Prospect: information for the patient

Dobutamine Hikma 12.5 mg/ml concentrate for infusion solution EFG

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you and should not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

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

It is used in adults:

- during open-heart surgery,

- to treat heart diseases,

- to treat heart failure,

- as an alternative to exercise for heart stress tests.

Pediatric population

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

Do not use Dobutamina Hikma:

Do not use Dobutamina Hikma also for examining your heart if:

Warnings and precautions

Speak with your doctor or nurse before using this medication.

Speak with 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 the concentration of potassium 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

The 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 appears to be observed more frequently in adult patients than in small children. Therefore, the use of dobutamine should be closely monitored in children.

Other medications and Dobutamina Hikma

Inform your doctor if you are using, have used recently or may use any other medication.

This is especially important with the following medications, as they may interact with your Dobutamina Hikma:

- Monoamine oxidase inhibitors (depression treatments)

- Beta-blockers such as propranolol or metoprolol

- Alpha-blockers (for high blood pressure or prostate enlargement)

- ACE inhibitors, e.g. captopril (for high blood pressure or heart failure)

- Antipsychotics (mental illness treatments)

- Oxytocin (used in childbirth)

- Peripheral vasoconstrictors such as norepinephrine

- Peripheral vasodilators (e.g. nitrates, sodium nitroprusside)

- Ergotamine or methysergide (migraine treatments)

- Dipiridamol (an anticoagulant)

- General anesthetics

- Theophylline (an asthma treatment)

- Entacapone (a medication for Parkinson's disease)

- Doxapram (for respiratory problems)

- Atropine sulfate (for iris inflammation or eye exams)

Pregnancy and breastfeeding

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

Driving and operating machinery

Not applicable due to the indications of use and the short half-life of the drug.

Dobutamina Hikma contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per milliliter, which is essentially "sodium-free".

Dobutamina Hikma contains sodium metabisulfite (E223)

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

A doctor or nurse will administer this medication in the hospital. This medication is diluted and infused into a vein.

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

Dose for heart stimulation.

Adults and elderly patients:

The usual dose is 2.5 to 10 micrograms/kg (body weight)/min, adjusted according to heart rate, blood pressure, cardiac output, and urine output. 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.

Older adults:

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) a recommended initial dose of 5 micrograms/kg/min is suggested, adjusted according to clinical response to 2-20 micrograms/kg/min. Occasionally, a dose as low as 0.5-1.0 micrograms/kg/min may produce a response. The dose required for children should be titrated to take into account the presumed "therapeutic window" that is smaller in children.

If you use more Dobutamina Hikma than you should

Since the injection will be administered by a doctor or nurse, it is unlikely that you will receive an excessive amount.

Like all medications, dobutamine may have side effects, although not everyone will experience them.

The following side effects have been described:

Very common (affects more than 1 in 10 patients)

Common (affects 1 to 10 patients per 100)

Uncommon (affects 1 to 100 patients per 1,000)

Rare (affects 1 to 10 patients per 10,000)

Very rare (affects fewer than 1 in 10,000 patients)

Unknown (cannot be estimated from available data)

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

Your doctor and pharmacist are responsible for the correct storage, use, and disposal of this medication.

Keep this medication out of the sight and reach of children.

Store below 25 °C.

Do not use this medication after the expiration date that appears on the box after CAD. The first number indicates the month and the last four numbers indicate the year. The expiration date refers to the last day of the month indicated.

Composition of Dobutamine Hikma

- The active ingredient is chlorhydrate of dobutamine.

- The other components are sodium metabisulphite (E223), sodium hydroxide, hydrochloric acid and water for injection.

Cada ml contiene 12,5 mg de dobutamina (como 14,01 mg de hidrocloruro de dobutamina).

Cada vial de 20 ml contiene 250 mg de dobutamina (como 280,2 mg de hidrocloruro de dobutamina).

Aspect of the product and content of the packaging

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

Holder of the marketing authorization and responsible for the manufacture

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 medication by contacting the local representative of the holder of the marketing authorization:

Hikma España, S.L.U.

