DOBUTAMINE HIKMA 12.5 mg/mL concentrate for infusion solution

Introduction

Package Leaflet: Information for the Patient

Dobutamine Hikma 12.5 mg/ml Concentrate for Solution for Infusion EFG

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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

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

This medicine contains the active ingredient dobutamine, which belongs to a group of medicines called beta-receptor agonists (heart stimulants).

In adults, it is used:

• in open-heart surgery,
• to treat heart diseases,
• to treat heart failure,
• as an alternative to exercise for the heart stress test.

Pediatric population

Dobutamine is indicated in all pediatric age groups (from newborns to 18 years) as inotropic support in states of hypoperfusion with low cardiac output resulting from decompensated heart failure, after cardiac surgery, cardiomyopathies, and in cardiogenic or septic shock.

2. What you need to know before you use Dobutamine Hikma

Do not use Dobutamine Hikma:

• If you are allergic to dobutamine, sodium metabisulfite, or any of the other ingredients of this medicine (described 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 kidney (pheochromocytoma).
• If you have low blood volume that has not been corrected (your doctor will know).
• If you have an obstruction that interferes with blood flow from your heart (your doctor will know).
• If you have an uncontrolled arrhythmia (heart rhythm)

Do not use Dobutamine Hikma also to examine your heart if:

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

Warnings and precautions

Talk to your doctor or nurse before using this medicine.

Talk to 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 where the potassium concentration in the blood is low (reduction of serum potassium concentration and hypokalemia).
• A liver or kidney disorder.
• Severe hypotension (low blood pressure).
• Asthma.
• Diabetes mellitus.
• Hypovolemia (dehydration).

Children and adolescents

Increases in heart rate and blood pressure appear to be more frequent and intense in children than in adults. It has been reported that the cardiovascular system of the newborn is less sensitive to dobutamine, and the hypotensive effect (low blood pressure) appears to be observed more frequently in adult patients than in small children. Consequently, the use of dobutamine in children should be closely monitored.

Other medicines and Dobutamine Hikma

Tell your doctor if you are using, have recently used, or might use any other medicines.

This is especially important with the following medicines, as they may interact with your Dobutamine Hikma:

• Monoamine oxidase inhibitors (treatments for depression)
• Beta-adrenergic blockers such as propranolol or metoprolol
• Alpha-adrenergic blockers (for high blood pressure or prostate enlargement)
• ACE inhibitors, e.g., captopril (for high blood pressure or heart failure)
• Antipsychotics (treatments for mental illnesses)
• Oxytocin (used in labor)
• Peripheral vasoconstrictor 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 for treating Parkinson's disease)
• Doxapram (for respiratory problems)
• Atropine sulfate (for eye inflammation or eye exams)

Pregnancy and breastfeeding

This medicine will not be given to you if you are pregnant or breastfeeding, unless your doctor considers it necessary.

Driving and using machines

Not applicable in view of the indications for use and the short half-life of the drug.

Dobutamine Hikma contains sodium

This medicine contains less than 23 mg of sodium (1mmol) per milliliter, i.e., it is essentially "sodium-free".

Dobutamine Hikma contains sodium metabisulfite (E223)

This medicine may cause severe allergic reactions and bronchospasm (sudden feeling of suffocation) because it contains "sodium metabisulfite".

3. How to use Dobutamine Hikma

A doctor or nurse will give you this medicine in the hospital. This medicine is diluted and infused into a vein.

Your doctor will decide the correct dose for you and how and when the injection will be given.

Dose for heart stimulation.

Adults and elderly patients:

The usual dose is 2.5 to 10 micrograms/kg (body weight)/min, which is adjusted according to heart rate, blood pressure, cardiac output, and urine production. Occasionally, doses of up to 40 micrograms/kg/min may be required.

Dose for heart stress test

Adults:

The recommended dose is an incremental increase of 5 to a maximum of 40 micrograms/kg/min.

Elderly:

The recommended dose is an incremental increase of 5 to a maximum of 20 micrograms/kg/min.

Use in children:

For all pediatric age groups (newborns 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 as low as 0.5-1.0 micrograms/kg/min will produce a response. The dose required for children should be titrated to take into account the supposed "narrower therapeutic range" in children.

If you use more Dobutamine Hikma than you should

Since the injection will be given by a doctor or nurse, it is unlikely that you will be given too much.

4. Possible side effects

Like all medicines, dobutamine can cause side effects, although not everybody gets them.

