Dobutamine Hikma

Package leaflet: Information for the patient

Dobutamine Hikma, 12.5 mg/ml,

Concentrate for solution for infusion
Dobutamine
Generic medicine
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to others. It may harm them, even if they have the same symptoms as you.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or nurse. See section 4.

Contents of this leaflet

1. What Dobutamine Hikma is and what it is used for
2. What you need to know before you use Dobutamine Hikma
3. How to use Dobutamine Hikma
4. Possible side effects
5. How to store Dobutamine Hikma
6. Contents of the pack and other information

1. What Dobutamina Hikma is and what it is used for

Dobutamina Hikma contains the active substance dobutamine, which belongs to a
group of medicines called beta-receptor agonists (cardiac stimulants).
In adults it is used:

• during open-heart surgery,
• to treat heart conditions,
• to treat heart failure,
• as an alternative to exercise stress testing for evaluating the heart.

Paediatric population
Dobutamine is indicated in all paediatric age groups (from neonates to 18 years) as
inotropic support in states of hypoperfusion due to reduced cardiac output following
decompensated heart failure, after cardiac surgery, cardiomyopathies, and in cases of
cardiogenic or septic shock.

2. What you need to know before using Dobutamina Hikma

Do not use Dobutamina Hikma:

• if you are allergic to dobutamine, sodium metabisulfite, or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.
• if you have high blood pressure due to a tumor near the kidneys (pheochromocytoma).
• if you have low blood volume that has not been corrected (your doctor will know).
• if you have an obstruction interfering with blood flow from the heart (your doctor will know).
• if you have uncontrolled arrhythmia (irregular heartbeat).

Do not use Dobutamina Hikma for cardiac stress testing if:

• you suffer from unstable (uncontrolled) angina.
• you suffer from electrolyte imbalance (salt imbalance).
• you have had a heart attack within the last 30 days.
• you have had an aortic aneurysm (a weakened and bulging area in the aorta, the main blood vessel supplying blood to the body).
• you suffer from uncontrolled high blood pressure.
• you suffer from severe anemia (low red blood cell count).
• you have had aortic dissection (bleeding caused by a tear in the wall of the aorta, the main blood vessel carrying blood to the body).

Warnings and precautions
Talk to your doctor or nurse before using Dobutamina Hikma.
Inform your doctor or nurse if you have any of the following conditions:

• Any heart disorder.
• Hyperthyroidism (overactive thyroid).
• A tumor of the adrenal gland.
• A condition in which potassium concentration in the blood is low (decreased serum potassium concentration and hypokalemia).
• Liver or kidney disorder.
• Severe hypotension (low blood pressure).
• Asthma.
• Diabetes mellitus.
• Hypovolemia (dehydration).

Children
Increases in heart rate and arterial pressure appear to be more frequent and pronounced in children than in adults. The neonatal cardiovascular system has been reported to be less responsive to dobutamine, and the hypotensive effect (low blood pressure) appears to be observed more often in adult patients than in young children. Therefore, the use of dobutamine in children must be carefully monitored.

Other medicines and Dobutamina Hikma
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
This is particularly important with the following medicines, as they may interact with Dobutamina Hikma:

• Monoamine oxidase inhibitors (treatments for depression)
• beta-adrenergic blockers such as propranolol or metoprolol
• alpha-adrenergic blockers (for high blood pressure or prostate gland enlargement)
• ACE inhibitors, e.g. captopril (for high blood pressure or heart failure)
• Antipsychotics (treatments for mental disorders)
• Oxytocin (used during labor)
• Peripheral vasoconstricting agents such as noradrenaline
• Peripheral vasodilators (e.g. nitrates, sodium nitroprusside)
• Ergotamine or methysergide (treatments for migraine)
• Dipyridamole (an anticoagulant)
• General anesthetics
• Theophylline (a treatment for asthma)
• Entacapone (a medicine used to treat Parkinson’s disease)
• Doxapram (for respiratory problems)
• Atropine sulfate (for inflammation of the iris of the eye or eye examinations)

Pregnancy and breastfeeding
You will not be given Dobutamina Hikma if you are pregnant or breastfeeding unless your doctor considers it necessary.

Driving and using machines
Not applicable, considering the indications for use and the short half-life of the drug.