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

28108 - Alcobendas, Madrid

Spain

This medication is authorized in the member states of the Economic European Space with the following names:

Italy:Dobutamine Hikma 12.5 mg/ml, Concentrate for solution for infusion

Portugal:Dobutamine Hikma

Last review date of this leaflet:02/2022

The detailed and updated information of this medication is available on the website of the Spanish Agency of Medicines and Medical Products (AEMPS)http://www.aemps.gob.es/

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The following information is only directed to healthcare professionals:

• Dosage and method of administration

Only for intravenous route.

Dosage

Adults

Cardiac inotropic support:

The usual dose is 2.5 to 10 micrograms/kg/minute, which should be adjusted according to the patient's heart rate, blood pressure, cardiac output and urine output. The infusion should start at a rate of 2.5 micrograms/kg/minute and the dose can be increased in 10-30 minute intervals until the desired hemodynamic response is achieved or until side effects such as excessive tachycardia, arrhythmia, headache or tremor limit, an additional increase in dose. The dose should be adjusted individually according to the patient's heart rate and rhythm, blood pressure and urine flow. Occasionally, a dose as low as 0.5 micrograms/kg/minute will produce a response. It may be necessary to administer up to 40 micrograms/kg/minute.

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

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 also require all the usual precautions required for such tests when dobutamine is used for this purpose, 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, infusing each dose for 3 minutes. In addition, atropine may be added during a new infusion of the maximum dose. Continuous ECG monitoring is required and the infusion should 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 infusion of dobutamine 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 or any intolerable side effect.

Older patients:

No dosage adjustment 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 increased gradually in 5 micrograms/kg/minute every 8 minutes until a maximum frequency of 20 micrograms/kg/minute is reached. 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 if side effects occur.

Pediatric population:

For all pediatric age groups (newborns to 18 years) a starting 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 superior/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 infusion rate of dobutamine.

A great variability has been observed between pediatric patients with respect 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 required dose for children cannot be determined a priori and should be titrated to allow the assumed "therapeutic range" to be as small as possible 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 patient's individual 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 prepared infusion, see section 6.4. High concentrations of dobutamine should only be administered with a syringe pump or other suitable device to ensure precise dosing. Due to its short half-life, dobutamine should be administered as an intravenous continuous infusion. Dobutamine should be administered intravenously through a needle or intravenous catheter. The following sterile solutions for intravenous infusion may be used to dilute dobutamine before use: 5% dextrose injection, 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection, 10% dextrose injection, electrolyte solution with 5% dextrose injection, lactate Ringer injection, 5% dextrose lactate Ringer injection, 20% mannitol in water for injection, 0.9% sodium chloride injection and sodium lactate injection.

Dose for infusion systems:

A vial of Dobutamine Hikma 12.5 mg/ml (250 mg/20 ml) diluted to a 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 halved.

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

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

Dosage for syringe pumps:

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

Pediatric population

For intravenous continuous infusion with a syringe pump, dilute to a concentration of 0.5 to 1 mg/ml (maximum 5 mg/ml if fluid restriction is present) with 5% glucose or 0.9% sodium chloride. Infuse solutions of higher concentration 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 solution. A rate of intravenous infusion of 0.5 ml/hour provides a dose of 5 micrograms/kg/minute.

• Incompatibilities

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

The injections of dobutamine Hikma should not be used with other agents or diluents that contain sodium metabisulphite and ethanol.

• Expiration date

2 years

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

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

• Special precautions for disposal and other manipulations

Dobutamine Hikma should be diluted at least with 50 ml, prior to administration in a 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,

-electrolyte solution with 5% dextrose;

-lactate Ringer solution;

-5% dextrose in lactate Ringer solution;

-20% mannitol in water for injection;

-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 contain 1,000 micrograms/ml of dobutamine

500 ml contain 500 micrograms/ml of dobutamine

The prepared solution should be used within 24 hours.

Any unused medication or waste should be disposed of in accordance with local requirements.