The following side effects have been reported:

Very common (affect more than 1 in 10 patients)

• increased heart rate
• severe chest pain
• arrhythmia (very slow or very fast heart beat)
• elevation of the ST segment of the electrocardiogram
• coronary artery spasm (sudden and temporary contraction in a place of the heart muscle)
• palpitations
• irregular heartbeats
• ventricular tachycardia (fast heart rate that originates in one of the heart's ventricles)

Common (affect 1 to 10 patients in 100)

• hypersensitivity reactions including rash
• eosinophilia (high concentration of eosinophil granulocytes in blood)
• hypertension
• marked increase in systolic blood pressure indicates overdose
• difficulty breathing
• nausea
• fever
• bronchospasm (sudden constriction of the muscles of the bronchiole walls)
• non-specific chest pain
• asthma
• headache

Uncommon (affect 1 to 100 patients in 1,000)

• atrial fibrillation (abnormal heart rhythm affecting the two upper chambers - atria)
• ventricular fibrillation (uncontrolled contractions of the heart muscle of the ventricles)
• left ventricular outflow tract obstruction
• hypotension
• mild vasoconstriction, especially in patients pretreated with beta-blockers

Rare (affect 1 to 10 patients in 10,000)

• phlebitis (formation of blood clots)
• local inflammatory changes
• anaphylactic reactions (severe allergic reaction of hypersensitivity)
• severe asthmatic episodes that are life-threatening may be due to sulfito sensitivity

Very rare (affect less than 1 in 10,000 patients)

• as with other catecholamines, decreases in serum potassium concentrations have occurred.
• myoclonus (involuntary muscle contractions) 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

Unknown (frequency cannot be estimated from the available data)

• urinary urgency
• heart muscle problems (stress cardiomyopathy, also known as Takotsubo syndrome) that cause chest pain, difficulty breathing, dizziness, fainting, and irregular heartbeats when dobutamine is used for a stress echocardiogram.

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Dobutamine Hikma

Your 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.

Store below 25°C.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The first two numbers indicate the month and the last four numbers indicate the year. The expiry date refers to the last day of the month indicated.

6. Contents of the pack and further information

Composition of Dobutamine Hikma

• The active substance is dobutamine hydrochloride.
• The other ingredients are sodium metabisulfite (E223), sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Each ml contains 12.5 mg of dobutamine (as 14.01 mg of dobutamine hydrochloride).

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

Appearance of the product and pack contents

Dobutamine Hikma is a clear, colorless to pale yellow solution, packaged in transparent glass vials, packed in cardboard boxes with 10 vials.

Marketing authorization holder and manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, nº8, 8A, 8B

Fervença

2705-906 Terrugem SNT

Portugal

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Italy: Dobutamina Hikma 12.5 mg/ml, Concentrato per soluzione per infusione

Portugal: Dobutamina Hikma

Date of the last revision of this leaflet:02/2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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The following information is intended for healthcare professionals only:

• Posology and method of administration

For intravenous use only.

Posology

Adults

Inotropic support of the myocardium:

The usual dose is 2.5 to 10 micrograms/kg/minute, this should be adjusted according to the heart rate, blood pressure, cardiac output, and urinary output of the patient. The infusion should be started at a rate of 2.5 micrograms/kg/minute and the dose may be increased at intervals of 10-30 minutes until the desired hemodynamic response is achieved or until side effects such as excessive tachycardia, arrhythmia, headache, or tremor limit further dose increases. The dose should be adjusted individually according to heart rate and rhythm, blood pressure, and urinary flow. Occasionally, a dose as low as 0.5 micrograms/kg/minute will produce a response. Up to 40 micrograms/kg/minute may be required.

During prolonged continuous infusion (48-72 hours), a decrease in hemodynamic response may occur, making a dose increase necessary.

Dose for cardiac stress test:

The use of dobutamine in cardiac stress tests should only be performed in units that already perform exercise stress tests and all normal care and precautions required for such tests when using dobutamine for this purpose are also required, including the availability of a defibrillator and specially trained personnel in resuscitation are present.

The recommended dose is a gradual increase in infusion rates of 5 micrograms/kg/minute to 10, 20, 30, and a maximum of 40 micrograms/kg/minute, each dose infused for 3 minutes. Additionally, atropine may be added during a new infusion of the maximum dose. Continuous monitoring of the electrocardiogram (ECG) is required and the infusion may be interrupted 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 a history of myocardial infarction or significant cardiac arrhythmias.

The dobutamine infusion should be interrupted if the heart rate reaches 85% of the predicted maximum for age, systolic blood pressure increases above 220 mmHg, or a symptomatic decrease in systolic blood pressure > 40 mmHg from the start, new wall motion abnormalities, severe chest pain occurs, or any intolerable adverse effect.

Elderly patients:

No dose variation is suggested. Close monitoring of blood pressure, urine flow, and peripheral tissue perfusion is required.