Dobutamina Hikma contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per millilitre and is essentially ‘sodium-free’.

Dobutamina Hikma contains sodium metabisulfite (E223)
It may rarely cause severe hypersensitivity reactions and bronchospasm.

3. How to use Dobutamine Hikma

Dobutamine Hikma will be administered to you in hospital by a doctor or nurse.
Dobutamine Hikma is diluted and infused into a vein.
Your doctor will decide the correct dosage for you and how and when the injection will be administered.

Dosage for cardiac stimulation
Adults and elderly:
The usual dosage is 2.5 to 10 µg/kg (body weight)/min, adjusted according to heart rate, blood pressure, cardiac output, and urinary output. Doses up to 40 µg/kg/min may occasionally be required.

Dosages for cardiac stress testing
Adults:
The recommended dosage is an incremental increase from 5 up to a maximum of 40 µg/kg/min.
Elderly:
The recommended dosage is an incremental increase from 5 up to a maximum of 20 µg/kg/min.

Use in children
For all pediatric age groups (from neonates up to 18 years), an initial dose of 5 μg/kg/min is recommended, adjusted according to clinical response to 2–20 μg/kg/min. Occasionally, a dose of 0.5–1.0 μg/kg/min may produce a response. The dose required in children should be carefully titrated, as the so-called "therapeutic window" is presumably narrower in children.

If you use more Dobutamine Hikma than you should
Since the injection will be administered by a doctor or nurse, it is unlikely that you will receive too much.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following side effects have been reported:

Very common (affects more than 1 in 10 people)

• increased heart rate
• severe chest pain
• arrhythmia (heart rate too fast or too slow)
• elevation of the ST segment on electrocardiogram
• coronary artery spasm (temporary, sudden contraction in a part of the heart muscle)
• palpitations
• irregular heartbeat
• ventricular tachycardia (accelerated heart rhythm originating in one of the heart's ventricles)

Common (affects 1 to 10 in 100 people)

• hypersensitivity reactions including skin rash
• eosinophilia (high concentration of eosinophilic granulocytes in the blood)
• hypertension
• marked increase in systolic blood pressure indicating overdose
• shortness of breath
• nausea
• fever
• bronchospasm (sudden constriction of the muscles in the walls of the bronchioles)
• non-specific chest pain
• asthma
• headache

Uncommon (affects 1 to 10 in 1,000 people)

• atrial fibrillation (abnormal heart rhythm affecting the two upper atrial chambers)
• ventricular fibrillation (uncontrolled contractions of the heart's ventricles)
• left ventricular outflow tract obstruction
• hypotension
• mild vasoconstriction, especially in patients previously treated with β-blockers

Rare (affects 1 to 10 in 10,000 people)

• phlebitis (formation of blood clots)
• local inflammatory changes
• anaphylactic reactions (severe allergic hypersensitivity reaction)
• severe, potentially life-threatening asthma episodes may be due to sensitivity to sulfite

Very rare (affects less than 1 in 10,000 people)

• as with other catecholamines, decreases in serum potassium concentrations have occurred
• myoclonus (involuntary muscle jerks) has been reported in patients with severe renal impairment receiving dobutamine
• skin necrosis
• myocardial ischemia (reduced blood supply to the heart muscle)
• myocardial infarction (heart attack)
• eosinophilic myocarditis (inflammation of the heart muscle)
• fatal cardiac rupture during dobutamine stress test

Not known (cannot be estimated from available data)

• urinary urgency
• heart muscle problems (stress cardiomyopathy, also known as Takotsubo syndrome), presenting with chest pain, shortness of breath, dizziness, fainting, and irregular heartbeat when dobutamine is used for stress echocardiography.

Reporting of side effects
If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dobutamine Hikma

The doctor and pharmacist are responsible for the correct storage, use, and
disposal of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after EXP.

6. Package contents and other information

What Dobutamine Hikma contains

• The active substance is dobutamine hydrochloride.
• The other components are sodium metabisulfite, sodium hydroxide, hydrochloric acid and water for injections.

Each ml contains 12.5 mg of dobutamine (14.01 mg as dobutamine hydrochloride).
Each 20 ml vial contains 250 mg of dobutamine (280.2 mg as dobutamine hydrochloride).

