tolerated dose in pediatric treatment has been shown to be lower than doses used in adults. Most adverse reactions (especially tachycardia) have been observed after administration of dobutamine at doses equal to or greater than 7.5 micrograms/kg body weight/min; however, adverse effects usually resolve rapidly upon reduction or discontinuation of dobutamine infusion.
Marked variability has been observed among children regarding both the plasma concentration of dobutamine required to elicit a hemodynamic response (threshold) and the rate of hemodynamic response to increasing plasma concentrations. This indicates that the required dose cannot be predetermined in children, and dosing should be individualized, considering the likely narrower therapeutic window in pediatric patients.
The following tables show the relationship between infusion rate and initial concentration for various dosage levels of the medicinal product.
Administration using infusion pumps
1 vial of Dobutamin hameln 12.5 mg/ml (250 mg in 20 ml) diluted to a final volume of 500 ml (final concentration 0.5 mg/ml)

* When using a twice higher concentration, i.e. 500 mg of dobutamine added to 500 ml, or 250 mg added to 250 ml of solution, the infusion rate must be halved.
Administration using syringe infusion pumps
1 ampoule of Dobutamin hameln 12.5 mg/ml (250 mg in 20 ml) diluted to a final volume of 50 ml (final concentration 5 mg/ml)

The selected infusion syringe pump must be suitable for the volume and rate of administration.
Detailed information on compatible diluents is provided in section 6.6 of the Summary of Product Characteristics.

Dobutamine stress echocardiography (adult population only)
Administration in stress echocardiography involves gradual increases in the dobutamine infusion.
The most commonly used dosing regimen starts at a dose of 5 micrograms/kg/min of dobutamine, increased every 3 minutes to 10, 20, 30, and 40 micrograms/kg/min until a diagnostic endpoint is reached (see method and duration of use).
If the endpoint has not been achieved, atropine sulfate may be administered in divided doses of 0.25–0.5 mg at 1-minute intervals, up to a total dose of 0.5–2 mg, to increase heart rate. Alternatively, the infusion rate of dobutamine may be increased to 50 micrograms/kg/min.

The use of dobutamine in children and adolescents is limited to the treatment of patients requiring positive inotropic support.

Method of administration
The concentrate for solution for infusion must be diluted before administration.
For intravenous infusion only. It must be diluted to a volume of 50 ml or greater.
Intravenous infusion of dobutamine is possible after dilution with compatible infusion solutions such as: 5% glucose solution (50 mg/ml), 0.9% sodium chloride (9 mg/ml), or 0.45% sodium chloride (4.5 mg/ml) in 5% glucose solution (50 mg/ml).
Infusion solutions should be prepared immediately before use.
Due to the short half-life of dobutamine, it must be administered as a continuous intravenous infusion.
When discontinuing treatment, the dose of dobutamine should be tapered gradually.
The duration of treatment depends on clinical requirements, determined by the physician, and should be as short as possible.
If dobutamine is administered continuously for more than 72 hours, tolerance may develop, requiring dose escalation.

During dobutamine administration, heart rate, cardiac rhythm, blood pressure, diuresis, and infusion rate must be closely monitored. If possible, cardiac output, central venous pressure (CVP), and pulmonary capillary pressure (PCP) should also be monitored.

Children and adolescents: To administer the medicinal product as a continuous infusion using an infusion pump, the solution should be diluted with 5% glucose solution (50 mg/ml) or 0.9% sodium chloride solution (9 mg/ml) to achieve a dobutamine concentration of 0.5 to 1 mg/ml (up to a maximum of 5 mg/ml when fluid volume is restricted). Solutions with higher concentrations may only be administered via a central venous line. The dobutamine infusion solution for intravenous use is incompatible with solutions containing bicarbonates and other strongly alkaline solutions.

Use in neonates requiring intensive care: Dilute 30 mg/kg body weight to a final volume of 50 ml of infusion solution. An infusion rate of 0.5 ml/hour provides a dose of 5 micrograms/kg/min.

Dobutamine stress echocardiography (adult population only)
To detect myocardial ischemia and myocardial viability, dobutamine may be administered only by a physician experienced in performing cardiac stress testing. Continuous monitoring of all cardiac areas using echocardiography and ECG, as well as blood pressure monitoring, is required.
Life-saving monitoring equipment and medications (e.g., defibrillator, intravenous beta-blockers, nitrates, etc.) must be available, along with personnel trained in resuscitation.
For instructions on dilution of the medicinal product prior to administration, see section 6.6 of the Summary of Product Characteristics.

2. Pharmaceutical incompatibilities
For information on solutions incompatible with dobutamine and sodium metabisulfite, see section 6.2 of the Summary of Product Characteristics.
This medicinal product must not be mixed with other medicinal products except those for which compatibility has been confirmed.

3. Storage
No special temperature storage requirements for the medicinal product.
Store ampoules in their outer packaging to protect from light.
Do not freeze.

After dilution:
The ready-to-administer infusion solution is chemically and physically stable for 24 hours at temperatures up to 25°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution precludes the risk of microbiological contamination, the product should be used immediately.
If not used immediately, the responsibility for storage duration and conditions during use lies with the user.