Cardiac stress test: when used as an alternative to exercise for cardiac stress testing, the recommended dose should start with 5 micrograms/kg/minute and the dose should be gradually increased by 5 micrograms/kg/minute every 8 minutes up to a maximum of 20 micrograms/kg/minute. Continuous ECG monitoring is essential and the infusion should be interrupted in case of ST segment depression > 3 mm or any ventricular arrhythmia. The infusion should also be interrupted if the heart rate reaches the maximum for age/sex, systolic blood pressure increases above 220 mmHg, or side effects occur.

Pediatric population:

For all pediatric age groups (newborns to 18 years), an initial dose of 5 micrograms/kg/minute is recommended, adjusted according to clinical response to 2 - 20 micrograms/kg/minute. Occasionally, a dose as low as 0.5-1.0 micrograms/kg/minute will produce a response.

There are reasons to believe that the minimum effective dose for children is higher than for adults. Caution should be exercised when applying high doses, as there are also reasons to believe that the maximum tolerated dose for children is lower than for adults. Most adverse reactions (tachycardia in particular) are observed when the dose was greater than or equal to 7.5 micrograms/kg/minute, but all that is required for the rapid reversal of adverse reactions is to reduce or interrupt the dobutamine infusion rate.

A great variability has been observed between pediatric patients with regard to both the plasma concentration required to initiate a hemodynamic response (threshold) and the rate of hemodynamic response to increasing plasma concentrations, demonstrating that the dose required for children cannot be determined a priori and must be titrated to allow for the supposed "therapeutic range" to be smaller in children.

Method of administration

Dobutamine Hikma should be diluted before use and administered only by intravenous infusion.

The concentration of dobutamine administered depends on the dose and the individual patient's fluid requirements. The final concentrations used for infusion are generally 250 micrograms/ml, 500 micrograms/ml, or 1000 micrograms/ml. For special precautions for the conservation of the diluted infusion prepared, see section 6.4. High concentrations of dobutamine should only be administered with an infusion pump or other suitable device to ensure precise dosing. Due to its short half-life, dobutamine should be administered as a continuous intravenous infusion. Dobutamine should be administered intravenously through an intravenous needle or catheter. The following sterile solutions for intravenous infusion can be used for the dilution of dobutamine before use: 5% injectable dextrose, 5% dextrose and 0.45% sodium chloride injectable, 5% dextrose and 0.9% sodium chloride injectable, 10% dextrose injection, electrolyte with 5% dextrose injectable, Ringer's lactate injectable, 5% dextrose Ringer's lactate injectable, 20% mannitol in water for injection, 0.9% sodium chloride injectable, and sodium lactate injectable.

Dose for infusion systems:

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

*For double concentration, e.g., 500 mg Dobutamine Hikma over 500 ml, or 250 mg over 250 ml of solution, the infusion rates should be reduced by half.

The dose to be administered can be calculated taking into account the following table.

The infusion rates in milliliters/minute can be obtained by multiplying the infusion rates for each concentration (ml/kg/minute) by the patient's weight (kg).

Dosing for syringe pumps:

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

Pediatric population

For continuous intravenous infusion with a syringe pump, dilute to a concentration of 0.5 to 1 mg/ml (maximum 5 mg/ml if there is fluid restriction) with 5% glucose or 0.9% sodium chloride. Infuse more concentrated solutions through the central venous catheter only. Intravenous infusion of dobutamine is incompatible with bicarbonate and other strong alkaline solutions.

Neonatal intensive care

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

• Incompatibilities

Do not add Dobutamine to an intravenous infusion of sodium bicarbonate 5% or other highly alkaline solutions. Due to possible physical incompatibilities, it is recommended that dobutamine hydrochloride not be mixed with other medications in the same solution.

Dobutamine Hikma injections should not be used with other agents or diluents that contain sodium metabisulfite and ethanol.

• Shelf life

2 years

Chemical and physical stability has been demonstrated for 24 hours at 25°C (room temperature).

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions before use are the responsibility of the user and normally would not exceed 24 hours between 2 and 8°C, unless the dilution has been performed under controlled and validated aseptic conditions.

• Special precautions for disposal and other handling

Dobutamine Hikma should be diluted to at least 50 ml prior to administration in an IV container with any of the following intravenous solutions:

• 5% dextrose solution
• 5% dextrose and 0.45% sodium chloride solution
• 5% dextrose and 0.9% sodium chloride solution
• 10% dextrose solution
• multi-electrolyte solution with 5% dextrose
• Ringer's lactate solution
• 5% dextrose in Ringer's lactate solution
• 20% mannitol in water for injectable preparations
• 0.9% sodium chloride solution
• sodium lactate solution

For example, diluting 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 should be used within 24 hours.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.