Description of the appearance of Dobutamine Hikma and contents of the pack
Dobutamine Hikma is a clear, colourless to slightly yellow solution, supplied in clear glass vials, packed in cardboard boxes containing 10 vials.

Marketing Authorisation Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, nº8, 8A, 8B
Fervença
2705-906 Terrugem SNT
Portugal

This medicinal product is authorised in the European Economic Area countries under the following names:
Italy: Dobutamina Hikma
Portugal: Dobutamina Hikma
Spain: Dobutamina Hikma 12,5 mg/ml concentrado para solución para perfusión EFG
France: Dobutamine Hikma 12,5 mg/ml, solution à diluer pour perfusion
United Kingdom / Northern Ireland: Dobutamine 12.5 mg/ml, Concentrate for solution for infusion

This leaflet was last reviewed on

The following information is intended for healthcare professionals only:

• Dosage and administration

For intravenous use only.
Dosage
Adults
Myocardial inotropic support:
The usual dosage range is 2.5 to 10 micrograms/kg/min, which should be adjusted based on the patient's heart rate, cardiac pressure, cardiac output, and urinary output.
Infusion should be initiated at a rate of 2.5 micrograms/kg/min, and the dose may be increased at intervals of 10–30 minutes until the desired haemodynamic response is achieved or until adverse effects such as excessive tachycardia, arrhythmia, headache, or tremor limit further dose escalation. The dose must be individually adjusted according to heart rate and rhythm, blood pressure, and urinary flow. Occasionally, a dose of 0.5 micrograms/kg/min may elicit a response. Doses up to 40 micrograms/kg/min may be required.
During prolonged continuous infusion (48–72 hours), a reduction in haemodynamic response may occur, necessitating an increase in dose.

Dosage for cardiac stress testing:
The use of dobutamine in cardiac stress testing should only be performed in units already experienced in exercise stress testing, and all standard precautions and safeguards required for such testing are necessary when using dobutamine for this purpose, including availability of a defibrillator and presence of personnel specifically trained in resuscitation.
The recommended dosage is incremental increase in infusion rate from 5 micrograms/kg/min to 10, 20, 30, and a maximum of 40 micrograms/kg/min, with each dose infused for 3 minutes. Additionally, atropine may be added during further infusion of the peak dose. Continuous electrocardiographic (ECG) monitoring is required, and infusion may be discontinued in case of ST-segment depression >0.2 mV (2 mm) measured 80 ms after the J point, ST-segment elevation >0.1 mV (1 mm) in patients without prior myocardial infarction, or significant cardiac arrhythmias.
Dobutamine infusion must be stopped if heart rate reaches 85% of the age-predicted maximum, systolic arterial pressure exceeds 220 mmHg, or there is a symptomatic decrease in systolic arterial pressure >40 mmHg from baseline, new wall motion abnormalities, severe chest pain, or any intolerable adverse effect.

Elderly:
No dosage adjustment is required. Careful monitoring of blood pressure, urinary output, and peripheral tissue perfusion is necessary.
Cardiac stress test: when used as an alternative to exercise for cardiac stress, the recommended dose should start at 5 micrograms/kg/min, increasing gradually by 5 micrograms/kg/min every 8 minutes up to a maximum of 20 micrograms/kg/min. Continuous ECG monitoring is essential, and infusion should be terminated in case of ST-segment depression >3 mm or any ventricular arrhythmia. Infusion should also be stopped if heart rate reaches age-/sex-predicted maximum, systolic blood pressure rises above 220 mmHg, or adverse effects occur.

Paediatric population
For all paediatric age groups (neonates up to 18 years), an initial dose of 5 micrograms/kg/min is recommended, adjusted according to clinical response to 2–20 micrograms/kg/min. Occasionally, a dose of 0.5–1.0 micrograms/kg/min may elicit a response.
There is evidence to suggest that the minimum effective dose in children may be higher than in adults. Caution should be exercised when administering high doses, as there is also evidence that the maximum tolerated dose in children may be lower than in adults. Most adverse reactions (particularly tachycardia) have been observed when dosing was ≥7.5 micrograms/kg/min; however, reduction or cessation of dobutamine infusion rate is usually sufficient to rapidly reverse undesirable effects.
Considerable inter-patient variability has been observed in paediatric patients regarding both the plasma concentration required to initiate a haemodynamic response (threshold) and the rate of haemodynamic response to increasing plasma concentrations, indicating that the dose required in children cannot be determined a priori and should be titrated to allow for the presumably narrower therapeutic window in children.

Method of administration
Dobutamine Hikma must be diluted before use and administered only by intravenous infusion.
The concentration of dobutamine administered depends on the dosage and individual patient's fluid requirements. Final concentrations commonly used for infusion are 250 micrograms/ml, 500 micrograms/ml, or 1000 micrograms/ml. For special precautions regarding storage of the prepared diluted infusion, see section 6.4. High concentrations of dobutamine must be administered only using an infusion pump or other suitable device to ensure accurate dosing. Due to its short half-life, dobutamine must be administered as a continuous intravenous infusion. Dobutamine should be administered intravenously through an intravenous needle or catheter. The following sterile intravenous infusion solutions may be used for dilution of dobutamine prior to use: 5% dextrose injection, 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection, 10% dextrose injection, 5% dextrose multi-electrolyte injection, Ringer's lactate injection, 5% dextrose in Ringer's lactate injection, 20% mannitol in water for injection, 0.9% sodium chloride injection, and sodium lactate injection.

Dosage for infusion delivery systems:
A vial of Dobutamine Hikma 12.5 mg/ml (250 mg/20 ml) diluted to a final volume of 500 ml solution (final concentration 0.5 mg/ml) with any of the approved diluents (see section 6.6).

* For a double concentration, i.e. 500 mg of Dobutamine Hikma added to 500 ml,
or 250 mg added to 250 ml of solution, infusion rates must be halved.
The dose to be administered can be calculated using the table below.
Infusion rates in millilitres/min can be obtained by multiplying the
infusion rates for each concentration (ml/kg/min) by the patient's weight (kg).

Dosing for syringe pumps:
One vial of Dobutamine Hikma 12.5 mg/ml (250 mg/20 ml) diluted to a final volume of
50 ml solution (final concentration 5 mg/ml) with any of the approved diluents
(see section 6.6).

Paediatric population
For continuous intravenous infusion using an infusion pump, dilute to a concentration
between 0.5 and 1 mg/ml (up to 5 mg/ml if fluid volume is limited) with 5% Glucose or
0.9% Sodium Chloride. Infuse higher concentration solutions only through a central
venous catheter. Intravenous infusion of dobutamine is incompatible with sodium
bicarbonate and other strong alkaline solutions.

Neonatal intensive care therapy
Dilute 30 mg/kg body weight to a final volume of 50 ml of infusion fluid. An intravenous
infusion rate of 0.5 ml/hour delivers a dose of 5 micrograms/kg/minute.

• Incompatibilities

Do not add Dobutamina Hikma to intravenous infusions of 5% sodium bicarbonate or
other strongly alkaline solutions. Due to potential physical incompatibilities, it is
recommended not to mix dobutamine hydrochloride with other medicinal products in
the same solution.
Dobutamina Hikma injections must not be used with other agents or diluents containing
both sodium metabisulfite and ethanol.

• Shelf life

2 years
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C
(room temperature).
From a microbiological standpoint, the product should be used immediately. If not used
immediately, the times and conditions of storage during use and prior to use are the
responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless
dilution has taken place under controlled and validated aseptic conditions.

• Special precautions for disposal and other handling

Dobutamina Hikma must be diluted to at least 50 ml before administration into an
intravenous container with one of the following intravenous solutions:

• 5% Dextrose Injection,
• 5% Dextrose and 0.45% Sodium Chloride Injection,
• 5% Dextrose and 0.9% Sodium Chloride Injection,
• 10% Dextrose Injection,
• 5% Dextrose with Multi-electrolyte Injection,
• Lactated Ringer’s Injection,
• 5% Dextrose in Lactated Ringer’s Injection,
• 20% Mannitol in Water for Injection,
• 0.9% Sodium Chloride Injection,
• Sodium Lactate Injection.

For example, dilution to 250 ml or 500 ml will provide the following concentrations for
administration:
250 ml contains 1,000 micrograms/ml of dobutamine
500 ml contains 500 micrograms/ml of dobutamine
The prepared solution must be used within 24 hours.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.